Download lidocaine

LIDOCAINE
DRUGDEX® Evaluations
OVERVIEW
1) Class
a) This drug is a member of the following class(es):
Amino Amide
Anesthetic, Local
Antiarrhythmic, Group IB
2) Dosing Information
a) Lidocaine
1) Adult
a) Local anesthesia, Topical
1) (5% ointment) single TOPICAL application not exceeding 5 g of ointment (containing
250 mg of lidocaine base); roughly equivalent to a 6 inch length of ointment from the
tube; MAX dose of 17 to 20 g of ointment (850 to 1000 mg lidocaine base) per day
[20]
b) Postherpetic neuralgia
1) apply up to 3 patches TOPICALLY at one time, for up to 12 hours within a 24-hour
period
[40]
2) Pediatric
a) Local anesthesia, Topical
1) (5% ointment) MAX dose of 4.5 mg/kg TOPICALLY
[20]
b) Lidocaine Hydrochloride
1) Adult
a) Cataract surgery - Topical local anesthetic
1) apply 2% gel TOPICALLY 3-5 times during 15-20 min prior to surgery; instill 2 drops
of 4% solution in both eyes, 6 times in the 60 min prior to surgery
b) Cervical sympathetic block
1) 5 mL of a 1% solution injection for a total dose of 50 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
c) Local anesthesia, by infiltration, Percutaneous
1) 1 to 60 mL of a 0.5 to 1% solution IV for a total dose of 5 to 300 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
d) Local anesthesia, Superficial dermatological procedures
1) (iontophoretic system) Ramp-up, 0-1.77 milliamperes over a 30-second period
[221]
2) (iontophoretic system) Main delivery, 1.77 milliamperes for 9 minutes
[221]
3) (iontophoretic system) Ramp-down, current is slowly ramped down to zero over a 30second period
[221]
e) Local anesthetic intravenous regional block
1) 10 to 60 mL of a 0.5% solution IV for a total dose of 50 to 300 mg
[65]
2) the maximum individual dose should not exceed 4 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
f) Local anesthetic lumbar epidural block
1) dose determined by number of dermatomes to be anesthetized (2 to 3 mL per
dermatome)
[65]
2) 15 to 20 mL of a 1.5% solution injection for a total dose of 225 to 300 mg or 10 to 15
mL of a 2% solution injection for a total dose of 200 to 300 mg
[65]
3) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
g) Local anesthetic sacral epidural block, Obstetrical analgesia
1) 20 to 30 mL of a 1% solution injection for a total dose of 200 to 300 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
h) Local anesthetic sacral epidural block, Surgical anaesthesia
1) 15 to 20 mL of a 1.5% solution injection for a total dose of 225 to 300 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
i) Local anesthetic thoracic epidural block
1) 20 to 30 mL of a 1% solution injection for a total dose of 200 to 300 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
j) Lumbar sympathetic block
1) 5 to 10 mL of a 1% solution injection for a total dose of 50 to 100 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
k) Operation on urinary system
1) (2% jelly) MALES: 15 mL (300 mg) instilled intraurethrally; an additional dose of 15
mL (300 mg) can be given for adequate anesthesia; MAX 600 mg in a 12-hour period
[198]
2) (2% jelly) FEMALES: 3 to 5 mL (60 to 100 mg) instilled intraurethrally; MAX 600 mg
in a 12-hour period
[198]
l) Paracervical block anesthesia
1) 10 mL of a 1% solution injection each side for a total dose of 100 mg on each side
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
m) Peripheral block anesthesia, Brachial
1) 15 to 20 mL of a 1.5% solution injection for a total dose of 225 to 300 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
n) Peripheral block anesthesia, Dental
1) 1 to 5 mL of a 2% solution injection for a total dose of 20 to 100 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
o) Peripheral block anesthesia, Intercostal
1) 3 mL of a 1% solution injection for a total dose of 30 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
p) Peripheral block anesthesia, Paravertebral
1) 3 to 5 mL of a 1% solution injection for a total dose of 30 to 50 mg
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
q) Peripheral block anesthesia, Pudendal
1) 10 mL of a 1% solution injection each side for a total dose of 100 mg each side
[65]
2) the maximum individual dose should not exceed 4.5 mg/kg and the maximum total
dose of 300 mg should not be exceeded
[65]
r) Procedure on eye - Topical local anesthetic
1) (ophthalmic gel) instill 2 drops TOPICALLY to eye in area of planned procedure; may
repeat to maintain anesthesia
[51]
s) Rapid sequence intubation, Preinduction
1) 1.5 mg/kg IV 2 to 3 minutes prior to intubation
[107]
t) Spinal anesthesia
1) obstetrical (vaginal delivery), 50 mg (1 mL) of 5% Xylocaine-MPF(R) with glucose
7.5% OR 9 to 15 mg (0.6 to 1 mL) of 1.5% Xylocaine-MPF(R) with dextrose 7.5%
2) surgical (abdominal) anesthesia, 75 to 100 mg (1.5 to 2 mL) of 5% Xylocaine-MPF(R)
with glucose 7.5%
u) Topical local anesthetic to mucous membrane
1) viscous lidocaine 2%: for the mouth, 15 mL swish and spit every 3 hours as needed;
for the pharynx, 15 mL gargled and may be swallowed every 3 hours as needed;
maximum 8 doses/day or 4.5 mg/kg lidocaine hydrochloride
[53]
v) Ventricular arrhythmia
1) loading dose, 50 to 100 mg (0.7 to 1.4 mg/kg) IV over 2 to 3 min, may repeat in 5 min
up to 300 mg in any 1-hr period; maintenance, at a rate of 1 to 4 mg/min (0.014 to 0.057
mg/kg/min) IV
[83]
w) Ventricular fibrillation
1) initial dose, 1 to 1.5 mg/kg IV; if ventricular fibrillation/pulseless ventricular
tachycardia persists, additional doses of 0.5 to 0.75 mg/kg IV every 5 to 10 minutes to a
maximum of 3 mg/kg can be given
[85]
2) Pediatric
a) Cervical sympathetic block
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
b) Local anesthesia, by infiltration, Percutaneous
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
c) Local anesthetic intravenous regional block
1) dilute solutions (0.25 to 0.5%) and total dosages not to exceed 3 mg/kg are
recommended for induction of intravenous regional anesthesia in children
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
d) Local anesthetic lumbar epidural block
1) the lowest effective concentration and dose should be used at all times
[65]
2) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
e) Local anesthetic sacral epidural block, Surgical anaesthesia
1) the lowest effective concentration and dose should be used at all times
[65]
2) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
f) Local anesthetic thoracic epidural block
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
g) Lumbar sympathetic block
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
h) Peripheral block anesthesia, Brachial
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
i) Peripheral block anesthesia, Dental
1) maximum recommended dose of lidocaine hydrochloride is 5 mg/kg of body weight
and 7 mg/kg of body weight with epinephrine; use caution in children under 2 years of
age
[73]
.
2) dental procedure, maximum recommended dose of lidocaine hydrochloride (with
epinephrine) is 7 mg/kg of body weight
[74]
3) administer the least volume of solution that produces effective local anesthesia
[74]
j) Peripheral block anesthesia, Intercostal
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
k) Peripheral block anesthesia, Paravertebral
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
l) Peripheral block anesthesia, Pudendal
1) children over 3 years of age with normal lean body mass and body development, the
maximum dose is determined by age and weight (3.3 to 4.4 mg/kg)
[65]
2) the lowest effective concentration and dose should be used at all times
[65]
m) Rapid sequence intubation, Preinduction
1) 1 to 2 mg/kg IV 2 to 5 minutes prior to intubation
[108]
[109]
n) Topical local anesthetic to mucous membrane
1) viscous lidocaine 2%: children 3 years and older, approximately 3.3 to 4.4 mg/kg
swish and split (for the mouth) or swish and swallow (for the pharynx) every 3 hours as
needed; maximum 8 doses/day
[53]
2) viscous lidocaine 2%: infants and children less than 3 years of age, 1.25 mL applied
TOPICALLY to immediate area with cotton-tipped applicator every 3 hours as needed;
maximum 8 doses/day
[53]
o) Topical local anesthetic to wound
1) 4% and 5% creams, children less than 10 kg, apply TOPICALLY to an area not larger
than 100 cm(2)
2) 4% and 5% creams, children 10-20 kg, apply TOPICALLY to an area not larger than
200 cm(2)
p) Ventricular arrhythmia
1) loading dose, 1 mg/kg IV/INTRAOSSEOUS (maximum dose 100 mg); infusion, 20 to
50 mcg/kg/min
[84]
3) Contraindications
a) Lidocaine
1) hypersensitivity to local anesthetics of the amide type or to any other component of
the product
[255]
[40]
[251]
b) Lidocaine Hydrochloride
1) sensitivity to local anesthetics of the amide type
[257]
or to any other component of the product
[73]
4) Serious Adverse Effects
a) Lidocaine
1) Anaphylaxis
2) Cardiac arrest
3) Cardiac dysrhythmia
4) Methemoglobinemia
b) Lidocaine Hydrochloride
1) Cardiac arrest
2) Cardiac dysrhythmia
3) Chondrolysis of articular cartilage
4) Heart block
5) Loss of consciousness
6) Methemoglobinemia
7) Seizure
8) Tremor
5) Clinical Applications
a) Lidocaine
1) FDA Approved Indications
a) Local anesthesia, Topical
b) Postherpetic neuralgia
b) Lidocaine Hydrochloride
1) Important Note
a) Lidocaine hydrochloride monohydrate powder intradermal injection system
(Zingo(TM)) was recalled on November 11, 2008 due to nonsafety-related regulatory
compliance issues which could affect product shelf life. Anesiva has no plans to
distribute Zingo(TM) in the future
[254]
.
2) FDA Approved Indications
a) Cervical sympathetic block
b) Local anesthesia, by infiltration, Percutaneous
c) Local anesthesia, Superficial dermatological procedures
d) Local anesthetic intravenous regional block
e) Local anesthetic lumbar epidural block
f) Local anesthetic sacral epidural block, Obstetrical analgesia
g) Local anesthetic sacral epidural block, Surgical anaesthesia
h) Local anesthetic thoracic epidural block
i) Lumbar sympathetic block
j) Operation on urinary system
k) Paracervical block anesthesia
l) Peripheral block anesthesia, Brachial
m) Peripheral block anesthesia, Dental
n) Peripheral block anesthesia, Intercostal
o) Peripheral block anesthesia, Paravertebral
p) Peripheral block anesthesia, Pudendal
q) Procedure on eye - Topical local anesthetic
r) Rapid sequence intubation, Preinduction
s) Spinal anesthesia
t) Topical local anesthetic to mucous membrane
u) Topical local anesthetic to wound
v) Ventricular arrhythmia
w) Ventricular fibrillation
3) Non-FDA Approved Indications
a) Cataract surgery - Topical local anesthetic
DOSING INFORMATION
Drug Properties
A) Information on specific products and dosage forms can be obtained by
referring to the Tradename List (Product Index)
B) Synonyms
Lido
Lidocaine
Lidocaine HCl
Lidocaine Hydrochloride
Lido HCl
Lignocaine
C) Orphan Drug Status
1) Lidocaine patch 5% has been designated an orphan product for use in
treatment of postherpetic pain following herpes zoster infection.
D) Physicochemical Properties
1) Molecular Weight
a) Base: 234.34
[763]
; hydrochloride: 270.8
[257]
; hydrochloride monohydrate: 288.8 Daltons
[56]
2) Partition Coefficient
a) Octanol-water: base, 43 at pH 7.4
[40]
3) pH
a) approximately 6.5 (range, 5 to 7)
[257]
4) Solubility
a) Lidocaine hydrochloride monohydrate is freely soluble in water, soluble in
alcohol and chloroform, and insoluble in ether
[56]
.
5) Lidocaine hydrochloride monohydrate has a melting point of about 74 to 79
degrees C
[56]
.
Storage and Stability
A) Lidocaine
1) Preparation
a) Topical application route
1) Improper use (applying too much, applying to a large area, applying to irritated
or broken skin, or covering the skin with a wrap or using a heating pad after
application) of topical anesthetics, including lidocaine, may lead to life-threatening
adverse effects
[30]
.
2) Patches may be cut into smaller sizes prior to removal of release liner. Apply to
intact skin and remove patch after a maximum of 12 hours of application within a
24-hour period
[40]
.
B) Lidocaine Hydrochloride
1) Preparation
a) General Information
1) Administration Technique
a) In two randomized, double-blinded studies, LIDOCAINE with or without
epinephrine and MEPIVACAINE have been shown to be statistically less painful
when buffered with SODIUM BICARBONATE
[63]
[64]
. Addition of 2 milliliters (mL) of sodium bicarbonate (1 milliequivalent per milliliter
(mEq/mL)) to 20 mL of local anesthetic (1% lidocaine with or without epinephrine
or 1% mepivacaine) raised the pH to 7.2. With the use of a linear visual analog
pain scale, normal volunteers compared the pain produced by the timed
infiltration on their dorsal hands of these unbuffered solutions (pH 5.98 to 6.21)
with the same buffered anesthetics. Infiltration with the unbuffered anesthetics
was found to be 2.8 to 5.7 times more painful as their buffered counterparts.
There was no significant difference detected in the time of onset or duration of
anesthesia or the surface area of skin anesthetized
[63]
.
b) Intravenous route
1) Intravenous Rate Of Administration
a) In pediatric patients (17 years and younger), it is recommended that lidocaine
be infused at a rate of 20 to 50 micrograms/kilogram/minute. The dilution can vary
but generally 2 grams is diluted in 500 milliliters of fluid. Patients should be
monitored for seizures, hypotension and depression of cardiac conductivity. The
drug may also be administered by direct intravenous push when diluted to 20
milligrams/milliliter or 40 milligrams/milliliter and infused at a rate of 1
milligram/kilogram over 2 minutes
[240]
.
c) Subcutaneous route
1) Subcutaneous Administration
a) Warming of lidocaine to body temperature (37 degrees centigrade) in a warm
water bath prior to drawing the lidocaine solution up into a syringe may reduce the
pain associated with subcutaneous injection
[234]
[235]
[236]
[237]
. In contrast, some studies have reported no benefit from warming lidocaine
solutions prior to injection
[238]
[239]
.
d) Topical application route
1) (Ointment) apply thin layer, use a sterile gauze pad for application to broken
and burned tissue
[251]
.
2) (Ointment) for endotracheal intubation, apply ointment to tube prior to
intubation
[251]
.
3) (Ointment) for sore nipples, apply on a small gauze, wash away ointment
before next feeding
[251]
.
4) (Solution) apply with sterile swab; discard after use; may use as a spray using
an atomizer
[252]
.
5) (Jelly) for endotracheal intubation, apply to tube prior to intubation; do not use
jelly to lubricate endotracheal stylettes
[253]
.
6) (Jelly) for surface anesthesia of urethra, sterilize plastic applicator cone for 5
min in boiling water and cool OR use gas or cold sterilization; attach to tube;
slowly instill jelly into urethra
[253]
.
C) Epidural route, Injection route, Intravenous route
1) Solution
a) Store at room temperature, approximately 25 degrees C (77 degrees F).
Protect from light
[517]
.
b) When packaged in 2 mL Tubex cartridges (20 mg/mL) potency was found to be
retained for 3 months at room temperature
[518]
.
c) When mixed with 5% dextrose injection in plastic infusion bags to a
concentration of 4 mg/mL, solution is chemically stable for up to 120 days at
either room temperature (30 degrees C) or refrigeration (4 degrees C)
[519]
.
d) Lidocaine (448 mg/L) is stable for 21 days in a buffered cardioplegic solution
containing potassium chloride (20 mEq/L), sodium bicarbonate (25 mEq/L),
dextrose (17 g/L), and sodium chloride (8.3 g/L) when refrigerated and stored in
glass bottles or large volume (500 mL) polyvinyl chloride bags
[520]
.
e) One study reports lidocaine 1% buffered to a pH of 7.38 to 7.41 remains
effective for as long as 1 week after preparation when stored at room
temperature. The lidocaine concentration of the buffered solution decreased by
about 10% after 1 week of storage, but this was not clinically significant
[521]
.
D) Ophthalmic route
1) Gel/Jelly
a) Store in original carton between 15 and 25 degrees C (59 and 77 degrees F).
Protect from light
[51]
.
E) Topical application route
1) Gel/Jelly/Patch, Extended Release/Solution
a) Gel/Jelly
1) Store at controlled room temperature, between 20 and 25 degrees C (68 and
77 degrees F)
[522]
.
b) Patch
1) Store at controlled room temperature, between 15 and 30 degrees C (59 and
86 degrees F). Envelope should remain sealed at all times when not in use
[523]
.
c) Solution
1) Store between 15 and 30 degrees C. Protect from freezing
[260]
.
F) Extemporaneous Formulation - Topical application route
1) LET Solution
a) An extemporaneously prepared topical anesthetic solution containing lidocaine
HCl 40 mg/mL, racepinephrine HCl 2.25 mg/mL, tetracaine hydrochloride 5
mg/mL, and sodium metabisulfite 0.63 mg/mL was found to be stable in amber
glass bottles for 4 weeks at 18 degrees C and for 26 weeks at 4 degrees C
[912]
.
Adult Dosage
Normal Dosage
Important Note
1) Lidocaine hydrochloride monohydrate powder intradermal
injection system (Zingo(TM)) was recalled on November 11, 2008
due to nonsafety-related regulatory compliance issues which could
affect product shelf life. Anesiva has no plans to distribute
Zingo(TM) in the future
[254]
.
Neurological deficits (eg, Cauda Equina syndrome) have been
reported with the use of small-bore needles and microcatheters for
lidocaine spinal anesthesia. The lidocaine solution used in these
case reports was 5% lidocaine with glucose 7.5%. The
manufacturer suggests that mixing 5% lidocaine with an equal
volume of cerebrospinal fluid (CSF) or preservative-free 0.9% saline
solution may reduce the risk of nerve injury. Use a spinal needle of
sufficient gauge to ensure adequate withdrawal of CSF and
intrathecal distribution of anesthetic before and after administration
into the subarachnoid space
[50]
.
Lidocaine
Oral route
Hiccoughs, Intractable
1) A 2% viscous lidocaine solution administered orally
at a dose of 5 mL up to 4 times daily was effective for
intractable hiccups in 4 cancer patients; the addition of
baclofen 20 to 30 mg/day orally may extend the
duration of lidocaine's efficacy
[19]
.
Topical application route
Local anesthesia, Topical
1) The recommended dose of the 5% ointment for
local anesthesia is a single topical application not
exceeding 5 g (containing 250 mg of lidocaine base).
This is approximately equivalent to a 6-inch length of
ointment from the tube. The maximum dose is 17 to 20
g of ointment (850 to 1000 mg of lidocaine base) per
day
[20]
.
Transdermal route
Postherpetic neuralgia
1) Lidocaine 5% patch (Lidoderm(R)) should be
applied to intact skin only, covering the most painful
area(s). Remove release liner and apply up to 3
patches at one time, for up to 12 hours within a 24hour period. Patches may be cut into smaller sizes
with scissors prior to removal of the release liner.
Clothing may be worn over the patches. Dose
reductions (eg, fewer patches, smaller areas of
treatment, shorter application times) may be required
in a debilitated patient or a patient with impaired
elimination (eg, hepatic disease). If irritation or burning
occurs at the application site, remove the patch(es)
and do not reapply until the irritation subsides. Store
and dispose of patches carefully, used patches
contain large amounts of lidocaine (up to 95%) and if
ingested or chewed, particularly by children or pets,
can lead to serious adverse effects. Wash hands after
handling patches and avoid contact with eyes. Use on
smaller patients, applying to broken or inflamed skin,
application of more than the recommended number of
patches, applying to larger areas, and applying for a
longer duration than recommended may increase the
risk of a serious adverse effect
[40]
[42]
.
Lidocaine Hydrochloride
Intradermal route
a) The addition of sodium bicarbonate to lidocaine decreases
the pain associated with intradermal infiltration of lidocaine. In
this prospective, randomized study, 40 patients received 4
intradermal injections consisting of 4 milliliters (mL) of 2%
lidocaine with or without 1 mL of 8.4% sodium bicarbonate
(resultant pH 7.26) via a 25- or 30-gauge needle. The
addition of sodium bicarbonate is more significant than
needle size in decreasing the pain associated with
intradermal injection of lidocaine
[227]
. Other studies have also reported that compared to plain
lidocaine, buffered lidocaine significantly decreases the pain
associated with local anesthetic infiltration
[61]
[62]
[63]
[64]
. In contrast, one study reported that buffered lidocaine is no
more effective than plain lidocaine for reducing the pain
associated with local anesthetic infiltration
[60]
.
Intramuscular route
Ventricular arrhythmia
1) The recommended intramuscular dose for the
treatment of ventricular arrhythmias is 300 milligrams
(3 milliliters of a 10% solution) injected into the deltoid
or quadriceps muscle
[99]
[66]
.
Intraperitoneal route
a) The efficacy and benefit of intraperitoneal administration of
lidocaine for local anesthesia or analgesia is questionable
[231]
[232]
[233]
. In 1 study, intraperitoneal administration of a lidocaine
solution into the pelvic cavity did not produce adequate
analgesia in patients undergoing abdominal hysterectomy.
The solution administered consisted of 20 milliliters (mL) of
2% lidocaine with epinephrine 1:200,000 diluted with saline to
a final volume of 50 mL
[231]
.
Intratracheal route
a) Available studies have used endotracheal lidocaine in
doses of 2.4 to 7.7 milligram/kilogram, which did result in
peak serum levels in the toxic range in some patients. In
most patients, these doses attained therapeutic serum levels
in approximately 5 minutes, with levels being maintained for
30 to 60 minutes
[226]
.
Intravenous route
Local anesthetic intravenous regional block
1) Recommended adult dose is 50 milligrams up to
300 milligrams (10 to 60 milliliters) as a 0.5% lidocaine
solution for intravenous regional infiltration. For
intravenous regional anesthesia, the dose
administered should not exceed 4 milligrams/kilogram
in adults. For percutaneous infiltration, the
recommended adult dose is 5 milligrams up to 300
milligrams (1 to 60 milliliters) as a 0.5 or 1% lidocaine
solution (Prod Info Xylocaine(R), 2000).
Ventricular arrhythmia
1) For the treatment of ventricular arrhythmias, the
recommended loading dose of lidocaine hydrochloride
is 50 to 100 mg (0.7 to 1.4 milligrams/kilogram (mg/kg)
intravenously at a rate of approximately 25 to 50
mg/minute (0.35 to 0.7 mg/kg/minute). A second dose
can be given after 5 minutes if desired clinical
response is not produced. ECG monitoring is
recommended during administration. After the loading
dose, a continuous intravenous infusion should be
initiated at a rate of 1 to 4 mg/minute (0.014 to 0.057
mg/kg/minute)
[83]
.
Ventricular fibrillation
1) In patients with ventricular fibrillation/pulseless
ventricular tachycardia, the initial dose of lidocaine
hydrochloride is 1 to 1.5 milligrams/kilogram (mg/kg)
intravenously. If ventricular fibrillation/pulseless
ventricular tachycardia persists, additional doses of
0.5 to 0.75 mg/kg every 5 to 10 minutes to a maximum
of 3 mg/kg can be given
[85]
.
Intravenous route/Parenteral route
Cervical sympathetic block
1) Cervical nerve block
a) The recommended adult dose is 50 milligrams (5
milliliters) as a 1% lidocaine solution for cervical
(stellate ganglion) nerve block. (Prod Info
Xylocaine(R), 2000).
Local anesthetic lumbar epidural block
1) Lumbar epidural anesthesia
a) Recommended total adult dose is 250 milligrams up
to 300 milligrams (25 to 30 milliliters) as a 1%
lidocaine solution for lumbar analgesia. For lumbar
anesthesia, the recommended total adult dose is 225
milligrams up to 300 milligrams (15 to 20 milliliters) as
a 1.5% lidocaine solution or 200 milligrams to 300
milligrams (10 to 15 milliliter) as a 2% lidocaine
solution. For thoracic anesthesia, the recommended
total adult dose is 200 milligrams up to 300 milligrams
(20 to 30 milliliters) as a 1% lidocaine solution. The
actual dose is based on the number of dermatomes to
be anesthetized (eg, 2 to 3 milliliters of the
recommended concentration per dermatome). As a
precaution against unintentional penetration into the
subarachnoid space, a test dose (eg, 2 to 3 milliliters
of 1.5% lidocaine) should be administered at least 5
minutes prior to injecting the total volume required for
a lumbar or caudal epidural block. If the patient is
moved in a manner that may have displaced the
catheter, the test dose should be repeated. For
continuous epidural anesthesia, the maximum dose
should not be repeated at intervals of less than 90
minutes (Prod Info Xylocaine(R), 2000).
b) Concentration and volume with a fixed total dose of
lidocaine can affect the quality of lumbar epidural
block. According to the results of 1 study, lumbar
epidural anesthesia with 10 milliliters (mL) of 2%
lidocaine produces a more intense blockade of large
and small diameter sensory nerves than 20 mL of 1%
lidocaine
[80]
.
c) The addition of epinephrine to lidocaine improves
the quality of sensory block during lumbar epidural
anesthesia. According to the results of 1 study, lumbar
epidural anesthesia using 10 milliliters of 1% lidocaine
with epinephrine 1:200,000 produces a more intense
sensory block of both large and small diameter
sensory nerve fibers than that with lidocaine alone.
There were no differences in maximal dermatomal
levels of loss of cold, pinprick, and touch sensations
between either of the lidocaine solutions. There were
no significant changes in arterial blood pressure, heart
rate, or pulse oximetry after either lidocaine solution
[81]
. Epinephrine's effect on the duration of sensory block
was not evaluated.
d) The addition of sodium bicarbonate to lidocaine
enhances the depth of epidural blockade (ie,
analgesia). In 1 study, the addition of 2 milliliters (mL)
of 8.4% sodium bicarbonate, added immediately
before injection, to 20 mL of 2% lidocaine
hydrochloride resulted in higher pain thresholds (p less
than 0.0001), a faster onset of action (p=0.009), and a
higher degree of motor block (p=0.004) compared with
lidocaine hydrochloride alone
[82]
.
Local anesthetic sacral epidural block, Obstetrical
analgesia
1) Caudal anesthesia
a) The recommended adult dose is 200 milligrams up
to 300 milligrams (20 to 30 milliliters) as a 1%
lidocaine solution for obstetrical analgesia
[79]
(Prod Info Xylocaine(R), 2000).
Myocardial infarction - Ventricular arrhythmia
1) Routine prophylactic use of lidocaine for the
treatment of ACUTE MYOCARDIAL INFARCTION is
NOT recommended. Episodes of ventricular fibrillation
(VF) and monomorphic ventricular tachycardia (VT)
associated with angina, pulmonary congestion, or
hypotension should be treated by defibrillation.
Monomorphic VT not associated with angina,
pulmonary congestion, or hypotension may be treated
with intravenous lidocaine. In addition, episodes of
VF/VT that are not easily converted by defibrillation
and epinephrine (ie, resistant VF/VT) may be treated
with lidocaine. Lidocaine is given in an initial bolus of 1
to 1.5 milligrams(mg)/kilogram(kg) (75 to 100 mg);
additional boluses of 0.5 to 0.75 mg/kg (25 to 50 mg)
can be given every 5 to 10 minutes (min) if needed up
to a maximum of 3 mg/kg. Loading is followed by a
maintenance infusion of 2 to 4 mg/min (30 to 50
micrograms/kg/min), reduced after 24 hours (to 1 to 2
mg/min) or in the setting of altered metabolism (eg,
heart failure, liver congestion) and as guided by blood
level monitoring. Ideally, if a lidocaine infusion is
initiated, it should be maintained for only 6 to 24 hours
and then discontinued so that the patient's need for
antiarrhythmic therapy can be reassessed (Anon,
2000)
[86]
[87]
[88]
[89]
[90]
.
2) Although the PROPHYLACTIC USE OF
LIDOCAINE IN THE SETTING OF ACUTE
MYOCARDIAL INFARCTION IS NO LONGER
RECOMMENDED, the following dosing data have
been retained for historical purposes. For prophylaxis
following an acute myocardial infarction, a loading
dose of 200 milligrams (mg) is given as four 50 mg
injections 5 minutes apart, or as a 20-mg/minute
intravenous infusion for 10 minutes. An infusion is
started simultaneously at a rate of 2 to 3 mg/minute,
and should be continued for 24 to 36 hours. If
symptomatic ventricular arrhythmias occur during
these infusions, a small bolus dose may be given and
the rate increased
[66]
. Alternatively, a loading dose of 100 mg may be
administered followed by a continuous infusion as 3
mg/minute
[192]
.
Paracervical block anesthesia
1) Paracervical
a) The recommended adult dose is 100 milligrams
(mg) (10 milliliters) as a 1% lidocaine solution for
obstetrical analgesia (each side). The maximum
recommended dose per 90 minute period of lidocaine
hydrochloride for paracervical block in obstetrical and
non-obstetrical patients is 200 mg total. Half of the
total dose is usually administered to each side The
injection should be slow with 5 minutes between sides
(Prod Info Xylocaine(R), 2000).
Peripheral block anesthesia, Brachial
1) The lidocaine dose for nerve block is dependent on
the desired nerve area to be blocked. The following
are the recommended adult lidocaine doses (Prod Info
Xylocaine(R), 2000):
Brachial
225 up to 300 milligrams (15 to 20 milliliters) as a
1.5% lidocaine solution
2) Alkalinization of plain lidocaine 1% with sodium
bicarbonate 0.1 mmol/L for median nerve block
increases the rate of motor block without changing the
onset or extent of sensory block. In this study the pH
of plain lidocaine was 6.4 and 7.7 for alkalinized
lidocaine
[72]
.
Peripheral block anesthesia, Dental
1) For local anesthesia in dental procedures, ORAL
INFILTRATION and/or MANDIBULAR BLOCK, initial
dosages of 1 to 5 milliliters of lidocaine 2% with
epinephrine 1:50,000 or 1:100,000 are usually
effective. Dosage requirements should be determined
on an individual basis. The dosage depends on the
physical status of the patient, the area of the oral
cavity to be anesthetized, the vascularity of the oral
tissues, and the technique of anesthesia. The smallest
volume that results in effective local anesthesia should
be administered. Aspiration is recommended to reduce
the possibility of intravascular injection. For healthy
adults, the dose of lidocaine with epinephrine should
be kept below 500 milligrams (mg) and should not
exceed 7 milligrams/kilogram (mg/kg) of body weight.
When used without epinephrine, the dose of lidocaine
should be kept below 300 mg and should not exceed
4.5 mg/kg (Prod Info Xylocaine(R), 2001).
Peripheral block anesthesia, Intercostal
1) The lidocaine dose for nerve block is dependent on
the desired nerve area to be blocked. The following
are the recommended adult lidocaine doses (Prod Info
Xylocaine(R), 2000):
Intercostal
30 milligrams (3 milliliters) as a 1% lidocaine solution
2) Alkalinization of plain lidocaine 1% with sodium
bicarbonate 0.1 mmol/L for median nerve block
increases the rate of motor block without changing the
onset or extent of sensory block. In this study the pH
of plain lidocaine was 6.4 and 7.7 for alkalinized
lidocaine
[72]
.
Peripheral block anesthesia, Paravertebral
1) The lidocaine dose for nerve block is dependent on
the desired nerve area to be blocked. The following
are the recommended adult lidocaine doses (Prod Info
Xylocaine(R), 2000):
Paravertebral
30 up to 50 milligrams (3 to 5 milligrams) as a 1%
solution.
2) Alkalinization of plain lidocaine 1% with sodium
bicarbonate 0.1 mmol/L for median nerve block
increases the rate of motor block without changing the
onset or extent of sensory block. In this study the pH
of plain lidocaine was 6.4 and 7.7 for alkalinized
lidocaine
[72]
.
Peripheral block anesthesia, Pudendal
1) The lidocaine dose for nerve block is dependent on
the desired nerve area to be blocked. The following
are the recommended adult lidocaine doses (Prod Info
Xylocaine(R), 2000):
Pudendal
100 milligrams (10 milliliters) per side a 1% lidocaine
solution. Do not repeat dose at intervals of less than
90 minutes.
2) Alkalinization of plain lidocaine 1% with sodium
bicarbonate 0.1 mmol/L for median nerve block
increases the rate of motor block without changing the
onset or extent of sensory block. In this study the pH
of plain lidocaine was 6.4 and 7.7 for alkalinized
lidocaine
[72]
.
Postoperative pain
1) Lidocaine in low doses of 2 milligrams/minute (2
grams in 500 milliliters saline) for 24 hours was
reported to significantly reduce the severity of
postoperative pain in patients undergoing elective
cholecystectomy
[118]
. Toxicity was not observed and effective serum levels
appeared to be 1 to 2 micrograms/milliliter. In another
time, 1.5 milligrams/kilogram loading dose followed by
a 2 milligrams/kilogram/hour infusion had no effect on
the intensity of pain after abdominal hysterectomy
[122]
.
2) For intravenous regional anesthesia in patients
undergoing ambulatory hand surgery, the addition of
clonidine 1 microgram/kilogram to lidocaine 0.5%
improved postoperative analgesia and reduced the
need for analgesic supplements during the first day
after the operation
[69]
.
Retrobulbar infiltration of local anesthetic
1) Recommended adult dose is 120 milligrams up to
200 milligrams (3 to 5 milliliters) as a 4% solution
[124]
.
2) The addition of clonidine 2 micrograms/kilogram to
3 to 4 milliliters of 2% lidocaine for retrobulbar block
during cataract surgery in elderly patients produces a
greater decrease in intraocular pressure (p less than
0.01) by 43% and a small but significant reduction in
blood pressure (p less than 0.01) compared with the
same dose of lidocaine without clonidine. The median
duration of analgesia (p less than 0.01) and akinesia
(p less than 0.05) was greater in patients receiving the
lidocaine-clonidine combination as compared to
lidocaine alone. In addition, the lidocaine-clonidine
combination produced a greater sedative effect than
lidocaine alone (p less than 0.01)
[123]
.
Seizure
1) LIDOCAINE has been successfully used in the
treatment of status epilepticus resistant to other drugs.
Intravenous lidocaine 1.5 to 2 milligrams/kilogram
(mg/kg) has been recommended for status epilepticus
refractory to benzodiazepines and phenytoin. If
lidocaine terminates the episode, a continuous
infusion of 3 to 4 mg/kg/hour can be considered to
prevent recurrence. The rate of infusion should be
reduced gradually until the drug may be completely
withdrawn, which may require several days
[126]
[127]
[66]
; (Morris, 1979)
[128]
[129]
[130]
[131]
.
Spinal anesthesia
1) The clinician should be aware of the specific
contraindications and precautions associated with
spinal anesthesia prior to administration. Spinal
anesthesia may be induced in the right or left lateral
recumbent or the sitting position. This hyperbaric
anesthetic solution will move in the direction of the
table tilt. The patient may be positioned for the
procedure after the desired level of anesthesia is
achieved and the anesthetic has become fixed
(usually 5 to 10 minutes). For single injection spinal
anesthesia, the safety of hyperbaric lidocaine has
been shown using 22 or 25 gauge spinal needles. It is
recommended that the free flow of cerebrospinal fluid
should be visible prior to injection. If the technique is
properly performed and the needle is properly placed
in the subarachnoid space, a second injection should
not be necessary. INJECTIONS SHOULD BE MADE
SLOWLY (Prod Info 5% Xylocaine-MPF(R), 2000;
Prod Info 1.5% Xylocaine-MPF(R), 2000).
a) OBSTETRICAL LOW SPINAL OR "SADDLE
BLOCK" ANESTHESIA
1) The recommended dose of 5% Xylocaine-MPF(R)
with glucose 7.5% for normal vaginal delivery is
approximately 50 milligrams (mg) (1 milliliter (mL))
(Prod Info 5% Xylocaine-MPF(R), 2000) and the
recommended dose of 1.5% Xylocaine-MPF(R) with
dextrose 7.5% for normal vaginal delivery is
approximately 9 to 15 mg (0.6 to 1 mL) (Prod Info
1.5% Xylocaine-MPF(R), 2000). The recommended
dose of 5% Xylocaine-MPF(R) with glucose 7.5% for
CAESAREAN SECTION and those deliveries requiring
intrauterine manipulations is 75 mg (1.5 mL) (Prod Info
5% Xylocaine-MPF(R), 2000).
b) SURGICAL ANESTHESIA
1) The recommended dose of 5% Xylocaine-MPF(R)
with glucose 7.5% for abdominal anesthesia is 75 to
100 milligrams (1.5 to 2 milliliters) (Prod Info 5%
Xylocaine-MPF(R), 2000).
2) Results of 1 study involving 48 patients indicate that
lidocaine 1% intrathecally can provide adequate spinal
anesthesia for short (1 hour) surgical procedures
involving the lower limbs and perineum. Subarachnoid
administration of 4 milliliters (mL) lidocaine 1% is
adequate for perineal surgery, but for surgery of the
lower limbs 6 mL provides a more complete motor
block and consistent sensory anesthesia above L1
dermatome. The authors do NOT recommend
administration of 8 mL lidocaine 1% for short surgical
procedures involving the lower limbs or perineum
because it results in an inappropriately high block, a
higher incidence of hypotension, and a slower
recovery time
[219]
.
3) According to the results of a prospective,
randomized, double-blind study, the minimum effective
anesthetic concentration (MEAC) of hyperbaric
lidocaine containing dextrose 7.5% in young patients
(n=43) undergoing knee and ankle surgery is 0.54%
with a dose of 48 milligrams (mg) and 0.3% with a
dose of 72 mg. In this study, the MEAC is defined as
the concentration of a spinal anesthetic that produces
surgical anesthesia within 20 minutes of administration
in 50% of patients. The MEAC is dose-dependent.
Anesthesia was achieved at lower concentrations by
increasing the dose of spinal lidocaine. Transient
neurological symptoms may still occur with the use of
dilute spinal lidocaine solutions
[220]
.
4) The results of 1 randomized, single-blind study
involving 30 women undergoing outpatient
LAPAROSCOPY indicate that small-dose hypobaric
lidocaine-fentanyl spinal anesthesia is more
advantageous than conventional-dose hyperbaric
lidocaine. In this study, patients were administered
either a small-dose hypobaric solution of 1% lidocaine
25 milligrams (mg) made up to 3 milliliters (mL) by the
addition of fentanyl 25 micrograms (mcg) (group 1) or
a conventional-dose hyperbaric solution of 5%
lidocaine 75 mg (in 7.5% dextrose) made up to 3 mL
by the addition of 1.5 mL 10% dextrose (group 2).
Intraoperative hypotension requiring treatment with
ephedrine occurred in 54% of patients in group 2 and
in 0% of group 1 patients. Median time for full motor
recovery was 50 minutes in group 1 patients
compared with 90 minutes in group 2 patients
(p=0.0005) and sensory recovery occurred faster in
group 1 patients than in group 2 patients (p=0.0001).
The incidence of pruritus was significantly higher in
group 1 patients than in group 2 patients (p less than
0.025). There was no significant difference between
the two groups in incidence of backache at any time.
Postoperative headache occurred in 38% of all
patients
[215]
. The results of a related study involving 64 women
undergoing outpatient laparoscopy indicate that 25
mcg appears to be the optimal dose of fentanyl
(compared with 0 mcg and 10 mcg fentanyl) to be
added to small-dose hypobaric lidocaine (20 mg)
spinal anesthesia for outpatient laparoscopy
[216]
.
LOADING DOSE
1) Following an initial priming dose of 75 milligrams of
lidocaine given intravenously over 2 minutes, a loading dose
given as a continuous infusion appears to be more
acceptable than a loading dose given as multiple injections.
On study showed this in 18 patients treated with lidocaine
[228]
. All patients received a priming dose of 75 milligrams.
Twelve patients received further lidocaine loading with a
continuous lidocaine infusion of 150 milligrams given over 18
minutes (8.33 milligrams/minute) and the other 6 patients
received further lidocaine loading by multiple injections (3 to
50 milligram injections given over 1 minute at 7, 13, and 19
minutes). The loading regimen was followed by a continuous
infusion of 2 milligrams/minute in all patients. Although the
multiple injection method produced wide variations in
lidocaine concentrations when compared to the rapid infusion
method, lidocaine levels were not measurably greater. All 6
patients receiving the multiple injection loading regimen
experienced side effects, including drowsiness, tinnitus,
dysarthria or paresthesias. During the rapid infusion loading
regimen only 1 of 12 patients experienced side effects
(drowsiness). Based on the results of this study, lidocaine
loading by continuous infusion is preferable to lidocaine
loading with multiple injections, however if continuous
infusion is not possible multiple injections are acceptable.
2) One study proposed a high rate of continuous infusion in
addition to a bolus dose for the loading of lidocaine
[229]
. A 100-milligram bolus followed by an 8-milligram/minute
infusion for 25 minutes followed by a 2-milligrams/minute
maintenance infusion was found to be superior to the
conventional 100-milligram bolus followed by a 2milligram/minute infusion. It was also superior to a multiple
bolus of 100 milligrams initially, and 50 milligrams 20 minutes
later, with a continuous maintenance infusion of 2
milligrams/minute, or a 2-infusion method of 8
milligrams/minute for 25 minutes followed by a continuous
maintenance infusion of 2 milligrams/minute. The three-step
method is thought to minimize the therapeutic gap between
bolus dose and accumulation of lidocaine following infusion.
3) One study proposed a method to deliver lidocaine by an
infusion rate that exponentially declines, from 10
milligrams/minute to 2 milligrams/minute, after the initial bolus
injection
[230]
. This method was utilized with good results in 8 volunteers.
MAXIMUM DOSAGES
1) In normal healthy adults, the individual maximum
recommended dose of lidocaine hydrochloride with
epinephrine should not exceed 7 milligrams/kilogram (mg/kg)
(3.5 mg/pound (lb)) and in general it is recommended that the
maximum total dose not exceed 500 mg. The individual
maximum recommended dose of lidocaine hydrochloride
without epinephrine should not exceed 4.5 mg/kg (2 mg/lb)
and in general it is recommended that the maximum total
dose not exceed 300 mg (Prod Info Xylocaine(R), 2000).
Nasal route
Headache
1) Intranasal instillation of 0.4 to 0.5 milliliter of 4%
lidocaine solution appears to be effective in the
treatment of MIGRAINE HEADACHE
[157]
[158]
.
2) Intranasal instillation of 1 milliliter of 4% lidocaine
solution has been used in the treatment of CLUSTER
HEADACHE. If necessary the dose could be repeated
once or twice within 15 minutes without significant risk
[159]
. In addition, 4 sprays of 4% lidocaine solution has
been used in the treatment of cluster headaches with
a repeat dose of 2 sprays in 15 minutes if necessary
[160]
.
Ophthalmic route
Cataract surgery - Topical local anesthetic
1) GEL/JELLY
a) For topical anesthesia in cataract surgery
(extracapsular cataract extraction and
phacoemulsification), lidocaine 2% gel applied 3 to 5
times during the 15 to 20 minutes prior to surgery has
been recommended
[139]
.
2) SOLUTION
a) For topical analgesia in cataract surgery, 2 drops of
lidocaine 4% (100 microliters) in both eyes, instilled 6
times in the 60 minutes prior to surgery (at 60, 50, 40,
30, 20, 10 minutes) has been recommended
[141]
.
Procedure on eye - Topical local anesthetic
1) The recommended dosage of lidocaine topical
ophthalmic gel 3.5% is 2 drops to the eye in the area
of planned procedure. Reapplication may be done to
maintain anesthesia
[51]
.
Oral route
a) Available data indicates that because of adverse reactions
and inadequate blood levels, oral lidocaine has limited value
in the treatment of VENTRICULAR ARRHYTHMIAS. Adverse
effects such as dizziness, light-headedness, and numbness
of the tongue have been reported with 500 milligram oral
doses of lidocaine. Therapeutic blood levels have not been
consistently achieved following oral dosing (Boyes, 1971)
[104]
[105]
.
Subcutaneous route
Topical local anesthetic to wound
1) For repair of simple lacerations, buffering lidocaine
does not reduce the pain associated with
subcutaneous infiltration in adults compared to plain
lidocaine. In this prospective, randomized, doubleblind, placebo-controlled study, patients (n=135; mean
age 34.1 years) received lidocaine 1% plus either 0.5
milliliter of 0.9% normal saline or 8.4% sodium
bicarbonate (resultant concentration ratio 10:1). Pain
scores for the plain and buffered lidocaine groups
were not significantly different
[60]
. In contrast, some studies have reported that
compared to plain lidocaine, buffered lidocaine
significantly decreases the pain associated with local
anesthetic infiltration
[61]
[62]
[63]
[64]
.
Warming of lidocaine to body temperature (37 degrees
centigrade) in a warm water bath prior to drawing the
lidocaine solution up into a syringe may reduce the pain
associated with subcutaneous injection
[234]
[235]
[236]
[237]
. In contrast, some studies have reported no benefit from
warming lidocaine solutions prior to injection
[238]
[239]
.
Topical application route
Topical local anesthetic to mucous membrane
1) A safe and effective total application dose of
lidocaine for surgery with laryngomicroscopy may be
within the range of 127 to 320 milligrams. In this study
(n=22), patients received 10 milliliters of 2% lidocaine
viscous in the oral cavity and pharynx for 5 minutes
then patients were instructed to expectorate any
remaining viscous and oral secretions after 5 minutes
so that they would not be swallowed. A 4% lidocaine
solution was then sprayed on the oropharyngeal
region for several seconds intermittently for about 5
minutes and again the patients were instructed to
expectorate any remaining solution and oral secretions
intermittently to avoid absorption. Serum lidocaine
concentrations after application were less than 1.8
micrograms/milliliter
[54]
.
Local anesthetic intravenous regional block
a) The addition of sufentanil, tramadol, or clonidine to
lidocaine for intravenous regional anesthesia in patients
undergoing ambulatory hand surgery shortened the onset of
the sensory block, lengthened the time to onset of tourniquet
pain, and reduced the need for intraoperative opioids. In a
randomized, double-blind, placebo-controlled study (n=60),
patients undergoing ambulatory hand or forearm surgery
received intravenous regional anesthesia using 35 milliliters
of lidocaine 0.5% plus either saline (group L), sufentanil 25
micrograms (mcg) (group LS), tramadol 100 milligrams
(group LT), or clonidine 1 mcg/kilogram (group LC). Sensory
block onset time was longer, initial time to tourniquet pain
was shorter, and total dose of intraoperative fentanyl was
significantly higher for patients in the control group (group L)
as compared to groups LS, LT, and LC (p less than 0.05, all
values). Sedation scores, sensory block recovery times, and
motor block onset and recovery times did not differ between
groups. Postoperative pain was also similar among all
treatment groups
[68]
.
b) For intravenous regional anesthesia in patients undergoing
ambulatory hand surgery, the addition of clonidine 1
microgram/kilogram to lidocaine 0.5% improved
postoperative analgesia and reduced the need for analgesic
supplements during the first day after the operation
[69]
.
c) Two lidocaine-containing regimens were similarly effective
and safe for intravenous regional anesthesia of an upper
limb. Forty patients undergoing forearm or hand surgery were
randomized to either lidocaine 3 milligrams/kilogram alone or
lidocaine 1.5 mg/kg in combination with fentanyl 1
microgram/kilogram and pancuronium 0.5 mg, all given
intravenously to the hand after placement of an arm
tourniquet. The onset of motor and sensory block was
significantly shorter (p less than 0.05) with lidocaine alone
(10 to 14 minutes) than with the other regimen (16 to 18
minutes). Similar percentages of patients achieved complete
blockade at 20 and 30 minutes (85% to 90%), and
postoperative analgesia was of similar duration (36 to 45
minutes). Use of the lower-dose lidocaine in combination with
an opioid and muscle relaxant may be a safer alternative if
the tourniquet deflates suddenly
[70]
.
d) The use of Bier block anesthesia (intravenous regional
anesthesia) has been a useful technique in the surgery of
injuries to the upper limbs. This technique may be desirable
when a general anesthetic is impractical or for elective
orthopedic operations in outpatients
[71]
.
Operation on urinary system
a) For surface ANESTHESIA OF THE ADULT MALE
URETHRA, slowly instill approximately 15 milliliters (mL) into
the urethra then apply a penile clamp at the corona for
several minutes (5 to 10 minutes). An additional dose of not
more than 15 mL can be instill for adequate anesthesia. Prior
to catheterization, smaller volumes of 5 to 10 mL are usually
adequate for lubrication. For surface ANESTHESIA OF THE
ADULT FEMALE URETHRA, slowly instill 3 to 5 mL into the
urethra. To achieve adequate anesthesia, several minutes
should be allowed prior to performing the procedure.
Lidocaine 2% jelly is ineffective when applied to intact skin
[208]
.
Tinnitus
See Drug Consult reference:
DRUG THERAPY OF TINNITUS
Dosage in Renal Failure
A) Lidocaine
1) Based on pharmacokinetic parameters, no dosage modification of
lidocaine appears to be necessary in patients with renal impairment
[45]
. However, although patients with renal failure generally do not require
dosage adjustment, the elimination of glycine xylidide (a major metabolite
of lidocaine) is dependent on renal function and may accumulate in these
patients. Accumulation of this metabolite may result in the development of
CNS toxicity
[46]
.
B) Lidocaine Hydrochloride
1) Based on pharmacokinetic parameters, no dosage modification of
lidocaine appears to be necessary in patients with renal impairment
[45]
. However, although patients with renal failure generally do not require
dosage adjustment, the elimination of glycinexylidide (a major metabolite of
lidocaine) is dependent on renal function and may accumulate in these
patients. Accumulation of this metabolite may result in the development of
central nervous system toxicity
[46]
.
Dosage in Hepatic Insufficiency
A) Lidocaine
1) When using lidocaine 5% patches (Lidoderm(R)) on patients with severe
hepatic disease, a dose reduction (eg, fewer patches, smaller areas of
treatment, shorter application times) may be required
[40]
.
2) One study reported that in the presence of hypotension, both liver blood
flow and lidocaine clearance are decreased significantly, based upon the
degree of hypotension
[47]
.
B) Lidocaine Hydrochloride
1) The presence of liver disease necessitates lower infusion rates due to
decreased hepatic clearance, but not altered loading doses
[48]
.
2) One study reported that in the presence of hypotension, both liver blood
flow and lidocaine clearance are decreased significantly, based upon the
degree of hypotension
[47]
. This suggests that in hypotensive patients, the maintenance dose of
lidocaine should be reduced and initial loading dose given by slow IV
infusion in order to avoid toxic serum concentrations.
Dosage in Geriatric Patients
A) Lidocaine Hydrochloride
1) In patients 70 years and older and in those with congestive heart failure,
cardiogenic shock, or hepatic disease, the loading dose should be
decreased markedly (approximately 50% of normal dose) and the infusion
rate should be reduced to 1 to 2 milligrams/minute
[66]
.
2) One study recommends that in elderly male patients without evidence of
congestive heart failure or other coexisting chronic disease, initial doses of
lidocaine should be the same as for younger patients
[241]
. However, to achieve comparable plasma levels and therapeutic effects
during continuous intravenous infusion, the elderly male should have the
infusion rate decreased by at least 35% due to prolongation of elimination
half-life in these patients and decreases in total metabolic clearance.
Dosage Adjustment During Dialysis
A) Lidocaine
1) The clearance of lidocaine by hemodialysis is reported to be negligible
[49]
. Dosing adjustments or supplementation of doses are not required
following hemodialysis procedures
[45]
.
B) Lidocaine Hydrochloride
1) The clearance of lidocaine by hemodialysis is reported to be negligible
[49]
. Dosing adjustments or supplementation of doses are not required
following hemodialysis procedures
[45]
.
Dosage in Other Disease States
A) Lidocaine Hydrochloride
1) CONGESTIVE HEART FAILURE
a) Dosage adjustment may be necessary in patients with congestive heart
failure receiving lidocaine for cardiac arrhythmias. Volume of distribution is
decreased in patients with heart failure, necessitating lower than normal
loading doses
[48]
. Clearance is significantly decreased in patients with heart failure,
resulting in a prolonged elimination half-life
[242]
. One study reported lidocaine toxicity in 72 patients with excessive serum
concentrations during maintenance infusions
[243]
. Fifty-one (72%) of these patients had severe CONGESTIVE HEART
FAILURE with lidocaine clearances of less than 1/2 of normal; 40 of these
became toxic in spite of a reduced infusion rate (30
micrograms/kilogram/minute). The authors recommend starting lidocaine at
a rate of 10 micrograms/kilogram/minute in patients presenting with any
evidence of circulatory insufficiency. However, some patients with
ventricular arrhythmias and severe heart failure may require very high
dosages of lidocaine without an unacceptable risk of toxicity
[244]
. Of 21 patients with complex ectopy who did not respond to conventional
loading doses (225 milligrams), 19 subsequently responded to lidocaine
when the dose was escalated to 275 to 375 milligrams. Only minor toxicity
was noted.
b) One study suggests the following regimen based upon the presence or
absence of heart failure in MI patients: 1 to 2 milligrams/kilogram
intravenous bolus then 35 to 88 micrograms/kilogram/minute in patients
without heart failure and 12 to 35 micrograms/kilogram/minute in patients
with HEART FAILURE. In this study, 13 of 16 plasma determinations with
these doses were in the therapeutic range
[245]
.
c) An example regimen of an initial 50 milligram intravenous bolus followed
by an infusion rate of 1 milligram/minute has been recommended
[246]
. One study recommends a reduction in dosage to 8 to 25
micrograms/kilogram/minute in patients with congestive heart failure
[247]
.
Pediatric Dosage
Normal Dosage
Important Note
1) Lidocaine hydrochloride monohydrate powder intradermal
injection system (Zingo(TM)) was recalled on November 11, 2008
due to nonsafety-related regulatory compliance issues which could
affect product shelf life. Anesiva has no plans to distribute
Zingo(TM) in the future
[254]
.
Neurological deficits (eg, Cauda Equina syndrome) have been
reported with the use of small-bore needles and microcatheters for
lidocaine spinal anesthesia. The lidocaine solution used in these
case reports was 5% lidocaine with glucose 7.5%. The
manufacturer suggests that mixing 5% lidocaine with an equal
volume of cerebrospinal fluid (CSF) or preservative-free 0.9% saline
solution may reduce the risk of nerve injury. Use a spinal needle of
sufficient gauge to ensure adequate withdrawal of CSF and
intrathecal distribution of anesthetic before and after administration
into the subarachnoid space
[50]
.
Lidocaine
Topical application route
Local anesthesia, Topical
1) The recommended maximum dose of the 5%
ointment for local anesthesia in children is 4.5 mg/kg
topically
[20]
.
Lidocaine Hydrochloride
Intraosseous route
Ventricular arrhythmia
1) For the treatment of ventricular arrhythmias, the
recommended loading dose of lidocaine hydrochloride
is 1 milligram/kilogram (mg/kg; maximum dose 100
mg) intravenously (or intraosseously) followed by an
infusion of 20 to 50 micrograms/kilogram/minute
[84]
.
Ventricular fibrillation
1) In patients with ventricular fibrillation/pulseless
ventricular tachycardia, the initial dose of lidocaine
hydrochloride is a bolus dose of 1 milligram/kilogram
(mg/kg) intravenously (or intraosseously), with a
maximum dose of 100 mg. The recommended dose
for continuous infusion is 20 to 50
micrograms/kg/minute
[84]
.
Intravenous route
Ventricular arrhythmia
1) For the treatment of ventricular arrhythmias, the
recommended loading dose of lidocaine hydrochloride
is 1 milligram/kilogram (mg/kg; maximum dose 100
mg) intravenously (or intraosseous) followed by an
infusion of 20 to 50 micrograms/kilogram/minute
[84]
.
2) In NEONATES with ventricular arrhythmia,
administer lidocaine 1 milligram/kilogram slowly then
10 micrograms/milliliter/kilogram/minute by infusion
and titrate (Batagol, 1993).
Ventricular fibrillation
1) In patients with ventricular fibrillation/pulseless
ventricular tachycardia, the initial dose of lidocaine
hydrochloride is a bolus dose of 1 milligram/kilogram
(mg/kg) intravenously (or intraosseously), with a
maximum dose of 100 mg. The recommended dose
for continuous infusion is 20 to 50
micrograms/kg/minute
[84]
.
MAXIMUM DOSE
1) The maximum recommended intravenous dose for
lidocaine in pediatric patients (17 years and younger) is 1.5
milligrams/kilogram/dose or 88 micrograms/kilogram/minute
by continuous infusion
[240]
.
Parenteral route
Local anesthetic intravenous regional block
1) Dilute solutions (0.25% to 0.5%) and total dosages
not to exceed 3 mg/kg are recommended for induction
of IV regional anesthesia in children. Use the lowest
effective concentration and dose at all times
[65]
.
Peripheral block anesthesia, Dental
1) In children, dosage should be individualized based
on age and weight. Calculate the lidocaine dosage
based on body weight up to 5 mg/kg and up to 7
mg/kg with the addition of epinephrine. Use with
caution in children younger than 2 years of age
[73]
.
2) For local anesthesia in dental procedures, the
maximum recommended dose of lidocaine
hydrochloride (with epinephrine) is 7 mg/kg of body
weight. Administer the least volume of solution that
produces effective local anesthesia
[74]
.
Subcutaneous route
Topical local anesthetic to wound
1) Lacerations
a) For repair of simple lacerations, buffering lidocaine
does not reduce the pain associated with
subcutaneous infiltration in children compared to plain
lidocaine. In this prospective, randomized, doubleblind, placebo-controlled study, pediatric patients
(n=136; mean age 5.7 years) received lidocaine 1%
plus either 0.5 milliliter of 0.9% normal saline or 8.4%
sodium bicarbonate (resultant concentration ratio
10:1). Pain scores for the plain and buffered lidocaine
groups were not significantly different
[60]
. In contrast, some studies have reported that
compared to plain lidocaine, buffered lidocaine
significantly decreases the pain associated with local
anesthetic infiltration
[61]
[62]
[63]
[64]
.
Topical application route
Topical local anesthetic to mucous membrane
1) One study evaluated plasma concentrations in
children (age 2 weeks to 12 years) following single
doses of lidocaine laryngeal spray (4
milligrams/kilogram in a 4% solution)
[55]
. The intravenous data indicate that lidocaine tracheal
spray in doses of 4 milligrams/kilogram are safe in
children, producing plasma levels below the toxic
range.
Dosage in Renal Failure
A) Lidocaine
1) Based on pharmacokinetic parameters, no dosage modification of
lidocaine appears to be necessary in patients with renal impairment
[45]
. However, although patients with renal failure generally do not require
dosage adjustment, the elimination of glycine xylidide (a major metabolite
of lidocaine) is dependent on renal function and may accumulate in these
patients. Accumulation of this metabolite may result in the development of
CNS toxicity
[46]
.
B) Lidocaine Hydrochloride
1) Based on pharmacokinetic parameters, no dosage modification of
lidocaine appears to be necessary in patients with renal impairment
[45]
. However, although patients with renal failure generally do not require
dosage adjustment, the elimination of glycinexylidide (a major metabolite of
lidocaine) is dependent on renal function and may accumulate in these
patients. Accumulation of this metabolite may result in the development of
central nervous system toxicity
[46]
.
Dosage in Hepatic Insufficiency
A) Lidocaine
1) The presence of liver disease necessitates lower infusion rates due to
decreased hepatic clearance, but not altered loading doses
[48]
.
2) One study reported that in the presence of hypotension, both liver blood
flow and lidocaine clearance are decreased significantly, based upon the
degree of hypotension
[47]
.
B) Lidocaine Hydrochloride
1) The presence of liver disease necessitates lower infusion rates due to
decreased hepatic clearance, but not altered loading doses
[48]
.
2) One study reported that in the presence of hypotension, both liver blood
flow and lidocaine clearance are decreased significantly, based upon the
degree of hypotension
[47]
. This suggests that in hypotensive patients, the maintenance dose of
lidocaine should be reduced and initial loading dose given by slow
intravenous infusion in order to avoid toxic serum concentrations.
Dosage Adjustment During Dialysis
A) Lidocaine
1) The clearance of lidocaine by hemodialysis is reported to be negligible
[49]
. Dosing adjustments or supplementation of doses are not required
following hemodialysis procedures
[45]
.
B) Lidocaine Hydrochloride
1) The clearance of lidocaine by hemodialysis is reported to be negligible
[49]
. Dosing adjustments or supplementation of doses are not required
following hemodialysis procedures
[45]
.
Dosage in Other Disease States
A) Lidocaine Hydrochloride
1) CARDIOPULMONARY RESUSCITATION
a) In the presence of shock, congestive heart failure, and cardiac arrest the
usual bolus dose may be given but the infusion should not be higher than 1
milliliter/kilogram/hour
[248]
.
PHARMACOKINETICS
Onset and Duration
A) Onset
1) Lidocaine
a) Initial Response
1) Local anesthesia, topical (5% ointment): 3 to 5 minutes
[458]
a) Onset of local anesthesia is 3 to 5 minutes when applied to mucous
membranes. Lidocaine 5% ointment is ineffective when applied to intact skin
[458]
.
2) Lidocaine Hydrochloride
a) Initial Response
1) Arrhythmias, IV: 45 to 90 seconds
[475]
a) Initial response to lidocaine hydrochloride was seen 45 to 90 seconds after IV
administration for arrhythmia
[475]
. The antiarrhythmic effect quickly decreases once the infusion is stopped
[481]
.
2) Local anesthesia, topical (2% jelly): 3 to 5 minutes
[482]
a) Onset of action is 3 to 5 minutes when instilled into the urethra. Lidocaine 2%
jelly is ineffective when applied to intact skin
[482]
.
3) Local anesthesia, ophthalmic (3.5% gel): 20 seconds to 1 minute
[51]
a) Local anesthesia generally occurs between 20 seconds and 1 minute after
ophthalmic application
[51]
.
4) Perineal anesthesia, intrathecal: rapid
[50]
a) The onset of action is rapid following intrathecal administration of lidocaine for
spinal anesthesia
[50]
.
B) Duration
1) Lidocaine Hydrochloride
a) Single Dose
1) Arrhythmias, IV: 10 to 20 minutes
[471]
[475]
[483]
a) In the absence of hepatic disease or congestive heart failure, the
antiarrhythmic effect of a single IV dose disappears within 10 to 20 minutes due to
drug redistribution
[471]
[475]
[483]
.
2) Local anesthesia, ophthalmic (3.5% gel): 5 to 30 minutes
[51]
a) Following ophthalmic application, local anesthesia persists for 5 to 30 minutes
[51]
.
3) Perineal anesthesia, intrathecal: 100 minutes
[50]
a) The mean duration of perineal anesthesia is 100 minutes following intrathecal
administration of 1 mL (50 mg) of lidocaine hydrochloride 5%/dextrose 7.5%
solution for intrathecal injection. Analgesia continues for an additional 40 minutes
[50]
.
4) Surgical anesthesia, intrathecal: approximately 2 hours
[50]
a) The mean duration of surgical anesthesia is approximately 2 hours following
intrathecal administration of 1.5 to 2 mL (75 to 100 mg) of lidocaine hydrochloride
5%/dextrose 7.5% solution for intrathecal injection
[50]
.
Drug Concentration Levels
A) Lidocaine
1) Peak Concentration
a) Transdermal patch 5%, single-dose, 2100 mg (3 patches): 0.13 mcg/mL
[282]
1) When studied in healthy volunteers (n=15), the application of 3 lidocaine 5%
transdermal patches to intact skin on the back, covering 420 cm(2) and worn for
12 hours, resulted in a mean Cmax of 0.13 mcg/mL (+/- 0.06 mcg/mL)
[282]
.
2) The amount of systemic absorption from a lidocaine 5% transdermal patch is
directly related to the duration of application and the surface area over which it is
applied
[282]
.
b) Repeated application of 3 patches worn simultaneously for 12 hours, once
daily for 3 days in healthy volunteers (n=15) did not produce an increase in mean
Cmax with daily use
[282]
.
c) Transdermal patch 5%, multiple-dose, 2800 mg (4 patches): 153.8
nanograms/mL
[459]
1) When studied in healthy volunteers (n=20), the application of 4 lidocaine 5%
transdermal patches once daily to intact skin on the back, and worn for 18 hours
for 3 consecutive days, resulted in a mean Cmax of 145.1 nanograms/mL and
153.8 nanograms/mL on day 1 and day 3, respectively
[459]
.
2) Time to Peak Concentration
a) Transdermal: 11 hours
[282]
1) When studied in healthy volunteers (n=15), the application of 3 lidocaine 5%
transdermal patches to intact skin on the back, covering 420 cm(2) and worn for
12 hours, resulted in a mean Tmax of 11 hours
[282]
.
B) Lidocaine Hydrochloride
1) Therapeutic Drug Concentration
a) Arrhythmias: 1.5 to 6 mcg/mL
[479]
[490]
[491]
1) Unbound lidocaine ranges from 0.5 to 1.5 mcg/mL. Measurement of unbound
levels may be preferable in postmyocardial infarction patients
[492]
. Values for whole blood would be 80% of plasma levels
[493]
.
b) Chronic pain: approximately 2 to 6 mcg/mL (not well established)
[479]
.
1) Therapeutic blood levels used to monitor arrhythmias appear to be clinically
effective for chronic pain
[479]
.
c) Epidural anesthesia: transient decrease with epinephrine coadministration
[494]
1) During continuous epidural anesthesia, the addition of epinephrine to lidocaine
solutions reduces plasma lidocaine concentrations only transiently
[494]
.
2) Peak Concentration
a) Laryngeal-tracheal, single dose, 1.5 mg/kg: 1.4 to 2.8 mcg/mL (adults)
[484]
1) Peak serum levels ranging from 1.4 to 2.8 mcg/mL within 5 to 10 minutes
following endotracheally administered lidocaine 1.5 mg/kg in sterile water have
been reported
[484]
.
b) Laryngeal-tracheal, single dose, 4 mg/kg: 4.3 to 5.6 mcg/mL (pediatrics)
[484]
[485]
1) In a study involving 96 pediatric patients, aged 2 weeks to 12 years, lidocaine 4
mg/kg as a 4% solution was sprayed on the larynx and subglottic area, the time to
peak ranged from 5.7 to 11.7 minutes and peak levels ranged from 4.3 to 5.6
mcg/mL
[485]
.
c) Paracervical, 343 mg: 3.03 to 7.32 mg/L
[486]
1) Mean peak lidocaine levels of 5.14 mg/L (range; 3.03 to 7.32 mg/L) were
reached in 10 minutes after a mean dose of 343 mg in patients undergoing
cervical plexus block
[486]
.
d) Parenteral: Cmax variable
[50]
1) The rate of absorption following parenteral administration is variable,
dependent on factors such as the site of administration, and the presence or
absence of a vasoconstrictor. Except for intravascular administration, the highest
blood levels of lidocaine are obtained following intercostal nerve block and the
lowest after subcutaneous administration
[50]
.
e) Oral topical mucus membrane: Cmax variable
[487]
1) The rate and extent of absorption of oral topically administered lidocaine to
mucus membranes is variable, due to factors such as concentration and total
dose administered, the specific site of administration, and duration of exposure.
The most rapid rate of absorption for oral topical administration of lidocaine is
obtained following intratracheal administration
[487]
.
3) Time to Peak Concentration
a) IM: 30 minutes to 2 hours
[488]
[489]
1) Peak serum levels are achieved 30 minutes to 2 hours following intramuscular
administration of lidocaine
[488]
[489]
.
b) Laryngeal-tracheal: 5 to 11.7 minutes
[484]
[485]
1) Peak serum levels ranging from 1.4 to 2.8 mcg/mL within 5 to 10 minutes
following endotracheally administered lidocaine 1.5 mg/kg in sterile water have
been reported
[484]
.
2) In a study involving 96 pediatric patients, aged 2 weeks to 12 years, lidocaine 4
mg/kg as a 4% solution was sprayed on the larynx and subglottic area, the time to
peak ranged from 5.7 to 11.7 minutes and peak levels ranged from 4.3 to 5.6
mcg/mL
[485]
.
c) Paracervical: 10 minutes
[486]
1) A mean Cmax of 5.14 mg/L (range 3.03 to 7.32 mg/L) was reached 10 minutes
after an average dose of lidocaine 343 mg in patients undergoing cervical plexus
block
[486]
.
ADME
Absorption
A) Lidocaine
1) Bioavailability
a) Transdermal: 3%
[282]
1) When applied according to manufacturer recommendations, 3% (+/2%) of the dose applied is expected to be absorbed from a lidocaine 5%
transdermal patch, with at least 95% (665 mg) of the drug remaining in the
used patch
[282]
.
2) The amount of systemic absorption from a lidocaine 5% transdermal
patch is directly related to the duration of application and the surface area
over which it is applied
[282]
.
b) The rate and extent of absorption following topical administration of
lidocaine to mucus membranes depends upon the specific site of
administration, duration of exposure, concentration and total dosage
[458]
.
B) Lidocaine Hydrochloride
1) Bioavailability
a) Epidural: extensive
[495]
1) During cesarean section, an epidural infusion of lidocaine 2% with
epinephrine 1:200,000 (5 mL) has elicited a mean peak maternal arterial
lidocaine concentration of 6.4 mcg/mL at 31 minutes. The ratio of umbilical
venous to maternal arterial levels was 0.43
[495]
.
2) During continuous epidural anesthesia, the addition of epinephrine to
lidocaine solutions reduces plasma lidocaine concentrations only
transiently
[494]
.
b) Intracameral: minimal
[496]
1) Serum lidocaine levels were below a minimum detectable level of 100
nanograms/mL following injection of 0.5 mL lidocaine 1% into the anterior
chamber of the eye during cataract surgery
[496]
.
c) IM: adequate for antiarrhythmic effect
[488]
[489]
1) Adequate therapeutic levels occur if injected into vascular muscle sites
(eg, deltoid muscle is preferable to the gluteus or vastus lateralas) and in
the presence of adequate blood circulation to that site
[489]
. One study reported that a single 300 mg IM injection (deltoid muscle)
produced therapeutic antiarrhythmic plasma levels within 2 hours
[488]
.
d) Oral: 35%
[476]
1) Lidocaine is absorbed from the gastrointestinal tract, enters the hepatic
portal circulation, and is rapidly metabolized by the liver. Only 35% of the
drug is absorbed and doses of 250 to 500 mg in adults result in
subtherapeutic plasma concentrations. However, oral absorption can
produce therapeutic and even toxic plasma levels
[476]
[497]
.
e) The rate of absorption following parenteral administration is variable,
dependent on factors such as the site of administration, and the presence
or absence of a vasoconstrictor. Except for intravascular administration,
the highest blood levels of lidocaine are obtained following intercostal
nerve block and the lowest after subcutaneous administration
[50]
.
f) The rate and extent of absorption following topical administration to
mucus membranes is variable, dependent on factors such as concentration
and total dose administered, the specific site of administration, and
duration of exposure. The most rapid rate of absorption for topical
administration of lidocaine is obtained following intratracheal administration
[487]
.
Distribution
A) Distribution Sites
1) Lidocaine
a) Protein Binding
1) 60% to 80%
[282]
[458]
a) With application of lidocaine 5% transdermal patch, lidocaine is
approximately 70% protein-bound, primarily to alpha-1-acid glycoprotein
[282]
.
b) At plasma concentrations of 1 to 4 mcg/mL of free base, lidocaine is
60% to 80% protein bound
[458]
.
c) The protein binding of lidocaine is concentration dependent, as the drug
plasma concentration increases the fraction of bound drug decreases.
Protein binding of lidocaine is also dependent upon the plasma
concentration of alpha-1-acid glycoprotein
[458]
.
d) Protein binding is increased in epileptic patients because of elevated
levels of alpha-1-acid glycoprotein
[460]
.
e) Protein binding is increased in uremic patients and renal transplant
recipients
[461]
.
b) Tissues and Fluids
1) Cerebrospinal Fluid
a) Lidocaine crosses the blood brain barrier by passive diffusion
[458]
[282]
.
2) Placenta
a) Placenta: rapid
[462]
[463]
[464]
1) Lidocaine crosses the placenta by passive diffusion
[458]
[282]
. Distribution across the placenta may be sufficient enough to enter the
fetus and reach toxic levels. Lidocaine is detectable in both maternal and
fetal blood following subarachnoid injection; however, concentrations are
very low compared with those following epidural use. Lidocaine appears in
fetal circulation within a few minutes after administration to the mother.
Cord to maternal serum ratios after intravenous and epidural anesthesia
range between 0.5 to 0.7, but have been reported as high as 1.32
[462]
[463]
[464]
.
2) Lidocaine Hydrochloride
a) Protein Binding
1) 60% to 80%
[50]
[498]
[499]
a) The protein binding of lidocaine is inversely related to concentration, as
the drug plasma concentration increases the fraction of bound drug
decreases. Protein binding of lidocaine is also dependent upon the plasma
concentration of alpha-1-acid glycoprotein. At concentrations of 1 to 4
mcg/mL of free base, lidocaine is 60% to 80% protein bound
[50]
[498]
[499]
.
b) Protein binding is increased in uremic patients and renal transplant
recipients
[461]
.
c) Protein binding is enhanced following acute myocardial infarction
because of elevated levels of alpha-1-acid glycoprotein. Free lidocaine
levels, however, do not change significantly during this time. Therefore,
therapeutic monitoring of total plasma levels may be misleading following
acute myocardial infarctions
[500]
[501]
.
d) Protein binding is enhanced in epileptic patients because of elevated
levels of alpha-1-acid glycoprotein
[460]
.
b) Tissues and Fluids
1) Cerebrospinal fluid: crosses blood-brain barrier by passive diffusion
[50]
a) Lidocaine crosses the blood-brain barrier by passive diffusion
[50]
. When the penetration of metabolites was analyzed it was found that
monoethylglycinexylidide penetration into the cerebral spinal fluid was
slow, but glycinexylidide could not be detected
[502]
.
2) Placenta: rapid
[462]
[463]
[464]
a) Lidocaine rapidly crosses the placenta by passive diffusion. Distribution
across the placenta may be sufficient enough to enter the fetus and reach
toxic levels. Lidocaine is detectable in both maternal and fetal blood
following subarachnoid injection; however, concentrations are very low
compared with those following epidural use. Lidocaine appears in fetal
circulation within a few minutes after administration to the mother. Cord to
maternal serum ratios after intravenous and epidural anesthesia range
between 0.5 to 0.7, but have been reported as high as 1.32
[462]
[463]
[464]
.
3) Tissues: extensive
[464]
[503]
a) Lidocaine is distributed initially into highly-perfused tissues (ie, kidneys,
lungs, liver, heart). Within 30 seconds, 70% of the injected drug has
entered these highly perfused tissues with less than 1% metabolized.
Lidocaine is also distributed into fat tissue
[464]
[503]
.
B) Distribution Kinetics
1) Lidocaine
a) Volume of Distribution
1) 1.5 L/kg
[282]
a) The mean Vd following intravenous administration of lidocaine to healthy
volunteers (n=15) was 1.5 L/kg (range, 0.7 to 2.7 L/kg)
[282]
.
2) Lidocaine Hydrochloride
a) Distribution Half-Life
1) 15 to 30 minutes
[477]
a) During cardiopulmonary bypass, the distribution half-life decreases and
the elimination half-life and volume of distribution at steady state
approximately double. However, the rate of clearance from the plasma
remains unaltered. One study attributes these changes to an increase in
unbound, free lidocaine caused by hemodilution of albumin during
cardiopulmonary bypass
[506]
.
b) Distribution half-life of monoethylglycinexylidide (MEGX) ranges from 4
to 48 minutes
[478]
[468]
.
b) Volume of Distribution
1) 0.8 to 1.3 L/kg
[475]
[477]
a) The Vd following intravenous administration is 0.8 to 1.3 L/kg in healthy
patients, and 1 L/kg in patients with heart failure
[475]
[477]
.
b) Distribution and metabolism are significantly impaired during
cardiopulmonary resuscitation
[504]
. Physiologic changes which occur during prolonged bed rest have not
been reported to effect distribution or elimination
[505]
.
c) During cardiopulmonary bypass, the distribution half-life decreases and
the elimination half-life and volume of distribution at steady state
approximately double. However, the rate of clearance from the plasma
remains unaltered. One study attributes these changes to an increase in
unbound, free lidocaine caused by hemodilution of albumin during
cardiopulmonary bypass
[506]
.
Metabolism
A) Metabolism Sites and Kinetics
1) Lidocaine
a) Liver: 90%
[465]
1) Approximately 90% of a dose is metabolized via N-deethylation in the
liver. CYP1A2 is the primary enzyme responsible for the metabolism of
lidocaine via oxidative N- deethylation and 3-hydroxylation. CYP3A4
appears to have a minor role in the biotransformation of lidocaine.
[465]
[466]
.
2) First pass metabolism appears to be enhanced in epileptic patients,
reducing oral bioavailability
[467]
.
2) Lidocaine Hydrochloride
a) Liver: 90%
[465]
[507]
.
1) Approximately 90% of a dose is metabolized via N deethylation in the
liver
[465]
[507]
. The metabolism reactions of lidocaine include oxidative N-dealkylation,
ring hydroxylation, cleavage of the amide linkage, and conjugation
[50]
. CYP1A2 is the primary enzyme responsible for the metabolism of
lidocaine via oxidative N- deethylation and 3-hydroxylation. CYP3A4
appears to have a minor role in the biotransformation of lidocaine. It has
been suggested that in patients with normal liver function taking a potent
inhibitor of CYP1A2, the lidocaine infusion rate should be reduced (by 50%
to 80%). In patients with liver dysfunction, inhibitors of CYP1A2 appear to
have less of an effect on the metabolism of lidocaine
[466]
.
2) The rate of metabolism is significantly dependent on the rate of hepatic
blood flow and, as a result, may be impaired in patients after acute
myocardial infarction and/or congestive heart failure. The reappearance of
arrhythmias shortly after initiating therapy in patients without heart failure
may be due to an enhanced hepatic clearance secondary to increased
hepatic blood flow. Hepatic clearance of intravenous lidocaine is enhanced
following the ingestion of a high protein meal due to an increase in hepatic
blood flow
[465]
[507]
.
3) Metabolism and distribution are significantly impaired during
cardiopulmonary resuscitation (CPR). Prolonged cardiac arrest is
associated with a sustained reduction in metabolism, suggesting that the
use of conventional doses could produce toxic plasma concentrations.
However, the results of 1 study suggests that there is no relationship
between duration of CPR and plasma lidocaine levels. In addition, the
effects of CPR on lidocaine metabolism appears to be of little clinical
significance in typical situations
[508]
[509]
[504]
.
4) First pass metabolism appears to be enhanced in epileptic patients,
reducing oral bioavailability
[467]
.
B) Metabolites
1) Lidocaine
a) Monoethylglycinexylidide (MEGX): active
[282]
[458]
1) Monoethylglycinexylidide (MEGX) is similar in pharmacology and toxicity
to lidocaine, but is less potent
[282]
[458]
. MEGX is further metabolized to xylidine and N-ethylglycine. Although all
the pharmacological effects of MEGX are not yet clearly elucidated, MEGX
does possess convulsant activity in rats
[468]
[469]
[470]
.
2) Following intravenous administration of lidocaine, MEGX concentrations
in the serum range from 11% to 36% of lidocaine concentrations
[282]
.
b) Glycinexylidide (GX): active
[282]
[458]
1) Glycinexylidide is similar in pharmacology and toxicity to lidocaine, but is
less potent
[282]
[458]
. Although all the pharmacological effects of glycinexylidide are not yet
clearly elucidated, glycinexylidide does produce central nervous system
toxicity (ie, headache, seizures)
[468]
[469]
[470]
.
2) Following intravenous administration of lidocaine, GX concentrations in
the serum range from 5% to 11% of lidocaine concentrations
[282]
.
2) Lidocaine Hydrochloride
a) Monoethylglycinexylidide (MEGX): active
[50]
[468]
1) Monoethylglycinexylidide (MEGX) is similar in pharmacology and toxicity
to lidocaine, but is less potent
[50]
. MEGX is further metabolized to xylidine and N-ethylglycine. Although all
the pharmacological effects of MEGX are not yet clearly elucidated, MEGX
does possess convulsant activity in rats
[468]
[469]
[470]
.
2) During continuous epidural anesthesia, the addition of epinephrine to
lidocaine solutions tends to result in lower plasma concentrations of
monoethylglycinexylidide (MEGX)
[494]
.
b) Glycinexylidide (GX): active
[50]
[468]
.
1) Glycinexylidide is similar in pharmacology and toxicity to lidocaine, but is
less potent
[50]
. Although all the pharmacological effects of glycinexylidide are not yet
clearly elucidated, glycinexylidide does produce central nervous system
toxicity (ie, headache, seizures)
[468]
[469]
[470]
.
2) During continuous epidural anesthesia, the addition of epinephrine to
lidocaine solutions does not appear to affect plasma concentrations of
glycinexylidide (GX)
[494]
.
Excretion
A) Kidney
1) Lidocaine
a) Renal Excretion (%)
1) 90% (10% unchanged)
[282]
a) Approximately 90% of administered lidocaine is excreted by the kidneys
in the form of various metabolites
[282]
, and less than 10% is excreted unchanged
[458]
[282]
.
b) Urinary excretion of unchanged drug is partly dependent on urinary pH.
Acidic urine is reported to result in a larger fraction excreted in the urine
[471]
.
2) Lidocaine Hydrochloride
a) Renal Excretion (%)
1) 90%, less than 10% unchanged
[50]
a) Following administration of lidocaine, approximately 90% of
administered dose is excreted by the kidneys changed and less than 10%
is excreted unchanged. The conjugate 4-hydroxy-2,6-dimethylaniline is the
primary metabolite in the urine
[50]
. Urinary excretion of unchanged drug is partly dependent on urinary pH.
Acidic urine is reported to result in a larger fraction excreted in the urine
[471]
.
B) Total Body Clearance
1) 0.64 L/min
[282]
a) In a pharmacokinetic study (n=15), the mean systemic clearance was
0.64 +/- 0.18 L/min (range, 0.33 to 0.9 L/min)
[282]
.
Elimination Half-life
A) Parent Compound
1) Lidocaine
a) 1.5 to 2 hours
[458]
1) Following IV bolus administration, the half-life is typically 1.5 to 2 hours
[458]
.
2) In a pharmacokinetic study (n=15), the mean elimination half-life of
lidocaine following IV administration was 107 +/- 20 minutes (range, 81 to
149 minutes)
[282]
.
3) In the absence of hepatic disease or congestive heart failure, the halflife is 1.5 to 2 hours (average: 1.8 hours)
[475]
[476]
[477]
.
4) Half-life may be prolonged in patients with liver failure (average 343
minutes) or heart failure (average 136 minutes)
[475]
.
2) Lidocaine Hydrochloride
a) 1.5 to 2 hours
[50]
.
1) Following an IV bolus dose of lidocaine, the elimination half-life is about
1.5 to 2 hours
[50]
.
2) In the absence of hepatic disease or congestive heart failure, the halflife is 1.5 to 2 hours (average: 1.8 hours)
[475]
[476]
[477]
.
3) Half-life may be prolonged in patients with liver failure (average 343
minutes) or heart failure (average 136 minutes)
[475]
, as much as 2-fold
[50]
.
4) During cardiopulmonary bypass, the distribution half-life decreases and
the elimination half-life and volume of distribution at steady state
approximately double. However, the rate of clearance from the plasma
remains unaltered. One study attributes these changes to an increase in
unbound, free lidocaine caused by hemodilution of albumin during
cardiopulmonary bypass
[506]
.
B) Metabolites
1) Lidocaine
a) Monoethylglycinexylidide (MEGX): 1 to 6 hours
[478]
[468]
.
1) In 1 study the half-life of MEGX was 1.2 to 3.3 hours. In another study
the mean half-life of MEGX was 6.4 +/- 2.2 hours
[478]
[468]
.
b) Glycinexylidide (GX): 1 hour
[479]
.
1) The elimination half-life of GX is 1 hour
[479]
.
2) Lidocaine Hydrochloride
a) Monoethylglycinexylidide (MEGX): 1 to 6 hours
[478]
[468]
1) In 1 study the half-life of MEGX was 1.2 to 3.3 hours. In another study
the mean half-life of MEGX was 6.4 +/- 2.2 hours
[478]
[468]
.
b) Glycinexylidide (GX): 1 hour
[479]
1) The elimination half-life of GX is 1 hour
[479]
.
Extracorporeal Elimination
A) Hemodialysis
1) Lidocaine
a) Dialyzable: Yes
[472]
1) No dosage adjustments are required after hemodialysis. In 2 end stage
renal failure patients on a lidocaine infusion of 0.5 and 0.2 mg/minute, 8.9
and 12.5 mg of the drug, respectively, was removed during 5 hours of
hemodialysis
[472]
.
2) Lidocaine Hydrochloride
a) Dialyzable: Yes
[472]
1) Although lidocaine is removed by hemodialysis, no dosage adjustments
or supplemental doses are required for patients receiving hemodialysis. In
2 end stage renal failure patients on a lidocaine infusion of 0.5 and 0.2
mg/minute, 8.9 and 12.5 mg of the drug, respectively, was removed during
5 hours of hemodialysis
[472]
.
B) Hemoperfusion
1) Lidocaine
a) Dialyzable: No
[473]
1) During treatment of digoxin toxicity, a beta-2-microglobulin absorption
column was connected to the arterial end of a hemodialysis unit. While
serum lidocaine concentrations were unchanged during these procedures,
serum digoxin levels dropped from 6.0 to 2.31 nanograms/mL over 4
hours. A second session 3 days later further reduced serum digoxin levels
from 3.59 to 1.70 nanograms/mL
[473]
.
2) Lidocaine Hydrochloride
a) Dialyzable: No
[473]
1) During treatment of digoxin toxicity, a beta-2-microglobulin absorption
column was connected to the arterial end of a hemodialysis unit. While
serum lidocaine concentrations were unchanged during these procedures,
serum digoxin levels dropped from 6.0 to 2.31 nanograms/mL over 4
hours. A second session 3 days later further reduced serum digoxin levels
from 3.59 to 1.70 nanograms/mL
[473]
.
C) Hemofiltration
1) Lidocaine
a) Dialyzable: Yes
[474]
1) When evaluated in 10 patients receiving continuous arteriovenous
hemofiltration, lidocaine was removed
[474]
.
2) Lidocaine Hydrochloride
a) Dialyzable: Yes
[474]
1) When evaluated in 10 patients receiving continuous arteriovenous
hemofiltration, lidocaine was removed
[474]
.
CAUTIONS
Contraindications
A) Lidocaine
1) hypersensitivity to local anesthetics of the amide type or to any other
component of the product
[255]
[40]
[251]
B) Lidocaine Hydrochloride
1) sensitivity to local anesthetics of the amide type
[257]
or to any other component of the product
[73]
Precautions
A) Lidocaine
1) aspiration may occur when swallowing is impaired by lidocaine (spray)
[255]
2) bradycardia; use with caution
[255]
[251]
3) cardiac conduction, impaired (oint)
[251]
4) cardiac failure; dose adjustment recommended (oint)
[251]
5) cardiovascular function, impaired
[255]
[251]
6) children over 12 years old weighing less than 25 kg; dose adjustment
recommended (oint)
[251]
7) concomitant use of class I antiarrhythmics (eg, tocainide and mexiletine)
[40]
8) concomitant use of other local anesthetics, drugs structurally related to amidetype local anesthetics (eg, antiarrhythmics such as mexiletine), or class III
antiarrhythmics (eg, amiodarone)
[251]
9) covering of application site; risk of increased systemic absorption and toxicity,
potentially resulting in life-threatening side effects
[30]
[256]
10) debilitated or acutely ill; risk of increased sensitivity to systemic effects;
reduced dose
[255]
[251]
11) drug sensitivities, known or history; cross-sensitivities may occur
[255]
[40]
[251]
12) elderly and pediatric patients; risk of increased sensitivity to systemic effects
(spray)
[255]
13) epilepsy
[255]
[251]
14) food or gum while mouth or throat anesthestized; swallowing impairment,
numbness of tongue and buccal mucosa creates potential for bite injuries (spray)
[255]
15) hepatic disease, severe; increased risk of lidocaine toxicity
[255]
[40]
[251]
16) hepatic function, impaired
[40]
[251]
17) irritated or broken skin; risk of increased systemic absorption and toxicity,
potentially resulting in life-threatening side effects (oint, patch, intradermal inject)
[30]
[256]
[40]
18) large doses and/or treatment areas; risk of increased systemic absorption and
toxicity, potentially resulting in life-threatening side effects
[30]
[256]
[40]
19) longer duration of application; increased risk of lidocaine toxicity (transdermal)
[40]
20) paralyzed while under general anesthesia; increased risk of toxicity (spray)
[255]
21) porphyria, acute (spray)
[255]
22) renal function, impaired
[40]
[251]
; risk of toxicity with severe impairment
[255]
23) sepsis and/or traumatized mucosa at application site; risk of rapid systemic
absorption
[255]
[251]
24) shock, severe
[255]
[251]
25) short intervals between doses; increased risk of systemic toxicity (spray, oint)
[255]
[251]
26) skin temperature increases; risk of increased systemic absorption and toxicity,
potentially resulting in life-threatening side effects
[30]
[256]
27) smaller patients; increased risk of lidocaine toxicity (transdermal)
[40]
28) store and dispose of topical patches out of the reach of children and pets;
chewing or swallowing a new or used patch can cause serious adverse effects
[40]
29)
B) Lidocaine Hydrochloride
1) arrhythmias, serious, dose-related; may occur with use of lidocaine in
combination with vasoconstrictors such as epinephrine during or after use of
potent inhalation anesthetics (injection)
[257]
2) cardiovascular impairment; risk of reduced ability to compensate for functional
changes associated with AV conduction prolongation (injection)
[257]
3) chondrolysis (ie, necrosis and destruction of cartilage) has been reported with
continuous postoperative, intra-articular infusions of local anesthetics with
elastomeric infusion devices (unapproved use)
[257]
4) covering of application site; risk of increased systemic absorption and toxicity,
potentially resulting in life-threatening side effects (topical)
[30]
[256]
5) debilitated, elderly, acutely ill, and pediatric patients; reduced tolerance to
elevated blood levels; dose adjustment recommended
[257]
[258]
[259]
[260]
[73]
6) end-artery areas (eg, digits, nose, external ear, penis) or areas of
compromised blood supply; risk of further blood-flow restriction (eg, ischemic
injury or necrosis) when lidocaine is in combination with vasoconstrictors
(injection)
[257]
7) endotracheal tube lubrication; risk of lumen obstruction due to product residue
and clumping upon drying (jelly)
[258]
8) epidural or spinal anesthesia; avoid using local anesthetic solutions containing
antimicrobial preservatives (injection)
[257]
9) ergot-type oxytocic agents should be avoided when lidocaine is in combination
with epinephrine or other vasopressors (injection)
[257]
10) familial malignant hyperthermia; may be triggered by local anesthetics
(injection)
[257]
[73]
11) food or gum while mouth or throat anesthestized; swallowing impairment,
danger of aspiration, numbness of tongue and buccal mucosa creates potential
for bite injuries
[258]
[259]
[260]
12) head and neck area anesthesia; confusion, convulsion, respiratory depression
and/or respiratory arrest, and cardiovascular stimulation or depression may occur;
do not exceed recommended doses (injection)
[257]
[73]
13) heart block or severe shock
[257]
[258]
[259]
[260]
[73]
14) hepatic disease, especially severe disease; increased risk of toxic plasma
concentrations
[257]
[258]
[259]
[260]
[73]
15) inflamed or septic skin site; should not be used as intended injection site
(injection)
[73]
16) irritated or broken skin; risk of increased systemic absorption and toxicity,
potentially resulting in life-threatening side effects (topical)
[30]
[256]
17) large doses and/or treatment areas; risk of increased systemic absorption and
toxicity, potentially resulting in life-threatening side effects (topical)
[30]
[256]
18) MAOIs or tricyclic antidepressants should be used with caution when
lidocaine is administered in combination with epinephrine or other vasopressors;
risk of severe prolonged hypertension (injection)
[257]
19) neurological disease, septicemia, spinal deformities, or severe hypertension;
use extreme caution with lumbar and caudal epidural administration (injection)
[257]
[73]
20) skin temperature increases; risk of increased systemic absorption and toxicity,
potentially resulting in life-threatening side effects (topical)
[30]
[256]
21) sulfite sensitivity; some lidocaine with epinephrine solutions contain sodium
metabisulfite; risk of sulfa allergy (injection)
[257]
22) topical use only; do not use for injection or as a gargle (4% topical)
[259]
23) vascular disease, hypertensive or peripheral, history; risk of exaggerated
vasoconstrictor response when lidocaine is in combination with vasoconstrictors
(injection)
[257]
Adverse Reactions
Cardiovascular Effects
Arteriospasm
1) Vascular insufficiency secondary to arterial spasms following the
periarterial injection of a lidocaine mixture has been reported.
Although lidocaine is used periarterially to prevent spasm before
vessel cannulation, lidocaine may precipitate rather than prevent
vasospasm. Arterial spasm should be considered as a possible
cause of vascular insufficiency following peri- or intra-arterial
injections
[263]
.
Asystole
1) Two fatal cases of asystole following lidocaine treatment of widecomplex tachycardia in the presence of hyperkalemia were
reported. In a 57-year-old male, wide-complex tachycardia (158
beats/minute) prompted administration of IV lidocaine 100 mg.
Asystole ensued immediately thereafter and all attempts at
resuscitation failed. Abnormal laboratory values included a
potassium level of 9.4 mEq/L and serum creatinine of 18.2 mg/dL. A
31-year-old female with end-stage renal disease developed cardiac
arrest after not obtaining dialysis for one week. After initial
resuscitation efforts, wide-complex tachycardia (168 beats/minute)
appeared and was treated with IV lidocaine 100 mg. As in the
previous case, asystole soon followed, with potassium at 7.8 mEq/L.
The patient was later removed from life support. The authors noted
that elevated serum potassium enhances lidocaine's sodiumchannel blocking activity. In such cases, initial management should
focus on aggressive correction of hyperkalemia rather than widecomplex tachycardia
[267]
.
2) Asystole has been reported following therapeutic doses and
overdoses of lidocaine. In 1 report, temporary complete heart block
and cardiorespiratory arrest occurred in a patient with recent
myocardial infarction following the inadvertent administration of 800
mg lidocaine for ventricular tachycardia. The serum level that will
produce cardiac arrest is dependent on inherent cardiac function.
The chance of cardiac arrest secondary to lidocaine increases as
serum levels increase. Cardiac standstill or conduction disturbances
with lidocaine have occurred secondary to toxic levels and with
therapeutic doses. It appears to develop with greater frequency in
patients with pre-existing conduction disturbances
[268]
[269]
.
Bradyarrhythmia
1) Cardiovascular reactions including bradycardia have occurred
[257]
[260]
[255]
[20]
[270]
.
2) Severe sinus bradycardia was reported in a 79-year-old male 15
seconds after a 100 mg IV bolus of lidocaine following induction of
anesthesia. The patient had a history of left ventricular failure
maintained with digoxin and furosemide; Premature ventricular
contractions (PVC) were controlled with procainamide prior to
surgery. After lidocaine, heart rate decreased from 92 to 60
beats/minute in normal sinus rhythm with an associated reduction in
arterial blood pressure
[271]
.
Cardiac arrest
1) Cardiovascular reactions including cardiovascular collapse
leading to arrest have occurred; systemic adverse effects from
topical lidocaine are unlikely
[257]
[260]
[255]
[20]
[270]
.
2) Two cases of transient cardiopulmonary arrest have been
reported following retrobulbar block with 2 mL of 2% lidocaine for
ophthalmic surgery. Cardiopulmonary resuscitation was performed
and both patients recovered without sequelae
[272]
.
3) Cardiac arrest occurred immediately following the administration
of ropivacaine and lidocaine for an interscalene brachial plexus
block in a 34-year-old man. The injection consisted of a mixture of
12 milliliters (mL) of lidocaine (10 milligrams (mg) per mL) with
epinephrine (10 micrograms per mL), 12 mL of lidocaine (20
mg/mL), and 20 mL of ropivacaine (7.5 mg/mL). Pulmonary edema
developed and mechanical ventilation was required for 22 hours
after the initial injection. Following extubation, recovery was
uneventful
[273]
.
Cardiac dysrhythmia
1) Cardiovascular reactions including arrhythmia have occurred
[260]
[255]
.
Disorder of implantable defibrillator
1) A 100 milligram lidocaine intravenous bolus just prior to insertion
of an implantable cardioverter defibrillator (ICD) increased the
defibrillation threshold from 10 to 34 joules in a single case report.
Lidocaine was administered to minimize the pain associated with
propofol injection for general anesthesia. Two trials of a 30 joule
biphasic shock failed to elicit defibrillation; a biphasic 34 joule
rescue shock restored sinus rhythm. Lidocaine serum concentration
was 3.8 micrograms/milliliter 30 minutes after injection. One hour
after the lidocaine bolus, the defibrillation threshold had decreased
to 10 joules
[275]
.
Electrocardiogram abnormal
1) Therapeutic serum levels of lidocaine produce negligible changes
in the EKG, which may include a slight shortening of the QT interval.
Lidocaine has no effect on the QRS complex
[264]
.
2) EKG manifestations of toxic lidocaine levels (plasma levels
greater that 5 mcg/mL) are similar to quinidine and are
characterized by widening of the QRS complex, prolongation of the
PR interval, ventricular tachyarrhythmias, and heart block
[265]
.
Heart block
1) High-grade heart block occurred in a 14-day-old infant following
IV lidocaine 2 mg/kg over 5 seconds. Lidocaine was given at the
end of cataract surgery to prevent coughing from tracheal tube
stimulation. A ventricular rate of 40 was also observed. The patient
was resuscitated successfully . It is suggested that titration of small
doses of the drug may decrease the potential for these effects
[274]
.
2) Temporary complete heart block in a patient with recent
myocardial infarction was reported following the inadvertent
administration of 800 mg lidocaine for ventricular tachycardia. The
patient developed generalized convulsive crisis which was followed
by cardiorespiratory arrest. The patient was resuscitated and the
conduction disturbance was temporary. No medications were given
and approximately 30 minutes post lidocaine, the ECG revealed
sinus tachycardia and first degree AV block. Two hours later the
ECG revealed stable normal sinus rhythm
[269]
.
3) The refractory period of the atrioventricular (AV) node may be
shortened in some individuals by lidocaine; however, these effects
are variable and usually no changes in AV conduction occur. The
refractory period of the His-Purkinje system is usually shortened by
lidocaine, but complete AV block may occur in patients with
underlying bundle-branch disease
[264]
.
Hypotension
1) Incidence: 3%
[257]
2) Hypotension was reported in 3% of patients receiving lidocaine
hydrochloride injection for spinal anesthesia
[257]
. Cardiovascular reactions including hypotension have occurred with
lidocaine topical solution, oral spray, ointment, and patch
[257]
[260]
[255]
[20]
[270]
.
3) Hypotension has been associated with the use of lidocaine
reported that of 336 patients undergoing this procedure, 20%
suffered at least a 20% fall in blood pressure and an additional 24%
required ephedrine to reverse the hypotension
[277]
.
Phlebitis
1) Phlebitis secondary to lidocaine infusion can be reduced by the
addition of heparin or hydrocortisone (or both) to the infusion, and
limiting the duration of the infusion to 24 hours. Concentrations
administered were heparin 4,000 units daily and/or hydrocortisone
20 mg per 24 hours
[276]
.
Sinus node dysfunction
1) Loss of consciousness and sinus standstill was noted in a 65year-old female following a 50 mg IV bolus dose of lidocaine
hydrochloride for ventricular premature beats. Although sinus
standstill can be a complication of acute myocardial infarction, for
which this patient was admitted to the intensive care unit, a definite
temporal relationship was seen between onset and lidocaine
administration, and between sinus rhythm recovery after 30 minutes
and the half-life of lidocaine. Lidocaine in conventional therapeutic
doses does not depress the sinus node, however when given in
combination with quinidine or phenytoin or in patients with sick sinus
syndrome, sinus standstill has been noted. It is speculated that the
sinus standstill noted in this patient was attributed to acute
myocardial infarction enhancing the inhibitory effect of lidocaine on
sinus node activity
[266]
.
2) Automaticity of the sinoatrial (SA) node is adversely effected by
lidocaine levels in excess of the normal therapeutic range of 2 to 4
mcg/ml in vitro. Sinus node suppression appears to occur more
commonly in the presence of severe underlying sinus disease,
concurrent use of SA node suppressant drugs, or ventricular
dysrhythmia following acute myocardial infarction. Risk for serious
SA nodal suppression in the absence of pre-existing dysfunction is
considered limited (Manyari-Orgeta & Brennan, 1978).
Vascular insufficiency
1) Vascular insufficiency secondary to arterial spasms following the
periarterial injection of a lidocaine mixture has been reported.
Although lidocaine is used periarterially to prevent spasm before
vessel cannulation, lidocaine may precipitate rather than prevent
vasospasm. Arterial spasm should be considered as a possible
cause of vascular insufficiency following peri- or intra-arterial
injections
[263]
.
Vasoconstriction
1) A 49-year-old woman experienced a decrease in sensation and a
feeling of warmth in her arm during the axillary approach to the
block of the brachial plexus with a lidocaine mixture. Within two to
three minutes the entire hand and arm blanched and pulses were
not palpable. Approximately 15 minutes later pulses reappeared
spontaneously and blood pressure, pulse and sensorium remained
stable
[263]
.
Dermatologic Effects
Abnormal sensation
1) During or following the application of lidocaine 5% patches, an
abnormal sensation may develop at the application site. This
reaction is usually mild and transient, resolving spontaneously within
a few minutes to hours
[270]
[323]
.
Achromia of skin
1) During or following the application of lidocaine 5% patches,
depigmentation may occur at the application site. This reaction is
usually mild and transient, resolving spontaneously within a few
minutes to hours
[282]
[323]
.
Blistering eruption
1) During or following the application of lidocaine 5% patches,
blisters or vesicles may occur at the application site. These
reactions are usually mild and transient, resolving spontaneously
within a few minutes to hours
[282]
[323]
.
Contact dermatitis
1) During or following the application of lidocaine 5% patches,
dermatitis may develop at the application site. This reaction is
usually mild and transient, resolving spontaneously within a few
minutes to hours
[282]
[323]
.
2) Allergic contact dermatitis (edema, tenderness, erythema, bullae)
has been reported following topical application of lidocaine
[327]
.
3) Contact sensitivity has been reported in a 70-year-old patient
following lidocaine administration for a dental procedure. The
reaction presented as swelling of the soft tissues over the right
zygoma which developed 48 hours after the procedure. Subsequent
use of prilocaine (8 days later) and mepivacaine (11 days after the
lidocaine reaction) resulted in similar swelling
[328]
.
4) One case report describes contact allergy to lidocaine after use of
an anti-hemorrhoidal suppository. Although the patient had never
handled an anti-hemorrhoidal suppository prior to this, she may
have been sensitized through her profession as a nurse when
handling lidocaine medications. Because the most reported source
of lidocaine sensitization is from anti-hemorrhoidal preparations, this
case study underscores the need for awareness of hypersensitivity
to lidocaine for use on mucous membranes
[329]
.
Contusion
1) During or following the application of lidocaine 5% patches,
bruising may occur at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
[323]
.
Discoloration of skin
1) During or following the application of lidocaine 5% patches, a
discoloration may occur at the application site. This reaction is
usually mild and transient, resolving spontaneously within a few
minutes to hours
[282]
[323]
.
Edema
1) In a pooled analysis of five randomized, double-blind, parallelarm, sham-placebo controlled trials of pediatric patients (3 to 18
years) administered lidocaine hydrochloride by an intradermal
injection system (n=906 (active treatment) and n=855 (placebo)),
edema at the application site was reported in 8% of patients
receiving lidocaine versus 3% for placebo
[57]
.
2) During or following the application of lidocaine 5% patches,
edema may occur at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
.
Erythema
1) In a pooled analysis of five randomized, double-blind, parallelarm, sham-placebo controlled trials of pediatric patients (3 to 18
years) administered lidocaine hydrochloride by an intradermal
injection system (n=906 (active treatment) and n=855 (placebo)),
erythema at the application site was reported in 53% of patients
receiving lidocaine versus 27% for placebo
[57]
.
2) During or following the application of lidocaine 5% patches,
erythema may occur at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
[323]
.
3) A 50-year-old male developed erythema following treatment with
amide local anesthetics. The patient developed several patches of
mild macular erythema internally and on his face to neck soon after
treatment with mepivacaine for a herniated disc and again following
a dental procedure with lidocaine. Lymphocyte stimulating tests
were negative for prilocaine, lidocaine, mepivacaine, and
propitocaine. Following a dental procedure using propitocaine and
felypressin, the patient developed slate-coloured, wellcircumscribed, round erythema on his face, upper arms, and his oral
and genital mucosa. Macular erythema reoccurred three times at
comparable sites. Fixed drug eruption was suspected and
propitocaine was discontinued. Treatment with topical clobetasol
and oral prednisolone was initiated. Symptoms resolved
approximately two weeks later. Patch testing showed the patient
positive for amide local anesthetic sensitivity. Tetracaine was used
for further dental treatment with no further reactions
[324]
.
Flushing
1) Flushing has been reported during postmarketing use of lidocaine
5% patch
[282]
.
Injection site pain
1) One study compared the level of pain induced by intradermal and
subcutaneous injections of etidocaine 1%, bupivacaine 0.5%,
mepivacaine 1%, chloroprocaine 2%, and lidocaine 1%; normal
saline was also administered as control. Each subject received 0.1
mL and 0.2 mL SC of each preparation, with etidocaine having the
highest mean pain score; this was followed, in order by bupivacaine,
mepivacaine, normal saline, chloroprocaine, and lidocaine. Lipid
solubility was the characteristic anesthetic which was closely
correlated with the local pain on injection; etidocaine, the most
painful anesthetic, is the most lipid soluble
[325]
.
2) The addition of sodium bicarbonate to lidocaine injection may
reduce pain on injection without altering onset or duration of
anesthesia. In the pilot phase of this double-blind study, 5 healthy
volunteers received (in random order at 5-minute intervals) lidocaine
with sodium bicarbonate, lidocaine with normal saline, and normal
saline alone. After each injection, patients were assessed for onset
and duration of action. During the second study phase, 37 subjects
received the same random-order treatment regimen and were asked
to self-assess pain after each injection. Subjective pain scores were
significantly lower during administration of lidocaine with sodium
bicarbonate, but onset and duration of anesthetic effect did not differ
among treatment groups
[326]
.
3) In two randomized, double-blinded studies, lidocaine with or
without epinephrine and mepivacaine have been shown to be
statistically less painful when buffered with sodium bicarbonate
[64]
. Addition of 2 milliliters (mL) of sodium bicarbonate (1
milliequivalent per milliliter (mEq/mL)) to 20 mL of local anesthetic
(1% lidocaine with or without epinephrine or 1% mepivacaine)
raised the pH to 7.2. With the use of a linear visual analog pain
scale, normal volunteers compared the pain produced by the timed
infiltration on their dorsal hands of these unbuffered solutions (pH
5.98 to 6.21) with the same buffered anesthetics. Infiltration with the
unbuffered anesthetics was found to be 2.8 to 5.7 times more
painful as their buffered counterparts. There was no significant
difference detected in the time of onset or duration of anesthesia or
the surface area of skin anesthetized
[63]
.
Papular reaction
1) During or following the application of lidocaine 5% patches,
papules may develop at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
[323]
.
Peeling of skin
1) During or following the application of lidocaine 5% patches,
exfoliation may occur at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
[323]
.
Petechiae
1) In a pooled analysis of five randomized, double-blind, parallelarm, sham-placebo controlled trials of pediatric patients (3 to 18
years) administered lidocaine hydrochloride by an intradermal
injection system (n=906 (active treatment) and n=855 (placebo)),
petechiae at the application site was reported in 44% of patients
receiving lidocaine versus 5% for placebo
[57]
.
2) During or following the application of lidocaine 5% patches,
petechiae may develop at the application site. This reaction is
usually mild and transient, resolving spontaneously within a few
minutes to hours
[282]
[323]
.
Pruritus
1) During or following the application of lidocaine 5% patches,
pruritus may develop at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
[323]
.
Sensation of burning of skin
1) During or following the application of lidocaine 5% patches, a
burning sensation may occur at the application site. This reaction is
usually mild and transient, resolving spontaneously within a few
minutes to hours
[282]
[323]
.
Skin irritation
1) During or following the application of lidocaine 5% patches, skin
irritation may occur at the application site. This reaction is usually
mild and transient, resolving spontaneously within a few minutes to
hours
[282]
[323]
.
Endocrine/Metabolic Effects
Acute intermittent porphyria
See Drug Consult reference:
DRUGS CONSIDERED UNSAFE- ACUTE PORPHYRIAS
Gastrointestinal Effects
Disorder of taste
1) Lidocaine has been associated with taste disturbances; although
the actual incidence is unknown, it is suggested that this is a rare
complication of lidocaine
[318]
.
Hoarse
1) Reversible hoarseness has been reported after use of lidocaine
non-aerosol spray
[255]
.
Loss of voice
1) Reversible loss of voice has been reported after use of lidocaine
non-aerosol spray
[255]
.
Nausea
1) Incidence: less than 1%
[257]
2) Nausea was reported by less than 1% of patients receiving
lidocaine hydrochloride for spinal anesthesia and 1% of patients
after use of lidocaine periodontal gel
[257]
.
3) Nausea has been reported during postmarketing use of lidocaine
5% patch
[282]
.
4) In a pooled analysis of five randomized, double-blind, parallelarm, sham-placebo controlled trials of pediatric patients (3 to 18
years) administered lidocaine hydrochloride by an intradermal
injection system (n=906 (active treatment) and n=855 (placebo)),
nausea was reported by 2% of patients
[57]
.
Pain in throat
1) Reversible sore throat has been reported after use of lidocaine
non-aerosol spray
[255]
.
Vomiting
1) Vomiting has been reported during postmarketing use of
lidocaine 5% patch
[282]
.
2) Most of the adverse effects associated with lidocaine are either
excitatory or depressant reactions including vomiting. CNS toxicity is
the major adverse effect of parenteral lidocaine administration.
Careful monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors,
depression, or drowsiness) is required since some of these early
warning signs may progress to more serious events
[257]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not occur
at all which may cause drowsiness to be the first sign of toxicity
possibly merging into loss of consciousness and respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more vulnerable
to lidocaine-induced CNS toxicity
[283]
.
3) In a pooled analysis of five randomized, double-blind, parallelarm, sham-placebo controlled trials of pediatric patients (3 to 18
years) administered lidocaine hydrochloride by an intradermal
injection system (n=906 (active treatment) and n=855 (placebo)),
vomiting was reported by 1% of patients
[57]
.
Hematologic Effects
Methemoglobinemia
1) Methemoglobinemia has occurred following intravenous and
topical administration of lidocaine. In most cases,
methemoglobinemia was mild, not clinically significant, and resolved
spontaneously; however, some patients have required treatment
with oxygen and/or methylene blue
[261]
; (Brisman et al, 1998; Kumar et al, 1997a)
[262]
.
2) Three cases of methemoglobinemia have been reported in
patients who received topical lidocaine for various endoscopic
procedures. Doses of lidocaine ranged from 4.4 to 7.6 mg/kg and
methemoglobin levels ranged from 14% to 37%. Two patients were
receiving other drugs (trimethoprim-sulfamethoxazole and
isosorbide mononitrate) that may have predisposed them to
methemoglobinemia. Only one patient received methylene blue; the
other two cases resolved spontaneously. None of the patients were
rechallenged. Most reported cases of topical anesthesia-induced
methemoglobinemia have been reported with benzocaine. Clinically
mild methemoglobinemia has been described with the use of
intravenous lidocaine but its association with topical lidocaine use is
not well defined. Clinicians should be aware that topical lidocaine
induced methemoglobinemia is clearly plausible and endoscopy
suites should have methylene blue available
[261]
.
3) Methemoglobinemia can occur following intravenous
administration of lidocaine, however it is probably not clinically
significant in most cases. One study reported statistically significant
increases in methemoglobin levels in cardiac patients receiving
intravenous lidocaine. Patients were given a 1 mg/kg IV bolus,
followed by a maintenance infusion of 2 mg/min, and then a second
"mini bolus" of 0.5 mg/kg at 15 minutes after the initial bolus
injection; the infusion was then adjusted to a range of 1 to 4 mg/min
according to clinical status. Mean methemoglobin levels at 1 and 6
hours after initiation of lidocaine were 0.51% and 0.65%,
respectively. The highest level at 1 hour was 1%, with 1.2% being
the highest level observed at 6 hours. Corresponding lidocaine
serum concentrations were 1.72 and 3.08 mcg/mL, respectively. It is
felt that determining methemoglobin levels is not required following
routine intravenous lidocaine therapy, however determination of
methemoglobin may be indicated in lidocaine toxicity as
methemoglobin could increase to potentially toxic levels
[262]
.
Immunologic Effects
Allergic reaction to drug
1) Incidence: rare
[282]
2) Allergic and anaphylactic reactions to lidocaine are rare but may
occur. Angioedema, bronchospasm, dermatitis, dyspnea,
hypersensitivity, laryngospasm, pruritus, shock, and urticaria should
be managed by conventional means. Sensitivity by skin testing is of
doubtful value
[282]
.
3) Allergic reactions of the amide type are rare but may occur.
Allergic reactions are characterized by skin lesions, urticaria, edema
or anaphylactic shock.
[257]
[260]
[255]
[20]
.
4) Allergic symptoms developed after 4 uneventful previous
administrations during dental therapy
[335]
.
5) Delayed-type hypersensitivity to lidocaine may be more common
than previously thought. Four out of 183 patients referred to a
dermatitis clinic had a positive patch test reaction to lidocaine, 2 of
whom were also sensitive to an intradermal injection of lidocaine.
The North American Contact Dermatitis Group preliminarily reported
that 12/1030 patients (0.7%) had a positive patch test for lidocaine,
suggesting that type IV hypersensitivity reactions may not be rare
[336]
.
6) In 1 case report, a delayed-type hypersensitivity reaction (edema,
eczematous dermatitis) occurred 1 day after subcutaneous use of
lidocaine for dental surgery
[337]
.
7) There have been no reported cases of cross-sensitivity between
lidocaine and procainamide. Lidocaine and procainamide have very
similar structures. However, the dissimilarities in the lipophilic group,
intermediate chain, and the differences in major metabolites,
appears to be sufficient to eliminate the chance of cross-sensitivity.
Cross-reactivity between ester-type drugs (procaine) and amide
type drugs (lidocaine) has been reported to be highly unlikely.
However, the pharmacodynamic effects of procainamide and
lidocaine may be similar enough to result in possible additive effects
and thus be interpreted as cross-sensitivity. Both drugs do not differ
fundamentally in their electrophysiological cardiac properties. Some
side effects such as drowsiness, confusion, and convulsions are
similar and may have a synergistic effect on the nervous system.
However, this should not be confused with cross-sensitivity
[338]
[339]
[340]
[341]
[342]
; (Ilyas et al, 1969).
Anaphylaxis
1) Incidence: rare
[282]
2) Allergic and anaphylactic reactions to lidocaine are rare but may
occur. Angioedema, bronchospasm, dermatitis, dyspnea,
hypersensitivity, laryngospasm, pruritus, shock, and urticaria should
be managed by conventional means. Sensitivity by skin testing is of
doubtful value
[282]
.
3) Anaphylactic shock occurred in a 26-year-old undergoing dental
surgery when lidocaine (15 mg without a preservative) was used as
an adjunct to propofol injection. Intradermal prick tests of the
anesthetic induction agents later confirmed that lidocaine was the
causative agent
[333]
.
4) Numerous cases of hypersensitivity reactions to lidocaine have
been reported during dental procedures. In 1 case, systemic
anaphylaxis developed within 15 minutes in a 4-year-old given
lidocaine (0.5 mL of 2% lidocaine) for a dental procedure. The
patient experienced dyspnea, cyanosis, respiratory arrest,
hypotension, and bradycardia, but following treatment completely
recovered without sequelae 4 days later
[334]
..
Immune hypersensitivity reaction
See Drug Consult reference:
LOCAL ANESTHETICS - ALLERGIC REACTION
Musculoskeletal Effects
Lidocaine
Backache
a) Back pain was reported by 3% of patients receiving
lidocaine hydrochloride injection for spinal anesthesia
[257]
.
b) A 75-year-old male developed severe lumbar back pain
associated with posterior thigh muscle spasm following
epidural injection of lidocaine and mepivacaine. The patient
was scheduled for elective femoral artery to popliteal artery
bypass grafting surgery. Epidural test doses of lidocaine and
epinephrine were negative. A total epidural dose of lidocaine
90 milligrams and mepivacaine 296 milligrams was
administered in increments to the patient. Following the last
incremental epidural dose, the patient experienced severe
lumbar back pain. Muscle spasms was observed in the
posterior right thigh and in the lumbar paraspinal musculature
region. Paralysis was initiated with vecuronium however,
reflex to painful stimuli continued. The epidural catheter was
eventually removed and the patient underwent general
anesthesia to complete the bypass graft surgery. The patient
was discharged on the 7th postoperative day in good health
[332]
.
Myasthenia gravis
See Drug Consult reference:
DRUG-INDUCED MYASTHENIA GRAVIS
Pain in lumbar spine, Transient
a) The incidence of transient neurologic symptoms (TNS),
(transient radicular irritation (TRI), or transient lumbar pain
(TLP)) characterized by moderate to severe pain and/or
dysesthesia in the buttocks or lower extremities with or
without back pain following spinal (intrathecal; subarachnoid;
epidural) anesthesia with lidocaine varies from 0.4% to 37%.
The etiology of TNS is unknown. Surgical position (sitting or
standing) or leg manipulation during surgery may be a
contributing factor in the development of TNS. Time to
mobilization (early or late ambulation) of the patient does not
appear to affect the incidence of TNS. It has occurred
following use of preservative-free isobaric (40 to 80 mg) and
hyperbaric (50 to 75 mg) lidocaine. The occurrence of TNS
appears to be independent of concentration and has been
reported at a similar rate of incidence with lidocaine
concentrations ranging from 0.5% to 5%. Diluting lidocaine
with cerebrospinal fluid 1:1 has not been effective in
preventing TNS. Some investigators consider TNS to be a
minor manifestation of the cauda equina syndrome. TNS has
occurred following obstetric and nonobstetric surgical
procedures of the lower body. Symptoms described as a
continuous bilateral burning radicular pain in the buttocks,
thighs, and knees (without sensory or motor deficit), typically
have an abrupt onset (within 12 to 24 hours), last from 45
minutes to 48 hours (rarely up to 5 days), and then
completely resolve without intervention or sequelae. TNS has
occurred more frequently with the use of lidocaine than with
some comparator agents (ie, prilocaine, procaine) and with a
similar incidence with other comparative agents (ie,
bupivacaine, mepivacaine)
[287]
[288]
[289]
[290]
[291]
[292]
[293]
[294]
[295]
[296]
[297]
[298]
[299]
[300]
[301]
[302]
[303]
[304]
[305]
[306]
[307]
.
b) A 75-year-old male developed severe lumbar back pain
associated with posterior thigh muscle spasm following
epidural injection of lidocaine and mepivacaine. The patient
was scheduled for elective femoral artery to popliteal artery
bypass grafting surgery. Epidural test doses of lidocaine and
epinephrine were negative. A total epidural dose of lidocaine
90 milligrams and mepivacaine 296 milligrams was
administered in increments to the patient. Following the last
incremental epidural dose, the patient experienced severe
lumbar back pain. Muscle spasms was observed in the
posterior right thigh and in the lumbar paraspinal musculature
region. Paralysis was initiated with vecuronium however,
reflex to painful stimuli continued. The epidural catheter was
eventually removed and the patient underwent general
anesthesia to complete the bypass graft surgery. The patient
was discharged on the 7th postoperative day in good health
[332]
.
Radiating pain
a) Incidence: Up to 1.9%
[330]
b) The incidence of transient neurologic symptoms (TNS),
(transient radicular irritation (TRI), or transient lumbar pain
(TLP)) characterized by moderate to severe pain and/or
dysesthesia in the buttocks or lower extremities with or
without back pain following spinal (intrathecal; subarachnoid;
epidural) anesthesia with lidocaine varies from 0.4% to 37%.
The etiology of TNS is unknown. Surgical position (sitting or
standing) or leg manipulation during surgery may be a
contributing factor in the development of TNS. Time to
mobilization (early or late ambulation) of the patient does not
appear to affect the incidence of TNS. It has occurred
following use of preservative-free isobaric (40 to 80 mg) and
hyperbaric (50 to 75 mg) lidocaine. The occurrence of TNS
appears to be independent of concentration and has been
reported at a similar rate of incidence with lidocaine
concentrations ranging from 0.5% to 5%. Diluting lidocaine
with cerebrospinal fluid 1:1 has not been effective in
preventing TNS. Some investigators consider TNS to be a
minor manifestation of the cauda equina syndrome. TNS has
occurred following obstetric and nonobstetric surgical
procedures of the lower body. Symptoms described as a
continuous bilateral burning radicular pain in the buttocks,
thighs, and knees (without sensory or motor deficit), typically
have an abrupt onset (within 12 to 24 hours), last from 45
minutes to 48 hours (rarely up to 5 days), and then
completely resolve without intervention or sequelae. TNS has
occurred more frequently with the use of lidocaine than with
some comparator agents (ie, prilocaine, procaine) and with a
similar incidence with other comparative agents (ie,
bupivacaine, mepivacaine)
[287]
[288]
[289]
[290]
[291]
[292]
[293]
[294]
[295]
[296]
[297]
[298]
[299]
[300]
[301]
[302]
[303]
[304]
[305]
[306]
[307]
. In contrast, several studies have reported a low incidence
(0% to 1.9%) of transient radicular pain following spinal
anesthesia with 3% and 5% hyperbaric lidocaine
[330]
[296]
[331]
Lidocaine Hydrochloride
Chondrolysis of articular cartilage
a) In postmarketing evaluations, chondrolysis, usually
involving the shoulder joint, has been reported in both adult
and pediatric patients who received intra-articular infusions of
local anesthetics following arthroscopic and other surgical
procedures (an unapproved use). Cases have been reported
with intra-articular infusions of 48 to 72 hours duration using
local anesthetics with and without epinephrine. The risk
associated with shorter infusions has not been determined.
Symptoms of chondrolysis (eg, joint pain, stiffness, loss of
motion) have appeared as early as 2 months after surgery,
and some patients have required arthroplasty or shoulder
replacement
[257]
.
Neurologic Effects
Lidocaine
Apprehension
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including
apprehension. CNS toxicity is the major adverse effect of
parenteral lidocaine administration. Careful monitoring of
early signs of lidocaine toxicity (ie, restlessness, anxiety,
tinnitus, dizziness, blurred vision, tremors, depression, or
drowsiness) is required since some of these early warning
signs may progress to more serious events
[257]
[282]
[260]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Cauda equina syndrome
a) Cauda equina syndrome is a rare, but serious neurological
complication of spinal or epidural anesthesia. Numerous
factors have been considered as possible causes including a
direct neurotoxic effect and drug pooling in the subarachnoid
space. Cauda equina syndrome has been associated with
continuous spinal anesthesia with 5% hyperbaric lidocaine
and with 2% isobaric lidocaine with and without epinephrine
used in continuous epidural anesthesia. Case reports of
neurologic deficits (ie, cauda equina syndrome) have also
been reported with the use of small bore needles and spinal
microcatheters to administer 5% Lidocaine/Glucose 7.5% for
spinal anesthesia. In these case reports, it was postulated
that neurotoxicity was caused by drug pooling and nonuniform distribution of the anesthetic mixture in the
subarachnoid space. By correcting suboptimal mixing of
anesthetic and withdrawal of spinal microcatheters, the risk of
nerve injury has been decreased (Prod Info 5% XylocaineMPF(R), 2000)
[309]
[310]
[311]
[312]
[313]
[314]
[315]
[316]
.
b) Cauda equina syndrome occurred in a 74-year-old man
after a single spinal injection of 100 mg lidocaine 5% in 7.5%
dextrose with 0.2 mg epinephrine through a 25-gauge
Whitacre needle
[310]
.
Confusion
a) There have been spontaneous reports of confusion during
postmarketing use of lidocaine 5% patch
[282]
.
b) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including confusion.
CNS toxicity is the major adverse effect of parenteral
lidocaine administration. Careful monitoring of early signs of
lidocaine toxicity (ie, restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness) is
required since some of these early warning signs may
progress to more serious events
[257]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Dizziness
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including dizziness.
CNS toxicity is the major adverse effect of parenteral
lidocaine administration. Careful monitoring of early signs of
lidocaine toxicity (ie, restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness) is
required since some of these early warning signs may
progress to more serious events
[257]
[282]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Euphoria
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including euphoria.
CNS toxicity is the major adverse effect of parenteral
lidocaine administration. Careful monitoring of early signs of
lidocaine toxicity (ie, restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness) is
required since some of these early warning signs may
progress to more serious events
[257]
[282]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Feeling nervous
a) There have been spontaneous reports of nervousness
during postmarketing use of lidocaine 5% patch
[282]
.
b) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including
nervousness. CNS toxicity is the major adverse effect of
parenteral lidocaine administration. Careful monitoring of
early signs of lidocaine toxicity (ie, restlessness, anxiety,
tinnitus, dizziness, blurred vision, tremors, depression, or
drowsiness) is required since some of these early warning
signs may progress to more serious events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Grand mal seizure
a) Grand mal seizures developed in a 17-month-old child
secondary to lidocaine toxicity during balloon dilatation of a
congenital pulmonary valve stenosis. The child received a
lidocaine dose of 38 mg/kg (recommended maximum dose is
4.5 mg/kg) during a 90 minute period. The child's serum
lidocaine level at the time of the seizures was 8.7 mg/L
(therapeutic range is 1.5 to 5 mg/L)
[286]
.
Headache
a) Incidence: 3%
[257]
b) Positional headache was reported in 3% of patients
receiving lidocaine hydrochloride injection for spinal
anesthesia
[257]
.
Lightheadedness
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including
lightheadedness. CNS toxicity is the major adverse effect of
parenteral lidocaine administration. Careful monitoring of
early signs of lidocaine toxicity (ie, restlessness, anxiety,
tinnitus, dizziness, blurred vision, tremors, depression, or
drowsiness) is required since some of these early warning
signs may progress to more serious events
[257]
[282]
[260]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Loss of consciousness
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including loss of
consciousness. CNS toxicity is the major adverse effect of
parenteral lidocaine administration. Careful monitoring of
early signs of lidocaine toxicity (ie, restlessness, anxiety,
tinnitus, dizziness, blurred vision, tremors, depression, or
drowsiness) is required since some of these early warning
signs may progress to more serious events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Numbness
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including sensations
of heat, cold or numbness. CNS toxicity is the major adverse
effect of parenteral lidocaine administration. Careful
monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision,
tremors, depression, or drowsiness) is required since some
of these early warning signs may progress to more serious
events
[257]
[282]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Paresthesia
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including circumoral
paresthesia. CNS toxicity is the major adverse effect of
parenteral lidocaine administration. Careful monitoring of
early signs of lidocaine toxicity (ie, restlessness, anxiety,
tinnitus, dizziness, blurred vision, tremors, depression, or
drowsiness) is required since some of these early warning
signs may progress to more serious events
[257]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
.
b) Lidocaine has been associated with paraesthesias;
although the actual incidence is unknown, it is suggested that
this is a rare complication of lidocaine
[318]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Peripheral nerve injury
a) Incidence: less than 1%
[257]
b) Peripheral nerve symptoms were reported in less than 1%
of patients receiving lidocaine hydrochloride injection for
spinal anesthesia
[257]
.
Seizure
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including twitching,
tremors and convulsions. CNS toxicity is the major adverse
effect of parenteral lidocaine administration. Careful
monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision,
tremors, depression, or drowsiness) is required since some
of these early warning signs may progress to more serious
events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
b) Oral ingestion of viscous lidocaine in children can produce
seizures, especially following high doses or prolonged
administration. Seizures have occurred in children after
accidental ingestion and when used therapeutically. The
likelihood of toxicity is enhanced by increasing the dose or
dosing interval, administering viscous lidocaine as a drink,
and/or swallowing the lidocaine. In children, lidocaine should
only be used by directly applying it to individual lesions with
an oral swab for a limited period of time
[279]
[280]
[281]
.
c) Convulsions in an 11-month-old male following topical
application of 2% Xylocaine viscous(R) (5 to 6 times daily for
1 week) for gum pain from erupting teeth has been reported.
Following one week of therapy, 2 generalized seizures
occurred which responded to 2 mg IV diazepam. Lidocaine
blood levels immediately following a seizure were 10
mcg/mL. The authors suggest that the inability of infants to
expectorate excess solution may result in an unintended
absorption
[279]
.
d) Seizures following accidental oral ingestion of lidocaine
(approximately 30 mL of a 4% of solution) for esophageal
anesthesia in an 89-year-old male have been reported. The
patient was also receiving cimetidine, which presumably
increased the bioavailability of lidocaine, and had congestive
heart failure, which may have reduced lidocaine clearance.
Both factors may have enhanced toxicity of the drug
[317]
.
Sensation of hot and cold
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including sensations
of heat, cold or numbness. CNS toxicity is the major adverse
effect of parenteral lidocaine administration. Careful
monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision,
tremors, depression, or drowsiness) is required since some
of these early warning signs may progress to more serious
events
[257]
[282]
[260]
[255]
[278]
[279]
[280]
[281]
The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Shivering or rigors
a) Incidence: 2%
[257]
b) Shivering was reported in 2% of patients receiving
lidocaine hydrochloride injection for spinal anesthesia
[257]
.
Somnolence
a) There have been spontaneous reports of somnolence
during postmarketing use of lidocaine 5% patch
[282]
.
b) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including
drowsiness. CNS toxicity is the major adverse effect of
parenteral lidocaine administration. Careful monitoring of
early signs of lidocaine toxicity (ie, restlessness, anxiety,
tinnitus, dizziness, blurred vision, tremors, depression, or
drowsiness) is required since some of these early warning
signs may progress to more serious events
[257]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Spasmodic movement
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including twitching,
tremors and convulsions. CNS toxicity is the major adverse
effect of parenteral lidocaine administration. Careful
monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision,
tremors, depression, or drowsiness) is required since some
of these early warning signs may progress to more serious
events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Tonic-clonic seizure
a) A 40-year-old female experienced generalized tonic-clonic
seizures (3 to 4 episodes, each lasting 30 to 40 seconds)
after intraureteral injection of two 20 mL doses of 2%
lidocaine jelly (400 milligrams) diluted to half strength with
normal saline. Seizures ensued within minutes of the second
lidocaine injection and were terminated with thiopental.
Follow-up neurologic exam was normal and no further
seizures occurred over the next year. The authors noted that
rapid systemic absorption of lidocaine through traumatized
mucosa might explain this toxic reaction
[284]
.
b) A generalized tonic-clonic seizure was described in an 80year-old male immediately following intraurethral instillation of
lidocaine (20 mL of 2% lidocaine jelly) prior to cystoscopy. A
second seizure occurred one week later following
intraurethral administration of 10 mL of 2% lidocaine jelly
[285]
.
Transient neurological symptoms
a) Incidence: 0.4% to 37%
[287]
b) The incidence of transient neurologic symptoms (TNS),
(transient radicular irritation (TRI), or transient lumbar pain
(TLP)) characterized by moderate to severe pain and/or
dysesthesia in the buttocks or lower extremities with or
without back pain following spinal (intrathecal; subarachnoid;
epidural) anesthesia with lidocaine varies from 0.4% to 37%.
The etiology of TNS is unknown. Surgical position (sitting or
standing) or leg manipulation during surgery may be a
contributing factor in the development of TNS. Time to
mobilization (early or late ambulation) of the patient does not
appear to affect the incidence of TNS. It has occurred
following use of preservative-free isobaric (40 to 80 mg) and
hyperbaric (50 to 75 mg) lidocaine. The occurrence of TNS
appears to be independent of concentration and has been
reported at a similar rate of incidence with lidocaine
concentrations ranging from 0.5% to 5%. Diluting lidocaine
with cerebrospinal fluid 1:1 has not been effective in
preventing TNS. Some investigators consider TNS to be a
minor manifestation of the cauda equina syndrome. TNS has
occurred following obstetric and nonobstetric surgical
procedures of the lower body. Symptoms described as a
continuous bilateral burning radicular pain in the buttocks,
thighs, and knees (without sensory or motor deficit), typically
have an abrupt onset (within 12 to 24 hours), last from 45
minutes to 48 hours (rarely up to 5 days), and then
completely resolve without intervention or sequelae. TNS has
occurred more frequently with the use of lidocaine than with
some comparator agents (ie, prilocaine, procaine) and with a
similar incidence with other comparative agents (ie,
bupivacaine, mepivacaine)
[287]
[288]
[289]
[290]
[291]
[292]
[293]
[294]
[295]
[296]
[297]
[298]
[299]
[300]
[301]
[302]
[303]
[304]
[305]
[306]
[307]
.
c) Transient neurologic symptoms (TNS) were reported
following spinal injection with isobaric 2% lidocaine in a 69year-old white female who was scheduled for outpatient
gynecologic procedures. Approximately 30 minutes after
recovery from spinal anesthesia to the T-7 level with 3 mL of
2% lidocaine and 100 mcg epinephrine, the patient
experienced moderate to severe pain and abnormal
sensation in the region of the buttocks radiating to the thighs
and legs. Neurologic examination confirmed the absence of
any motor or sensory deficits. With spinal anesthesia,
obesity, and the lithotomy position as factors in this case,
TNS was assumed to have occurred. The patient
experienced severe pain for 24 hours, but by 36 hours her
pain was mild and at 72 hours she was pain free
[308]
.
Tremor
a) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including twitching,
tremors and convulsions. CNS toxicity is the major adverse
effect of parenteral lidocaine administration. Careful
monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision,
tremors, depression, or drowsiness) is required since some
of these early warning signs may progress to more serious
events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Lidocaine Hydrochloride
Headache
a) Headache has been commonly reported with the use of
lidocaine hydrochloride ophthalmic gel
[51]
.
Ophthalmic Effects
Lidocaine
Blurred vision
a) Visual disturbances, such as blurred vision, have been
reported with the postmarketing use of lidocaine 5% patch
[282]
.
b) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including blurred
vision. CNS toxicity is the major adverse effect of parenteral
lidocaine administration. Careful monitoring of early signs of
lidocaine toxicity (ie, restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness) is
required since some of these early warning signs may
progress to more serious events
[257]
[260]
[255]
[278]
[279]
[280]
[281]
The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Diplopia
a) Incidence: less than 1%
[257]
b) Double vision was reported in less than 1% of patients
receiving lidocaine hydrochloride for spinal anesthesia
[257]
.
c) Most of the adverse effects associated with lidocaine are
either excitatory or depressant reactions including double
vision. CNS toxicity is the major adverse effect of parenteral
lidocaine administration. Careful monitoring of early signs of
lidocaine toxicity (ie, restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness) is
required since some of these early warning signs may
progress to more serious events
[257]
[260]
[255]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not
occur at all which may cause drowsiness to be the first sign
of toxicity possibly merging into loss of consciousness and
respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more
vulnerable to lidocaine-induced CNS toxicity
[283]
.
Lidocaine Hydrochloride
Burning sensation in eye
a) Burning upon instillation has been commonly reported with
the use of lidocaine hydrochloride ophthalmic gel
[51]
.
Conjunctival hyperemia
a) Conjunctival hyperemia has been commonly reported with
the use of lidocaine hydrochloride ophthalmic gel
[51]
.
Corneal epithelial defect
a) Corneal epithelial changes have been commonly reported
with the use of lidocaine hydrochloride ophthalmic gel
[51]
.
Otic Effects
Tinnitus
1) Tinnitus has occurred with the use of lidocaine 5% patch
[282]
.
2) Most of the adverse effects associated with lidocaine are either
excitatory or depressant reactions including tinnitus. CNS toxicity is
the major adverse effect of parenteral lidocaine administration.
Careful monitoring of early signs of lidocaine toxicity (ie,
restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors,
depression, or drowsiness) is required since some of these early
warning signs may progress to more serious events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not occur
at all which may cause drowsiness to be the first sign of toxicity
possibly merging into loss of consciousness and respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more vulnerable
to lidocaine-induced CNS toxicity
[283]
.
Psychiatric Effects
Lidocaine
Psychotic disorder
a) Psychosis in 6 patients (48 to 75 years) following IV
administration of lidocaine has been reported. Five patients
recovered after discontinuation of lidocaine; one patient
responded to treatment with trifluoperazine
[343]
.
Lidocaine Hydrochloride
Psychotic disorder
a) Psychosis in 6 patients (48 to 75 years) following IV
administration of lidocaine has been reported
[343]
. Five patients recovered after discontinuation of lidocaine;
one patient responded to treatment with trifluoperazine.
Respiratory Effects
Acute respiratory distress syndrome
1) Adult respiratory distress syndrome (ARDS) has been reported
following inhalation of lidocaine. The syndrome recurred upon
subsequent subcutaneous injection
[320]
.
Blocked endotracheal tube
1) Lidocaine jelly has been reported to obstruct an endotracheal
tube during surgery, prolonging both the inspiratory and the
expiratory phases of ventilation. It was determined that lidocaine
jelly when exposed to gas (nitrous oxide and oxygen) flow forms a
sheet-like substance on the inner surface of the tube. This film-like
material lining the tube may peel and clump following flexion of the
tube causing a narrowing of the lumen or a complete obstruction.
This has not been observed with lidocaine ointment. This difference
is attributed to the vehicle in which the lidocaine is placed. Lidocaine
jelly is in a vehicle of methylcellulose, and lidocaine ointment a
vehicle of polyethylene and propylene glycol. The material lining the
obstructed tube was analyzed and found to be methylcellulose.
Lidocaine jelly should not be used as a lubricant for either
endotracheal tubes or stylets
[322]
.
Bronchospasm
1) The occurrence of fatal bronchospasm in a 67-year-old male with
emphysema and bronchitis following topical lidocaine (80 mg of
10% spray) for routine premedication for fiberoptic bronchoscopy
has been reported. Within 2 minutes, the patient developed
wheezing, dyspnea and cyanosis followed in one minute by cardiac
arrest. Despite intensive resuscitative efforts, the patient died 20
minutes later. It was felt that the patient died secondary to a
hypersensitivity reaction to lidocaine
[321]
.
Respiratory arrest
1) Most of the adverse effects associated with lidocaine are either
excitatory or depressant reactions including respiratory depression
and arrest. CNS toxicity is the major adverse effect of parenteral
lidocaine administration. Careful monitoring of early signs of
lidocaine toxicity (ie, restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness) is required since
some of these early warning signs may progress to more serious
events
[257]
[260]
[255]
[20]
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not occur
at all which may cause drowsiness to be the first sign of toxicity
possibly merging into loss of consciousness and respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more vulnerable
to lidocaine-induced CNS toxicity
[283]
2) Respiratory arrest has occurred following spinal anesthesia with
fentanyl and lidocaine. A 45-year-old man received 80 mg of
lidocaine 5% with fentanyl 20 mcg intrathecally for hernia repair.
During recovery, the patient suddenly lost consciousness and
developed apnea. He was revived with bag-mask resuscitation and
administration of naloxone. Fentanyl was most likely the causative
agent
[319]
.
Respiratory depression
1) Incidence: less than 1%
[257]
2) Respiratory inadequacy was reported in less than 1% of patients
receiving lidocaine hydrochloride for spinal anesthesia
[257]
.
3) Most of the adverse effects associated with lidocaine are either
excitatory or depressant reactions including respiratory depression.
CNS toxicity is the major adverse effect of parenteral lidocaine
administration. Careful monitoring of early signs of lidocaine toxicity
(ie, restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors,
depression, or drowsiness) is required since some of these early
warning signs may progress to more serious events
[257]
[260]
[255]
[20]
and arrest
[278]
[279]
[280]
[281]
. The excitatory manifestations may be very brief or may not occur
at all which may cause drowsiness to be the first sign of toxicity
possibly merging into loss of consciousness and respiratory arrest
[257]
[282]
[260]
[255]
. Patients with liver disease or heart failure appear more vulnerable
to lidocaine-induced CNS toxicity
[283]
.
Teratogenicity/Effects in Pregnancy/Breastfeeding
A) Teratogenicity/Effects in Pregnancy
1) U.S. Food and Drug Administration's Pregnancy Category: Category B (All
Trimesters)
a) Either animal-reproduction studies have not demonstrated a fetal risk but there
are no controlled studies in pregnant women or animal-reproduction studies have
shown adverse effect (other than a decrease in fertility) that was not confirmed in
controlled studies in women in the first trimester (and there is no evidence of a
risk in later trimesters).
See Drug Consult reference:
PREGNANCY RISK CATEGORIES
2) Crosses Placenta: Yes
3) Clinical Management
a) Lidocaine use in pregnancy has not been associated with adverse fetal effects
in limited studies available. However, until more data become available, use
caution when considering the use of lidocaine in pregnant women.
4) Literature Reports
a) Data from the Collaborative Perinatal Project suggest that exposure to
lidocaine early in pregnancy is not associated with an increased risk of
malformations
[451]
. In animal studies, doses up to 6.6 times the human dose revealed no harm to
the fetus
[450]
.
b) One study has provided guidelines for the rational use of antiarrhythmic agents
for arrhythmias during pregnancy, based upon clinical experience and evaluation
of the literature. Lidocaine is considered safe for use in pregnancy
[452]
.
B) Breastfeeding
1) American Academy of Pediatrics Rating: Maternal medication usually
compatible with breastfeeding.
2) World Health Organization Rating: Compatible with breastfeeding.
3) Micromedex Lactation Rating: Infant risk is minimal.
a) The weight of an adequate body of evidence and/or expert consensus
suggests this drug poses minimal risk to the infant when used during
breastfeeding.
4) Clinical Management
a) Lidocaine is considered compatible with breastfeeding by the American
Academy of Pediatrics. The majority of uses of lidocaine are acute, and although
some lidocaine appears in breast milk after intravenous administration, the
concentration is not considered to be pharmacologically significant. Any amount
found in breast milk is further reduced by poor oral bioavailability to the
breastfeeding infant
[457]
.
5) Literature Reports
a) A 34-year-old woman received 20 mg of lidocaine injection for dental surgery
while breastfeeding. Samples of milk and plasma were tested for lidocaine and
monoethylglycinexylidide by high performance liquid chromatography. Milk
concentrations for the lidocaine ranged from 44-66 mcg/L giving a milk/plasma
ratio 1.1. Milk concentrations for the metabolite monoethylglycinexylidide ranged
from 35-41 mcg/L giving a milk/plasma ratio of 1.8. The infant levels for the parent
drug and metabolite were estimated to be less than 0.01 mg/kg/day; these levels
were not considered to be pharmacologically significant
[455]
.
b) In one study assessing the magnitude of excretion of lidocaine, bupivacaine
and PPX (a metabolite of bupivacaine) in the breast milk of 27 patients
undergoing cesarean delivery, the milk/serum ratios based on AUC values were
1.07 +/- 0.82, 0.34+/- 0.24 and 1.37 +/- 0.61, respectively. The majority of the
infants appeared to be in good health and the authors concluded that there were
no adverse effects to the infants related to the local anesthetic agents
[456]
.
6) Drug Levels in Breastmilk
a) Lidocaine
1) Parent Drug
a) Milk to Maternal Plasma Ratio
1) 1.1
[455]
2) Active Metabolites
a) Monoethylglycinexylidide
[455]
1) Milk to Maternal Plasma Ratio
a) 1.8
[455]
b) Lidocaine Hydrochloride
1) Parent Drug
a) Milk to Maternal Plasma Ratio
1) 1.1
[455]
2) Active Metabolites
a) Monoethylglycinexylidide
[455]
1) Milk to Maternal Plasma Ratio
a) 1.8
[455]
Drug Interactions
Drug-Drug Combinations
Acecainide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class III antiarrhythmic agent, such as amiodarone, bretylium,
sotalol or dofetilide, should be exercised with caution, and close
surveillance and ECG monitoring considered, since cardiac effects
may be additive. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class III antiarrhythmic agent, such as amiodarone,
bretylium, sotalol or dofetilide, should be exercised with caution, and
close surveillance and ECG monitoring considered, since cardiac
effects may be additive.
7) Probable Mechanism: additive cardiac effects
Amiodarone
1) Interaction Effect: lidocaine toxicity (cardiac arrhythmia, seizures,
coma)
2) Summary: Two case reports suggest reduced lidocaine clearance
by amiodarone
[393]
[394]
. In contrast, a small prospective study found no change in lidocaine
pharmacokinetics with concomitant amiodarone
[395]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Monitor patients receiving amiodarone and
lidocaine, especially the elderly. The lidocaine dose may need to be
decreased.
7) Probable Mechanism: decreased lidocaine metabolism
8) Literature Reports
a) A 71-year-old male developed a seizure following
coadministration of lidocaine and amiodarone. The serum lidocaine
level increased from 5.4 milligrams/Liter (mg/L) to 12.6 mg/L after
two to three days of amiodarone loading. The lidocaine dose was 2
milligrams/minute (mg/min) and the initial loading dose of
amiodarone was 600 mg twice daily. Concurrent use of the two
drugs appeared to decrease lidocaine clearance, possibly due to
inhibition of the cytochrome P450 system by amiodarone
[390]
.
b) Amiodarone did not affect lidocaine pharmacokinetics in a study
of 10 patients. Patients had received oral amiodarone for one month
before receiving an intravenous bolus of lidocaine. It was suggested
that liver blood flow would be the determining factor in the rate of
lidocaine clearance and no reason emerged indicating that
amiodarone might affect this
[391]
.
c) Severe sinus bradycardia and a long sinoatrial arrest occurred
following administration of IV lidocaine in a 64-year-old male with
sick sinus syndrome who was receiving amiodarone 600 mg daily.
The authors suspect the sinoatrial arrest was secondary to the
effects of both lidocaine and amiodarone in depressing the sinus
node, especially in patients with the sick sinus syndrome
[392]
.
Amiodarone
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class III antiarrhythmic agent, such as amiodarone, bretylium,
sotalol or dofetilide, should be exercised with caution, and close
surveillance and ECG monitoring considered, since cardiac effects
may be additive. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class III antiarrhythmic agent, such as amiodarone,
bretylium, sotalol or dofetilide, should be exercised with caution, and
close surveillance and ECG monitoring considered, since cardiac
effects may be additive.
7) Probable Mechanism: additive cardiac effects
Amprenavir
1) Interaction Effect: increased lidocaine serum concentrations and
potential toxicity (hypotension, cardiac arrhythmias)
2) Summary: Coadministered amprenavir may increase serum
concentrations of lidocaine, causing a potential risk of arrhythmias
or other serious adverse effects. Currently no interaction study has
been conducted. Amprenavir and lidocaine are both metabolized by
cytochrome P450 3A4 enzymes, and the competition for metabolism
could result in increased plasma concentrations of lidocaine.
Plasma concentrations of systemic lidocaine should be closely
monitored in patients also receiving amprenavir
[404]
.
3) Severity: major
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: If concomitant therapy with amprenavir and
lidocaine is unavoidable, plasma concentrations of lidocaine should
be closely monitored and dose adjustments made accordingly. Also
monitor patients for signs and symptoms of lidocaine toxicity
(hypotension, cardiac arrhythmias).
7) Probable Mechanism: inhibition of cytochrome P450 3A4mediated lidocaine metabolism
Arbutamine
1) Interaction Effect: an increased risk of cardiac arrhythmias
2) Summary: Arbutamine may exacerbate or precipitate
supraventricular and ventricular arrhythmias. Because of the
proarrhythmic effects of lidocaine, arbutamine should not be
administered to a patient receiving lidocaine therapy
[351]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Arbutamine should not be administered to
patients on lidocaine therapy because of the potential for cardiac
arrhythmias.
7) Probable Mechanism: additive cardiac effects
Atazanavir
1) Interaction Effect: increased plasma concentrations of lidocaine
and an increased risk of cardiotoxicity (QT prolongation, torsades de
pointes, cardiac arrest)
2) Summary: Coadministration of lidocaine and atazanavir has not
been studied. However, the coadministration of lidocaine and
atazanavir has the potential to produce serious and/or life
threatening adverse events due to an increase in plasma
concentrations of lidocaine
[407]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: probable
6) Clinical Management: If atazanavir and systemic lidocaine are
used concomitantly, monitoring of the electrocardiogram and/or
plasma concentrations of lidocaine is recommended.
7) Probable Mechanism: inhibition of cytochrome P450 3A-mediated
lidocaine metabolism
Bretylium
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class III antiarrhythmic agent, such as amiodarone, bretylium,
sotalol or dofetilide, should be exercised with caution, and close
surveillance and ECG monitoring considered, since cardiac effects
may be additive. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class III antiarrhythmic agent, such as amiodarone,
bretylium, sotalol or dofetilide, should be exercised with caution, and
close surveillance and ECG monitoring considered, since cardiac
effects may be additive.
7) Probable Mechanism: additive cardiac effects
Cimetidine
1) Interaction Effect: lidocaine toxicity (neurotoxicity, cardiac
arrhythmias, seizures)
2) Summary: Effects of cimetidine on a lidocaine infusion are
reported as decreased clearance by 25% to 30%, decreased
volume of distribution, decreased protein binding, increased peak
level, and prolonged half-life. Lidocaine levels have increased up to
75% over pre-cimetidine levels. An increased incidence of
neurotoxicity was also reported. Ranitidine does not significantly
alter lidocaine pharmacokinetics
[386]
[387]
.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Monitor for lidocaine toxicity (e.g.,
neurotoxicity, cardiac arrhythmias, seizures) and adjust the dose
accordingly. Suggest switching to another H2-antagonist (e.g.,
ranitidine or famotidine) which has less potential to alter the
metabolism of lidocaine.
7) Probable Mechanism: decreased metabolism
8) Literature Reports
a) In early trials cimetidine was reported to affect the elimination of
lidocaine by reducing liver blood flow
[370]
[371]
[372]
[373]
, or decreasing the hepatic metabolism of lidocaine
[374]
. Subsequent studies on hepatic blood flow using sorbitol clearance
[375]
, galactose clearance
[376]
, direct hepatic vein catheterization
[377]
, and electromagnetic flow measurement
[378]
have shown that cimetidine has no clinically significant effect on
hepatic blood flow in man
[379]
. The clinical importance of this interaction is not known, however,
careful clinical monitoring and lidocaine blood level monitoring are
recommended. Empiric reduction of lidocaine infusion rate in
patients receiving concomitant cimetidine therapy may not be
appropriate and could potentially result in ineffective treatment
[380]
. Ranitidine may be an alternative choice due to the apparent lack of
effect on lidocaine disposition.
b) Case reports and limited clinical trials have observed lidocaine
toxicity and increased serum lidocaine levels in patients receiving
concomitant cimetidine therapy
[381]
[373]
[371]
[382]
, however,
[383]
found that concomitant administration of intravenous lidocaine and
intravenous or oral cimetidine resulted in minimal changes in
lidocaine pharmacokinetics. Oral cimetidine increased lidocaine
plasma concentrations by 15% and decreased formation of
lidocaine metabolites; similar effects were observed with
intravenous cimetidine. It was suggested that the cimetidinelidocaine interaction is probably of minor clinical importance.
c) In a group of patients with suspected myocardial infarction,
[384]
reported that continuous infusion of cimetidine was not associated
with a significant rate of lidocaine accumulation. None of the
patients demonstrated evidence of lidocaine toxicity.
d) Cimetidine 300 mg, as a single oral dose and repeated four hours
later, was given 11 to 20 hours following the initiation of lidocaine
infusions in six patients with acute myocardial infarction
[380]
. Total lidocaine concentrations increased by approximately 28%
after 24 hours when compared to baseline and unbound lidocaine
concentrations increased by about 18%. Only a small increase in
serum lidocaine concentrations occurs following cimetidine
administration; however, no control group was used in this trial.
e) In nine healthy volunteers who received 120 mg of lidocaine
applied to the posterior pharynx by a metered-dose aerosol on two
occasions, cimetidine 300 mg every six hours for two days before
one of the treatments significantly increased the area under the
plasma concentration-time curve (AUC) for lidocaine. Cimetidine
also increased alpha-acid glycoprotein concentrations, which led to
the speculation that volume of distribution changes contributed to
the increased AUC
[381]
.
f) Combined therapy with cimetidine or ranitidine and epidural
lidocaine for elective cesarean section resulted in no significant
change in lidocaine concentrations in one randomized study
[385]
. In this report, 34 patients were randomly assigned to receive three
antacid regimens: oral sodium citrate 30 mL alone (controls),
ranitidine plus sodium citrate, or cimetidine plus sodium citrate.
Ranitidine was administered as a single oral dose of 150 mg at least
two hours prior to anesthesia; intramuscular cimetidine was given as
a single 300 mg dose at least one hour prior to anesthesia.
Lidocaine 2% with epinephrine 1:200,000 was given via an epidural
catheter as 25 mL over five minutes. Lidocaine concentrations
tended to be higher in cimetidine-treated patients and approached
toxic levels in one patient, although no symptoms of toxicity were
observed. Based upon these data, the authors suggest ranitidine
over cimetidine when H(2)-receptor antagonist therapy is required in
cesarean section patients who also receive epidural lidocaine
anesthesia. However, this study involved a small number of patients
and only single doses of cimetidine and ranitidine were prescribed.
The previously reported interaction between cimetidine and
lidocaine may be dose-related and duration-dependent. More
studies are required to evaluate multiple doses of H(2)-receptor
antagonists with epidural lidocaine.
Cisatracurium
1) Interaction Effect: enhanced neuromuscular blocking action
2) Summary: Some medications, including magnesium salts, lithium,
local anesthetics, procainamide, and quinidine, may enhance the
neuromuscular blocking effect of cisatracurium
[346]
. Dose adjustments of cisatracurium may be needed when these
agents are being used concurrently.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: theoretical
6) Clinical Management: The dose of cisatracurium may need to be
adjusted downward in patients receiving concurrent lidocaine.
7) Probable Mechanism: unknown
Clonidine
1) Interaction Effect: reduced lidocaine absorption following
combined epidural administration
2) Summary: Combined epidural administration of clonidine 300
micrograms plus lidocaine 2% 20 mL resulted in greater than 50%
reduction of peak serum lidocaine concentrations at 30 minutes
following injection. No significant changes in other lidocaine
pharmacokinetic parameters were noted
[350]
.
3) Severity: minor
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Combined use of clonidine plus lidocaine
for epidural anesthesia provides for prolonged pain relief with a
lower potential for adverse reactions due to excessive lidocaine
serum levels.
7) Probable Mechanism: clonidine-induced reduction in local blood
flow reducing rate of lidocaine systemic absorption
8) Literature Reports
a) Twenty-four ASA physical status 1 patients were randomized to
receive 20 mL of 2% epidural lidocaine alone or in combination with
either clonidine 300 micrograms, epinephrine 1:200000, or both
clonidine and epinephrine. The only significant change in lidocaine
pharmacokinetic parameters over the following 360 minutes was
reduction of peak serum concentrations by 37% to 54% measured
at 20 to 30 minutes following administration; the combination of
lidocaine, clonidine, and epinephrine did not result in additive
effects. No patient experienced a drop in systemic blood pressure
greater than 25%. Lower clonidine doses (90 to 150 micrograms)
have previously been shown to have no effect on lidocaine
pharmacokinetics
[348]
.
b) Clonidine prolongs lidocaine sensory block. Nine volunteers were
enrolled in a study where microdialysis probe placement and local
anesthetic blockade was performed. The addition of clonidine (10
mcg/mL) significantly prolonged the duration of lidocaine anesthesia
(1%) to pin prick, touch, and cold sensation. Clonidine prolongs
local anesthetic block, slowing lidocaine elimination from the
injection site, is most pronounced in the first 60 minutes after
injection, and is simultaneous with a reduction in local blood flow
relative to plain lidocaine
[349]
.
Cobicistat
1) Interaction Effect: increased lidocaine concentration
2) Summary: Concurrent use of cobicistat and systemic lidocaine
may lead to increased concentrations of lidocaine. If concurrent
therapy is necessary, measure lidocaine plasma concentrations if
available
[359]
, and monitor for lidocaine toxicity.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Concomitant use of cobicistat and systemic
lidocaine may lead to increased plasma concentrations of lidocaine.
If coadministration is necessary, measure lidocaine plasma
concentrations, if available
[359]
, and monitor for lidocaine toxicity.
7) Probable Mechanism: unknown
Dalfopristin
1) Interaction Effect: an increased risk of lidocaine toxicity
(neurotoxicity, cardiac arrhythmias, seizures)
2) Summary: Quinupristin/dalfopristin is a potent inhibitor of
cytochrome P450 3A4 enzymes and may cause an increase in
lidocaine concentrations when administered concurrently. Because
lidocaine possesses a narrow therapeutic window, doses of
lidocaine may need to be adjusted accordingly
[424]
.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Monitor for lidocaine toxicity (eg,
neurotoxicity, cardiac arrhythmias, seizures) and adjust the dose
accordingly.
7) Probable Mechanism: inhibition of cytochrome P450 3A4mediated lidocaine metabolism
Darunavir
1) Interaction Effect: increased lidocaine plasma concentrations
2) Summary: Coadministration of lidocaine and darunavir/ritonavir
may result in increased lidocaine plasma concentrations. Use
caution if these agents are used concurrently and monitor patients
for lidocaine adverse effects (dizziness, hypotension, ventricular
arrhythmias) and monitor serum lidocaine concentrations if available
[435]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Coadministration of lidocaine and
darunavir/ritonavir may result in increased lidocaine plasma
concentrations. Use caution when these agents are coadministered.
Monitor patients lidocaine adverse effects (dizziness, hypotension,
ventricular arrhythmias) and monitor serum lidocaine concentrations
if available.
7) Probable Mechanism: unknown
Delavirdine
1) Interaction Effect: increased risk of lidocaine toxicity (ventricular
arrhythmias, hypotension, exacerbation of heart failure)
2) Summary: Coadministration of delavirdine and lidocaine may
result in an increased risk of lidocaine toxicity (ventricular
arrhythmias, hypotension, exacerbation of heart failure). Use
caution if these agents are used concurrently and monitor serum
lidocaine concentrations, if possible
[357]
. Monitor patients for lidocaine adverse effects.
3) Severity: major
4) Onset: delayed
5) Substantiation: theoretical
6) Clinical Management: Use caution if delavirdine and lidocaine are
coadministered. Monitor patients for lidocaine adverse effects and
monitor serum lidocaine concentrations, if possible.
7) Probable Mechanism: unknown
Dihydroergotamine
1) Interaction Effect: extreme elevation of blood pressure
2) Summary: Coadministration of dihydroergotamine with lidocaine
may cause an extreme elevation in blood pressure and is therefore
contraindicated
[353]
.
3) Severity: contraindicated
4) Onset: rapid
5) Substantiation: theoretical
6) Clinical Management: The concurrent use of dihydroergotamine
with lidocaine is contraindicated.
7) Probable Mechanism: unknown
Disopyramide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Dofetilide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class III antiarrhythmic agent, such as amiodarone, bretylium,
sotalol or dofetilide, should be exercised with caution, and close
surveillance and ECG monitoring considered, since cardiac effects
may be additive. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class III antiarrhythmic agent, such as amiodarone,
bretylium, sotalol or dofetilide, should be exercised with caution, and
close surveillance and ECG monitoring considered, since cardiac
effects may be additive.
7) Probable Mechanism: additive cardiac effects
Dronedarone
1) Interaction Effect: an increased risk of torsade de pointes
2) Summary: Due to the potential for additive effects on the QT
interval prolongation and increased risk of torsade de pointes, the
concomitant use of dronedarone and lidocaine is contraindicated
[358]
.
3) Severity: contraindicated
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Concomitant use of dronedarone and
lidocaine is contraindicated due to the potential for additive effects
on the QT interval and an increased risk of torsade de pointes
[358]
.
7) Probable Mechanism: additive effects on the QT interval
prolongation
Encainide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Etravirine
1) Interaction Effect: decreased lidocaine plasma concentrations
2) Summary: Caution should be exercised when lidocaine is used
concomitantly with etravirine. The combination of lidocaine and
etravirine may result in decreased lidocaine plasma concentrations
due to CYP3A4-mediated induction of lidocaine by etravirine
[347]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Use caution when coadministering
lidocaine and etravirine. Coadministering the two drugs may result
in reduced lidocaine plasma concentrations due to induction of the
CYP3A4-mediated metabolism of lidocaine by etravirine. Monitoring
lidocaine concentrations and response to antiarrhythmic therapy is
recommended when lidocaine and etravirine are used concomitantly
[347]
.
7) Probable Mechanism: induction of CYP3A4-mediated metabolism
of lidocaine by etravirine
Flecainide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Fosamprenavir
1) Interaction Effect: increased lidocaine serum concentrations and
potential toxicity (hypotension, cardiac arrhythmias)
2) Summary: Coadministration of fosamprenavir may increase
serum concentrations of lidocaine, causing a potential risk of
arrhythmias or other serious, potentially life-threatening adverse
effects. Fosamprenavir is a prodrug of amprenavir, a CYP3A4
inhibitor. Amprenavir and lidocaine are both metabolized by the
CYP3A4 isoenzyme, and the dual mechanism of amprenavir
inhibition of P450-3A4 combined with competition for P450-3A4mediated metabolism could result in increased plasma
concentrations of lidocaine. Plasma concentrations of lidocaine
should be closely monitored in patients receiving fosamprenavir
[389]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: If concomitant therapy with fosamprenavir
and lidocaine is unavoidable, closely monitor plasma concentrations
of lidocaine and adjust dose accordingly. Concurrently monitor
patients for signs and symptoms of lidocaine toxicity (hypotension,
cardiac arrhythmias)
[389]
.
7) Probable Mechanism: inhibition of CYP3A4-mediated lidocaine
metabolism
Fosphenytoin
1) Interaction Effect: additive cardiac depressive effects; decreased
lidocaine serum concentrations
2) Summary: Phenytoin and lidocaine are both class IB
antiarrhythmics. Combined use may produce additive cardiac
depression
[399]
. In addition, there is evidence that phenytoin may stimulate the
hepatic metabolism of lidocaine resulting in reduced serum lidocaine
concentrations
[400]
[401]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: This combination should be given with
considered caution. Monitor cardiac status of patients administered
concomitant lidocaine and phenytoin. If possible, avoid giving this
combination to patients with known heart disease.
7) Probable Mechanism: hepatic enzyme induction and increased
lidocaine metabolism; additive pharmacologic effects
8) Literature Reports
a) One case of sinoatrial arrest may have occurred as a result of
intravenous coadministration of phenytoin and lidocaine
[396]
.
b) Epileptic patients stabilized on phenytoin exhibited increased
metabolism of lidocaine when it was given intravenously; a
significant decrease in lidocaine serum concentrations occurred
when it was administered orally with phenytoin
[397]
[398]
.
Hyaluronidase
1) Interaction Effect: an increased incidence of a systemic reaction
to the anesthetic
2) Summary: Hyaluronidase will effectively increase the diffusion of
local anesthetics
[412]
[413]
[414]
[415]
. It hastens the onset of anesthesia, tends to reduce swelling
caused by local infiltration, and prevents the onset of hematoma,
due to the action of the spreading factor
[416]
. However, these beneficial effects of hyaluronidase are offset by an
increased incidence of systemic toxic reactions due to increased
absorption of the local anesthetic
[417]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: theoretical
6) Clinical Management: Monitor patients for local anesthetic
toxicity. Hyaluronidase effectively increases topical diffusion of local
anesthetics. However, due to its propensity to increase the
incidence of systemic reactions to local anesthetics and because
there are newer anesthetic agents which penetrate very effectively,
its use can no longer be justified.
7) Probable Mechanism: unknown
8) Literature Reports
a) One case of temporary blindness has been reported following
retrobulbar injection of an anesthetic to which hyaluronidase had
been added
[409]
. Cardiopulmonary arrest was reported immediately after retrobulbar
block with a mixture of 2 ml of 0.5% bupivacaine, 2% mepivacaine,
and hyaluronidase
[410]
. The authors speculated it was precipitated by the local anesthetic
being transported through the ophthalmic artery to the carotid artery
and the other midbrain structures. In addition, hypersensitivity
reactions and anaphylaxis have occurred following the use of
hyaluronidase
[409]
. Hyaluronidase also shortens the duration of anesthesia. The
addition of epinephrine prolongs the duration of anesthesia, but
does not affect the diffusion facilitated by the hyaluronidase
[411]
.
Ibutilide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class III antiarrhythmic agent, such as amiodarone, bretylium,
sotalol or dofetilide, should be exercised with caution, and close
surveillance and ECG monitoring considered, since cardiac effects
may be additive. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class III antiarrhythmic agent, such as amiodarone,
bretylium, sotalol or dofetilide, should be exercised with caution, and
close surveillance and ECG monitoring considered, since cardiac
effects may be additive.
7) Probable Mechanism: additive cardiac effects
Indinavir
1) Interaction Effect: increased plasma concentrations of lidocaine
2) Summary: Lidocaine is metabolized by cytochrome P450 3A4,
which is inhibited by indinavir. Increased plasma lidocaine
concentrations may result with coadministration of indinavir, leading
to prolonged therapeutic and adverse effects of lidocaine
[423]
.
3) Severity: moderate
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Observe patient for prolonged therapeutic
and adverse effects of lidocaine. Patients on indinavir treatment,
initiate lidocaine at low doses and titrate based on response and
development of toxicity. Monitoring of the electrocardiogram and/or
plasma concentrations of lidocaine is recommended.
7) Probable Mechanism: inhibition of cytochrome P450 3A4mediated metabolism of lidocaine by indinavir
Lopinavir
1) Interaction Effect: increased lidocaine serum concentrations and
potential toxicity (hypotension, cardiac arrhythmias)
2) Summary: Inhibition of CYP3A4 by lopinavir/ritonavir may result
in increased serum concentrations of lidocaine, causing a potential
risk of arrhythmias or other serious cardiac adverse effects.
Consider monitoring plasma concentrations of systemic lidocaine in
patients also receiving lopinavir/ritonavir
[402]
.
3) Severity: major
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: If concomitant therapy with
lopinavir/ritonavir and lidocaine is unavoidable, plasma
concentrations of lidocaine should be closely monitored and dose
adjustments made accordingly. Also monitor patients for signs and
symptoms of lidocaine toxicity including hypotension, cardiac
arrhythmias, confusion, constipation, nausea and vomiting.
7) Probable Mechanism: inhibition of cytochrome P450 3A4mediated lidocaine metabolism by lopinavir/ritonavir
Metoprolol
1) Interaction Effect: lidocaine toxicity (anxiety, myocardial
depression, cardiac arrest)
2) Summary: Propranolol, metoprolol, and nadolol may increase
lidocaine levels by 20% to 30%
[431]
[432]
[433]
[434]
.
3) Severity: major
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: With concurrent beta blocker therapy,
monitor lidocaine levels more closely (at least every 24 hours) and
adjust lidocaine infusion rates appropriately.
7) Probable Mechanism: decreased lidocaine metabolism
8) Literature Reports
a) Concomitant lidocaine and beta blocker therapy may reduce the
clearance of lidocaine from plasma. This effect may be attributed to
beta blocker-induced reduction in cardiac output and hepatic blood
flow, and inhibition of hepatic microsomal enzymes. A 30% increase
in mean steady-state concentrations of lidocaine has been observed
during concomitant propranolol therapy. Propranolol, metoprolol,
and nadolol have been reported to reduce lidocaine clearance by
15% to 45%. This difference is of clinical significance and the
lidocaine dosage should be adjusted. This effect will be additive to
the accumulation seen during continuous lidocaine infusions.
Additionally, the negative inotropic effect of propranolol, and
possibly other beta blockers, may be enhanced by lidocaine
[426]
[427]
[428]
[429]
.
b) Both nadolol and propranolol are reported to decrease lidocaine
plasma clearance in healthy volunteers
[427]
. Six patients received three separate 30-hour infusions of lidocaine
2 mg/min, one given alone, one given following 3 days of
pretreatment with nadolol 160 mg PO daily, and one following 3
days of pretreatment with propranolol 80 mg PO Q8H. In addition to
reductions in lidocaine plasma clearance, lidocaine plasma levels
were increased by both drugs, and hepatic blood flow (determined
by indocyanine green) decreased with nadolol (1275 to 902
mL/minute) and propranolol (1275 to 957 mL/minute). The hepatic
extraction ratio for lidocaine was increased to a similar degree by
each drug; lidocaine intrinsic clearance was not changed by either
drug. These data suggest that both beta blockers can reduce
lidocaine clearance by a reduction in hepatic blood flow, but not by
inhibition of lidocaine metabolism.
c) A study presented 2 cases of lidocaine toxicity during
concomitant administration of normal doses of propranolol and
lidocaine. The first case was a 56-year-old woman receiving 40 mg
of oral propranolol daily who was given a 50 mg bolus of lidocaine to
control ventricular premature contractions. The patient was then
placed on a lidocaine drip, and within 15 minutes reported
lightheadedness and accentuated bradycardia, which led to sinus
arrest. The second case involved a 40-year-old woman on 160 mg
of oral propranolol daily who received a 100 mg bolus of lidocaine to
control ventricular tachycardia. A continuous lidocaine infusion at a
rate of 2 mg/minute was initiated, and after 3.5 hours, the patient
became hysterical and combative. The infusion was discontinued,
and the patient returned to a normal mental state within 15 minutes.
The lidocaine infusion was resumed at 1 mg/minute with no
difficulties
[430]
.
Mexiletine
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Moricizine
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Morphine Sulfate Liposome
1) Interaction Effect: increased peak morphine concentration
2) Summary: Concomitant administration of epidural morphine
sulfate liposome with epidural lidocaine/epinephrine results in
increased peak concentrations of morphine. Flush the epidural
catheter with 1 milliliter of preservative-free 0.9% saline and wait 15
minutes after epidural administration of lidocaine/epinephrine before
epidural administration of morphine sulfate liposome
[408]
.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: established
6) Clinical Management: Flush the epidural catheter with 1 milliliter
of preservative-free 0.9% saline and wait 15 minutes after epidural
administration of lidocaine/epinephrine before epidural
administration of morphine sulfate liposome.
7) Probable Mechanism: unknown
8) Literature Reports
a) Peak concentrations of morphine increased without reported
adverse events in a pharmacokinetic study evaluating the effects of
a test dose of epidural lidocaine/epinephrine before epidural
administration of morphine liposome. The peak concentration of
morphine increased approximately 3-fold when 3 milliliters of
lidocaine 1.5% and epinephrine 1:200,000 followed by a saline flush
was administered 3 minutes before epidural morphine liposome 15
milligrams (mg). When 15 mg of epidural morphine sulfate liposome
was administered 15 minutes after epidural lidocaine/epinephrine
and a saline flush, the maximum concentration of morphine was
similar to when no lidocaine/epinephrine was administered
[408]
.
Nadolol
1) Interaction Effect: lidocaine toxicity (anxiety, myocardial
depression, cardiac arrest)
2) Summary: Propranolol, nadolol, and metoprolol may increase
lidocaine levels by 20% to 30%
[445]
[446]
[447]
.
3) Severity: major
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: With concurrent beta blocker therapy,
monitor lidocaine levels more closely (at least every 24 hours) and
adjust lidocaine infusion rates appropriately.
7) Probable Mechanism: decreased lidocaine metabolism
8) Literature Reports
a) Concomitant lidocaine and beta-blocker therapy may reduce the
clearance of lidocaine from plasma. This effect may be attributed to
beta-blocker-induced reduction in cardiac output and hepatic blood
flow, and inhibition of hepatic microsomal enzymes. A 30% increase
in mean steady-state concentrations of lidocaine has been observed
during concomitant propranolol therapy. Propranolol, metoprolol,
and nadolol have been reported to reduce lidocaine clearance by
15% to 45%. This difference is of clinical significance and the
lidocaine dosage should be adjusted. This effect will be additive to
the accumulation seen during continuous lidocaine infusions.
Additionally, the negative inotropic effect of propranolol, and
possibly other beta-blockers, may be enhanced by lidocaine
[440]
[441]
[442]
[443]
.
b) Both nadolol and propranolol are reported to decrease lidocaine
plasma clearance in healthy volunteers
[440]
. Six patients received three separate 30-hour infusions of lidocaine
2 mg/min, one given alone, one given following 3 days of
pretreatment with nadolol 160 mg PO daily, and one following 3
days of pretreatment with propranolol 80 mg PO Q8H. In addition to
reductions in lidocaine plasma clearance, lidocaine plasma levels
were increased by both drugs and hepatic blood flow (determined
by indocyanine green) decreased with nadolol (1275 to 902
mL/minute) and propranolol (1275 to 957 mL/minute). The hepatic
extraction ratio for lidocaine was increased to a similar degree by
each drug; lidocaine intrinsic clearance was not changed by either
drug. These data suggest that both beta-blockers can reduce
lidocaine clearance by a reduction in hepatic blood flow, but not by
inhibition of lidocaine metabolism. Two cases of lidocaine toxicity
were reported during concomitant administration of normal doses of
propranolol and lidocaine. The first case was a 56-year-old woman
receiving 40 mg of oral propranolol daily who was given a 50 mg
bolus of lidocaine to control ventricular premature contractions. The
patient was then placed on a lidocaine drip, and within 15 minutes
reported lightheadedness and accentuated bradycardia, which led
to sinus arrest. The second case involved a 40-year-old woman on
160 mg of oral propranolol daily who received a 100 mg bolus of
lidocaine to control ventricular tachycardia. A continuous lidocaine
infusion at a rate of 2 mg/minute was initiated, and after 3.5 hours,
the patient became hysterical and combative. The infusion was
discontinued and the patient returned to a normal mental state
within 15 minutes. The lidocaine infusion was resumed at 1
mg/minutes with no difficulties
[444]
.
Nevirapine
1) Interaction Effect: decreased plasma concentrations of lidocaine
2) Summary: Nevirapine is an inducer of cytochrome P450 3A4
enzymes, which are also involved in the metabolism of lidocaine.
Although studies involving nevirapine and lidocaine have not been
conducted, coadministration of nevirapine with lidocaine may induce
the metabolism of lidocaine, thereby decreasing lidocaine
bioavailability and possibly, its clinical effect. Use caution when
these agents are used concurrently and adjust lidocaine dosage, if
necessary
[418]
.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: theoretical
6) Clinical Management: Caution is advised when lidocaine and
nevirapine are coadministered. Dose adjustment of lidocaine may
be needed due to possible decrease in clinical effect.
7) Probable Mechanism: induction of cytochrome P450 3A4mediated metabolism of lidocaine by nevirapine
Nitrous Oxide
1) Interaction Effect: nitrous oxide toxicity (asphyxia)
2) Summary: Lidocaine has been reported to lower the minimum
effective concentration for inhalation anesthetic agents
[352]
.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: theoretical
6) Clinical Management: If concurrent therapy is required, a
reduction in the dose of nitrous oxide may be required. Monitor for
nitrous oxide toxicity (ie, asphyxia).
7) Probable Mechanism: lowers nitrous oxide threshold
Penbutolol
1) Interaction Effect: an increase in the volume of distribution and a
prolongation of the elimination half-life of lidocaine
2) Summary: One study has shown that penbutolol increases the
volume of distribution and the elimination half-life of lidocaine during
a single intravenous administration
[355]
. Possible mechanisms for the alteration in the pharmacokinetic
profile of lidocaine include changes in the pattern of peripheral blood
flow induced by penbutolol, causing a change in the characteristics
of lidocaine tissue uptake and distribution.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Monitor patients receiving a lidocaine
loading dose and penbutolol for reduced lidocaine effectiveness. A
higher loading dose of lidocaine may be necessary.
7) Probable Mechanism: unknown
8) Literature Reports
a) A study was conducted on the pharmacokinetics of lidocaine in
seven healthy volunteers when administered as a single intravenous
dose alone and when preceded by three days of therapy with
penbutolol 60 mg daily. Penbutolol coadministration resulted in an
increased lidocaine volume of distribution, from 3.36 L/kg to 4.85
L/kg (p less than 0.005). The increase in volume of distribution
caused a prolongation of the half-life of lidocaine from 2.0 hours to
2.5 hours (p less than 0.025). However, the total metabolic
clearance of lidocaine was not significantly altered. The authors
concluded that while a higher loading dose of lidocaine may be
required in a patient receiving penbutolol, the steady-state
concentration of lidocaine during a continuous infusion should
remain unchanged by penbutolol coadministration
[354]
.
Phenytoin
1) Interaction Effect: additive cardiac depressive effects; decreased
lidocaine serum concentrations
2) Summary: Phenytoin and lidocaine are both class IB
antiarrhythmics. Combined use may produce additive cardiac
depression
[399]
. In addition, there is evidence that phenytoin may stimulate the
hepatic metabolism of lidocaine resulting in reduced serum lidocaine
concentrations
[400]
[401]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: This combination should be given with
considered caution. Monitor cardiac status of patients administered
concomitant lidocaine and phenytoin. If possible, avoid giving this
combination to patients with known heart disease.
7) Probable Mechanism: hepatic enzyme induction and increased
lidocaine metabolism; additive pharmacologic effects
8) Literature Reports
a) One case of sinoatrial arrest may have occurred as a result of
intravenous coadministration of phenytoin and lidocaine
[396]
.
b) Epileptic patients stabilized on phenytoin exhibited increased
metabolism of lidocaine when it was given intravenously; a
significant decrease in lidocaine serum concentrations occurred
when it was administered orally with phenytoin
[397]
[398]
.
Procainamide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Propafenone
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Propofol
1) Interaction Effect: an increased hypnotic effect of propofol
2) Summary: A controlled study examined the effects of
intramuscular lidocaine on the dose of propofol necessary to induce
anesthesia. Pretreatment with lidocaine at a dose greater than or
equal to 1.0 mg/kg resulted in a significant decrease in the hypnotic
requirements for propofol
[439]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: In patients receiving lidocaine in soft tissue
before induction of anesthesia with propofol, downward dosage
adjustments in propofol are necessary.
7) Probable Mechanism: unknown
8) Literature Reports
a) Tthe effects of propofol alone and when preceded with
intramuscular lidocaine or bupivacaine were compared in 90
patients undergoing minor gynecological surgery. The patients were
randomized to 9 groups that received propofol combined with
intramuscular lidocaine, bupivacaine, or saline. Patients were given
doses of lidocaine that varied from 0.5 mg/kg to 3.0 mg/kg or
bupivacaine doses that varied from 0.25 mg/kg to 1.0 mg/kg before
induction of anesthesia. Propofol was then administered in
intravenous 0.2 mg/kg bolus doses every 30 seconds until the
patient did not respond to verbal stimuli. The lowest doses of
lidocaine and bupivacaine tested (0.5 mg/kg and 0.25 mg/kg,
respectively) did not significantly reduce the dose of propofol
required to induce hypnosis. The next higher dose of lidocaine and
bupivacaine tested in the study, 1.0 mg/kg and 0.5 mg/kg,
respectively, reduced the necessary dose of propofol significantly.
The highest dose of lidocaine and bupivacaine tested (3.0 mg/kg
and 1.0 mg/kg, respectively) reduced the hypnotic requirement of
propofol by 34.4% and 39.6%, respectively. The authors concluded
that if lidocaine or bupivacaine is injected into soft tissue before
induction of anesthesia with propofol, a downward dosage
adjustment of propofol is necessary
[438]
.
Propranolol
1) Interaction Effect: increased lidocaine toxicity
2) Summary: Use caution with the coadministration of lidocaine and
propranolol, which may significantly reduce lidocaine clearance.
Lidocaine toxicity has been reported following coadministration with
propranolol
[360]
. According to some studies, propranolol, metoprolol, and nadolol
may increase lidocaine levels by 20% to 30%
[366]
[367]
[368]
[369]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Use caution when lidocaine is administered
with propranolol which may reduce lidocaine clearance
[360]
. Monitor for lidocaine toxicity closely.
7) Probable Mechanism: decreased lidocaine clearance
8) Literature Reports
a) Concomitant lidocaine and beta-blocker therapy may reduce the
clearance of lidocaine from plasma. This effect may be attributed to
reduction in cardiac output and hepatic blood flow, and betablocker-induced inhibition of hepatic microsomal enzymes. A 30%
increase in mean steady-state concentrations of lidocaine has been
observed during concomitant propranolol therapy. Propranolol,
metoprolol, and nadolol have been reported to reduce lidocaine
clearance by 15% to 45%. This difference is of clinical significance
and the lidocaine dosage should be adjusted. This effect will be
additive to the accumulation seen during continuous lidocaine
infusions. Additionally, the negative inotropic effect of propranolol,
and possibly other beta-blockers, may be enhanced by lidocaine
[361]
[362]
[363]
[364]
.
b) Both nadolol and propranolol are reported to decrease lidocaine
plasma clearance in healthy volunteers. Six patients received 3
separate 30-hour infusions of lidocaine (2 mg/min), one given alone,
one given following 3 days of pretreatment with oral nadolol (160 mg
daily), and one following 3 days of pretreatment with oral
propranolol (80 mg every 8 hours). In addition to reductions in
lidocaine plasma clearance, lidocaine plasma levels were increased
by both drugs and hepatic blood flow (determined by indocyanine
green) decreased with nadolol (1275 to 902 mL/min) and
propranolol (1275 to 957 mL/min). The hepatic extraction ratio for
lidocaine was increased to a similar degree by each drug; lidocaine
intrinsic clearance was not changed by either drug. These data
suggest that both beta-blockers can reduce lidocaine clearance by a
reduction in hepatic blood flow, but not by inhibition of lidocaine
metabolism
[364]
.
c) A study presented 2 cases of lidocaine toxicity during
concomitant administration of normal doses of propranolol and
lidocaine. The first case was a 56-year-old woman receiving 40 mg
of oral propranolol daily who was given a 50-mg bolus of lidocaine
to control ventricular premature contractions. The patient was then
placed on a lidocaine drip, and within 15 minutes reported
lightheadedness and accentuated bradycardia, which led to sinus
arrest. The second case involved a 40-year-old woman on 160 mg
of oral propranolol daily who received a 100-mg bolus of lidocaine to
control ventricular tachycardia. A continuous lidocaine infusion at a
rate of 2 mg/minute was initiated, and after 3.5 hours, the patient
became hysterical and combative. The infusion was discontinued
and the patient returned to a normal mental state within 15 minutes.
The lidocaine infusion was resumed at 1 mg/minute with no
difficulties
[365]
.
Quinidine
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Quinupristin
1) Interaction Effect: an increased risk of lidocaine toxicity
(neurotoxicity, cardiac arrhythmias, seizures)
2) Summary: Quinupristin/dalfopristin is a potent inhibitor of
cytochrome P450 3A4 enzymes and may cause an increase in
lidocaine concentrations when administered concurrently. Because
lidocaine possesses a narrow therapeutic window, doses of
lidocaine may need to be adjusted accordingly
[424]
.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Monitor for lidocaine toxicity (eg,
neurotoxicity, cardiac arrhythmias, seizures) and adjust the dose
accordingly.
7) Probable Mechanism: inhibition of cytochrome P450 3A4mediated lidocaine metabolism
Rapacuronium
1) Interaction Effect: enhanced neuromuscular blockade
2) Summary: Some medications, including magnesium salts
administered for toxemia of pregnancy, lithium, local anesthetics,
procainamide, and quinidine, may enhance the neuromuscular
blocking effect of rapacuronium
[425]
. Dose adjustments of rapacuronium may be needed when these
agents are being used concurrently.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: theoretical
6) Clinical Management: The dose of rapacuronium may need to be
adjusted downward in patients receiving local anesthetics.
7) Probable Mechanism: unknown
Ritonavir
1) Interaction Effect: increased lidocaine serum concentrations and
potential toxicity (hypotension, cardiac arrhythmias)
2) Summary: Coadministered ritonavir may significantly increase
serum concentrations of lidocaine, resulting in lidocaine toxicity.
Monitor lidocaine therapeutic levels when available
[448]
.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: theoretical
6) Clinical Management: Monitor patients for signs and symptoms of
lidocaine toxicity (hypotension, cardiac arrhythmias). Therapeutic
concentration monitoring is recommended for lidocaine, if available.
Reduce doses of lidocaine as required.
7) Probable Mechanism: decreased lidocaine metabolism
Saquinavir
1) Interaction Effect: increased lidocaine exposure and increased
risk of ventricular arrhythmias
2) Summary: Lidocaine and saquinavir are both metabolized
primarily by CYP3A and using these agents together may increase
the exposure of lidocaine resulting in additive effects on QT and/or
PR interval prolongation and Torsades de pointes. Therefore, the
concomitant use of lidocaine and saquinavir is contraindicated
[388]
.
3) Severity: contraindicated
4) Onset: delayed
5) Substantiation: theoretical
6) Clinical Management: Concomitant use of lidocaine and
saquinavir is contraindicated. Both lidocaine and saquinavir are
metabolized primarily by CYP3A4 and using these agents together
may cause increased levels of lidocaine, and an increased risk of
QT and/or PR interval prolongation and Torsades de pointes
[388]
.
7) Probable Mechanism: inhibition of CYP3A4-mediated lidocaine
metabolism
Sotalol
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class III antiarrhythmic agent, such as amiodarone, bretylium,
sotalol or dofetilide, should be exercised with caution, and close
surveillance and ECG monitoring considered, since cardiac effects
may be additive. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class III antiarrhythmic agent, such as amiodarone,
bretylium, sotalol or dofetilide, should be exercised with caution, and
close surveillance and ECG monitoring considered, since cardiac
effects may be additive.
7) Probable Mechanism: additive cardiac effects
St John's Wort
1) Interaction Effect: an increased risk of cardiovascular collapse
and/or delayed emergence from anesthesia
2) Summary: St. John's Wort use prior to surgery using anesthesia
has been associated with complications such as hypotension during
anesthesia in one case and delayed emergence from anesthesia in
another case
[421]
[422]
. Definite causality has not been determined, but the two patients
were 21 and 23 years of age, had no known medical conditions, and
were not on any regular medicines besides St. John's Wort. To
avoid complications, it is recommended to discontinue St. John's
Wort at least 5 days prior to the use of anesthesia
[421]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: Discontinue St. John's Wort at least 5 days
before surgery using anesthetics.
7) Probable Mechanism: unknown
8) Literature Reports
a) A healthy 23-year-old female experienced hypotension during
general anesthesia for hysteroscopy. She had been taking St.
John's Wort for the prior 6 months and no other medications. She
had no known drug allergies. General anesthesia was induced with
fentanyl, propofol, tubocurarine, and succinylcholine, and
maintained with isoflurane, nitrous oxide, and oxygen. The patient
became hypotensive (blood pressure 60/20 mmHg) shortly after
induction, and received fluid boluses, ephedrine, and phenylephrine
which raised her blood pressure to 70/40 mmHg. An additional
bolus of epinephrine raised her blood pressure to 110/80 mmHg.
The hypotensive episode lasted approximately 10 minutes with no
additional symptoms. A previous surgery 2 years prior to this one
using the same anesthetics was uneventful. The authors
acknowledged that the anesthetics may have caused the
hypotension, it is also possible that St. John's Wort may alter the
adrenergic system, reducing its ability to respond to the stress of
anesthesia
[419]
.
b) A 21-year-old female experienced delayed emergence from
general anesthesia using fentanyl, propofol, sevoflurane, oxygen,
and nitrous oxide. The patient was taking St. John's Wort 1000
milligrams (mg) three times daily with a product standardized to
0.3% hypericin for the previous 3 months for depression, and no
other medications. Total anesthesia time was approximately 10
minutes. The patient emerged from the anesthesia after 90 minutes.
Lab tests for blood glucose, blood count, electrolytes, arterial blood
gases, and toxicology screen were within normal limits. The event
was considered associated with St. John's Wort and the authors
hypothesized that St. John's Wort may have caused the profound
sedation through interaction with the anesthetic agents centrally, at
neurotransmitter receptor sites, and at hepatocellular enzyme sites
(particularly cytochrome P450 3A4). The authors recommend that
St. John's Wort be discontinued at least 5 days prior to surgery
[420]
.
Succinylcholine
1) Interaction Effect: succinylcholine toxicity (respiratory depression,
apnea)
2) Summary: Both animal and human studies have shown that when
these two drugs are used concurrently, there is a prolongation of
neuromuscular blockade and possibly respiratory depression.
Lidocaine may interfere with the release of acetylcholine. Caution is
warranted especially with higher levels of lidocaine
[436]
[437]
.
3) Severity: major
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: If used concurrently, monitor carefully for
prolonged neuromuscular blockade and respiratory depression.
7) Probable Mechanism: synergistic
Telaprevir
1) Interaction Effect: increased lidocaine plasma concentrations
2) Summary: Caution is warranted with the concurrent
administration of lidocaine and telaprevir as it may result in
increased lidocaine plasma concentrations. Due to the potential for
serious and/or life-threatening events with increased lidocaine
concentrations, clinical monitoring is recommended
[356]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Caution is warranted with the concurrent
administration of lidocaine and telaprevir as it may result in
increased lidocaine plasma concentrations. Due to the potential for
serious and/or life-threatening events with increased lidocaine
concentrations, clinical monitoring is recommended
[356]
.
7) Probable Mechanism: unknown
Tocainide
1) Interaction Effect: an increased risk of cardiotoxicity (decreases in
cardiac output, total peripheral resistance and mean arterial
pressure)
2) Summary: Use of prilocaine/lidocaine in patients receiving a
Class I antiarrhythmic agent, such as tocainide or mexiletine, should
be exercised with caution, since the toxic effects are additive and
may be synergistic. An increased risk of cardiotoxicity , decreases in
cardiac output, total peripheral resistance and mean arterial
pressure, are possible and monitoring ECG for cardiovascular
manifestations should be considered
[403]
.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: The use of prilocaine/lidocaine in patients
receiving a Class I antiarrhythmic agent, such as tocainide or
mexiletine, should be exercised with caution, since the toxic effects
are additive and may be synergistic. Monitor ECG for cardiovascular
manifestations.
7) Probable Mechanism: additive toxic effects
Tocainide
1) Interaction Effect: CNS toxicity (seizures)
2) Summary: In a comprehensive review,
[406]
recommended that tocainide not be used with other class 1B
antiarrhythmic agents. Toxic effects may be additive whereas
antiarrhythmic response may not be significantly improved through
use of 2 medications with similar effects. Administering lidocaine to
a patient receiving tocainide could result in serious toxic reactions.
3) Severity: moderate
4) Onset: rapid
5) Substantiation: probable
6) Clinical Management: During concurrent use, monitor carefully for
changes in control of arrhythmias or toxicity, especially, tremors or
seizures.
7) Probable Mechanism: additive
8) Literature Reports
a) A combination of lidocaine and tocainide was reported to result in
tonic-clonic seizure activity in a 79-year-old male
[405]
. The seizures occurred during conversion from intravenous
lidocaine to oral tocainide. It is speculated that, since the patient
tolerated each drug separately at serum levels similar to those
preceding the seizure (without neurological sequelae), the
complication was a result of an interaction of tocainide and
lidocaine.
Drug-Lab Modifications
Creatinine measurement
1) Interaction Effect: falsely increased serum creatinine values
2) Summary: In patients receiving systemic lidocaine treatment,
serum creatinine values may be falsely elevated using the Kodak
Ektachem. The Jaffe method should be considered for serum
creatinine determination in patients receiving lidocaine therapy
[449]
.
3) Severity: moderate
4) Onset: unspecified
5) Substantiation: probable
6) Clinical Management: Consider alternative methods, such as the
Jaffe method, to determine serum creatinine levels in patients
receiving lidocaine.
7) Probable Mechanism: assay interference
8) Literature Reports
a) Serum creatinine assays using a coupled enzymatic method have
yielded falsely elevated values in patients receiving lidocaine as
measured by a Kodak Ektachem 700 (slide generation 05). In a
case report of a patient receiving a lidocaine infusion, a serum
creatinine value of 2.1 mg/dL obtained via the Ektachem was
compared to 0.8 mg/dL obtained at the same time by the Jaffe
reaction. An ultrasound revealed normal kidney size, renal blood
flow studies were normal, urine output was normal, and the urea
clearance was higher than what the Ektachem creatinine results
suggested. This interaction was seen with serum lidocaine levels
above 2.5 mcg/ml. Cessation of lidocaine therapy resulted in
readings by the Ektachem consistent with the Jaffe reaction, and
subsequent lidocaine rechallange resulted in increased creatinine
readings by the Ektachem. Earlier generations of Ektachem slides
have shown falsely elevated serum creatinine measurements in
patients receiving lidocaine, however, the elevations in serum
creatinine were clinically insignificant. Lidocaine is metabolized in
the liver to N-ethylglycine, which resembles the creatinine byproduct
sarcosine (N-methylglycine). N-ethylglycine acts as a substrate for
sarcosine oxidase in the single-slide method, creating positive
interference with the Ektachem analyzer
[449]
.
Intravenous Admixtures
Drugs
Lidocaine
Acetylcysteine
a) Compatible
1) Acetylcysteine 10% inhalation solution is stated as
compatible with lidocaine hydrochloride 2% (conditions
not specified)
[853]
.
Alteplase, Recombinant
a) Compatible
1) Lidocaine (physically compatible with alteplase if
added to a running alteplase solution via a Y-site)
[806]
2) Alteplase (1 mg/mL with lidocaine 8 mg/mL, no
evidence of incompatibility was observed, visually or
spectrophotometrically, in 12 days; temperature not
specified)
[791]
Aminophylline
a) Compatible
1) Aminophylline (500 mg/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
; (1 g/L with lidocaine 2 g/L visually compatible for 24
hours at 25 degrees C in the following solutions:
Dextrose 5% in water, Lactated Ringer's injection,
Sodium Chloride 0.9%) (Kirschenbaum, 1982)
2) Lidocaine (2 g/L with aminophylline 1 g/L visually
compatible for 24 hours at 25 degrees C in Dextrose
5% in water, Lactated Ringer's injection or Sodium
chloride 0.9%)
[842]
; (2 g/L with aminophylline 500 mg/L physically
compatible; conditions not specified)
[843]
Amiodarone
a) Compatible
1) Amiodarone 4 mg/mL in Dextrose 5% in water or
Sodium chloride 0.9% with lidocaine 8 mg/mL, visually
compatible for 24 hours at 21 degrees C
[867]
2) Amiodarone 1.8 g/L in Dextrose 5% in water or
Sodium chloride 0.9% with lidocaine 4 g/L, visually
compatible with 9% or less amiodarone loss in 24
hours under fluorescent light in polyolefin or
polyvinylchloride containers
[868]
Amphotericin B
a) Incompatible
1) Amphotericin B (causes precipitation with lidocaine)
[805]
2) Lidocaine (causes precipitation of amphotericin B)
[861]
Atracurium
a) Compatible
1) Atracurium with lidocaine, stable in Dextrose 5% in
water for 24 hours at 5 or 30 degrees C
[872]
Bretylium
a) Compatible
1) Bretylium 1 g/L with lidocaine 2 mg/mL, visually
compatible for 48 hours at 25 degrees C in Dextrose
5% in water or Sodium chloride 0.9%
[771]
2) Bretylium 1 g/L with lidocaine 2 g/L, visually
compatible for 24 hours at 25 degrees C in Dextrose
5% in water, Lactated Ringer's injection, or Sodium
chloride 0.9%
[772]
3) Bretylium 10 g/L with lidocaine 1 g/L, physically
compatible and both drugs stable for 48 hours at 25
and 40 degrees C, under high intensity light at 25
degrees C and 7 days at 4 degrees C in Dextrose 5%
in sodium chloride 0.9% in glass or polyvinylchloride
containers
[773]
Calcium Chloride
a) Compatible
1) CALCIUM CHLORIDE (1 g/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
2) Lidocaine (2 g/L with calcium chloride 1 g/L
physically compatible; conditions not specified)
[845]
Calcium Gluceptate
a) Compatible
1) CALCIUM GLUCEPTATE (5 g/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
2) Lidocaine (2 g/L with calcium gluceptate 5 mL/L
physically compatible; conditions not specified)
[845]
Calcium Gluconate
a) Compatible
1) CALCIUM GLUCONATE (2 g/L with lidocaine 2 g/L
visually compatible for 24 hours at 25 degrees C in the
following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium Chloride 0.9%)
(Kirschenbaum, 1982)
2) Lidocaine (2 g/L with calcium gluconate 2 g/L
visually compatible in Dextrose 5% in water, Lactated
Ringer's injection, or Sodium chloride 0.9% for 24
hours at 25 degrees C)
[871]
Carbenicillin
a) Compatible
1) Lidocaine (stated to be physically compatible with
carbenicillin in direct admixture in syringe; conditions
not specified)
[852]
2) Carbenicillin (reportedly compatible with lidocaine in
syringe)
[805]
Cefamandole
a) Incompatible
1) Cefamandole (incompatible with lidocaine;
conditions not specified)
[789]
Cefazolin
a) Incompatible
1) Cefazolin 1 g reconstituted with 3 mL of 0.5%
lidocaine injection, precipitate formed within 3 to 4
hours at 4 degrees C; when frozen at (-)20 degrees C,
solution was not clear upon thawing
[854]
.
Cefoperazone
a) Compatible
1) Lidocaine (0.5%) with cefoperazone 300 mg/mL, in
glass or plastic container, stable for 24 hours at 15 to
25 degrees C or 5 days at 2 to 8 degrees C
[811]
Cefotaxime
a) Incompatible
1) Cefotaxime (incompatible with lidocaine; conditions
not specified)
[789]
2) Lidocaine (incompatible with cefotaxime; conditions
not specified)
[848]
Cefotetan
a) Compatible
1) Cefotetan 0.5 to 30 mg/mL with lidocaine 1%
injection, stable for 30 weeks at (-)20 degrees C and
thawed in a microwave oven
[798]
Cefoxitin
a) Compatible
1) Lidocaine (0.5% injection, parabens preserved, 8%
cefoxitin decomposition in 48 hours at 25 degrees C,
5% cefoxitin decomposition in 1 week and 10%
cefoxitin decomposition in 1 month at 5 degrees C;
cefoxitin stable for 26 weeks at (-)20 degrees C and
for 24 hours at 25 degrees C or 48 hours at 5 degrees
C after thawing; 1% injection parabens preserved, 7%
cefoxitin decomposition in 48 hours at 25 degrees C,
2% cefoxitin decomposition in 1 week and 10%
cefoxitin decomposition in 1 month at 5 degrees C)
[824]
Cephaloridine
a) Compatible
1) Lidocaine (appears to be physically compatible with
cephaloridine; conditions not specified)
[830]
Cephalothin
a) Incompatible
1) Cephalothin with lidocaine, incompatible; conditions
not specified
[788]
Cephapirin
a) Incompatible
1) Cephapirin (incompatible with lidocaine; conditions
not specified)
[789]
Chloramphenicol
a) Compatible
1) Chloramphenicol 1 g/L with lidocaine 2 g/L,
physically compatible; conditions not specified
[785]
Chlorothiazide
a) Compatible
1) Lidocaine (2 g/L with chlorothiazide 500 mg/L
physically compatible; conditions not specified)
[875]
Cifenline
a) Compatible
1) Cifenline 10 mg/mL with lidocaine 8 mg/mL visually
compatible for 24 hours at 25 degrees C in Dextrose
5% in water or Sodium chloride 0.9% under
fluorescent light
[777]
Cimetidine
a) Compatible
1) Cimetidine 3 g/L with lidocaine 2.5 g/L, visually
compatible and cimetidine chemically stable for 24
hours at 25 degrees C in Dextrose 5% in water;
lidocaine not tested
[776]
Clonidine Hydrochloride
a) Compatible
1) Mixtures of lidocaine 200 micrograms/mL plus
clonidine hydrochloride 200 micrograms/L prepared in
bacteriostatic water for injection (for regional nerve
block in podiatric surgery) were chemically and
physically stable for up to 8 days at 0, 20, and 45
degrees C
[829]
.
Dacarbazine
a) Compatible
1) Dacarbazine (concentration not stated), with
lidocaine 1% or 2%, physically compatible; conditions
not specified (Tech Info Cetus, 1988)
Dexamethasone
a) Compatible
1) Dexamethasone (4 mg/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
2) Lidocaine (2 g/L with dexamethasone 4 mg/L
physically compatible; conditions not specified)
[849]
Diatrizoate Meglumine
a) Compatible
1) DIATRIZOATE MEGLUMINE 5 mL of a solution
containing iodine 282 mg/mL with lidocaine 5 mg/mL,
no change after mixing
[823]
Diatrizoate Sodium
a) Compatible
1) DIATRIZOATE SODIUM 5 mL of a solution
containing iodine 300 mg/mL with lidocaine 5 mg/mL,
no change after mixing
[823]
Digoxin
a) Compatible
1) Lidocaine (2 g/L with digoxin 1 mg/L visually
compatible for 24 hours at 25 degrees in the following
solutions: Dextrose 5% in water, Lactated Ringer's
injection, Sodium chloride 0.9%)
[838]
2) Digoxin (1 mg/L with lidocaine 2 g/L visually
compatible for 24 hours at 25 degrees C in the
following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium Chloride 0.9%)
(Kirschenbaum, 1982)
Diphenhydramine
a) Compatible
1) Diphenhydramine (50 mg/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
2) Lidocaine (2 g/L with diphenhydramine 50 mg/L
physically compatible; conditions not specified)
[846]
Dobutamine
a) Compatible
1) Lidocaine (4 or 10 g/L with dobutamine 1 g/L
visually compatible for 24 hours at 21 degrees C in
Dextrose 5% in water or Sodium chloride 0.9%)
(Hasegawa & Eder, 1984); (4 g/L with dobutamine 1
g/L visually compatible for 24 hours at 25 degrees C in
Dextrose 5% in water and Sodium chloride 0.9%)
[774]
2) Dobutamine (1 g/L with lidocaine 2 g/L visually
compatible for 24 hours at 25 degrees C in Dextrose
5% in water or Sodium Chloride 0.9%) (Kirschenbaum,
1982); (1 g/L with lidocaine 4 or 10 g/L visually
compatible for 24 hours at 21 degrees in Dextrose 5%
in water or Sodium Chloride 0.9%)
[775]
Dopamine
a) Compatible
1) Dopamine 800 mg/L with lidocaine 2 g/L, visually
compatible for 24 hours at 25 degrees C in the
following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium Chloride 0.9%
[792]
2) Dopamine 800 mg/L with lidocaine 4 g/L, physically
compatible and both drugs stable for 24 hours at 25
degrees C in Dextrose 5% in water in glass or
polyvinylchloride containers
[793]
Doxycycline Hyclate
a) Incompatible
1) Doxycycline hyclate with lidocaine, incompatible via
infusion or should be completed within 6 hours;
conditions not specified
[825]
Enalaprilat
a) Compatible
1) Enalaprilat at 50 mcg/mL in Sodium chloride 0.9%
with lidocaine 4 mg/mL in Dextrose 5% in water,
visually compatible for 24 hours at room temperature
under fluorescent light
[817]
Ephedrine
a) Compatible
1) Lidocaine (2 g/L with ephedrine 50 mg/L physically
compatible for 24 hours; temperature not specified)
[787]
2) Ephedrine (50 mg/L with lidocaine 2 g/L physically
compatible for 24 hours)
[765]
Epinephrine
a) Conflicting Data
1) Incompatible
a) Epinephrine (in combination with lidocaine, pH may
be raised above 5.5 and epinephrine may begin to
deteriorate within several hours)
[765]
2) Compatible
a) Epinephrine (admixture should be used quickly
since decomposition of the sympathomimetic occurs
within several hours)
[805]
b) Lidocaine (1 mL of 1% or 2% solution and
epinephrine 1:100,000 with gentamicin 80 mg/2 mL
physically compatible without significant loss of
potency in 24 hours at 25 or 4 degrees C)
[851]
Eptifibatide
a) Compatible
1) Eptifibatide and lidocaine may be administered in
the same intravenous line
[857]
.
Erythromycin Lactobionate
a) Compatible
1) Lidocaine (2 g/L with erythromycin lactobionate 1
g/L physically compatible; conditions not specified)
[820]
2) Erythromycin lactobionate (1 g/L with lidocaine 2
g/L physically compatible for 24 hours)
[765]
Famotidine
a) Compatible
1) Famotidine (0.2 mg/mL with lidocaine 4 mg/mL
visually compatible for 4 hour study period at 25
degrees C in Dextrose 5% in water under fluorescent
light)
[800]
; (prepared as an intravenous solution according to
manufacturer's instructions in Dextrose 5% in water
with lidocaine 1 mg/mL in Dextrose 5% in water
visually compatible for 14 hours; exact famotidine
concentration and test conditions not specified)
[801]
2) Lidocaine (4 mg/mL with famotidine 0.2 mg/mL
visually compatible for a 4-hour study period at 25
degrees C in Dextrose 5% in water under fluorescent
light)
[802]
; (1 mg/mL in Dextrose 5% in water with famotidine,
prepared as an intravenous solution according to
manufacturer's instructions in Dextrose 5% in water
visually compatible for 14 hours; exact famotidine
concentration and test conditions not specified)
[803]
Gentamicin
a) Compatible
1) Gentamicin (80 mg/2 mL with lidocaine 1 mL of 1%
or 2% solution physically compatible without significant
loss of potency in 24 hours at 25 or 4 degrees C)
[805]
2) Lidocaine (1 mL of 1% or 2% solution with
gentamicin 80 mg/2 mL physically compatible without
significant loss of potency in 24 hours at 25 or 4
degrees C (Trissel, 1988)
3) Lidocaine (1 mL of 1% or 2% solution and
epinephrine 1:100,000 with gentamicin 80 mg/2 mL
physically compatible without significant loss of
potency in 24 hours at 25 or 4 degrees C)
[851]
Glycopyrrolate
a) Compatible
1) Glycopyrrolate with lidocaine physically compatible
in syringe and pH within the stability range - less than
6 - for glycopyrrolate for 48 hours at 25 degrees C;
specific drug concentrations listed below
[850]
:
lidocaine 2 mg/1 mL with glycopyrrolate 200 mcg/1 mL
lidocaine 2 mg/1 mL with glycopyrrolate 400 mcg/2 mL
lidocaine 4 mg/2 mL with glycopyrrolate 200 mcg/1 mL
lidocaine 10 mg/1 mL with glycopyrrolate 200 mcg/1
mL
lidocaine 10 mg/1 mL with glycopyrrolate 400 mcg/2
mL
lidocaine 20 mg/2 mL with glycopyrrolate 200 mcg/1
mL
lidocaine 20 mg/1 mL with glycopyrrolate 200 mcg/1
mL
lidocaine 20 mg/1 mL with glycopyrrolate 400 mcg/2
mL
lidocaine 40 mg/2 mL with glycopyrrolate 200 mcg/1
mL
Haloperidol
a) Compatible
1) Haloperidol 5 or 0.5 mg/mL with lidocaine 4 mg/mL
visually compatible in Dextrose 5% in water for 24
hours at 21 degrees C under fluorescent light
[786]
Heparin
a) Compatible
1) Heparin 32,000 U/L with lidocaine 4 g/L, physically
compatible and potency of heparin retained for 24
hours in Sodium chloride 0.9%; temperature not
specified
[780]
2) Heparin 20,000 U/L with lidocaine 2 g/L, physically
compatible; conditions not specified
[781]
3) Heparin 2500 U/1 mL with lidocaine 100 mg/5 mL,
physically compatible for at least 5 minutes in direct
admixture in syringe
[782]
4) LIDOCAINE (20 mg/mL and heparin 1000 U/L with
hydrocortisone sodium succinate 100 mg/L visually
compatible, macroscopically and microscopically, for a
4-hour study period at 25 degrees C in the following
solutions)
[799]
:
Dextrose 5% in water
Lactated Ringer's injection
Sodium chloride 0.9%
5) Heparin 1000 U/L and hydrocortisone sodium
succinate 100 mg/L with lidocaine 20 mg/mL, visually
compatible, macroscopically and microscopically, for 4
hour study period at 25 degrees C in the following
solutions
[844]
:
Dextrose 5% in water
Lactated Ringer's injection
Sodium chloride 0.9%
Hydrocortisone Sodium Succinate
a) Compatible
1) LIDOCAINE (20 mg/mL and heparin 1000 U/L with
hydrocortisone sodium succinate 100 mg/L visually
compatible, macroscopically and microscopically, for a
4-hour study period at 25 degrees C in the following
solutions)
[799]
:
Dextrose 5% in water
Lactated Ringer's injection
Sodium chloride 0.9%
2) Hydrocortisone sodium succinate (250 mg/L with
lidocaine 2 g/L physically compatible for 24 hours)
[765]
3) Lidocaine (2 g/L with hydrocortisone sodium
succinate 250 mg/L physically compatible; conditions
not specified)
[815]
;
4) Heparin 1000 U/L and hydrocortisone sodium
succinate 100 mg/L with lidocaine 20 mg/mL, visually
compatible, macroscopically and microscopically, for 4
hour study period at 25 degrees C in the following
solutions
[844]
:
Dextrose 5% in water
Lactated Ringer's injection
Sodium chloride 0.9%
Hydroxyzine
a) Compatible
1) Hydroxyzine 100 mg/L with lidocaine 2 g/L,
physically compatible for 24 hours; conditions not
specified
[778]
2) Hydroxyzine 50 or 100 mg/2 mL with lidocaine 2 mL
of a lidocaine 2% solution, physically compatible in
syringe; conditions not specified
[779]
Inamrinone
a) Compatible
1) Lidocaine 8 mg/mL in Dextrose 5% in water with
inamrinone 3 mg/mL in Sodium chloride 0.9%
physically compatible for at least 4 hours at 25
degrees C under fluorescent light
[804]
2) Inamrinone (3 mg/mL with lidocaine 1 mg/mL
visually compatible for 24 hours at 21 degrees C under
fluorescent light)
[805]
Insulin
a) Compatible
1) Insulin (1000 U/L with lidocaine 2 g/L visually
compatible for 24 hours at 25 degrees C in the
following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium Chloride 0.9%)
(Kirschenbaum, 1982)
Insulin, Regular
a) Compatible
1) Lidocaine (2 g/L with insulin 1000 U/L, visually
compatible for 24 hours at 25 degrees C in Dextrose
5% in water, Lactated Ringer's injection or Sodium
chloride 0.9%)
[784]
Iodine
a) Compatible
1) Iopamidol 5 mL of a solution containing iodine 300
mg/mL with lidocaine 5 mg/mL, no change after mixing
[796]
2) Iohexol 5 mL of solution containing iodine 300
mg/mL with lidocaine 5 mg/mL, no change after mixing
[814]
3) DIATRIZOATE SODIUM 5 mL of a solution
containing iodine 300 mg/mL with lidocaine 5 mg/mL,
no change after mixing
[823]
4) DIATRIZOATE MEGLUMINE 5 mL of a solution
containing iodine 282 mg/mL with lidocaine 5 mg/mL,
no change after mixing
[823]
5) Ioxaglate 5 mL of a solution containing iodine 320
mg/mL with lidocaine 5 mg/mL, no change after mixing
[862]
6) Iothalamate 5 mL of a solution containing iodine
282 mg/mL with lidocaine 5 mg/mL, no change after
mixing
[870]
Iohexol
a) Compatible
1) Iohexol 5 mL of solution containing iodine 300
mg/mL with lidocaine 5 mg/mL, no change after mixing
[814]
Iopamidol
a) Compatible
1) Iopamidol 5 mL of a solution containing iodine 300
mg/mL with lidocaine 5 mg/mL, no change after mixing
[796]
Iothalamate
a) Compatible
1) Iothalamate 5 mL of a solution containing iodine
282 mg/mL with lidocaine 5 mg/mL, no change after
mixing
[870]
Ioversol
a) Compatible
1) Ioversol 68% with lidocaine 1% mixed in a 10:1 or
1:1 ratio exhibited no significant physical changes in 1
hour at room temperature
[841]
Ioxaglate
a) Compatible
1) Ioxaglate 5 mL of a solution containing iodine 320
mg/mL with lidocaine 5 mg/mL, no change after mixing
[862]
Ioxaglate Meglumine
a) Compatible
1) Ioxaglate meglumine (39.3%) and ioxaglate sodium
(19.6%) 5 mL with lidocaine 50 mg/1 mL, a clear
solution was reported; conditions were not specified
[847]
Ioxaglate Sodium
a) Compatible
1) Ioxaglate meglumine (39.3%) and ioxaglate sodium
(19.6%) 5 mL with lidocaine 50 mg/1 mL, a clear
solution was reported; conditions were not specified
[847]
Isoproterenol
a) Conflicting Data
1) Incompatible
a) Lidocaine with isoproterenol: admixture pH above 6
may cause significant decomposition of isoproterenol;
this admixture should be used immediately after
preparation
[808]
2) Compatible
a) Isoproterenol with lidocaine: admixture pH above 6
may cause significant decomposition of isoproterenol;
this admixture should be used immediately after
preparation
[807]
Labetalol
a) Compatible
1) Lidocaine (20 mg/mL with labetalol 1 mg/mL
visually compatible for 24 hours at 18 degrees C in
Dextrose 5% in water under fluorescent light)
[863]
2) Labetalol (1 mg/mL with lidocaine 20 mg/mL
visually compatible for 24 hours at 18 degrees C in
Dextrose 5% in water under fluorescent light)
[864]
Meperidine
a) Compatible
1) Lidocaine (1 mg/mL in Dextrose 5% in water with
meperidine 10 mg/mL visually compatible for a 4-hour
study period at 25 degrees C under fluorescent light)
[767]
Mephentermine
a) Compatible
1) Lidocaine (2 g/L with mephentermine 1 g/L
physically compatible for 24 hours; conditions not
specified)
[818]
2) Mephentermine (1 g/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
Metaraminol
a) Compatible
1) Lidocaine 2 g/L with metaraminol 100 mg/L,
physically compatible for 24 hours; conditions not
specified
[856]
Methicillin
a) Compatible
1) Lidocaine (stated to be physically compatible with
methicillin in direct admixture in syringe; conditions not
specified)
[819]
Methohexital
a) Incompatible
1) Lidocaine 2 g/L with methohexital 2 g/L, immediate
precipitation reported in Dextrose 5% in water
[783]
Metoclopramide
a) Compatible
1) Lidocaine 50 mg/5 mL with metoclopramide 10
mg/2 mL physically compatible in syringe for 48 hours
at 25 degrees C (Tech Info Reglan(R), 1990)
2) Lidocaine 50 mg/5 mL with metoclopramide 160
mg/32 mL physically compatible in syringe for 48
hours at 25 degrees C (Tech Info Reglan(R), 1990)
3) Lidocaine 100 mg/10 mL with metoclopramide 10
mg/2 mL physically compatible in syringe for 48 hours
at 25 degrees C (Tech Info Reglan(R), 1990)
4) Lidocaine 100 mg/10 mL with metoclopramide 160
mg/32 mL physically compatible in syringe for 48
hours at 25 degrees C (Tech Info Reglan(R), 1990)
Mezlocillin
a) Compatible
1) Lidocaine 0.5% or 1% solution with mezlocillin 250
mg/mL, stable for 24 hours at 25 degrees C
[770]
Morphine
a) Compatible
1) Lidocaine 1 mg/mL in Dextrose 5% in water with
morphine 1 mg/mL, visually compatible for a 4-hour
study period at 25 degrees C under fluorescent light
[835]
Moxalactam
a) Conflicting Data
1) Incompatible
a) Moxalactam (incompatible with lidocaine; conditions
not specified)
[789]
2) Compatible
a) Moxalactam (1 g/L with 3 mL of 0.5% or 1%
lidocaine injection physically compatible with 7%
moxalactam decomposition in 24 hours at 25 degrees
C and 4% moxalactam decomposition in 96 hours at 5
degrees C)
[816]
Nafcillin
a) Compatible
1) Lidocaine 2% - 1.7 mL used to reconstitute nafcillin
500 mg/mL, physically compatible for 48 hours at 5
degrees C with less than 3% loss in activity for either
drug
[855]
Nitrofurantoin
a) Compatible
1) Lidocaine 2 g/L with nitrofurantoin 240 mg/L,
physically compatible for 24 hours in dextrose 5% in
water, sodium chloride 0.9%, or dextrose-sodium
chloride combinations
[768]
Nitroglycerin
a) Compatible
1) Lidocaine (4 g/L with nitroglycerin 400 mg/L visually
compatible with no significant nitroglycerin
decomposition in 48 hours at 23 degrees C in
Dextrose 5% in water or Sodium chloride 0.9%;
lidocaine concentration not tested)
[821]
2) Nitroglycerin (400 mg/L with lidocaine 4 g/L
physically compatible and nitroglycerin stable for 48
hours at 23 degrees C in Dextrose 5% in water or
Sodium chloride 0.9%; lidocaine stability not tested)
[822]
Nitroprusside
a) Incompatible
1) Lidocaine 10 mg/mL with nitroprusside 10 mg/mL, a
1.8% change in absorbance values was reported
within 30 minutes when the admixture was tested
spectrophotometrically
[812]
; however, another study of short-term effects found
this combination to be compatible.
Norepinephrine
a) Conflicting Data
1) Incompatible
a) Norepinephrine (in combination with lidocaine, pH
may be raised above 5.5 and norepinephrine may
begin to deteriorate within several hours)
[805]
b) Lidocaine (norepinephrine is alkali labile and
caution should be employed in the preparation of any
admixture which will result in a final pH above 6.0)
[813]
2) Compatible
a) Norepinephrine (admixture should be used quickly
since decomposition of the sympathomimetic occurs
within several hours)
[805]
Oxytetracycline
a) Compatible
1) Lidocaine (2 g/L with oxytetracycline 500 mg/L
physically compatible; conditions not specified)
[836]
2) Oxytetracycline (500 mg/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
Penicillin G Potassium
a) Compatible
1) Lidocaine (2 g/L with penicillin G potassium 1
million U/L physically compatible; conditions not
specified)
[865]
2) Penicillin G potassium (1 million U/L with lidocaine 2
g/L physically compatible for 24 hours)
[765]
Pentobarbital
a) Compatible
1) Lidocaine 2 g/L with pentobarbital 500 mg/L,
physically compatible; conditions not specified
[873]
Phenylephrine
a) Compatible
1) Lidocaine 2 g/L with phenylephrine 20 mg/L,
physically compatible; conditions not specified
[809]
2) Lidocaine 2% with phenylephrine 0.25%, stable for
a 66-day study period at 25 degrees C
[810]
Phenytoin
a) Incompatible
1) Phenytoin (1 g/L with lidocaine 2 g/L reported
immediate formation of a white cloudy precipitate in
the following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium Chloride 0.9%)
(Kirschenbaum, 1982); (incompatible with lidocaine;
conditions not specified)
[789]
2) Lidocaine (2 g/L with phenytoin 1 g/L, immediate
precipitate formation reported in Dextrose 5% in water,
Lactated Ringer's injection or Sodium chloride 0.9%)
[837]
Potassium Chloride
a) Compatible
1) Potassium chloride (40 mEq/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
; (40 mEq/L with lidocaine 20 g/L visually compatible,
macroscopically and microscopically, for at least 4
hours at 25 degrees C in the following solutions:
Dextrose 5% in water, Lactated Ringer's injection,
Sodium chloride 0.9%)
[826]
2) Lidocaine (2 g/L with potassium chloride 40 mEq/L
physically compatible; conditions not specified)
[827]
; (20 mg/mL with potassium chloride 40 mEq/L visually
compatible, macroscopically and microscopically, for a
4-hour study period at 25 degrees C in the following
solutions)
[828]
:
Dextrose 5% in water
Lactated Ringer's injection
Sodium chloride 0.9%
Procainamide
a) Compatible
1) Lidocaine 2 g/L with procainamide 1 g/L, visually
compatible for 24 hours at 25 degrees C in the
following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium chloride 0.9%
[874]
Prochlorperazine
a) Compatible
1) Lidocaine 2 g/L with prochlorperazine 10 mg/L,
physically compatible for 24 hours; conditions not
specified
[797]
Promazine
a) Compatible
1) Lidocaine 2 g/L with promazine 100 mg/L,
physically compatible; conditions not specified
[769]
Propofol
a) Compatible
1) Lidocaine (1 mL of a 1% solution with propofol 19
mL of a 1% solution, physically compatible and
propofol chemically stable; no conditions or duration
for stability was specified and it was recommended
that this admixture be used immediately after
preparation)
[839]
.
2) It is recommended that the addition of lidocaine to
propofol injectable emulsion not exceed quantities
greater than 20 mg lidocaine to 200 mg propofol
injectable emulsion, and should be added together
immediately prior to administration due to instability of
the resulting emulsion and increases in globule sizes
over time. In animal studies this has reduced
anesthetic potency
[840]
.
Ranitidine
a) Compatible
1) Lidocaine 250 mg/100 mL with ranitidine 100
mg/100 mL, compatible for 24 hours at 25 degrees C
in dextrose 5% in water; lidocaine concentration not
tested
[794]
2) Lidocaine 1 or 8 mg/mL with ranitidine 0.05 or 2
mg/mL in 0.9% Sodium chloride or 5% Dextrose in
polyvinylchloride containers, stable with less than 10%
ranitidine decomposition in 48 hours at room
temperature; lidocaine stability not tested
[795]
Rapacuronium
a) Compatible
1) Rapacuronium is physically compatible with
lidocaine; drug concentration and conditions not
specified
[869]
.
Sodium Bicarbonate
a) Conflicting Data
1) Incompatible
a) Sodium bicarbonate (may precipitate with lidocaine)
(VanDerLinde & Campbell, 1977)
2) Compatible
a) Lidocaine (1 g/L with sodium bicarbonate 2.4 mEq/L
physically compatible for 24 hours in Dextrose 5% in
water; temperature not specified)
[831]
b) Lidocaine (2 g/L with sodium bicarbonate 40 mEq/L
physically compatible; conditions not specified)
[832]
c) Sodium bicarbonate (40 mEq/L with lidocaine 2 g/L
physically compatible; 2.4 mEq/L with lidocaine 1 g/L
physically compatible for 24 hours in Dextrose 5% in
water)
[805]
Sodium Lactate
a) Compatible
1) Sodium lactate (50 mEq/L with lidocaine 2 g/L
physically compatible)
[805]
Streptokinase
a) Compatible
1) Lidocaine (8 mg/mL with streptokinase 30,000
U/mL, no evidence of incompatibility observed, visually
or spectrophotometrically, in 72 hours, but trace
crystal formation was detected at 96 hours;
temperature not specified)
[790]
2) Streptokinase (30,000 U/mL with lidocaine 8
mg/mL, no evidence of incompatibility observed,
visually or spectrophotometrically, in 72 hours, but
trace crystal formation was detected at 96 hours;
temperature not specified)
[791]
Sulfadiazine
a) Incompatible
1) Lidocaine 2 g/L with sulfadiazine 4 g/L, crystal
formation reported in Dextrose 5% in water; conditions
not specified
[866]
Sulfisoxazole
a) Compatible
1) Lidocaine (2 g/L with sulfisoxazole 4 g/L physically
compatible for 24 hours; conditions not specified)
[860]
2) Sulfisoxazole (4 g/L with lidocaine 2 g/L physically
compatible for 24 hours in Dextrose 5% in water,
Sodium chloride 0.9% or Dextrose - Sodium chloride
combinations)
[765]
Tetracycline
a) Compatible
1) Lidocaine (2 g/L with tetracycline 500 mg/L
physically compatible for 24 hours; conditions not
specified)
[764]
2) Tetracycline (500 mg/L with lidocaine 2 g/L
physically compatible for 24 hours)
[765]
Tirofiban
a) Compatible
1) Lidocaine 1 mg/mL in Dextrose 5% in water or 20
mg/mL in Sodium chloride 0.9% with tirofiban 0.05
mg/mL was physically and chemically compatible at
room temperature in Dextrose 5% in water or Sodium
chloride 0.9% under ambient fluorescent light for a 4hour study period in a simulated Y-site administration
[859]
.
Tobramycin
a) Compatible
1) Lidocaine (compatible with tobramycin in Dextrose
5% in water or Sodium chloride 0.9% for 24 hours;
drug concentrations not specified)
[766]
Verapamil
a) Compatible
1) Lidocaine 2 g/L with verapamil 80 mg/L, visually
compatible for 48 hours in Dextrose 5% in water or
Sodium chloride 0.9%; no temperature specified
[858]
Vitamin B Complex/Ascorbic Acid
a) Compatible
1) Lidocaine 2 g/L with vitamin B complex with C 10
mL/L, physically compatible for 24 hours
[833]
2) Lidocaine 20 mg/mL with vitamin B complex with C
2 mL/L, visually compatible, macroscopically and
microscopically, for at least 4 hours at 25 degrees C in
the following solutions: Dextrose 5% in water, Lactated
Ringer's injection, Sodium chloride 0.9%
[834]
Lidocaine Hydrochloride
Acetaminophen
a) Compatible
1) Acetaminophen with lidocaine hydrochloride in a
50:50 admixed ratio was physically and chemically
compatible for up to 4 hours at room temperature
using Y-site methodology in a one-way compatibility
test (stability of acetaminophen only was tested). The
manufacturer does not recommend that any drug be
admixed, infused simultaneously through the same IV
line, or added to an infusion device containing
acetaminophen
[890]
.
Ampicillin Sodium
a) Conflicting Data
1) Incompatible
a) Ampicillin sodium 250 mg reconstituted with 1.5 mL
of lidocaine hydrochloride 0.5% or 2.5% in a syringe,
occasional turbidity noted at room temperature
[883]
; however, the same 2 drugs were found to be
compatible under different conditions
[883]
2) Compatible
a) Ampicillin sodium 500 mg reconstituted with 1.5 mL
of lidocaine hydrochloride 0.5% or 2.5% in a syringe,
physically compatible at room temperature
[884]
; however, the same 2 drugs were found to be
incompatible under different conditions
[884]
Ampicillin Sodium/Sulbactam Sodium
a) Compatible
1) Ampicillin sodium 250 mg/mL plus sulbactam
sodium 125 mg/mL with lidocaine hydrochloride 0.5%
or 2% had a utility time of 1 hour at 24 degrees C, with
6% ampicillin decomposition and 1% sulbactam
decomposition
[895]
Cefamandole
a) Compatible
1) Cefamandole 285 g/L with lidocaine hydrochloride
0.5% injection, physically compatible with 2%
cefamandole decomposition in 72 hours at 25 degrees
C or 10 days at 5 degrees C
[886]
2) Cefamandole 285 g/L with lidocaine hydrochloride
1% injection, physically compatible with 5%
cefamandole decomposition in 72 hours at 25 degrees
C and 1% cefamandole decomposition in 10 days at 5
degrees C
[886]
3) Cefamandole 285 g/L with lidocaine hydrochloride
2% injection, physically compatible with 9%
cefamandole decomposition in 72 hours at 25 degrees
C and 3% cefamandole decomposition in 10 days at 5
degrees C
[886]
4) Cefamandole with lidocaine hydrochloride 0.5%,
1%, or 2%; 10% or greater cefamandole concentration
or turbidity, precipitate or both reported
[887]
5) Cefamandole (incompatible with lidocaine;
conditions not specified)
[888]
Cefazolin
a) Compatible
1) Cefazolin sodium 40 mg/mL with lidocaine
hydrochloride 8 mg/mL, both in Dextrose 5% in water
or in Sodium chloride 0.9%, visually compatible over 3
hours in Viaflex IV bags at ambient laboratory
temperature under constant fluorescent light
[891]
; another study, however, describes some evidence of
physical incompatibility of this admixture under closer
scrutiny
[892]
.
Ceftaroline Fosamil
a) Compatible
1) Lidocaine hydrochloride 10 mg/mL (undiluted) and
ceftaroline fosamil 2.22 mg/mL (diluted with either
0.9% sodium chloride, 5% dextrose, or lactated Ringer
injection) were compatible for at least 4 hours at room
temperature (23 degrees C) under fluorescent light
during simulated Y-site administration
[893]
.
Diltiazem Hydrochloride
a) Compatible
1) Diltiazem hydrochloride in Dextrose 5% injection 1
mg/mL with lidocaine hydrochloride in Dextrose 5%
injection 8 mg/mL, mixed in a test tube in a 1:1 ratio
simulating Y-site administration, visually compatible for
up to 24 hours, admixture stored at room temperature
under fluorescent light; chemical stability was not
tested
[880]
Dobutamine Hydrochloride
a) Compatible
1) Lidocaine hydrochloride 8 mg/mL with dobutamine
hydrochloride 4 mg/mL and sodium nitroprusside 0.4
mg/mL in Dextrose 5% in water or in Sodium chloride
0.9%, no evidence of physical incompatibility for 3hour study period at ambient laboratory temperature
[882]
Dopamine Hydrochloride
a) Compatible
1) Lidocaine hydrochloride 8 mg/mL with dopamine
hydrochloride 3.2 mg/mL and sodium nitroprusside 0.4
mg/mL in Dextrose 5% in water or in Sodium chloride
0.9%, no evidence of physical incompatibility for 3hour study period at ambient laboratory temperature
[882]
Fenoldopam Mesylate
a) Compatible
1) Fenoldopam mesylate 80 mcg/mL in Sodium
chloride 0.9% injection with lidocaine hydrochloride 10
mg/mL in Sodium chloride 0.9% injection, visually and
physically compatible for up to 4 hours at 23 degrees
C in a clear glass tube under constant fluorescent light
during simulated Y- site administration
[894]
.
Iomeprol
a) Compatible
1) Iomeprol 5 mL (400 mg iodine per mL) was mixed
with lidocaine hydrochloride 1 mL and 2 mL (5 mg/mL)
and clarity was checked immediately and after 10, 60,
and 120 minutes. No formation of precipitate was
noted at any observation time
[878]
.
Linezolid
a) Compatible
1) Lidocaine hydrochloride 10 mg/mL (diluted in 5%
dextrose injection) with linezolid 2 mg/mL (tested
undiluted) is physically compatible for 4 hours at room
temperature (approximately 23 degrees C) under
fluorescent light during simulated Y-site administration
[879]
.
Micafungin Sodium
a) Compatible
1) Lidocaine hydrochloride 10 mg/mL with micafungin
sodium 1.5 mg/mL (both diluted in 0.9% sodium
chloride injection) is physically compatible for 4 hours
at room temperature, approximately 23 degrees C,
under fluorescent light during simulated Y-site
administration
[877]
.
Milrinone
a) Compatible
1) Lidocaine hydrochloride 10 mL of a 1% solution with
milrinone 5.25 mL of a 1 mg/mL solution, both drugs
chemically stable for a 20-minute study period in a
glass container at 23 degrees C under fluorescent light
[889]
Nafcillin
a) Compatible
1) Lidocaine hydrochloride 0.6 mg/mL in Dextrose 5%
in water or 0.9% Sodium chloride injection with
nafcillin 20 mg/mL, stable for 48 hours at 22-23
degrees C
[896]
Nicardipine Hydrochloride
a) Compatible
1) Lidocaine hydrochloride 4 mg/mL with nicardipine
hydrochloride 100 mcg/mL, visually compatible for 24
hours at room temperature in dextrose 5% in water
under fluorescent light
[881]
Nitroglycerin
a) Compatible
1) Lidocaine hydrochloride 8 mg/mL with nitroglycerin
0.4 mg/mL and sodium nitroprusside 0.4 mg/mL in
Dextrose 5% in water or in Sodium chloride 0.9%, no
evidence of physical incompatibility for 3-hour study
period at ambient laboratory temperature
[882]
Propofol
a) Compatible
1) Propofol 1% injectable emulsion and lidocaine
hydrochloride 10 milligrams/milliliter in a 1:1 volume
mixture (simulated Y-site administration) are visually
compatible in polycarbonate test tubes at 15 minutes
and 1 hour at approximately 23 degrees Celsius as
determined by visualization with fluorescent light and a
high-intensity, mono-directional light source (Tyndall
beam)
[885]
.
2) It is recommended that the addition of lidocaine to
propofol injectable emulsion not exceed quantities
greater than 20 mg lidocaine to 200 mg propofol
injectable emulsion, and should be added together
immediately prior to administration due to instability of
the resulting emulsion and increases in globule sizes
over time. In animal studies this has reduced
anesthetic potency
[840]
.
Sodium Nitroprusside
a) Compatible
1) Lidocaine hydrochloride 8 mg/mL with nitroglycerin
0.4 mg/mL and sodium nitroprusside 0.4 mg/mL in
Dextrose 5% in water or in Sodium chloride 0.9%, no
evidence of physical incompatibility for 3-hour study
period at ambient laboratory temperature
[882]
2) Lidocaine hydrochloride 8 mg/mL with sodium
nitroprusside 0.4 mg/mL in Dextrose 5% in water or in
Sodium chloride 0.9%, no evidence of physical
incompatibility for 3-hour study period at ambient
laboratory temperature
[882]
3) Lidocaine hydrochloride 8 mg/mL with dopamine
hydrochloride 3.2 mg/mL and sodium nitroprusside 0.4
mg/mL in Dextrose 5% in water or in Sodium chloride
0.9%, no evidence of physical incompatibility for 3hour study period at ambient laboratory temperature
[882]
4) Lidocaine hydrochloride 8 mg/mL with dobutamine
hydrochloride 4 mg/mL and sodium nitroprusside 0.4
mg/mL in Dextrose 5% in water or in Sodium chloride
0.9%, no evidence of physical incompatibility for 3hour study period at ambient laboratory temperature
[882]
Tigecycline
a) Compatible
1) Lidocaine hydrochloride and tigecycline (diluted with
either 0.9% sodium chloride or 5% dextrose) were
compatible during simultaneous administration via Ysite infusion
[876]
.
Solutions
Lidocaine
CARDIOPLEGIC SOLUTION
a) Compatible
1) Cardioplegic solution (with lidocaine 450 mg/L, no
significant lidocaine decomposition in 21 days at 4
degrees C when stored in glass containers or filled
large volume polyvinylchloride bags; specific
composition of cardioplegic solution follows)
[520]
:
Lidocaine HCl
450 mg/L
Potassium chloride
20 mEq/L
Sodium bicarbonate 25 mEq/L
Dextrose
5 g/L
Sodium chloride 0.9% q.s. to 1 L
Dextrose 10% in Sodium chloride 0.225%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 10% in Sodium chloride
0.225% is compatible for 24 hours in glass or
polyolefin containers; conditions not specified (Tech
Info American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 10% in Sodium chloride
0.225% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
Dextrose 10% in Sodium chloride 0.45%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 10% in Sodium chloride
0.45% is compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 10% in Sodium chloride
0.45% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
Dextrose 10% in Sodium chloride 0.9%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 10% in Sodium chloride
0.9% is compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 10% in Sodium chloride
0.9% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
Dextrose 10% in water
a) Compatible
1) Lidocaine 1 g/L in Dextrose 10% in water is
compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
Dextrose 2.5% in Sodium chloride 0.45%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 2.5% in Sodium
chloride 0.45% is compatible for 24 hours in glass or
polyolefin containers; conditions not specified (Tech
Info American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 2.5% in Sodium
chloride 0.45% is compatible for 24 hours; conditions
not specified (Tech Info American McGaw, 1985):
Dextrose 2.5% in Sodium chloride 0.9%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 2.5% in Sodium
chloride 0.9% is compatible for 24 hours in glass or
polyolefin containers; conditions not specified (Tech
Info American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 2.5% in Sodium
chloride 0.9% is compatible for 24 hours; conditions
not specified (Tech Info American McGaw, 1985):
Dextrose 2.5% in water
a) Compatible
1) Lidocaine 1 g/L in Dextrose 2.5% in water is
compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
Dextrose 5% in Lactated Ringer's injection
a) Compatible
1) Dextrose 5% in Lactated Ringer's injection with
lidocaine 1 g/L, compatible for 24 hours in glass or
polyolefin containers; conditions not specified (Tech
Info American McGaw, 1985)
2) Dextrose 5% in Lactated Ringer's injection with
lidocaine 2 g/L, visually compatible without significant
lidocaine decomposition in 14 days at 25 degrees C in
glass or polyvinylchloride containers under fluorescent
light
[897]
3) Dextrose 5% in Lactated Ringers's injection with
lidocaine 1 g/L, potency retained for 24 hours at 5
degrees C
[898]
Dextrose 5% in ringer's injection
a) Compatible
1) Dextrose 5% in ringer's injection with lidocaine 1
g/L, compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985)
Dextrose 5% in Sodium chloride 0.11%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.11% is compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.11% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
Dextrose 5% in Sodium chloride 0.225%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.225% is compatible for 24 hours in glass or
polyolefin containers; conditions not specified (Tech
Info American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.225% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
Dextrose 5% in Sodium chloride 0.33%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.33% is compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.33% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
Dextrose 5% in Sodium chloride 0.45%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.45% is compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Dextrose 5% in Sodium chloride 0.45% with
lidocaine 2 g/L, visually compatible without significant
lidocaine decomposition in 14 days at 25 degrees C in
glass or polyvinylchloride containers under fluorescent
light
[897]
3) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.45% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
4) Dextrose 5% in Sodium chloride 0.45% with
lidocaine 2 g/L, visually compatible without significant
lidocaine decomposition in 14 days at 25 degrees C in
glass or polyvinylchloride containers under fluorescent
light
[899]
Dextrose 5% in Sodium chloride 0.9%
a) Compatible
1) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.9% is compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Dextrose 5% in Sodium chloride 0.9% with lidocaine
1 g/L, potency retained for 24 hours at 5 degrees C
[898]
3) Lidocaine 1 g/L in Dextrose 5% in Sodium chloride
0.9% is compatible for 24 hours; conditions not
specified (Tech Info American McGaw, 1985):
4) Dextrose 5% in Sodium chloride 0.9% with lidocaine
1 g/L, potency retained for 24 hours at 5 degrees C
(Trissel, 1990
Dextrose 5% in water
a) Compatible
1) Lidocaine 1 g/L in Dextrose 5% in water is
compatible for 24 hours in glass or polyolefin
containers; conditions not specified (Tech Info
American McGaw, 1985):
2) Dextrose 5% in water with lidocaine 1 g/L, potency
retained for 24 hours at 5 degrees C
[898]
3) Dextrose 5% in water with lidocaine 2 g/L, visually
compatible without significant lidocaine decomposition
in 14 days at 25 degrees C in glass or
polyvinylchloride containers under fluorescent light
[897]
4) Dextrose 5% in water with lidocaine 4 g/L,
chemically stable up to 120 days at 4 degrees C and
30 degrees C
[900]
5) Dextrose 5% in water with lidocaine 450 mg/L, no
significant lidocaine decomposition in 21 days at 22
degrees C
[901]
LACTATED RINGER'S INJECTION
a) Compatible
1) LACTATED RINGER'S INJECTION (with lidocaine
1 g/L compatible for 24 hours; conditions not specified)
(Tech Info American McGaw, 1985)
2) LACTATED RINGER'S INJECTION (with lidocaine
1 g/L, potency retained for 24 hours at 5 degrees C)
[805]
; (with lidocaine 2 g/L visually compatible without
significant lidocaine decomposition in 14 days at 25
degrees C in glass or polyvinylchloride containers
under fluorescent light)
[902]
Sodium chloride 0.45%
a) Compatible
1) Lidocaine 1 g/L in Sodium chloride 0.45% is
compatible for 24 hours; conditions not specified (Tech
Info American McGaw, 1985):
2) Lidocaine 2 g/L in Sodium chloride 0.45%, visually
compatible without significant lidocaine decomposition
in 14 days at 25 degrees C in glass or
polyvinylchloride containers under fluorescent light
[899]
Sodium chloride 0.9%
a) Compatible
1) Lidocaine 1 g/L in Sodium chloride 0.9% is
compatible for 24 hours; conditions not specified (Tech
Info American McGaw, 1985):
2) Lidocaine 2 g/L in Sodium chloride 0.9%, visually
compatible without significant lidocaine decomposition
in 14 days at 25 degrees C in glass or
polyvinylchloride containers under fluorescent light
[899]
3) Lidocaine 1 g/L in Sodium chloride 0.9%, potency
retained for 24 hours at 5 degrees C
[903]
4) Lidocaine 450 mg/L in Sodium chloride 0.9%, no
significant lidocaine decomposition in 21 days at 22
degrees C
[904]
Sodium lactate
a) Compatible
1) Lidocaine (2 g/L with Sodium lactate 50 mEq/L
physically compatible)
[905]
TOTAL PARENTERAL NUTRITION
a) Compatible
1) Lidocaine (200 mg/50 mL in Dextrose 5% in water
or Sodium chloride 0.9% added via a Y-site to a total
parenteral nutrition solution containing intravenous fat
emulsion 10% visually compatible for a 4-hour study
period at 25 degrees C; specific composition of total
parenteral nutrition solution - 1500 mL - listed below)
[906]
Amino acids 10%
750 mL
Dextrose 70%
429 mL
Lipid emulsion 20%
225 mL
Sterile water for injection 15 mL
Calcium gluconate 10% 20 mL
Magnesium sulfate 50% 2 mL
Potassium chloride
40 mEq
Sodium chloride
60 mEq
Sodium phosphate
15 mM
Heparin sodium
6000 U
Multivitamins - 12
10 mL
Trace minerals
3 mL
2) Lidocaine (1 g/L in a total parenteral nutrition
solution consisting of amino acids 4.25% in dextrose
25% exhibited no significant change in appearance,
particulate matter levels or pH in 24 hours at 5
degrees C)
[907]
3) Lidocaine (200 mg/50 mL in Dextrose 5% in water
or Sodium chloride 0.9% added to a total parenteral
nutrition solution visually compatible for 4 hours;
specific composition of total parenteral nutrition
solution follows)
[908]
:
Amino acids 10%
750 mL
Dextrose 70%
429 mL
Lipid emulsion 20%
225 mL
Sterile water for injection 15 mL
Sodium phosphate
15 mM
Magnesium sulfate 50% 2 mL
Heparin sodium
6000 U
Sodium chloride
60 mEq
Potassium chloride
40 mEq
Trace minerals - 4
3 mL
Multivitamins - 12
10 mL
4) Lidocaine (1 g/L in a total parenteral nutrition
solution - ProcalAmine(R) - physically compatible for
48 hours under refrigeration followed by 24 hours at
25 degrees C; specific composition of total parenteral
nutrition solution listed below)
[909]
:
Amino acids 3%
Glycerol
3%
Electrolytes present
5) Total parenteral nutrition solution (with lidocaine
200 mg/50 mL in Dextrose 5% in water or Sodium
chloride 0.9% visually compatible for 4 hours; specific
composition of total parenteral nutrition solution
follows)
[910]
Amino acids 10%
Dextrose 70%
750 mL
429 mL
Lipid emulsion 20%
225 mL
Sterile water for injection 15 mL
Sodium phosphate
15 mM
Magnesium sulfate 50% 2 mL
Heparin sodium
6000 U
Sodium chloride
60 mEq
Potassium chloride
40 mEq
Trace minerals - 4
3 mL
Multivitamins - 12
10 mL
6) Total parenteral nutrition (ProcalAmine(R) - with
lidocaine 1 g/L physically compatible for 48 hours
under refrigeration followed by 24 hours at 25 degrees
C; specific composition of total parenteral nutrition
solution listed below) (Tech info ProcalAmine(R),
1985):
Amino acids 3%
Glycerol
3%
Electrolytes present
Lidocaine Hydrochloride
ALKALINE SOLUTIONS
a) Incompatible
1) Alkaline solutions with lidocaine hydrochloride,
formation of precipitates; conditions not specified
[911]
CLINICAL APPLICATIONS
Monitoring Parameters
A) Lidocaine
1) Toxic
a) Physical Findings
1) Lidocaine overdose from topical application is unlikely, but lidocaine blood
levels should be measured if overdose is suspected
[270]
.
B) Lidocaine Hydrochloride
1) Therapeutic
a) Electrocardiogram and plasma concentrations should be monitored to
determine therapeutic effect.
b) Monitor cardiovascular and respiratory function (ie, adequacy of ventilation),
vital signs, and patient's state of consciousness after each local anesthetic
injection.
1) SALIVA CONCENTRATIONS
a) One study reported a good correlation between saliva and plasma levels of
lidocaine
[514]
. The mean saliva: plasma concentration range was 1.3:7. Another study reported
that mixed lidocaine salivary concentrations (lidocaine and metabolite) are a
relatively poor guide to drug concentrations at steady state, even if corrections
are made for pH changes
[515]
.
2) Toxic
a) Physical Findings
1) Patients receiving a test dose of lidocaine hydrochloride during epidural
anesthesia should be monitored for signs and symptoms of CNS and
cardiovascular toxicity
[65]
.
2) Careful and constant monitoring of cardiovascular and respiratory vital signs
and the patient's state of consciousness should be accomplished after each local
anesthetic injections
[65]
.
3) Monitor for signs and symptoms of familial malignant hyperthermia
(tachycardia, tachypnea, labile blood pressure, metabolic acidosis, temperature
elevation)
[65]
.
4) Patients receiving local anesthetics in the head and neck area should have
their circulation and respiration monitored and be constantly observed
[65]
.
5) The mother's blood pressure and fetal heart rate should be monitored when
lidocaine is used for regional anesthesia during labor and delivery
[65]
.
6) Blood pressure, and subjective central nervous system symptoms such as
behavioral changes, irritability or somnolence which are often subtle should be
observed to avoid further toxicities
[65]
.
7) Monitoring lidocaine plasma concentrations is essential to reduce toxicity; at
concentrations above 5 mcg/mL, central nervous system depression, stimulation,
or seizures may occur
[516]
.
8) Electrocardiographic monitoring in patients receiving lidocaine is essential for
detecting lidocaine toxicity. Signs of cardiac depression associated with lidocaine
administration may include sinus node dysfunction, prolongation of the P-R
interval and QRS complex or the appearance or aggravation of arrhythmias. If
lidocaine toxicity is suspected or observed, adjust the dosage (ie, decrease the
rate of the continuous intravenous infusion) or discontinue the drug immediately
[65]
.
9) Systemic toxicity (ie, either CNS depression or irritability) may in some cases
progress to frank convulsions and ultimately lead to respiratory depression and/or
arrest. It is crucial to have resuscitative equipment and resuscitative and
anticonvulsant drugs available to manage such patients
[65]
.
Patient Instructions
A) Lidocaine (By mouth)
Lidocaine
Relieves pain caused by cold sores or fever blisters.
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to lidocaine,
procaine, butacaine, benzocaine, or other anesthetics (numbing medicine).
How to Use This Medicine:
Powder, Liquid, Kit, Spray
Take your medicine as directed.
For best results, use the medicine when you first feel early signs of a cold sore
such as tingling, itching, or burning.
To use, drop several drops of the medicine on a cotton swab and dab it onto the
affected area. Allow the medicine to dry for 15 minutes.
Do not apply this medicine in large quantities over raw or affected areas.
This medicine is flammable. Do not use this medicine near heat, fire, or open
flame.
Follow the instructions on the medicine label if you are using this medicine without
a prescription.
Read and follow the patient instructions that come with this medicine. Talk to your
doctor or pharmacist if you have any questions.
This medicine is not for long-term use.Do not use this medicine for more than 7
days.
If a Dose is Missed:
Take a dose as soon as you remember. If it is almost time for your next dose, wait
until then and take a regular dose. Do not take extra medicine to make up for a
missed dose.
How to Store and Dispose of This Medicine:
Store the medicine in a closed container at room temperature, away from heat,
moisture, and direct light.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of
any outdated medicine or medicine no longer needed.
Keep all medicine out of the reach of children. Never share your medicine with
anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthe-counter medicines, vitamins, and herbal products.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breast feeding.
Call your doctor if your symptoms do not improve or if they get worse.
You should not use this medicine on a child under 2 years of age without a
doctor's approval.
Do not get this medicine into your eyes. If it does, rinse your eyes with water for
ten minutes and call your doctor right away.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or
tingling in your mouth or throat, chest tightness, trouble breathing
Swelling, rash, or fever.
If you notice these less serious side effects, talk with your doctor:
If you notice other side effects that you think are caused by this medicine, tell your
doctor.
B) Lidocaine (Injection)
Lidocaine
Causes numbness or loss of feeling in an area of your body. Given before and
during surgery, childbirth, or dental work. Also treats emergency heart rhythm
problems.
When This Medicine Should Not Be Used:
You should not receive this medicine if you have had an allergic reaction to
lidocaine or other types of local anesthetic (numbing medicine).
How to Use This Medicine:
Injectable
A nurse or other health provider will give you this medicine.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthe-counter medicines, vitamins, and herbal products.
Make sure your doctor knows if you are using amiodarone (Cordarone®),
amprenavir (Agenerase®), atazanavir (Reyataz®), digoxin (Lanoxin®), phenytoin
(Dilantin®) or St. John's wort. Tell your doctor if you use ergot medicines such as
Cafergot®. Make sure your doctor knows if you use phenothiazines such as
Compazine®, Phenergan®, Thorazine®, or Trilafon®. Your doctor will need to
know if you are using blood pressure medicine such as metoprolol, nadolol,
propranolol, Corgard®, Inderal®, or Toprol®. Also, tell your doctor if you are using
medicine for depression such as amitriptyline, nortriptyline, Norpramin®, or
Vivactil®.
Tell your doctor if you drink alcohol or if you are using any medicine that makes
you sleepy, such as allergy medicine or narcotic pain medicine.
Warnings While Using This Medicine:
If you are not receiving this medicine for childbirth, make sure your doctor knows
if you are pregnant or breast feeding. Tell your doctor if you have asthma,
diabetes, liver disease, kidney disease, or seizures (epilepsy). Make sure your
doctor knows if you have thyroid problems, circulation problems, high blood
pressure, low blood pressure, or a blood-iron disorder called methemoglobinemia.
Tell your doctor if you have any heart problems such as congestive heart failure
or heart rhythm disorders (especially Wolff-Parkinson-White syndrome).
This medicine may make you dizzy or drowsy. Avoid driving, using machines, or
doing anything else that could be dangerous if you are not alert.
It may be easier to hurt yourself while your treated body area is still numb. Be
careful to avoid injury until you have regained all the feeling and are no longer
numb.
If you are receiving this medicine as an epidural to ease labor pains, it may take
longer than normal for you to push your baby out. It is also possible that the baby
may have unwanted effects after birth (sleepiness, slow responses). Talk to your
doctor if you have questions about how this medicine might affect your baby.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or
tingling in your mouth or throat, chest tightness, trouble breathing
Bluish colored lips or fingernails, pale skin.
Chest pain or uneven heartbeat.
Light-headedness or fainting.
Numbness in another part of your body that is not being treated.
Unusual bleeding, bruising, or weakness.
If you notice these less serious side effects, talk with your doctor:
Back pain.
Constipation, nausea, or vomiting.
Headache.
Numbness, tingling, or burning of treated areas in the hours or days after surgery.
Pain, redness, or swelling where the needle was placed.
Shivering, shaking, or tremors.
If you notice other side effects that you think are caused by this medicine, tell your
doctor.
C) Lidocaine (Into the eye)
Lidocaine
Used in the eye to cause numbness or loss of feeling before certain procedures.
This medicine is a topical anesthetic (numbing medicine).
When This Medicine Should Not Be Used:
You should not receive this medicine if you have had an allergic reaction to
lidocaine or to any other numbing medicines.
How to Use This Medicine:
Gel/Jelly, Drop
A nurse or other trained health professional will give you this medicine. This
medicine is given as a drop into your eye.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthe-counter medicines, vitamins, and herbal products.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breastfeeding.
After this medicine is applied to the eye, do not rub or wipe the eye until the
feeling in the eye returns. To do so may cause injury or damage to the eye.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or
tingling in your mouth or throat, chest tightness, trouble breathing
Blurred vision or other changes in vision.
Burning or irritation of your eye.
Redness or itching of the eyelids and the whites of your eyes.
If you notice these less serious side effects, talk with your doctor:
Headache.
If you notice other side effects that you think are caused by this medicine, tell your
doctor.
D) Lidocaine (On the skin)
Lidocaine
Relieves the pain of a sore mouth or throat, minor burns, sunburn, insect bites,
and other medical problems. May also be used by men to treat premature
ejaculation (a sex problem) and prolong an erection.
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to lidocaine
or related medicines such as tetracaine or dibucaine.
How to Use This Medicine:
Foam, Cream, Pad, Gel/Jelly, Liquid, Lotion, Ointment, Spray
Your doctor will tell you how much of this medicine to use, where to apply it, and
how often to apply it. Do not use more medicine or use it more often than your
doctor tells you to. Unless directed by your doctor, do not apply this medicine to
open wounds, burns, broken or inflamed skin, or to a large area of skin.
Follow the instructions on the medicine label if you are using this medicine without
a prescription.
Do not cover the treated area with a bandage unless directed by your doctor.
You might have trouble swallowing if you spray this medicine in your throat, or the
back of your mouth. Do not eat or drink for 60 minutes after using this medicine in
your mouth or throat.
You might need to shake the spray form well just before each use.
Do not get this medicine in your eyes. If the medicine does get in your eyes, wash
your eyes with water right away.
For men using this medicine to treat problems with sex: Spray it on your penis
before you have sex. Most men need to spray the medicine at least 3 times. Do
not spray the medicine more than 10 times during each session. Over time, you
will learn how many times, and how early, to spray the medicine for your
condition.
If a Dose is Missed:
If you are using this medicine on a regular schedule: Take a dose as soon as you
remember. If it is almost time for your next dose, wait until then and take a regular
dose. Do not take extra medicine to make up for a missed dose.
How to Store and Dispose of This Medicine:
Store the medicine in a closed container at room temperature, away from heat,
moisture, and direct light.
Ask your pharmacist or doctor how to dispose of the medicine container and any
leftover or expired medicine.
Keep all medicine out of the reach of children. Never share your medicine with
anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthe-counter medicines, vitamins, and herbal products.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breastfeeding.
Using too much of this medicine or using it on a large part of your skin can cause
serious side effects. Stop using this medicine and contact your doctor right away
if you have any of these symptoms: lightheadedness, dizziness, vision problems,
irregular or slow heartbeat, difficulty with breathing, or seizures.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or
tingling in your mouth or throat, chest tightness, trouble breathing
Blurred or double vision.
Confusion, dizziness, or lightheadedness.
Difficulty breathing.
Skin or throat swelling, redness, itching, rash, or pain.
Slow, irregular, or uneven heartbeat.
Tremor or seizures.
If you notice these less serious side effects, talk with your doctor:
If you notice other side effects that you think are caused by this medicine, tell your
doctor.
E) Lidocaine Patch (On the skin)
Lidocaine
Treats nerve pain that is caused by herpes zoster, or "shingles."
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to lidocaine
or other "numbing" medicines, or to adhesive bandages.
How to Use This Medicine:
Patch
Your doctor will tell you how many patches to use, where to apply them, and how
often to apply them. Do not use more patches or apply them more often than your
doctor tells you to.Do not leave a skin patch on for longer than your doctor tells
you to.
The usual dose of this medicine is 1 to 3 patches applied to the painful skin area.
The patch can be worn for up to 12 hours. Do not wear the patch for longer than
12 hours in any 24-hour period.
Wash your hands with soap and water before and after applying a patch.After
applying a patch, do not touch anything until you have washed your hands.
Before you remove the patch liner, you may trim the patch with scissors or cut it
into smaller pieces to fit your skin areas.
Do not put the patch over burns, cuts, or irritated skin.If you feel a slight stinging
or burning where you apply the patch, remove it right away. You may put the
patch back on once the stinging or burning goes away.
Put on a new patch if the old one has fallen off and cannot be reapplied.
If a Dose is Missed:
If you forget to wear or change a patch, put one on as soon as you can. If it is
almost time to put on your next patch, wait until then to apply a new patch and
skip the one you missed. Do not apply extra patches to make up for a missed
dose.
How to Store and Dispose of This Medicine:
Store the patches at room temperature in a closed container, away from heat,
moisture, and direct light.Keep the patches inside the resealable envelope until
you are ready to use one. Reseal the envelope and keep it closed at all times
when storing it.
It is very important to store the patches where children or pets cannot reach them.
Each patch has enough medicine to cause serious illness in a pet or small child
who might chew on it.
Fold the used patch in half with the sticky sides together. Throw any used patch
away so that children or pets cannot get to it. You will also need to throw away old
patches after the expiration date has passed.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthe-counter medicines, vitamins, and herbal products.
Make sure your doctor knows if you are using medicine to treat abnormal heart
rhythm, such as disopyramide, flecainide, mexiletine, procainamide, propafenone,
quinidine, Mexitil®, Norpace®, Procanbid®, Rythmol®, or Tambocor®. Tell your
doctor if you are using any other medicines on your skin.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breast feeding, or if you have
liver disease. Tell your doctor if you are allergic to any type of medicine.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or
tingling in your mouth or throat, chest tightness, trouble breathing
Dizziness, lightheadedness, or fainting.
Muscle twitches or tremors that you cannot control.
Ringing in your ears.
Slow heartbeat.
If you notice these less serious side effects, talk with your doctor:
Blurry or double vision.
Feeling restless, jittery, or more tired than usual.
Redness, swelling, burning, itching, bruising, or rash where you apply the patch.
Vomiting.
If you notice other side effects that you think are caused by this medicine, tell your
doctor.
Place In Therapy
A) ACUTE MYOCARDIAL INFARCTION (AMI)
1) Prophylactic use of lidocaine for AMI has been associated with a trend toward
increased mortality. Routine prophylactic use of lidocaine for the treatment of AMI
is NOT recommended, with the possible exception being situations in which a
defibrillator is unavailable. Lidocaine is the drug of choice for AMI when episodes
of ventricular fibrillation/ventricular tachycardia (VF/VT) are not easily converted
by defibrillation and epinephrine (ie, resistant VF/VT).
B) ANESTHESIA
1) LIDOCAINE is frequently used for nerve block, infiltration, regional, epidural
and subarachnoid anesthesia, as well as for topical anesthesia.
C) LIVER FUNCTION ASSESSMENT
1) Lidocaine's primary metabolite, monoethylglycinexylidide (MEGX), has been
used to assess hepatic function and to predict morbidity and mortality related to
complications of liver disease.
D) MIGRAINE HEADACHE
1) Intranasal lidocaine is effective in the treatment of migraine headache.
Intranasal lidocaine provides complete or partial relief of headache and related
symptoms within 5 minutes. Lidocaine may be more effective for unilateral, as
opposed to bilateral, headaches.
E) SEIZURES
1) Lidocaine is effective in the treatment of seizures resistant to other drugs.
F) VENTRICULAR ARRTHYTHMIAS
1) Lidocaine is effective for the treatment of serious ventricular arrhythmias.
Lidocaine is considered the drug of choice for acute treatment of ventricular
tachycardia, ventricular fibrillation, and digitalis-induced ventricular
tachyarrhythmias.
Mechanism of Action / Pharmacology
A) Lidocaine
1) Mechanism of Action
a) Lidocaine is used as a local anesthetic and as an antiarrhythmic agent. It
provides anesthesia by preventing both the generation and the conduction of the
nerve impulse. Local anesthetics block conduction by decreasing or preventing
the large transient increase in the permeability of the membrane to sodium ion.
The threshold for electrical excitability gradually increases and produces a block
of conduction
[480]
. The penetration of lidocaine through intact skin will produce an analgesic effect
but is not sufficient to produce complete sensory block
[282]
.
B) Lidocaine Hydrochloride
1) Mechanism of Action
a) Lidocaine is used as a local anesthetic and as an antiarrhythmic agent. It
provides anesthesia by preventing both the generation and the conduction of the
nerve impulse. Local anesthetics block conduction by decreasing or preventing
the large transient increase in the permeability of the membrane to sodium ion.
The threshold for electrical excitability gradually increases and produces a block
of conduction
[480]
[50]
. Lidocaine is an amide type anesthetic and is widely used for infiltration, nerve
block, epidural, intravenous regional, and subarachnoid anesthesia. It is also
frequently used for topical anesthesia. Lidocaine, when compared to procaine has
a more rapid onset of action, is more potent and has a longer duration of action
[511]
.
b) Lidocaine is commonly used in the treatment of ventricular arrhythmias. It acts
by depressing diastolic depolarization and automaticity in the ventricles. It has
little effect on atrial tissue and in therapeutic doses does not significantly depress
myocardial contractility or AV conduction
[511]
.
c) One study demonstrated that lidocaine selectively depresses conduction in
ischemic or depolarized myocardium
[510]
. Ten patients with complete atrial ventricular block were given lidocaine 1.5
mg/kg IV followed by a 3 mg/minute infusion. AV block was secondary to acute
myocardial infarction in 3 patients, however, in the other 7 patients it was not. In
patients with AV block due to an acute myocardial infarction, lidocaine caused
severe bradycardia or asystole in two of three patients. However in the other
group, lidocaine had only a slight depressing effect on the rate of the escaped
pacemaker. It is suggested that therapeutic concentrations of lidocaine do not
affect conduction of the normal myocardium, however, in the ischemic
myocardium lidocaine slows conduction and decreases diastolic excitability
[512]
[513]
. The mechanism by which lidocaine depresses arrhythmias may be its ability to
depress conduction in ischemic myocardium rather than to improve conduction or
to suppress the normal or abnormal automaticity
[510]
.
Therapeutic Uses
Lidocaine
Anal fissure
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Pediatric, Ineffective
Recommendation: Pediatric, Class III
Strength of Evidence: Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Combination lidocaine-prilocaine (topically) was more effective than
lidocaine only for healing of anal fissures in pediatric patients
[1]
.
c) Pediatric:
1) Nitroglycerin ointment or combination lidocaine-prilocaine
ointment were both more effective for symptomatic relief and
healing of anal fissures than were lidocaine only ointment or
Vaseline(R) (placebo) in children with anal fissures (n=102, mean 3
years of age). Subjects were randomized to 1 of 4 ointments:
Vaseline(R) (placebo, n=20), lidocaine 10% (n=24), a eutectic
mixture of lidocaine 5%-prilocaine 5% (n=25), or nitroglycerin 0.2%
(glyceryl trinitrate, n=22). The ointment was applied to the distal
anal canal twice daily for 8 weeks. Progress was measured at 10
days and 8 weeks, using scales for relief of symptoms (0=no relief;
1=some relief; 2=complete relief) and fissure healing (0=deep
fissures with bleeding; 1=pale, shallow fissures without bleeding,
and 3=complete healing). On day 10, proportions of patients with
scores of 0 (no progress) in symptom relief and fissure healing were
significantly higher in the placebo and lidocaine groups compared
with the lidocaine-prilocaine and glyceryl trinitrate groups (both p
less than 0.05). After 8 weeks, the highest number of patients with
scores of 0 were in the control group (50%), followed by the
lidocaine group (12%) (p less than 0.05, lidocaine group vs
placebo); no one in the lidocaine-prilocaine and glyceryl trinitrate
groups had a 0 score at 8 weeks. Ten-day rates of complete
symptomatic relief and complete healing were 45% and 4%,
respectively, for glyceryl trinitrate-treated subjects compared with
20% and 0%, respectively, for lidocaine-prilocaine-treated subjects.
Percentages with complete relief and healing at 8 weeks were 91%
and 82%, respectively, for the glyceryl trinitrate group and 76% and
64%, respectively, for the lidocaine-prilocaine group (no significant
difference lidocaine-prilocaine vs glyceryl trinitrate)
[1]
.
Asthma
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class III; Pediatric, Class III
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine may reduce or eliminate use of oral glucocorticoid therapy
in severe chronic asthma.
Aerosolized lidocaine produces rapid bronchoconstriction, which
may be followed by bronchodilation in some asthmatic patients.
Both IV and inhaled lidocaine significantly and similarly attenuate
bronchial hyperreactivity, but at lower plasma levels following
inhalation.
Nebulized lidocaine has generally been ineffective in preventing
airway constriction in patients with exercise-induced asthma and
may actually exacerbate the condition.
c) Adult:
1) General
a) Studies have revealed that in contrast to a normal healthy adult,
in which aerosolized lidocaine produces little effect on pulmonary
function, some patients with reactive airway disease have displayed
a bimodal response. Initial bronchoconstriction followed by delayed
bronchodilation has been demonstrated in some individuals with
asthma following the inhalation of nebulized lidocaine
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
. The mechanism involved in the initial bronchoconstriction following
nebulized lidocaine is unknown. Aerosolized lidocaine may stimulate
and irritate receptors by exerting a nonspecific noxious stimulus,
which may result in bronchoconstriction, until these receptors are
anesthetized. Asthmatic patients also develop reflex mediated
coughing and bronchoconstriction in response to inhaled stimuli that
would generally not initiate a response in nonasthmatic subjects.
The hyperactivity of the airway may account for the initial
bronchoconstriction observed following the administration of
aerosolized lidocaine. Prophylactic aerosolized atropine or
isoproterenol may prevent or minimize the initial bronchoconstriction
produced by nebulized lidocaine. This finding also suggests that the
mechanism of aerosolized lidocaine-induced bronchoconstriction is
a reflex, mediated by the vagal nerve, and presumably initiated by
stimulation of receptors located in airway epithelium. Therefore, it is
not surprising that complete anesthesia of the airways, with the
interruption of the reflex arc, results in bronchodilation
[10]
[6]
[11]
[9]
[12]
. Biochemically, the bimodal response from aerosolized lidocaine is
thought to be due to the dose-dependent release of prostaglandins
and calcium. Low doses of lidocaine are theorized to displace
calcium from membranes to the interior of muscle cells causing the
activation of contractile proteins, while higher doses of lidocaine are
thought to bind cytoplasmic calcium, leading to myorelaxation
[7]
.
2) The results of a randomized, double-blind, placebo-controlled
study involving 15 patients with bronchial hyperreactivity indicate
that IV and inhalational administration of lidocaine significantly and
similarly attenuate reflex bronchoconstriction following inhalational
histamine challenge. Inhaled lidocaine produced the same
attenuation of bronchial hyperreactivity as IV lidocaine, but at
significantly lower plasma concentrations. However, inhaled
lidocaine produces an initial decrease in FEV-1. On separate days,
patients received inhaled lidocaine (5 mg/kg in saline), IV lidocaine
(1.5 mg/kg over 20 minutes then a constant dose of 3 mg/kg/hour),
or IV saline. Both inhalational and IV administration of lidocaine
doubled the histamine threshold (p=0.0007). Peak lidocaine plasma
concentrations following IV and inhalational administration were 2.4
mcg/mL and 1.5 mcg/mL, respectively (p=0.0229)
[13]
.
3) Nebulized lidocaine may be a useful therapy for patients with
severe, glucocorticoid-dependent chronic asthma, permitting a
reduction or elimination of oral glucocorticoid therapy. In an open
study involving 20 patients with glucocorticoid-dependent asthma,
patients received nebulized lidocaine 40 to 160 mg 4 times daily
(2% or 4% solution). During a mean of 12 months of treatment, 17
of 20 patients were able to reduce the amount of glucocorticoid
needed by 80% to 100% of their initial maintenance dosage; 13
patients were able to discontinue oral use of glucocorticoids
completely, 4 patients reduced their daily glucocorticoid
requirements, and 3 patients did not respond to treatment with
lidocaine. No measurable serum lidocaine levels were found in any
patient within 15 minutes after nebulized lidocaine treatment
[14]
.
4) Lidocaine inhalation has been reported to have no effect on the
obstructive or ventilatory response to exercise in asthmatics
[2]
[4]
[3]
. However, 1 study reported that aerosolized lidocaine 1
milligram/kilogram was effective in blocking exercise-induced
bronchoconstriction in 10 asthmatic patients
[5]
.
d) Pediatric:
1) Nebulized lidocaine may be effective in pediatric patients with
severe, glucocorticoid-dependent asthma, permitting elimination of
oral glucocorticoid therapy and reducing hospitalizations. In this
open, uncontrolled, pilot study, 6 pediatric patients (mean age 11
years; range 8 to 14 years) with severe, glucocorticoid-dependent
asthma received nebulized lidocaine 0.8 to 2.5 mg/kg/dose (40 to
100 mg) 3 or 4 times daily. Patients continued all other medications
while receiving lidocaine. During a mean of 11.2 months (range 7 to
16 months) of therapy, 5 of 6 patients completely discontinued the
use of oral glucocorticoids within an average time of 3.4 months
(range 1 to 7 months). In addition, fewer hospitalizations occurred
during nebulized lidocaine therapy. One patient did not improve with
nebulized lidocaine and discontinued it after 7 months. Bitter taste
and transient oropharyngeal anesthesia were the only adverse
effects reported during nebulized lidocaine therapy
[15]
.
Burn
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Effective
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Effective for partial-thickness burns
c) Adult:
1) Topical lidocaine (1 mg/cm(2) of a 5% cream) was reported
effective in the treatment of partial-thickness burns (total body
surface area (TBSA) 5 to 28%) in an open study involving 30
patients
[16]
. No allergic, infectious or cardiovascular complications were
observed as a result of topical lidocaine. Plasma concentrations
remained fairly constant during the first 4 hours post-application
(mean levels, 2.7 mcg/mL). Burn wounds up to 28% TBSA treated
with 4.5 grams lidocaine did not result in systemic toxicity (plasma
level, 5.8 mcg/mL). A controlled study is required to further evaluate
the efficacy of topical lidocaine in partial-thickness burns.
Cancer pain
See Drug Consult reference:
MANAGEMENT OF CANCER-RELATED PAIN IN ADULT
PATIENTS
Diabetic neuropathy
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
5% lidocaine patches were well tolerated and reduced pain in
patients with diabetic neuropathy
[17]
In a multi-center, randomized, open-label trial, combination therapy
with pregabalin and lidocaine 5% medicated plaster improved
numeric rating scale (NRS-3) pain scores in patients with diabetic
polyneuropathy (DPN) or post herpetic neuralgia (PHN) who had an
unsatisfactory response after 4 weeks of monotherapy
[18]
.
c) Adult:
1) Patches containing lidocaine 5%, applied to areas of maximal
pain, reduced pain and improved quality of life in patients with
diabetic polyneuropathy (DPN). In an open, uncontrolled trial with 56
patients with DPN (19 with allodynia and 37 without), up to 4
lidocaine patches were applied to the area of greatest pain for 18
hours per day for 3 weeks. All patients had a stable analgesic drug
regimen for at least a week before the start of the study; increases
in analgesic regimen were not permitted during the study. Twenty
patients continued treatment for an additional 5 weeks, with the
option to taper concomitant analgesic therapy while maintaining
pain control. Seventy percent of patients (68% of those with
allodynia and 72% of those without) had a reduction of at least 30%
in pain rating scores between baseline and the end of week 3.
Thirty-two percent of patients with allodynia and 50% of patients
without allodynia had a 50% reduction in pain scores by week 3.
Improvements in sleep quality and all aspects of pain interference
paralleled improvements in pain. Depression and mood scores also
improved. Among the 28 patients who continued using lidocaine
patches for 8 weeks, 7 were able to taper their concomitant
analgesic medication. Three had complete discontinuation (2 of
gabapentin and 1 of amitriptyline), and 4 reduced their doses (50%
and 67% reductions of gabapentin, 50% reduction of tramadol, and
25% reduction of amitriptyline). Four patients withdrew due to
adverse events, mainly application-site pain or burning. There were
no systemic adverse events reported
[17]
.
a) Combination therapy
1) In a multi-center, randomized, open-label trial, combination
therapy with pregabalin and lidocaine 5% medicated plaster
improved numeric rating scale (NRS-3) pain scores in patients with
diabetic polyneuropathy (DPN) or post herpetic neuralgia (PHN)
who had an unsatisfactory response after 4 weeks of monotherapy.
In the 4-week comparative phase, patients with DPN (distal,
symmetrical sensorimotor polyneuropathy of the lower extremities
for at least 3 months) or PHN (neuropathic pain for at least 3
months following healing of herpes zoster skin rash) were
randomized 1:1 to receive either pregabalin (150 mg daily for one
week, then 300 mg daily for one week, and then up to 600 mg daily
if needed) or lidocaine 5% medicated plaster (up to 3 plasters (PHN)
or up to 4 plasters (DPN) for up to 12 hours during each 24 hour
period). The 8-week combination phase followed, and patients were
randomized according to their response at the end of the 4 weeks of
monotherapy. Patients with an average NRS-3 score below 4 on the
11-point scale for the previous 3 days continued with either
lidocaine (n=71; mean age, 61.6 +/- 9.9 years; mean NRS-3 score,
2.7 +/- 1.2 points) or pregabalin (n=57; mean age, 61 +/- 8.9 years;
mean NRS-3 score, 2.8 +/- 1.2 points) and patients with an average
NRS-3 score above 4 for the previous 3 days (unsatisfactory
response) received combination therapy; lidocaine patients received
pregabalin (n=57; mean age, 63 +/- 11.5 years; mean NRS-3 score,
6.1 +/- 1 points) and pregabalin patients received lidocaine (n=44;
mean age, 61.5 +/- 10.5; mean NRS-3 score, 5.8 +/- 0.8 points).
Concomitant use of other drugs or therapies for neuropathic pain
was not permitted. After 8 weeks, all 4 groups experienced a
reduction in mean NRS-3 scores (primary endpoint) compared with
baseline (lidocaine, -0.7 +/- 1.2 points; pregabalin, -0.6 +/- 1.3
points; lidocaine plus pregabalin, -2.5 +/- 1.6 points; pregabalin plus
lidocaine, -1.7 +/- 1.8 points). Additionally, the percentage of
patients that scored much and very much improved on the Patient
and Clinical Global Impression of Change scale was increased in all
4 groups; including the lidocaine plus pregabalin group (baseline,
15.8% and 17.6%; after addition of pregabalin for 8 weeks, 64.9%
and 66.6%, respectively) and in the pregabalin plus lidocaine group
(baseline, 25% and 31.8%; after addition of lidocaine for 8 weeks,
65.1% and 62.8%). Drug-related adverse events occurred more
frequently in the lidocaine plus pregabalin group compared with the
lidocaine, pregabalin, and pregabalin plus lidocaine groups (26.7%
vs 5.1%, 7.9%, and 6.3%, respectively)
[18]
.
Hiccoughs, Intractable
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
A 2% viscous lidocaine solution was effective for treating intractable
hiccups in 4 cancer patients; the addition of oral baclofen extended
lidocaine's effect in 1 case
[19]
.
c) Adult:
1) A 2% viscous lidocaine solution was effective for treating
intractable hiccups in 4 cancer patients. A 42-year-old man with
relapsed colon cancer was successfully treated with 2% viscous
lidocaine gel after suffering from intractable hiccups for 18 months
and failing therapy with metoclopramide, baclofen, haloperidol,
amitriptyline, carbamazepine, gabapentin, and pregabalin. A 5-mL
dose of 2% viscous lidocaine stopped the hiccups for at least 1 day,
and the patient's symptoms were controlled with lidocaine doses on
demand. A 5-mL dose of 2% viscous lidocaine administered 2 to 3
times per day, in combination with baclofen 20 mg/day, terminated
hiccups in a 69-year-old man with metastatic pancreatic cancer who
had suffered from hiccups for almost 3 months. The patient had
previously tried and failed treatment with ursodeoxycholic acid,
baclofen, and various neuroleptic medications. Viscous lidocaine
was also successful when administered 3 to 4 times per day to a 62year-old man with non-Hodgkin lymphoma who had received 6
cycles of chemotherapy. Upon recurrence of hiccups with his next
cycle of chemotherapy, baclofen 20 mg/day monotherapy failed, but
the addition of 2% viscous lidocaine solution was successful; the
addition of baclofen extended the duration of lidocaine's efficacy
compared with the patient's initial course of lidocaine monotherapy.
A 54-year-old man with non-Hodgkin lymphoma was also treated
successfully with baclofen and 2% viscous lidocaine combination
therapy at doses of 30 mg/day and 5 mL 1 to 2 times per day,
respectively
[19]
.
Local anesthesia, Topical
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIa; Pediatric, Class IIa
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Effective anesthesia was produced with the following lidocainetopical forms:
Cream for chemical peeling associated pain
[21]
Patch applied to the maxillary and mandibular mucosa for reducing
needle insertion pain
[22]
Solution (tetracaine, lidocaine, and adrenaline) applied to minor
lacerations
[23]
[24]
[25]
[26]
[27]
Spray produced better conditions for insertion of a laryngeal mask
[28]
Tape for needle insertion pain for stellate ganglion block
[29]
Life-threatening adverse events have been reported when topical
anesthetics, like lidocaine, are used improperly
[30]
c) Adult:
1) Important Note
a) For information regarding topical lidocaine and prilocaine
combination formulations, consult the Drug Evaluation on
lidocaine/prilocaine.
2) Aerosol
a) Pre-treatment with endotracheal 0.4 mL lidocaine 8% spray, but
not IV administration of lidocaine (32 mg), reduces isofluraneinduced tachycardia which typically follows a rapid increase in
isoflurane concentration. In this randomized study, patients (n=72)
were initially stabilized with oxygen and isoflurane 1%. Following a
rapid increase to 3% isoflurane, the increase in heart rate was
significantly less (p less than 0.05) in patients that received pretreatment with endotracheal lidocaine compared with those that
received pre-treatment with IV lidocaine or did not receive any pretreatment. Heart rate increased similarly in the IV lidocaine group
and the no pre-treatment group. The plasma lidocaine concentration
was lower in the endotracheal group (0.4 mcg/mL) than in the IV
group (1.5 mcg/mL) (p less than 0.05)
[31]
.
b) Topical lidocaine spray followed by thiopentone produced better
conditions for insertion of a laryngeal mask when compared to
lidocaine and thiopentone IV administration
[28]
. This was a randomized, single-blind study of 90 nonpremedicated
adult patients who were given lidocaine 0.5 mg/kg IV (group 1),
lidocaine 1.5 mg/kg IV (group 2) or 40 mg of topical lidocaine spray
to the posterior pharyngeal (group 3) prior to fentanyl 1 mcg/kg and
thiopentone 5 mg/kg. Topical lidocaine group coughed or gagged
less often and had a lower incidence of laryngospasm.
3) Cream
a) Both EMLA(R) cream and ELA-Max(R) cream (lidocaine 4%)
similarly and significantly reduce the discomfort felt during mediumdepth combination 70% glycolic acid-35% trichloroacetic acid
chemical peeling without affecting the clinical or histopathologic
result. Glycolic acid was applied to the entire face of 10 patients and
removed after 2 minutes. EMLA(R), ELA-Max(R), and a placebo
cream were then applied to separate areas of the face for 30
minutes without occlusion and then removed. Trichloroacetic acid
was then applied over the entire face. Both EMLA(R) and ELAMax(R) significantly decreased discomfort during the procedure
compared with placebo (p less than 0.01). There was no significant
difference in pain perception between EMLA(R) and ELA-Max(R) at
any stage of the peel. Glycolic acid may enhance the anesthetic
effects of EMLA(R) and ELA-Max(R). Use of EMLA(R) and ELAMax(R) after application of glycolic acid results in better anesthesia
than when these agents are applied to untreated skin
[21]
.
1) Compared with Infiltration
a) Results of a prospective, randomized study involving 538 adults
indicate that use of EMLA(R) cream significantly (p=0.0001)
reduces pain associated with radial artery cannulation, lowers the
failure rate of cannulation, and shortens the insertion time compared
with subcutaneous local lidocaine infiltration. In this study, EMLA(R)
cream was applied 2 hours prior to cannulation and lidocaine
infiltration occurred 5 minutes prior to cannulation
[32]
. The results of 1 study involving 41 women undergoing postpartum
tubal ligation indicate that application of EMLA(R) cream is more
effective than infiltration with lidocaine for reducing pain associated
with spinal needle insertion for administration of spinal anesthesia.
In this study, patients received either EMLA(R) cream 30 minutes
prior to the procedure or infiltration with 3 milliliters of 1% lidocaine
prior to spinal needle insertion (25-gauge spinal needle via a 20gauge introducer). Pain scores were significantly lower in patients
administered EMLA(R) cream than in patients given lidocaine
infiltration (p less than 0.001)
[33]
.
4) Gel
a) Application of lidocaine gel prior to mammography minimally
reduced discomfort during the screening in women who expected
discomfort in a prospective, double-blind, placebo-controlled trial
(n=418)
[34]
; furthermore, there is an association between improper use of
topical anesthetics and life-threatening adverse events
[30]
. Women aged 32 to 89 years who expected discomfort of 40 or
higher, out of a visual analog scale (VAS) from no pain (0) to worst
pain imaginable (100), during mammography were assigned to 1 of
the following 12 groups: 1) 1000 mg acetaminophen, 2) 800 mg of
ibuprofen, 3) oral placebo, 4) 1 ounce (oz) or less of 4% lidocaine
gel, 5) gel placebo, 6) 1000 mg of acetaminophen and 1 oz or less
of 4% lidocaine gel, 7) 1000 mg of acetaminophen and gel placebo,
8) 800 mg of ibuprofen and 1 oz or less of 4% lidocaine gel, 9) 800
mg of ibuprofen and gel placebo, 10) oral placebo and 1 oz of less
of 4% of lidocaine gel 11) oral placebo and gel placebo, 12) usual
care for mammographic screening. Oral medications were
administered 36 to 129 minutes (mean 81.3 minutes) before
mammography. Topical gel was applied 30 to 75 minutes (mean
47.8 minutes) before mammography and covered with plastic. There
was a delay of 30 to 65 minutes between gel removal and first
mammographic film. Despite a statistically (p=0.01) significant
difference between lidocaine gel only and placebo gel only the
confidence intervals of the VAS between the 2 groups overlapped
and the absolute difference in VAS between the 2 groups was 5.
The adjusted (expected discomfort, age, breast density, and history
of previous screening and for the combination of technologist and
mammography machine) mean VAS was 32.7 (95% CI, 23.3 to
42.1) for lidocaine gel only, 37.7 (95% CI, 28.9 to 46.5) for placebo
gel only, and 36 (95% CI, 26.7 to 45.3) for no intervention. There
was no significant differences in satisfaction, a secondary endpoint,
by gel type (p=0.55). Mild pruritus and pink discoloration of the skin,
which resolved within 1 hour, occurred in 3 subjects in the lidocaine
group and 2 in the placebo gel group. Lidocaine did not effect the
quality of the films
[34]
. Life-threatening events have been reported during improper use,
including application to a large area and covering the skin with a
wrap, of topical anesthetics
[30]
.
5) Patch
a) The results of a double-blind, randomized, placebo-controlled
study involving 101 patients indicate that intraoral 10% (23 mg) and
20% (46 mg) lidocaine patches are safe and more effective than
placebo for reducing needle insertion pain in the maxillary and
mandibular premolar mucosa of adults. Onset of analgesia was
evident within 2.5 to 5 minutes after placement in the mandibular
arch and within 5 minutes after placement in the maxillary arch.
Maximum analgesic effects occurred between 5 and 15 minutes
after placement of the lidocaine patch. Analgesic effects were
evident 30 minutes after patch removal. Analgesia was dose related
with the 20% patch producing analgesia that was more profound
and of longer duration than the 10% patch. Systemic blood levels of
lidocaine following application of the patches were lower (16 to 22
nanograms/milliliter (ng/mL)) than levels reported following
infiltration injection of a single cartridge of 2% lidocaine with
1:100,000 epinephrine (average 220 ng/mL). There were no
differences in the incidence of adverse effects between the lidocaine
and placebo patches
[22]
.
6) Solution
a) The use of topical anesthetic solutions containing tetracaine,
adrenaline, and cocaine (TAC or TEC), lidocaine and adrenaline
(LE), or tetracaine, lidocaine, and adrenaline (TLE or LET) are
effective methods for providing local anesthesia when treating minor
lacerations. These solutions should not be used on mucous
membranes, large abrasions, digits, pinna of the ear, penis, over
burned or denuded areas, or in other conditions which would
increase the potential for systemic adverse effects
[23]
[24]
[25]
[26]
[27]
.
7) Tape
a) A self-adhesive lidocaine tape available in Japan (Penles(R))
provided relief of pain associated with needle insertion for stellate
ganglion block in a crossover study (n=30). Chronic pain patients
received each of the following in random order, as pretreatment for
a series of stellate ganglion blocks: placebo tape, lidocaine tape (18
mg in a controlled-release polymer matrix) administered for 7
minutes, 15 minutes, 30 minutes, and 60 minutes prior to needle
insertion. Visual analog and verbal rating scores for pain were
significantly reduced with lidocaine tape for all time durations as
compared with placebo. Transient skin erythema occurred more
frequently with lidocaine tape (50% with 7 minutes contact, up to
83% with 30 minutes contact)
[29]
.
b) In a placebo-controlled study (n=90), a 60% lidocaine tape
(Penles(R), Japan) successfully decreased the pain associated with
propofol injection when applied for 120 minutes. Pain reduction was
statistically similar to that achieved by mixing lidocaine 40 mg with
propofol for IV injection
[35]
.
d) Pediatric:
1) Gel/Solution
a) General Information
1) The use of topical anesthetic solutions and gels containing
tetracaine, epinephrine (adrenaline), and cocaine (TEC or TAC) or
tetracaine, lidocaine, and epinephrine (TLE or LET) are effective for
topical anesthesia for the repair (suturing) of minor dermal
lacerations of the face and scalp in children
[36]
[37]
[38]
. However, application of topical aqueous 1% lidocaine alone, when
placed on a laceration for 10 minutes, does not decrease pain from
the subsequent lidocaine injection in children with simple lacerations
[39]
.
b) Topical anesthetic solutions or gels containing lidocaine (4%),
epinephrine (0.1%), and tetracaine (0.5%) (LET) are equally
effective for providing local anesthesia during suturing of
uncomplicated lacerations of the face and scalp in children. The gel
may be preferred because it is easier to apply and it tends to remain
where it is placed, therefore it has less potential to drain out of the
laceration and onto mucous membranes and ocular surfaces
[36]
.
c) The combination solution of lidocaine, epinephrine, and
tetracaine (LET) is as effective as the combination of tetracaine,
epinephrine, and cocaine (TEC) for topical anesthesia during
suturing of uncomplicated lacerations on the face and scalp in
children. A double-blind, randomized, controlled study involving 171
children with lacerations on the face and scalp requiring suturing
found that LET is an effective alternative to TEC in children. There
was no difference between LET and TEC in adequacy of anesthesia
or duration of anesthesia before or during suturing
[38]
.
Postherpetic neuralgia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes (topical patch formulation only); Pediatric,
no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine patch is safe and effective for the relief of pain associated
with post-herpetic neuralgia
[41]
[42]
[43]
[44]
.
Two separate double-blind crossover studies involving a total of 67
patients demonstrated the effectiveness of lidocaine patch 5% for
the treatment of pain associated with post-herpetic neuralgia
[40]
.
In a multicenter, randomized, open-label trial, combination therapy
with pregabalin and lidocaine 5% medicated plaster improved
numeric rating scale (NRS-3) pain scores in patients with diabetic
polyneuropathy or post herpetic neuralgia who had an
unsatisfactory response after 4 weeks of monotherapy
[18]
.
c) Adult:
1) General Information
a) Topically applied 5% lidocaine in the form of a nonwoven
polyethylene adhesive patch is effective for relieving the pain
associated with post-herpetic neuralgia. The topical lidocaine
patches have been well tolerated without systemic adverse effects
[41]
[42]
[43]
[44]
. The authors of a review article list the lidocaine patch as 1 of 3
first-line options (along with tricyclic antidepressants and
gabapentin) for treatment of post-herpetic neuralgia. The lidocaine
patch may be preferred in cases with marked allodynia
[41]
.
2) Clinical Trials
a) Two separate double-blind crossover studies involving a total of
67 patients demonstrated the effectiveness of lidocaine patch 5%
for the treatment of pain associated with post-herpetic neuralgia.
From 4 to 12 hours, pain intensity and pain relief scores were
statistically better with lidocaine patch compared with a vehicle
patch. Additionally, time to exit from the trial comparing lidocaine
patch with observation was statistically significant in favor of
lidocaine (14 vs 3.8 days; p less than 0.001). The differences in
daily average pain relief and patient's preference of treatment were
also significant
[40]
.
b) Results of a randomized, double-blind, vehicle-controlled
(placebo), 2-period crossover study indicate that topical 5%
lidocaine patches are effective for the treatment of post-herpetic
neuralgia (PHN). In this study, patients (n=32) applied either a
lidocaine or vehicle (placebo) patch to the PHN region. Most
patients applied 3 patches daily for a maximum coverage of 420
cm(2). The duration of each treatment period was variable, between
2 and 14 days, depending on the patient's pain response in each
treatment period. Patients exited either treatment phase if their pain
relief score decreased 2 or more categories for any 2 consecutive
days. The median time to exit for the lidocaine patch period was
greater than 14 days compared with 3.8 days for the vehicle patch
(p less than 0.001). At the end of the study (28 days maximum),
78.1% (25 of 32) of patients preferred the lidocaine patch compared
with 9.4% (3 of 32) for the placebo patch (p less than 0.001). There
were no significant differences between the lidocaine and vehicle
patches with regards to adverse effects
[43]
.
c) In a randomized, double-blind, vehicle-controlled study involving
35 patients with post-herpetic neuralgia, 5% lidocaine patches
applied to the area of greatest pain, covering a maximum of 420
cm(2), was more effective than no treatment and patches containing
vehicle only. Minimal systemic absorption of lidocaine was reported.
The highest blood lidocaine level measured was 0.1 mcg/mL. The
5% lidocaine patches were effective and well tolerated, without
systemic adverse effects
[44]
.
3) Combination Therapy
a) In a multicenter, randomized, open-label trial, combination
therapy with pregabalin and lidocaine 5% medicated plaster
improved numeric rating scale (NRS-3) pain scores in patients with
diabetic polyneuropathy (DPN) or post herpetic neuralgia (PHN)
who had an unsatisfactory response after 4 weeks of monotherapy.
In the 4-week comparative phase, patients with DPN (distal,
symmetrical sensorimotor polyneuropathy of the lower extremities
for at least 3 months) or PHN (neuropathic pain for at least 3
months following healing of herpes zoster skin rash) were
randomized 1:1 to receive either pregabalin (150 mg daily for 1
week, then 300 mg daily for 1 week, and then up to 600 mg daily if
needed) or lidocaine 5% medicated plaster (up to 3 plasters (PHN)
or up to 4 plasters (DPN) for up to 12 hours during each 24-hour
period). The 8-week combination phase followed, and patients were
randomized according to their response at the end of the 4 weeks of
monotherapy. Patients with an average NRS-3 score below 4 on the
11-point scale for the previous 3 days continued with either
lidocaine (n=71; mean age, 61.6 +/- 9.9 years; mean NRS-3 score,
2.7 +/- 1.2 points) or pregabalin (n=57; mean age, 61 +/- 8.9 years;
mean NRS-3 score, 2.8 +/- 1.2 points) and patients with an average
NRS-3 score above 4 for the previous 3 days (unsatisfactory
response) received combination therapy; lidocaine patients received
pregabalin (n=57; mean age, 63 +/- 11.5 years; mean NRS-3 score,
6.1 +/- 1 points) and pregabalin patients received lidocaine (n=44;
mean age, 61.5 +/- 10.5; mean NRS-3 score, 5.8 +/- 0.8 points).
Concomitant use of other drugs or therapies for neuropathic pain
was not permitted. After 8 weeks, all 4 groups experienced a
reduction in mean NRS-3 scores (primary endpoint) compared with
baseline (lidocaine, -0.7 +/- 1.2 points; pregabalin, -0.6 +/- 1.3
points; lidocaine plus pregabalin, -2.5 +/- 1.6 points; pregabalin plus
lidocaine, -1.7 +/- 1.8 points). Additionally, the percentage of
patients that scored much and very much improved on the Patient
and Clinical Global Impression of Change scale was increased in all
4 groups; including the lidocaine plus pregabalin group (baseline,
15.8% and 17.6%; after addition of pregabalin for 8 weeks, 64.9%
and 66.6%, respectively) and in the pregabalin plus lidocaine group
(baseline, 25% and 31.8%; after addition of lidocaine for 8 weeks,
65.1% and 62.8%). Drug-related adverse events occurred more
frequently in the lidocaine plus pregabalin group compared with the
lidocaine, pregabalin, and pregabalin plus lidocaine groups (26.7%
vs 5.1%, 7.9%, and 6.3%, respectively)
[18]
.
Lidocaine Hydrochloride
Adverse reaction to drug - Ventricular tachycardia
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective for drug-induced ventricular tachyarrhythmias
c) Adult:
1) The efficacy of LIDOCAINE in the treatment of new sustained
ventricular tachycardia secondary to FLECAINIDE therapy in a 69year-old black male has been reported
[153]
. The patient had received FLECAINIDE in doses of 100 milligrams
orally twice daily. Following 3 doses of FLECAINIDE, a sustained
wide QRS tachycardia was observed resulting in nausea and
dizziness; the tachycardia was different than any observed
previously, and was much faster in rate. FLECAINIDE was
discontinued and LIDOCAINE was administered (75 mg IV bolus
followed by 50 mg IV in 10 minutes, then a continuous IV infusion of
2 mg/minute); the new arrhythmia abated 8 minutes following the
second IV bolus of LIDOCAINE and the infusion was given for 24
hours and then discontinued. The arrhythmia recurred in 20 hours,
and again resolving following LIDOCAINE administration. The
patient was eventually treated with AMIODARONE without
recurrence of tachycardia. More studies are required to fully
evaluate the efficacy of LIDOCAINE for the treatment of
FLECAINIDE-induced arrhythmias.
Aortocoronary bypass grafting
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
May prevent ischemic changes in the myocardium during
aortocoronary bypass surgery
Decreased incidence of reperfusion ventricular fibrillation in a
placebo-controlled trial
c) Adult:
1) LIDOCAINE by IV infusion (1 mg/minute) was reported beneficial
in aortocoronary bypass surgery to prevent ischemic changes in the
myocardium. The drug was started prior to anesthesia and
continued throughout surgery and 24-hour post-operatively
[135]
.
2) When administered as a 100-milligram bolus via bypass pump
two minutes prior to aortic cross-clamp release, lidocaine effectively
reduced the rate of reperfusion ventricular fibrillation (VF) in patients
undergoing coronary artery bypass grafting. Of 17 subjects
randomized to lidocaine bolus, 2 (12%) developed VF (one resolved
spontaneously and the other remitted after a single countershock).
In contrast, VF occurred in 12 of 17 (71%) placebo recipients (p less
than 0.0005), necessitating single to multiple direct current
applications. Atrioventricular block was infrequent and transient. The
only significant difference in hemodynamic parameters was a
significantly higher mean cardiac output (6.4 liters/minute (L/min)) in
the lidocaine group compared to the placebo group (5.3 L/min, p
less than 0.05) 15 minutes after bypass weaning
[136]
.
Asthma
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class III; Pediatric, Class III
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
May reduce or eliminate use of oral glucocorticoid therapy in severe
chronic asthma
Aerosolized lidocaine produces rapid broncho- constriction, which
may be followed by broncho- dilation in some asthmatic patients
Both intravenous and inhaled lidocaine significantly and similarly
attenuate bronchial hyperreactivity, but at lower plasma levels
following inhalation
Nebulized lidocaine has generally been ineffective in preventing
airway constriction in patients with exercise-induced asthma and
may actually exacerbate the condition
According to a case report, epidural anesthesia with lidocaine may
improve bronchospasm in patients with bronchial asthma
c) Adult:
1) GENERAL
a) Studies have revealed that in contrast to a normal healthy adult,
in which aerosolized lidocaine produces little effect on pulmonary
function, some patients with reactive airway disease have displayed
a bimodal response. Initial bronchoconstriction followed by delayed
bronchodilation has been demonstrated in some individuals with
asthma following the inhalation of nebulized lidocaine
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
. The mechanism involved in the initial bronchoconstriction following
nebulized lidocaine is unknown. Aerosolized lidocaine may stimulate
and irritate receptors by exerting a nonspecific noxious stimulus,
which may result in bronchoconstriction, until these receptors are
anesthetized. Asthmatic patients also develop reflex mediated
coughing and bronchoconstriction in response to inhaled stimuli that
would generally not initiate a response in non-asthmatic subjects.
The hyperactivity of the airway may account for the initial
bronchoconstriction observed following the administration of
aerosolized lidocaine. Prophylactic aerosolized atropine or
isoproterenol may prevent or minimize the initial bronchoconstriction
produced by nebulized lidocaine. This finding also suggests that the
mechanism of aerosolized lidocaine-induced bronchoconstriction is
a reflex, mediated by the vagal nerve, and presumably initiated by
stimulation of receptors located in airway epithelium. Therefore, it is
not surprising that complete anesthesia of the airways, with the
interruption of the reflex arc, results in bronchodilation
[10]
[6]
[11]
[9]
[12]
. Biochemically, the bimodal response from aerosolized lidocaine is
thought to be due to the dose-dependent release of prostaglandins
and calcium. Low doses of lidocaine are theorized to displace
calcium from membranes to the interior of muscle cells causing the
activation of contractile proteins, while higher doses of lidocaine are
thought to bind cytoplasmic calcium, leading to myorelaxation
[7]
.
2) The results of a randomized, double-blind, placebo-controlled
study involving 15 patients with bronchial hyperreactivity indicate
that intravenous (IV) and inhalational administration of lidocaine
significantly and similarly attenuate reflex bronchoconstriction
following inhalational histamine challenge. Inhaled lidocaine
produced the same attenuation of bronchial hyperreactivity as IV
lidocaine, but at significantly lower plasma concentrations. However,
inhaled lidocaine produces an initial decrease in FEV-1. On
separate days, patients received inhaled lidocaine (5
milligrams/kilogram (mg/kg) in saline), IV lidocaine (1.5 mg/kg over
20 minutes then a constant dose of 3 mg/kg/hour), or IV saline. Both
inhalational and IV administration of lidocaine doubled the histamine
threshold (p=0.0007). Peak lidocaine plasma concentrations
following IV and inhalational administration were 2.4 mcg/mL and
1.5 mcg/mL, respectively (p=0.0229)
[13]
.
3) In a case report involving a surgical patient with bronchial
asthma, active wheezing gradually diminished 20 minutes after an
epidural injection of 13 mL 2% lidocaine and completely
disappeared over 155 minutes during a continuous epidural infusion
of 2% lidocaine (6 mL/hour). The lidocaine plasma concentration
during epidural anesthesia ranged from 2.5 to 3.9 mcg/mL.
Postoperatively, wheezing reoccurred 55 minutes after
discontinuation of the continuous epidural infusion. The plasma
concentration of lidocaine at this time was 1.9 mcg/mL
[137]
.
4) Nebulized lidocaine may be a useful therapy for patients with
severe, glucocorticoid-dependent chronic asthma, permitting a
reduction or elimination of oral glucocorticoid therapy. In an open
study involving 20 patients with glucocorticoid-dependent asthma,
patients received nebulized lidocaine 40 to 160 milligrams 4 times
daily (2% or 4% solution). During a mean of 12 months of treatment,
17 of 20 patients were able to reduce the amount of glucocorticoid
needed by 80% to 100% of their initial maintenance dosage; 13
patients were able to discontinue oral use of glucocorticoids
completely, 4 patients reduced their daily glucocorticoid
requirements, and 3 patients did not respond to treatment with
lidocaine. No measurable serum lidocaine levels were found in any
patient within 15 minutes after nebulized lidocaine treatment
[14]
.
5) LIDOCAINE inhalation has been reported to have no effect on the
obstructive or ventilatory response to exercise in asthmatics
[2]
[4]
[3]
. However, 1 study reported that aerosolized lidocaine 1
milligram/kilogram was effective in blocking exercise-induced
bronchoconstriction in 10 asthmatic patients
[5]
.
d) Pediatric:
1) Nebulized lidocaine may be effective in pediatric patients with
severe, glucocorticoid-dependent asthma, permitting elimination of
oral glucocorticoid therapy and reducing hospitalizations. In this
open, uncontrolled, pilot study, 6 pediatric patients (mean age 11
years; range 8 to 14 years) with severe, glucocorticoid-dependent
asthma received nebulized lidocaine 0.8 to 2.5 milligrams
(mg)/kilogram/dose (40 to 100 mg) 3 or 4 times daily. Patients
continued all other medications while receiving lidocaine. During a
mean of 11.2 months (range 7 to 16 months) of therapy, 5 of 6
patients completely discontinued the use of oral glucocorticoids
within an average time of 3.4 months (range 1 to 7 months). In
addition, fewer hospitalizations occurred during nebulized lidocaine
therapy. One patient did not improve with nebulized lidocaine and
discontinued it after 7 months. Bitter taste and transient
oropharyngeal anesthesia were the only adverse effects reported
during nebulized lidocaine therapy
[15]
.
Barotrauma of ascent
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Intravenously may be useful as adjunctive therapy for
decompression illness
c) Adult:
1) Two cases have demonstrated the usefulness of intravenous
lidocaine as adjunctive therapy in the treatment of decompression
illness. In 1 case improvement occurred only after lidocaine 1
milligram/kilogram bolus followed by continuous infusion at 2
mg/min was added to standard treatment. In the second case, a
patient presented with 0/5 motor strength bilaterally in the legs,
sensory deficits from approximately T10 distally, and neurogenic
bladder 36 hours after sustaining neurologic deficits. Although poor
outcomes are associated with delayed presentations, lidocaine
therapy was initiated as previously described with infusion
continuing over the first 24 hours. Clinical improvement occurred
shortly after the treatment began
[151]
. In related reports, lidocaine has been shown to reduce intracranial
hypertension associated with arterial gas embolism (Evans &
Kobrine, 1987), preserve nerve conduction in isolated nerves (Fink,
1982), and have a membrane-stabilizing effect.
Bone metastasis - Pain from metastases
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Injection directly into metastatic bone lesions may give prompt relief
for 24 to 72 hours
c) Adult:
1) Intractable bone pain secondary to bone metastases from cancer
may be temporarily relieved by LIDOCAINE injections. An injection
of 2% LIDOCAINE directly into the metastatic bone lesion will give
prompt relief to some patients. Patients who respond to the
LIDOCAINE injection will obtain prolonged pain relief, lasting from
24 to 72 hours, when again injected with a mixture of 2%
LIDOCAINE and PENICILLIN G PROCAINE, 600,000 units/mL. The
rationale for this combination is that the LIDOCAINE will be
adsorbed onto the surface of the insoluble PROCAINE PENICILLIN
and be slowly released as the PROCAINE PENICILLIN is
solubilized or cleaved. The patient will then experience sustained
pain relief. Lesions of the spine should not be treated in this way
[138]
.
Burn
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Effective
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective for partial-thickness burns
c) Adult:
1) Topical LIDOCAINE (1 milligram/square centimeter of a 5%
cream) was reported effective in the treatment of partial-thickness
burns (total body surface area (TBSA) 5 to 28%) in an open study
involving 30 patients
[16]
. No allergic, infectious or cardiovascular complications were
observed as a result of topical LIDOCAINE. Plasma concentrations
remained fairly constant during the first 4 hours post-application
(mean levels, 2.7 mcg/mL). Burn wounds up to 28% TBSA treated
with 4.5 grams LIDOCAINE did not result in systemic toxicity
(plasma level, 5.8 mcg/mL). A controlled study is required to further
evaluate the efficacy of topical LIDOCAINE in partial-thickness
burns.
Cataract surgery - Topical local anesthetic
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Topically applied lidocaine provides effective anesthesia for cataract
surgery
c) Adult:
1) GENERAL INFORMATION
a) Topical anesthesia with lidocaine 4% drops or lidocaine 2% gel
provides effective anesthesia for cataract surgery
[139]
[140]
[141]
. Topically applied lidocaine 4% drops appears to be an effective
alternative to peribulbar or retrobulbar anesthesia in
phacoemulsification and intraocular lens implantation
[142]
. Use of intracameral lidocaine 1% to 2% as a supplement to topical
anesthesia for small incision cataract surgery does not appear to
affect intraoperative or postoperative pain scores or reduce
photophobia
[143]
[144]
. Intracameral lidocaine 1% along with topical anesthesia may be an
alternative to peribulbar anesthesia in cataract surgery
[145]
.
2) TOPICAL
a) Topically applied lidocaine 2% gel provides effective anesthesia
for cataract surgery (extracapsular cataract extraction and
phacoemulsification). Lidocaine 2% gel appears to be comparable
to other modes of topical anesthesia for cataract surgery. The best
results occur when the gel is applied 3 to 5 times during the 15 to 20
minutes prior to surgery
[139]
[140]
.
b) Topically applied lidocaine 4% drops provides adequate
analgesia for cataract surgery. In this study, 30 patients undergoing
surgery for cataracts by phacoemulsification received (in both eyes)
either 2 drops (100 microliters) 3 times during the 30 minutes prior
to surgery or 2 drops 6 times in the 60 minutes prior to surgery. The
lidocaine 4% was a preservative-free, single-dose preparation. After
3 and 6 instillations, mean aqueous humor lidocaine levels were
8.68 mcg/mL and 23.21 mcg/mL, respectively. Intraocular levels
below 12 mcg/mL were associated with more pain during surgery.
Blood levels of lidocaine were negligible. The authors recommend 6
instillations (2 drops in each eye) in the hour preceding surgery
[141]
.
c) Topical anesthesia with lidocaine 4% drops is a safe and effective
alternative to peribulbar or retrobulbar anesthesia in
phacoemulsification and intraocular lens implantation combined with
pars plana vitrectomy. In this prospective study performed in 45
patients (45 eyes) the mean amount of lidocaine 4% drops required
during each procedure was 0.5 milliliter. Patients received 1 drop 15
minutes before surgery, 1 drop at the beginning of the procedure,
and 1 drop every 30 minutes during the procedure. No patients
required additional anesthesia or experienced pain postoperatively
[142]
.
3) INTRACAMERAL
a) Intracameral lidocaine 1% combined with topical anesthesia may
be an alternative to peribulbar anesthesia in cataract surgery. In this
prospective study, cataract patients (n=200) randomly received
either 0.15 mL intracameral 1% unpreserved lidocaine along with
topical anesthesia (oxybuprocaine) or 6 mL prilocaine peribulbar
prior to phacoemulsification with sclerocorneal tunnel incision.
Patients receiving intracameral lidocaine reported more
intraoperative pain during cautery than patients given peribulbar
anesthesia (p=0.01). However, during the other steps of surgery
there was no significant difference in pain between the two methods
of anesthesia. Surgery was significantly faster with peribulbar
anesthesia than with lidocaine anesthesia (p=0.0001). Squeezing
and eye movement occurred significantly less frequently with
peribulbar anesthesia (p=0.01). The motion of instruments could be
recognized significantly more often with lidocaine (p=0.01).
Significantly more patients experienced postoperative pain in the
first 2 hours after surgery with intracameral lidocaine than with
peribulbar anesthesia (p=0.0017), but after 4 and 6 hours there was
no significant difference. When patients who received peribulbar
anesthesia in their first eye and intracameral lidocaine in their
second eye were asked which method of anesthesia they prefer,
there was no statistically significant preference for either method
[145]
.
Cervical sympathetic block
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Produces effective cervical nerve block
c) Adult:
1) GENERAL INFORMATION
a) LIDOCAINE is frequently used for infiltration, regional, nerve
block, spinal anesthesia, as well as for topical anesthesia.
LIDOCAINE has a more rapid onset of action than PROCAINE and
longer duration of action; the drug is also more potent (Prod Info
Xylocaine(R), 2000)
[66]
. For surgical procedures of 1 to 2 hours duration, LIDOCAINE (or
MEPIVACAINE or PRILOCAINE) is generally used for epidural
anesthesia, whereas BUPIVACAINE or ETIDOCAINE are preferred
for longer procedures. Similarly, during spinal anesthesia
LIDOCAINE provides a short duration of anesthesia as compared to
that of BUPIVACAINE, AMETHOCAINE, and CINCHOCAINE
[67]
.
Complex regional pain syndrome
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine reduces pain and other symptoms associated with
complex regional pain syndrome types I and/or II, also known as
REFLEX SYMPATHETIC DYSTROPHY and CAUSALGIA,
respectively
c) Adult:
1) Results of a 4- to 8-week pilot study indicate that subcutaneous
infusions of 10% lidocaine reduces pain and other symptoms (eg,
dysesthesia, allodynia, hyperpathia, decreased range of motion of
involved extremities) associated with complex regional pain
syndrome (CRPS) types I and/or II in patients with chronic long-term
(30 to 96 months) CRPS resistant to prior treatments. During the
inpatient phase, patients (n=5) received a continuous infusion at an
initial rate of 200 milligrams (mg)/hour (hr) for the first hour and
subsequent final infusion rates were 100 to 190 mg/hr (average 150
mg/hr) depending on tolerance. Patients remained on the
continuous infusion 4 to 5 days after maximum pain relief was
achieved. Serum lidocaine levels were 0.09 to 8.06 mcg/mL
(average 3.7 mcg/mL). The average effective serum lidocaine level
was 3.69 mcg/mL. During the outpatient phase of the study, if pain
returned, infusions were given via an ambulatory infusion pump at a
rate equal to the rate the patient tolerated with maximum benefits
and minimal adverse effects during the continuous infusion phase.
Maintenance infusions were continued for 12 to 24 hours after
maximum pain relief was achieved. All patients experienced a
significant reduction in pain (p less than 0.0005) and all symptoms
improved or completely resolved following treatment. In addition, all
patients demonstrated increased daily activity, less depression, and
less use of pain medications. After discontinuation of the infusion,
patients appear to maintain the pain relief. Lidocaine infusions
appear equally effective in patients who have symptoms in one or
multiple areas of their bodies. Periodic maintenance infusions may
become less frequent and the length of subsequent maintenance
infusions may be reduced over time
[146]
. Further studies are warranted.
Complication of infusion - Pain
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Reduces drug-related pain on injection
c) Adult:
1) There is no clinical documentation regarding the use of an
analgesic (ie, lidocaine) in large volume parenterals containing
potassium supplements. However, the addition of lidocaine in
concentrations of 0.1% to 1% to methohexital and propofol has
been shown to reduce the incidence of pain and discomfort
associated with the injection of either agent
[163]
[164]
[165]
[166]
. A low dose continuous infusion of lidocaine has been shown to
decrease the severity of postoperative pain and was not associated
with adverse effects
[118]
.
2) Epidural and intravenous (IV) lidocaine are equally effective at
reducing the severity of pain associated with injection of propofol. In
this prospective, double-blind study, 120 female patients undergoing
gynecological laparotomy were randomized into one of three
groups. Patients in group C were given epidural normal saline (NS)
(0.08 milliliter/centimeter body height (mL/cm)) followed 12 minutes
(min) later by IV NS (0.05 mL/kg) then 3 min later IV propofol (2.5
milligrams/kilogram; rate of injection 3 mg/kg/min) through the same
vein used for injection of NS. Patients in group E were given
epidural 2% lidocaine (0.08mL/cm) followed 12 min later by IV NS
then 3 min later IV propofol (similar dose used in group C) through
the same vein as NS. Patients in group V were given epidural NS
(0.08mL/cm) followed 12 min later by IV 2% lidocaine (0.05 mL/kg)
then 3 min later IV propofol (similar dose used in group C) through
the same vein as lidocaine. The median pain scores in groups E
and V were significantly lower than that in group C (p less than
0.001). There was no difference in the pain scores between groups
E and V. Of note, peak plasma lidocaine levels were significantly
lower after IV injection (group V) than after epidural injection (group
E) (1.58 mcg/mL vs 2.73 mcg/mL, respectively; p less than 0.001),
yet there was no significant difference in pain scores between the 2
groups
[167]
.
3) Mixing propofol with 0.1% lidocaine significantly reduces the
incidence and intensity of pain on injection of propofol. In this
prospective, randomized, double-blind study, female patients
(n=240) undergoing dilation and curettage received propofol 18
milliliters (mL) (10 milligrams/mL) containing either normal saline
(Group A; control), 0.05% lidocaine (Group B), 0.1% lidocaine
(Group C), or 0.2% lidocaine (Group D). Each mixture was injected
at a rate of 2 mL every 5 seconds. The incidence of pain on injection
was significantly lower in Groups C and D (8.3% and 10%,
respectively) compared with either Group A (91.7%) or B (76.7%) (p
less than 0.001). The incidence of recall of pain on injection was
significantly lower in Groups C (6.7%) and D (6.7%) as compared
with Groups A (71.7%) or B (55%) (p less than 0.001). No significant
difference was seen between Groups C and D and between Groups
A and B regarding the incidence of pain on injection or the incidence
of recall of pain on injection. In this study, increasing the
concentration of lidocaine above 0.1% did not further reduce
injection pain. Although 0.1% lidocaine is an effective concentration
for reducing injection pain caused by propofol, the optimal
concentration of lidocaine may vary depending on numerous factors
such as premedication, site and rate of injection, and pH and
temperature of propofol
[163]
.
4) The addition of lidocaine may significantly reduce propofol-related
pain on injection, due to a pH-lowering effect. A controlled study
enrolled 44 patients undergoing elective surgery to determine
whether the pain relief was caused by a local anesthetic effect or pH
change. Subjects received two of the following three mixtures via
intravenous cannula, one in each hand: propofol 1% combined in a
10 to 1 ratio with either saline, lidocaine 1%, or hydrochloric acid
0.0064 mole/liter begin_of_the_skype_highlighting
0064
mole/liter FREE end_of_the_skype_highlighting. Ratings for pain
on injection did not differ between the lidocaine and hydrochloric
acid mixtures; however, both were significantly improved over the
saline combination. The pH of the lidocaine/propofol solution was
6.32 (lower than either of the 2 ingredients separately: 8 for propofol
and 6.75 for lidocaine), which was comparable to the
propofol/hydrochloric acid solution. The investigators noted that the
lower pH drives propofol from the aqueous to the lipid phase of its
emulsion, which decreases pain on injection
[164]
.
5) Results of a prospective, randomized, double-blind study
involving 40 patients undergoing day surgery indicate that
iontophoretically applied lidocaine significantly reduces pain
associated with cannulation and injection of propofol. In the
iontophoresis group, the negative electrode containing 4% lidocaine
1.5 mL in a hydrogel was placed on the dorsum of the hand over the
site for cannulation. The control group was treated similarly, except
no current was passed through the electrodes. Pain of cannulation
was significantly reduced in the iontophoresis group compared with
the control group (p less than 0.005). The frequency and severity of
pain after propofol injection was significantly reduced in the
iontophoresis group at 10 seconds (s) (p less than 0.002), 20 s (p
less than 0.001), and 30 s (p less than 0.001) compared with the
control group. In the control group, 50% of patients experienced
moderate to severe pain after propofol injection. In the iontophoresis
group, 75% of patients experienced no pain and 25% only mild pain
after propofol injection. The only adverse effect was erythema at the
site of the negative electrode
[168]
.
6) Iontophoretically applied lidocaine does not reduce the pain
associated with intravenous (IV) propofol administration to the same
extent as IV lidocaine. This study was a double-blind, prospective,
randomized trial (n=60; mean age, 36.9 years; range 18 to 71
years) comparing active iontophoresis of 1.5 milliliters (mL)
lidocaine 4% followed by propofol containing 2 mL sterile saline and
sham iontophoresis followed by administration of propofol
containing 2 mL lidocaine 2%. Patients were asked to record their
pain on a 100 mm visual analog score (VAS) 10 minutes after the
administration of propofol. They were also asked to rank their pain
on a four point scale (none, mild, moderate, severe). The incidence
of moderate or severe pain, as assessed by categorical pain scores
was significantly (p less than 0.05) higher in the iontophoresis group
(8 of 30 patients had moderate or severe pain vs. 2 of 30 in the IV
lidocaine group). Pain measured by VAS following venous
cannulation was significantly (p less than 0.05) less in the
iontophoresis group
[169]
.
Cough
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Inhalation effective for cough suppression in patients with intractable
cough
Intravenously suppresses cough reflex during cataract surgery
Intravenously prevents cough and laryngospasm prior to extubation
c) Adult:
1) INHALATION
a) Use of nebulized lidocaine, preceded by use of a bronchodilator
(eg, nebulized albuterol), is effective for suppressing cough in
patients with intractable cough severe enough to affect the patient's
quality of life. Nebulized lidocaine has been successfully used to
suppress cough in patients with asthma, reactive airways disease,
and chronic obstructive pulmonary disease (COPD). Initially, 1
milliliter (mL) of a 1% solution diluted in 4 mL of saline to give a
0.25% solution is administered along with oxygen 4 to 6 L/min until
nebulization is completed. This dose may be repeated every 4 to 6
hours or increased to 2 mL of a 1% solution every 4 hours (more
concentrated solutions of up 4% may be used if necessary). This
dosage gives the equivalent of 10 to 20 milligrams (mg) of lidocaine
every 4 to 6 hours or 40 to 120 mg daily. It has been recommended
that all patients, whether asthmatic or not, should be administered a
nebulized bronchodilator prior to use of lidocaine in order to prevent
lidocaine-induced bronchospasm. Short-term use of nebulized
lidocaine produces almost instantaneous relief of cough which
allows sufficient time for more definitive therapies (eg,
corticosteroids) to take effect. In general, nebulized lidocaine in
varying concentrations from 1% to 4% has been well tolerated
[147]
. Additional studies are required in order to clearly establish safety
and efficacy.
b) Prolonged suppression of cough was achieved with inhalation of
nebulized LIDOCAINE in a 34-year-old male with PULMONARY
SARCOID
[148]
. Ten mL of 4% LIDOCAINE was given in a nebulizer (Devilbiss
646(R)) powered by compressed oxygen at the rate of 6
liters/minute. The patient was unresponsive to codeine.
2) TOPICAL
a) Topical lidocaine spray followed by thiopentone produced better
conditions for insertion of a laryngeal mask when compared to
lidocaine and thiopentone intravenous administration
[28]
. This was a randomized, single-blind study of 90 unpremedicated
adult patients who were given lidocaine 0.5 mg/kg IV (group 1),
lidocaine 1.5 mg/kg IV (group 2) or 40 mg of topical lidocaine spray
to the posterior pharyngeal (group 3) prior to fentanyl 1 mcg/kg and
thiopentone 5 mg/kg. Topical lidocaine group coughed or gagged
less often and had a lower incidence of laryngospasm.
3) INTRAVENOUS
a) One study reported benefits of LIDOCAINE intravenously in
suppressing the cough reflex during cataract surgery
[149]
. Effective doses were 1 to 2 milligrams/kilogram, producing cough
suppression within 1 minute. The authors suggest intravenous
LIDOCAINE for intraocular procedures for the treatment of coughing
episodes.
b) One study reported that intravenous LIDOCAINE (2 mg/kg of a
2% solution) was effective in preventing coughing and
LARYNGOSPASM when administered prior to extubation in the
recovery period following general anesthesia
[150]
.
Diabetic neuropathy
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Intravenously reduces painful symptoms of diabetic neuropathy
[152]
c) Adult:
1) Intravenous LIDOCAINE infusions were reported effective in
reducing painful symptoms of diabetic NEUROPATHY in one report
[152]
. Patients received LIDOCAINE by IV infusion in doses of 5 mg/kg
over 30 minutes during continuous EKG monitoring.
Elective abortion
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine 1% induces permanent fetal cardiac asystole in late-term
(20 to 36 gestational weeks) abortion
c) Adult:
1) Lidocaine is an effective agent for late-term termination of
pregnancy with low risk to the mother. Fifty patients undergoing
termination of pregnancy between 20 and 36 weeks of gestation for
severe fetal abnormalities or severe maternal conditions were given
600 milligrams (mg) of mifepristone followed by 5 micrograms of
sufentanil and 7 to 30 milliliters of 1% lidocaine by umbilical vein
puncture 48 hours later. The lethal dose of lidocaine to the fetus,
approximately 100 mg/kilogram (kg), remains within the safe dose
range (2.8 to 4.2 mg/kg) for the mother in the event of accidental
injection into maternal circulation. Permanent fetal cardiac asystole
was achieved in 46/50 (92%) of the cases with no maternal side
effects
[133]
.
Fibromyalgia
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Pain and psychosocial measures improved significantly after
treatment with intravenous lidocaine in a retrospective, uncontrolled
study
c) Adult:
1) Intravenous lidocaine therapy improved pain and a range of
psychosocial measures significantly in a retrospective study of 50
patients responding to a questionnaire (91% response rate). Serial
infusions of lidocaine were given over 6 consecutive days. Infusions
were started at 5 milligrams (mg)/kilogram (kg) minus 100 mg and
increased by 50 mg/day to 5 mg/kg plus 150 mg with a maximum
infusion of 550 mg infused over 6 hours in 500 milliliters of
Hartman's solution. Pain was rated as a 9 on a 0 to 10 scale before
treatment, and a 5 afterwards (p less than 0.001). Except for
patient's ability to work, all psychosocial parameters measured,
including depression, hours/day in pain, sleep, dependency, social
and sex life, significantly improved (p less than 0.001). Two major
(pulmonary edema and supraventricular tachycardia), and 42 minor
side effects, the most common being hypotension (17/106) were
reported in a related prospective study. Randomized control trials
are needed to confirm the results
[155]
.
Headache
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Intranasal lidocaine appears to be effective in the treatment of
migraine headache; however, contrasting data exist
Can provide complete or partial relief of headache and related
symptoms within 5 minutes
May be more effective for unilateral, as opposed to bilateral,
headaches
c) Adult:
1) In contrast with previous studies, a randomized, double-blind,
placebo-controlled study in an emergency department setting found
intranasal lidocaine to be ineffective for providing immediate relief of
migraine headache pain. In this study, patients with a diagnosis of
migraine were given 1 milliliter of 4% lidocaine (n=27) or normal
saline (n=22) intranasally in split doses 2 minutes apart and
intravenous prochlorperazine 10 milligrams. There was no
significant difference between the two groups in the proportion of
patients experiencing pain relief at various times up to 30 minutes
after the initial dose. Approximately 7% of patients given lidocaine
and 14% of patients given saline reported successful pain reduction
at 5 minutes (p=NS). No adverse effects attributable to intranasal
lidocaine were reported. The authors report that patients in this
study had higher initial pain scores than patients in previous studies
and that it may be that patients with more severe pain are less likely
to respond to treatment
[156]
.
2) The results of a prospective, randomized, double-blind, placebocontrolled study indicate that intranasal lidocaine 0.5 mL of a 4%
solution is effective in the treatment of MIGRAINE HEADACHE. In
this study 29 of 53 patients (55%) receiving intranasal lidocaine had
at least a 50% reduction of headache compared with 6 of 28
patients (21%) receiving placebo. Complete or nearly complete
relief of headache was reported in 21% of patients receiving
lidocaine and in 7% of patients receiving placebo. Following
intranasal lidocaine, relief of headache pain, nausea, and
photophobia occurred within 5 minutes. Additional headache relief
medications were required in 28% of patients receiving lidocaine
compared with 71% of patients receiving placebo. Among patients
with initial relief of headache, relapse of headache occurred in 42%
of patients receiving lidocaine compared with 83% of patients
receiving placebo. Relapse typically occurred within the first hour
after treatment. No headache characteristics predictive of a
response to intranasal lidocaine were identified
[157]
.
3) In an open study involving 23 patients with migraine headache,
intranasal treatment with 0.4 mL of lidocaine 4% resulted in
complete or almost complete relief of moderate or severe acute
migraine attacks in 12 of the 23 patients. Pain relief was achieved
within 5 minutes in 8 of the 12 successfully treated patients. In no
case did an aborted attack return to more than a dull level within 24
hours. Nausea was relieved in 5 of the 6 successfully treated
patients who experienced this symptom. Intranasal lidocaine was
significantly more effective in patients treated for unilateral, as
opposed to bilateral, headaches. Adverse effects included bitter
taste, mild nasal and eye irritation of short duration (seconds), and
oropharyngeal numbness lasting approximately 20 minutes
[158]
.
Hiccoughs, Intractable
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Intravenous and nebulized lidocaine may be an effective treatment
for relief of intractable hiccups
c) Adult:
1) Intravenous lidocaine may be an effective treatment for chronic,
intractable hiccups. In 1 case report, a 47-year-old patient who had
a history of recurrent bouts of hiccups developed hiccups
(approximately every 10 seconds) following an exploratory
laparotomy. An intravenous infusion of lidocaine (100 milligrams
(mg)) was administered over 5 minutes, and the hiccups resolved
within a few minutes. The patient remained hiccup-free for 8 hours.
On postoperative day 2 the hiccups recurred. The patient received
50 mg of intravenous lidocaine and the hiccups again resolved. The
patient remained hiccup-free until discharge. The authors suggest
that the membrane-stabilizing effect of lidocaine may have played a
role in the cessation of hiccups
[161]
.
2) Nebulized lidocaine may be effective for relief of intractable
hiccups. According to 1 case report, nebulized lidocaine was
successfully used to treat a patient with a 5 month history of
intractable hiccups after previous therapies (eg, dilation of an
esophageal stricture, cisapride, chlorpromazine, compazine) had
failed. The patient was treated with 3 cubic centimeters of 4%
lidocaine nebulized in a standard small-particle nebulizer. The
patient used 1 treatment a day for 3 days with complete resolution
of hiccups. Three weeks after the last nebulized lidocaine treatment
hiccups recurred, but were less severe than before and again
responded to nebulized lidocaine. Short-term loss of the gag reflex
was the only adverse effect reported
[162]
.
Indigestion
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Combination antacid and viscous lidocaine is effective for dyspepsia
of unknown etiology
c) Adult:
1) One study reported that a single dose of antacid and viscous
LIDOCAINE provides a significantly greater degree of immediate
pain relief than antacid alone
[154]
. Seventy-three patients presenting to the emergency room with
dyspeptic symptoms were randomized to receive 30 mL of antacid
alone (Mylanta II(R)) (34) or 30 mL of antacid plus 15 milliliters of
2% viscous LIDOCAINE (39). Patients recorded their pain score on
an 11-cm linear analog scale prior to and 30 minutes after
treatment. Improvement in pain score with treatment was 4 cm in
patients treated with LIDOCAINE compared to 0.9 cm in those
treated with antacid alone. This difference is statistically significant.
No adverse effects were noted with either treatment. A single dose
of antacid with LIDOCAINE is appropriate acute symptomatic
treatment of dyspepsia in the emergency room when the etiology of
pain is unknown.
Lipomatosis dolorosa
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
In several case reports, intravenous lidocaine provided effective
pain relief
c) Adult:
1) Two patients with adiposis dolorosa (DERCUM'S DISEASE) were
successfully treated with lidocaine. The first patient, an 84 year-old
woman, was given 200 milligrams (mg) intravenous lidocaine over
30 minutes with pain relief lasting 25 days. Over the next 6 months,
8 lidocaine infusions and 12 isotonic glucose infusions were given
double-blind in random order. The glucose infusions always resulted
in no perceived pain relief as reported by the patient. Oral mexiletine
(600 mg/day) was then given successfully over the next 8 months.
The second patient, a 43 year-old woman, was given a total of ten
infusions of intravenous lidocaine (5 milligrams per kilogram (mg/kg)
body weight) or equal volumes of isotonic glucose in a double-blind
fashion over a 6-month period. The placebo infusion has no effect
on the pain. The patient was subsequently treated with 600 mg/day
of oral mexiletine (Petersen & Kastrup, 1987).
2) A 60-year-old woman with a 20 year history of adiposis dolorosa
was treated with lidocaine after experiencing no pain relief with
other therapies. Lidocaine (1300 milligrams per day (mg/day)) was
given daily for 4 days. The patient was free from pain for 3 weeks.
At 5 weeks, a second series of lidocaine infusions were given over 4
days. This time the pain relief lasted 2 months. The patient was then
brought back to the clinic and given a placebo infusion (0.9%
sodium chloride) without pain relief
[134]
.
3) A 48-year-old woman with adiposis dolorosa, diabetes mellitus,
hyperlipidemia, and atherosclerotic cardiovascular disease was
given lidocaine for associated with adiposis dolorosa. She received
200 milligrams (mg) intravenous lidocaine over 35 minutes. Fifteen
minutes after the end of the infusion, her pain over the fatty tumors
was gone but her foot pain secondary to diabetic neuropathy
persisted. The pain relief continued for 2 months. When she
returned with pain associated with the adiposis dolorosa, she was
told she would be given lidocaine but instead was given a 5%
dextrose infusion. The patient reported no relief of pain. She
required lidocaine infusions approximately every 6 months over the
next 2 years. The patient experienced prolonged pain relief after
each lidocaine infusion (Atkinson, 1982).
Liver function tests - general
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class IIa; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Primary metabolite (MEGX) used to predict morbidity and mortality
related to liver dysfunction
Greatest sensitivity of the MEGX test occurs 60 minutes after IV
lidocaine administration
MEGX test can be used to monitor hepatic function in liver
transplant recipients; pre- and post-transplant liver function
Compared to IV administration, oral administration of lidocaine may
improve the sensitivity and specificity of the MEGX test
The MEGX test may be useful for assessing hepatic function and for
predicting morbidity and mortality in pediatric patients with liver
disease
c) Adult:
1) LIVER DISEASE
a) Lidocaine's primary metabolite following conversion by the
cytochrome P450-3A4 isoenzyme is monoethylglycinexylidide
(MEGX). Following an intravenous dose of lidocaine, MEGX
appears in the blood and its serum level reaches steady state within
15 minutes. It has been suggested that MEGX can be used to
assess hepatic function and to predict morbidity and mortality
related to complications of liver disease. In cases of chronic
hepatitis and cirrhosis, MEGX production declines stepwise with
increasing severity. Serial monitoring of MEGX may be used to track
hepatic metabolic function in patients with chronic hepatitis and
cirrhosis. The MEGX test is performed by administering 1 mg/kg of
2% lidocaine (maximum dose of 100 mg) by slow intravenous
infusion over 1 to 2 minutes. Serum is obtained prior to and 15
minutes after administration. The MEGX value is the difference
between baseline and at 15 minutes. However, according to 1
study, the greatest sensitivity of the MEGX test as an indicator of
liver dysfunction is observed when blood is sampled 60 minutes
after IV lidocaine administration. A majority of patients with MEGX of
less than 20 ng/mL had cirrhosis confirmed by histologic evaluation.
Severe life-threatening complications of cirrhosis were only reported
in patients with MEGX production below 20 ng/mL. One-year
survival for patients with an MEGX value of less than 10 ng/mL was
50% and in patients with an MEGX value of greater than 10 ng/mL it
was 80%. However, this test has not been used as a routine liver
function test because of a wide variability in MEGX values between
patients with various hepatic histologies. The rate of MEGX
production reflects the rate of lidocaine clearance, which after IV
administration, is dependent on hepatic blood flow. Since lidocaine
has a hypotensive effect, blood pressure must be constantly
monitored when this test is performed. Lidocaine clearance has
been shown to decrease with advancing age; therefore, the rate of
MEGX formation can be expected to decrease with age. MEGX
formation is also decreased in patients with sickle cell disease. In
addition, the degree of hepatic inflammation and fibrosis, gender,
and several drugs affect MEGX production. MEGX does not appear
to be useful in assessing patients with fulminant hepatic failure
[171]
[172]
; (Orlando et al, 1997)
[173]
[174]
[175]
[176]
[177]
[178]
[179]
[180]
[181]
.
b) Following intravenous administration, the sensitivity, specificity
and diagnostic accuracy of the MEGX test for cirrhosis were 96%,
78%, and 84%, respectively, in a study of 200 patients with liver
disease of various etiologies. With an MEGX level above 50
nanograms/milliliter (ng/mL) considered normal, 96% and 23% of
patients with and without cirrhosis registered abnormal MEGX levels
(p less than 0.05). Corresponding average MEGX values were 35.6
and 77.8 ng/mL, respectively (p = 0.005). Subjects of Child-Pugh
class A exhibited a mean MEGX value of 43.3 ng/mL, compared to
11.5 ng/mL for Child-Pugh classes B or C (p less than 0.05). In the
subset who underwent liver resection (n=85), only 6.5% with normal
preoperative MEGX levels experienced postoperative complications
versus 23% and 77% with MEGX between 25 and 50 ng/mL or
below 25 ng/mL, respectively. No significant gender differences
were observed with respect to MEGX in this trial
[182]
.
c) The results of 1 study indicate that the greatest sensitivity of the
MEGX test as an indicator of liver dysfunction, providing the most
accurate data for differentiating between healthy subjects and
patients with cirrhosis or between patients with different degrees of
liver dysfunction, is observed when blood is sampled 60 minutes
after IV lidocaine administration. In this study 10 healthy subjects
and 20 patients with either grade A or grade C liver cirrhosis were
administered intravenous lidocaine (1 mg/kg) over 2 minutes. Blood
MEGX concentrations were measured at 15, 30, 45, and 60 minutes
after administration of lidocaine. The specificity, sensitivity,
diagnostic accuracy, and predictive values of the MEGX test
increased with the sampling time and, overall, were maximal at 60
minutes. MEGX concentrations correlated significantly with serum
albumin levels, prothrombin times, and Pugh's scores (p=0.00001).
The correlation between MEGX concentration and these 3 variables
tended to increase with the sampling time, with the highest value
being observed with the 60-minute MEGX concentration
[175]
.
d) MEGX testing correlated well with histological scores and ChildPugh classification for chronic hepatitis and cirrhosis, respectively,
in 284 consecutive patients. A stepwise decline in MEGX levels
indicated increasing severity of liver dysfunction. The MEGX cutoff
value of 50 ng/mL measured 30 minutes after a 1 mg/kg lidocaine
infusion had 94% sensitivity and 77% specificity in distinguishing
between chronic hepatitis and cirrhosis. No gender differences were
noted in those 50 years of age and older; however, women under
age 50 had statistically lower MEGX levels than men of the same
age group and disease severity
[173]
. The MEGX test reliably differentiated liver function between 10
healthy women and 10 women with Child's class A cirrhosis
(average age 55 years) in a small study. When compared with data
from a separate trial, healthy women exhibited statistically higher
MEGX levels than healthy men, but no gender differences in MEGX
levels occurred in subjects with cirrhosis
[183]
.
e) In a study of 92 subjects with primary biliary cirrhosis, MEGX
levels less than 25 ng/mL were associated with a greater incidence
of transplantation or death after 2 to 63 months follow-up.
Conversely, a Mayo Clinic score less than 6 was a significant
predictor of transplant-free survival. Unlike the Mayo score, MEGX
testing can be used to monitor the early, asymptomatic progression
of primary biliary cirrhosis
[184]
.
f) Monoethylglycinexylidide (MEGX) concentrations differed
significantly between young and elderly healthy volunteers (n=33)
when sampled at least 30 minutes after infusion of lidocaine 1
milligram/kilogram. The mean MEGX plasma concentrations at 30,
45, and 60 minutes in young subjects (mean age 28 years) were
63.6, 71.6, and 76.7 nanograms/milliliter (ng/mL), respectively. The
corresponding MEGX levels in elderly subjects (mean age 69 years)
were 49.8, 54.1, and 55.9 ng/mL, respectively
[185]
.
g) Results of a preliminary study indicate that oral administration of
lidocaine may improve the sensitivity and specificity of the MEGX
test and may be better suited to discriminate between normal
subjects and cirrhotic patients. In this open study, 8 healthy subjects
and 16 cirrhotic patients (only 2 cirrhotic patients were scored as
Child C; the healthy subjects were younger than the cirrhotics)
received lidocaine 1 milligram/kilogram (mg/kg) over a mean
infusion time of 4.5 minutes on one occasion and at another time
(median 6 days later; range 1 to 56 days later) ingested a solution of
lidocaine (3 mg/kg in orange juice). The MEGX concentration test
60 minutes after the oral dose had a better sensitivity and specificity
than the values obtained 10 minutes after the end of the infusion
(approximately 15 minutes after its start). This study was not
capable of assessing the predictive value of the oral MEGX test for
the survival of cirrhotics and for the selection of potential liver grafts;
larger prospective studies are required to establish the clinical
usefulness of the oral MEGX test
[186]
.
2) LIVER TRANSPLANTATION
a) In general, for orthotopic liver transplantation, post-transplant
graft survival rates have correlated with donor MEGX values.
However, when comparing graft survival rates with donor MEGX
values study results have varied. In one study, when the MEGX test
was conducted in 171 donors, the rates of graft survival 20 days
post-transplantation were 85% when the 15-minute MEGX value
was greater than or equal to 90 mcg/L and 57% when less than or
equal to 90 mcg/L. In a similar study involving 103 donors, the graft
survival rate was 83% when the 15-minute MEGX value was 90
mcg/L or more and 66% when 50 mcg/L or less. In contrast some
studies have demonstrated a lack of correlation. When the MEGX
test was conducted in 63 donors, the graft survival rate was 87%
when the 15-minute MEGX value was greater than or equal to 90
mcg/L, 97% when 50 to 90 mcg/L, and 93% when less than or equal
to 50 mcg/L. When the MEGX test was conducted in 35 donors, the
graft survival rate was 70% when the 15-minute MEGX value was
greater than or equal to 80 mcg/L and 100% when less than or
equal to 80 mcg/L
[171]
. Additional studies are required in order to substantiate the
relationship.
b) When evaluating a cirrhotic patient for placement on a transplant
waiting list, the addition of a MEGX test value to a Child-Pugh score
can improve the mid- and long-term prediction of mortality by almost
10%. In one study, a Child-Pugh score of greater than 8 and a
MEGX value of less than 15 mcg/L had the greatest specificity in
predicting mid- and long-term survival
[187]
.
c) The lidocaine-monoethylglycinexylidide (MEGX) test, when used
in conjunction with conventional liver function tests, can be used to
monitor hepatic function in liver transplant recipients (ie, graft
function) and predict graft survival after liver transplantation. The
MEGX test may be a sensitive index of rejection with a decrease in
MEGX occurring before other indications of rejection. The flowdependent clearance of lidocaine makes it a sensitive indicator of
disturbed liver blood flow. Following allografting, initial MEGX
concentrations are significantly correlated with the donor MEGX
concentration. Livers from donors with high MEGX values (greater
than 80 mcg/L) and shorter ischemic times are associated with
improved graft survival when compared with livers from donors with
low MEGX values. However, high MEGX values do not appear to
correlate with the acceptability of donor livers. In the recipient, the
MEGX concentration is approximately 50% that of the donor value.
A number of factors can contribute to a low MEGX concentration
including a high pretransplant bilirubin level in the recipient, use of
segmental grafts, hepatic artery thrombosis, rejection, sepsis,
cardiac failure, pulmonary effusions, hepatic ischemia, and
cholestasis. The lowest MEGX concentrations (less than 25 mcg/L)
were reported in recipients who required retransplantation or who
died within 2 months of transplantation
[171]
[188]
[189]
[190]
.
d) The monoethylglycinexylidide (MEGX) test used in conjunction
with other liver function tests (eg, aminotransferases, bilirubin)
permitted accurate, early assessment of graft function and
postoperative complications in a study of 80 consecutive liver
transplants (n=71 subjects). MEGX values above 60
micrograms/liter (mcg/L) 24 hours after unclamping were associated
with an uncomplicated postoperative course. The combination of
abnormal MEGX levels and normal conventional liver function tests
indicated either poor cytochrome P450-3A4 activity or a
complication such as infection or hypoxia. When both MEGX and
other liver function tests were altered, graft injury had occurred.
Patients with MEGX values below 20 mcg/L required
retransplantation
[189]
.
e) Investigators reported a correlation between MEGX values and
survival in a study of 35 patients awaiting liver transplantation. Ten
of 35 received a transplant within 1 year. Of the remaining 25
subjects still on the waiting list at 1 year, 19 patients survived past 1
year and subsequently underwent transplantation, while 6 died
within 1 year. Their corresponding mean MEGX values at initial
evaluation were 23.6 versus 10.7 nanograms/milliliter, respectively
(p less than 0.03). Evaluation of MEGX values in liver donors failed
to demonstrate statistical differences in terms of whether or not the
livers could be harvested or in predicting graft function in the
recipients
[182]
.
d) Pediatric:
1) Although limited data are available, the MEGX test may be useful
for assessing hepatic function, improving liver transplant candidate
selection, determining the timing of transplantation, and for
predicting morbidity and mortality in pediatric patients with liver
disease. In a study involving 24 pediatric patients with chronic endstage liver disease, consistently low MEGX values (less than 10
mcg/L; 3 evaluations at 3-month intervals), obtained 30 minutes
after IV administration of lidocaine, have been associated with an
unfavorable outcome
[171]
.
Local anesthesia, by infiltration, Percutaneous
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Produces effective anesthesia by percutaneous infiltration
c) Adult:
1) LIDOCAINE is frequently used for infiltration, regional, nerve
block, spinal anesthesia, as well as for topical anesthesia.
LIDOCAINE has a more rapid onset of action than PROCAINE and
longer duration of action; the drug is also more potent (Prod Info
Xylocaine(R), 2000)
[66]
. For surgical procedures of 1 to 2 hours duration, LIDOCAINE (or
MEPIVACAINE or PRILOCAINE) is generally used for epidural
anesthesia, whereas BUPIVACAINE or ETIDOCAINE are preferred
for longer procedures. Similarly, during spinal anesthesia
LIDOCAINE provides a short duration of anesthesia as compared to
that of BUPIVACAINE, AMETHOCAINE, and CINCHOCAINE
[67]
.
Local anesthesia, Peritubular block
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
PERITUBULAR BLOCKLocal anesthetic solution of 2% lidocaine 5
mL and 0.75% bupivacaine 5 mL with 150 units of hyaluronidase
result in safe blood levels of lidocaine and bupivacaine after
peritubular block. Although levels varied widely, peak levels for both
local anesthetics were achieved within 20 minutes if the initial block
was successful. With administration of supplementary block, peak
levels occurred 10 minutes later. Maximum doses utilized in the
study were 200 milligrams for lidocaine and 75 mg for bupivacaine
without the use of a vasoconstrictor. Toxic thresholds of lidocaine
and bupivacaine were not observed and clinical findings of toxicity
were not apparent
[213]
.
Local anesthesia, Superficial dermatological procedures
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes (iontophoretic system); Pediatric, yes (5
yrs and older (iontophoretic system))
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIa; Pediatric, Class IIa
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine hydrochloride, as part of an iontophoretic delivery system,
is indicated to provide local analgesia for superficial dermatological
procedures, including venipuncture, intravenous cannulation, and
laser ablation of superficial skin lesions
[221]
c) Adult:
1) Iontophoresis with lidocaine provided effective local anesthesia
prior to shave biopsy in adult patients. In a randomized, doubleblind, placebo-controlled study, patients with nevi, seborrheic
keratosis or actinic keratosis (lesion size not greater than 2.5 x 4.5
centimeters) underwent iontophoresis with either 2% lidocaine with
1:100,000 epinephrine (n=21) or placebo (n=20) for local anesthesia
prior to shave biopsy. The treatment area was tested for sensation
to pinprick immediately following iontophoresis and patients in
whom treatment was considered a failure received supplemental 1%
lidocaine. Ninety percent (19/21) of patients who received
iontophoretically applied lidocaine did not require supplemental
anesthesia prior to shave biopsy as compared with only 10% (2/20)
of patients who received placebo (p less than 0.001). Lidocainetreated patients also rated the pain associated with the dermatologic
procedure as significantly less severe than patients in the placebo
group (p less than 0.001). Blanching and/or erythema occurred in 37
patients, but resolved within 24 hours
[222]
.
2) Results of a prospective, randomized, double-blind study
involving 40 patients undergoing day surgery indicate that
iontophoretically applied lidocaine significantly reduces pain
associated with cannulation and injection of propofol. In the
iontophoresis group, the negative electrode containing 4% lidocaine
1.5 mL in a hydrogel was placed on the dorsum of the hand over the
site for cannulation. The control group was treated similarly, except
no current was passed through the electrodes. Pain of cannulation
was significantly reduced in the iontophoresis group compared with
the control group (p less than 0.005). The frequency and severity of
pain after propofol injection was significantly reduced in the
iontophoresis group at 10 seconds (s) (p less than 0.002), 20 s (p
less than 0.001), and 30 s (p less than 0.001) compared with the
control group. In the control group, 50% of patients experienced
moderate to severe pain after propofol injection. In the iontophoresis
group, 75% of patients experienced no pain and 25% only mild pain
after propofol injection. The only adverse effect was erythema at the
site of the negative electrode
[168]
.
3) Iontophoretically applied lidocaine does not reduce the pain
associated with intravenous (IV) propofol administration to the same
extent as IV lidocaine. This study was a double-blind, prospective,
randomized trial (n=60; mean age, 36.9 years; range 18 to 71
years) comparing active iontophoresis of 1.5 milliliters (mL)
lidocaine 4% followed by propofol containing 2 mL sterile saline and
sham iontophoresis followed by administration of propofol
containing 2 mL lidocaine 2%. Patients were asked to record their
pain on a 100 mm visual analog score (VAS) 10 minutes after the
administration of propofol. They were also asked to rank their pain
on a four point scale (none, mild, moderate, severe). The incidence
of moderate or severe pain, as assessed by categorical pain scores
was significantly (p less than 0.05) higher in the iontophoresis group
(8 of 30 patients had moderate or severe pain vs. 2 of 30 in the IV
lidocaine group). Pain measured by VAS following venous
cannulation was significantly (p less than 0.05) less in the
iontophoresis group
[169]
.
d) Pediatric:
1) SUMMARY: Lidocaine iontophoresis reduces pain associated
with venipuncture and intravenous cannulation in children
[223]
[224]
.
2) Lidocaine iontophoresis is safe and effective for reducing
venipuncture pain in children. In this prospective, placebocontrolled, randomized study, 60 patients (mean age, 11.7 years)
were enrolled to assess the efficacy and safety of lidocaine
iontophoresis (lidocaine 2% with 1:100,000 epinephrine) for the
prevention of venipuncture pain during routine blood sampling. The
placebo treatment was the same preparation without lidocaine. Pain
assessments were performed by the patient, parent, and research
nurse using a 100-mm visual analog scale (VAS). Satisfaction with
iontophoresis was also evaluated using an 11- point scale. Results
showed that VAS scores were significantly less in the lidocaine
iontophoresis group for all evaluators (p less than 0.001). Similarly,
satisfaction ratings were significantly higher in the lidocaine group.
Adverse events were generally mild in both groups; however, 2
subjects in the placebo group stopped iontophoresis shortly after
initiation because of discomfort
[223]
.
3) Lidocaine iontophoresis reduces the intensity of pain associated
with intravenous cannulation in children (7 to 18 years old). In a
double-blind, randomized trial, children (n=42) received either
iontophoresis of 2% lidocaine with 1:100,000 epinephrine or normal
saline with 1:100,000 epinephrine. Approximately 10 minutes was
required for iontophoresis in both the lidocaine and placebo groups.
Pain was significantly reduced during intravenous placement
following lidocaine iontophoresis compared with placebo as reported
by patients (p=0.005), parents (p=0.001), intravenous personnel
(p=0.009), and investigators (p=0.0002). In both groups, tingling,
itching, urticaria, and erythema occurred during iontophoresis which
resolved prior to discharge. The success rate for intravenous access
was not compromised by iontophoresis. Intravenous placement was
successful in 75% and 86% of patients in the placebo and lidocaine
groups, respectively
[224]
.
Local anesthesia, Tumescent anesthesia
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
An observational study has suggested that lidocaine may be
effective for tumescent anesthesia in patients undergoing
liposuction procedures
c) Adult:
1) Observational data from 60 patients undergoing liposuction
suggest that lidocaine doses of up to 55 milligrams/kilogram for
tumescent anesthesia are safe. The tumescent anesthetic solution,
consisting of lidocaine 500 to 1000 milligrams, epinephrine 0.5
milligram, sodium bicarbonate 10 milliequivalents, triamcinolone 10
milligrams, and normal saline 1 liter, was infiltrated into the
subcutaneous tissue of the area undergoing liposuction at a rate of
150 milliliters/hour over an average 90 to 120 minutes. Patients who
required more than the previously recommended maximum
lidocaine dose for tumescent anesthesia (35 milligrams/kilogram)
were prospectively evaluated over 24 hours post-liposuction for
signs and symptoms of toxicity. Despite a mean dose of 57
milligrams/kilogram in this group, no toxicity was reported. Plasma
sampling of another 10 patients revealed that the average peak
plasma lidocaine level ranged from 1.1 to 3.6 micrograms/milliliter,
occurring 4 to 8 hours after infusion of an average 55
milligram/kilogram dose. All levels remained below the toxicity
threshold of 5 micrograms/milliliter, with no adverse effects noted.
Only negligible amounts of lidocaine were removed by the
liposuction procedure itself
[225]
.
Local anesthetic intravenous regional block
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective for regional anesthesia
Local anesthetic lumbar epidural block
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Provides anesthesia via epidural route
Local anesthetic sacral epidural block, Obstetrical analgesia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Provides obstetrical analgesia via epidural route
Local anesthetic sacral epidural block, Surgical anaesthesia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine hydrochloride is indicated to provide surgical anesthesia
as a caudal nerve block
[79]
Local anesthetic thoracic epidural block
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine hydrochloride is indicated to provide local anesthesia as a
thoracic epidural block
[79]
Lumbar sympathetic block
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine hydrochloride is indicated to provide lumbar sympathetic
nerve block
[79]
Myocardial infarction - Ventricular arrhythmia
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Routine prophylactic use of lidocaine for the treatment of acute
myocardial infarction (MI) is not recommended
Lidocaine is a drug of choice for acute MI when treatment is
indicated for premature ventricular complexes, ventricular
tachycardia, or ventricular fibrillation
c) Adult:
1) GENERAL INFORMATION
a) Routine prophylactic use of lidocaine for the treatment of acute
myocardial infarction is NOT recommended, with the possible
exception being situations in which a defibrillator is unavailable.
Studies have shown that prophylaxis with lidocaine significantly
reduces the incidence of primary ventricular fibrillation (VF) in the
pre-hospital and early hospital settings; however, prophylactic use
of lidocaine has been associated with a trend toward increased
mortality, most likely from fatal episodes of bradycardia, asystole,
and electromechanical dissociation. Episodes of VF and
monomorphic ventricular tachycardia (VT) associated with angina,
pulmonary congestion, or hypotension should be treated with
immediate direct-current countershock. Monomorphic VT not
associated with angina, pulmonary congestion, or hypotension
should be treated with intravenous lidocaine, procainamide, or
amiodarone. Episodes of VF/VT that are not easily converted by
defibrillation and epinephrine (ie, resistant VF/VT) may be treated
with lidocaine. Ideally, if a lidocaine infusion is initiated, it should be
maintained for only 6 to 24 hours and then discontinued so that the
patient's need for antiarrhythmic therapy can be reassessed
[86]
[87]
[88]
[89]
[90]
[91]
[92]
[94]
[97]
[98]
. In contrast, a nonrandomized, observational analysis suggests that
because of the widespread use of thrombolytics and beta-blockers,
the routine prophylactic use of lidocaine may not be associated with
increased mortality rates
[191]
.
Operation on urinary system
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes (2% jelly); Pediatric, no
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIa; Pediatric, Class IIa
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Dorsal penile nerve block effective for circumcision
Intravesically improves detrusor stability and bladder capacity
IV lidocaine improves bowel function, reduces pain, and shortens
hospitalization in patients undergoing radical retropubic
prostatectomy
Intrarectal lidocaine gel reduced pain of transrectal prostate biopsy
in 1 study; however, lidocaine solution given intra- rectally did not
significantly decrease pain in another study of prostate biopsy
c) Adult:
1) Iontophoresis of dexamethasone, lidocaine and verapamil is well
tolerated and is an effective nonsurgical treatment for PEYRONIE'S
DISEASE, particularly for painful lesions of less than 12 months in
duration and for deviations less than 60-degrees. In this
uncontrolled, prospective study, patients (n=100) with Peyronie's
disease received 3 weekly courses of iontophoresis
(dexamethasone 8 milligrams (mg) and lidocaine 40 mg for painful
plaques and dexamethasone 8 mg and verapamil 5 mg for painless
lesions). Pain was eliminated in 63% of patients (38/60) and
significantly improved in 33% of patients (20/60). Pain at the plaque
site disappeared 1 week after initiation of therapy and was
maximally reduced after 2 to 3 weeks. Cavernous plaques
completely disappeared in 14% of patients (11/79) and were
reduced in 39% of patients (31/79). Penile deviation improved with
complete straightening or more than a 30-degree reduction in
deviation in 16% of patients (12/77) and a less pronounced
reduction in curvature occurred in 21% of a patients (16/77).
Restoration of erectile function occurred in 39% of patients (7/23)
and sexual activity improved in 44% of patients (19/43). Patients
with a shorter duration of disease (less than 3 months compared to
more than 12 months) benefited the most from iontophoresis
therapy. After the initial therapy, symptoms recurred in 15 of 100
patients after a mean of 5.5 months (range 2 to 10 months). In 10 of
these patients a second course of therapy again improved
symptoms and 5 patients required surgery
[199]
.
2) Results of 1 prospective, placebo-controlled study indicate that
intravenous lidocaine initiated before anesthesia and continued for 1
hour postoperatively can speed up the return of bowel function,
reduce postoperative pain, and shorten the hospital stay in patients
undergoing radical retropubic PROSTATECTOMY. Forty patients
undergoing radical retropubic prostatectomy received either a
lidocaine bolus (1.5 milligrams/kilogram) and infusion (2 to 3
milligrams/minute) or a saline infusion. Lidocaine significantly
shortened hospitalization (p less than 0.05) (1.1 fewer days in the
hospital) and the time to the first bowel movement (p less than 0.02)
compare with saline. In addition, although all patients received the
same amount of postoperative pain medication, patients treated with
lidocaine were more comfortable, based on daily pain scores
[200]
.
3) Intravesical lidocaine solution has been shown to improve
detrusor stability
[201]
. In one small study, 40 milliliters of 1% lidocaine solution and 40 mL
of 8.4% sodium bicarbonate solution were instilled into the bladder
of 20 patients. Lidocaine was able to increase bladder capacity,
alter the bladder sensation, change the character of the
cystometrogram, and lower the maximum detrusor pressure during
bladder filling in most patients. All 20 patients tolerated the
investigation well and no local or systemic adverse reactions to the
1% lidocaine solution were experienced. Lidocaine 2% has also
been used safely as a topical anesthetic in patients undergoing
ureterocystoscopic procedures
[202]
[203]
.
4) Intravesical lidocaine had a variable effect on detrusor contraction
and bladder capacity in an uncontrolled study of patients with spinal
cord injuries (n=48) or cerebrovascular disease (n=67). Lidocaine
was administered in concentrations of 1% or 4% (total volume 20
milliliters), to be retained in the bladder for 15 minutes, followed by
cystometry. Only the 4% lidocaine significantly increased bladder
capacity in patients with cerebrovascular disease, while both
strengths were efficacious in spinal cord-injured patients whose
injury occurred at least one year prior to the study. The increase in
bladder capacity with the higher concentration was significantly
different between groups (91.6% for spinal cord injuries versus
31.9% for cerebrovascular disease, p less than 0.01). Detrusor
contractions were eliminated in 37.5% and 5.4% of the 2 groups,
respectively (p less than 0.01). The authors note that intravesical
lidocaine may assist in distinguishing the origin (brain versus spinal
cord lesion) of overactive detrusor
[204]
.
5) In a randomized, double-blind study (n=100), 2% LIDOCAINE
solution (20 cubic centimeters) administered intrarectally to men 20
minutes before transrectal ultrasound-guided prostate biopsy made
no significant difference compared with placebo in the amount of
pain perceived by the patients. This outcome contradicts the
findings from another study, although 2% lidocaine gel was used
intrarectally in the other study. When lidocaine solution was used,
mean visual analog scale (VAS) scores were 4.7 for the lidocainetreated subjects and 4.5 for controls (higher score indicated more
pain; p=0.643). Proportions of patients with pain scores of 5 or more
on the 10-point scale were 50% and 66% for the lidocaine and
placebo groups, respectively (p=0.156). Complication rates did not
differ between groups, and no adverse effects were reported
[205]
.
6) Intrarectal administration of 2% lidocaine gel (10 milliliters) 10
minutes prior to transrectal prostate biopsy demonstrated effective
and safe analgesia in a randomized, double-blind study (n=50). The
average visual analogue pain scores on a scale of zero to ten were
2 and 5 in the lidocaine and control groups, respectively
(p=0.00001), with 1% and 13% grading pain at 5 or higher (p less
than 0.00001). No patients reported adverse effects
[206]
.
7) Lidocaine 2% gel, 20 milliliters administered intraurethrally for at
least 15 minutes, significantly reduced the pain and discomfort of
flexible CYSTOSCOPY in a controlled trial (n=150 men). Subjects
rated pain and discomfort on a 4-point descriptive scale and a 100
millimeter visual analog scale. The study initially determined that
plain lubricating gel was as effective as lidocaine gel when applied
only five minutes prior to cystoscopy. However, when applied and
retained for 25 minutes, lidocaine gel provided superior analgesia to
the placebo gel. A second part of the study assessing lidocaine 2%
gel alone found no significant difference between the 15 minute and
25 minute durations of application
[207]
.
8) Lidocaine 2% jelly is indicated for prevention and control of pain
in male and female urethral procedures. It is also effective for the
topical treatment of painful urethritis
[208]
.
9) The results of a randomized, prospective, double-blind study
involving 179 patients indicate that intraurethral 2% lidocaine jelly is
more effective than plain lubricant for reducing pain during
outpatient rigid cystoscopy in men. However, intraurethral 2%
lidocaine jelly is no more effective than plain lubricant for reducing
pain during outpatient rigid cystoscopy in women. In this study
adequate urethral filling was accomplished by using 30 cc of each
agent and then waiting 20 minutes before performing cystoscopy.
Cystoscopy was performed using a 17 to 21F rigid instrument. Pain
perception in men was significantly reduced when lidocaine jelly
was used (p=0.002). However, in women there was no difference in
pain perception when lidocaine jelly or plain lubricant was used
(p=0.823). Patient race, performance of a related procedure,
cystoscope size, or history of cystoscopy did not significantly affect
pain perception. A decrease in pain perception was noted with
increasing age (p=0.021)
[209]
.
d) Pediatric:
1) Dorsal penile nerve block (DPNB) with lidocaine is a more
effective means of providing anesthesia for neonatal circumcision
than EMLA(R) cream. In a double-blind, placebo-controlled study,
term newborns (n=60) received either placebo cream under an
occlusive dressing 1 hour before the procedure and standard
technique DPNB with 0.8 mL (total volume) of 1% lidocaine or 1
gram of EMLA(R) cream under an occlusive dressing 1 hour before
the procedure and DPNB with sodium chloride. Distress scores and
heart rates were significantly higher (p=0.04 and p=0.047,
respectively) in the EMLA(R) group compared with the lidocaine
DPNB group
[210]
.
2) According to the results of a prospective, randomized, doubleblind, placebo-controlled study involving 42 children undergoing
circumcision with dorsal penile nerve block (DPNB), EMLA(R)
cream is effective for preventing pain associated with needle
penetration for DPNB; however, it has no beneficial effect during
infiltration of the anesthetic
[211]
.
3) Dorsal PENILE NERVE BLOCK utilizing LIDOCAINE 1% (without
EPINEPHRINE) was effective in reducing behavioral distress and
attenuating the adrenocortical response to circumcision in a
controlled study involving 60 newborn infants
[212]
. In addition, the injection itself did not increase stress reactions in
newborns, and did not offset the beneficial effects of local
anesthesia. The dorsal penile nerve block technique was reported to
be safe and a simple procedure to learn, and is advocated for
circumcision to reduce pain and stress in the newborn.
Pain - Peripheral angiography
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective for reducing or relieving pain associated with peripheral
angiography
c) Adult:
1) LIDOCAINE mixed with contrast media (Conray 60) has been
shown to be effective in reducing or relieving pain in patients
undergoing peripheral angiography. LIDOCAINE 2 milligrams was
mixed with 1 mL of contrast medium (1 mL of 2% LIDOCAINE per
10 mL of contrast medium)
[193]
.
Paracervical block anesthesia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Effective
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Produces effective anesthesia by the paracervical route of
administration
c) Adult:
1) GENERAL INFORMATION
a) LIDOCAINE is frequently used for infiltration, regional, nerve
block, spinal anesthesia, as well as for topical anesthesia.
LIDOCAINE has a more rapid onset of action than PROCAINE and
longer duration of action; the drug is also more potent (Prod Info
Xylocaine(R), 2000)
[66]
. For surgical procedures of 1 to 2 hours duration, LIDOCAINE (or
MEPIVACAINE or PRILOCAINE) is generally used for epidural
anesthesia, whereas BUPIVACAINE or ETIDOCAINE are preferred
for longer procedures. Similarly, during spinal anesthesia
LIDOCAINE provides a short duration of anesthesia as compared to
that of BUPIVACAINE, AMETHOCAINE, and CINCHOCAINE
[67]
.
2) PARACERVICAL ANESTHESIA
a) For paracervical anesthesia, bacteriostatic SALINE was safer
than buffered LIDOCAINE with similar efficacy in patients
undergoing brief suction curettage procedures. Twenty-seven
women were randomized to bacteriostatic saline, prepared with
0.9% sodium chloride and 0.9% benzyl alcohol. Twenty-eight
women received buffered lidocaine, prepared with 5 milliliters 8.4%
sodium bicarbonate solution and 50 milliliters of 1% lidocaine. A
total of 20 milliliters of solution was injected into each cervix. While
there was no difference in overall pain or pain progression during
the procedure, 3 patients (11%) receiving lidocaine experienced
systemic adverse reactions (numbness in the lips, tinnitus,
dizziness) suggesting intravascular absorption of lidocaine.
Vasovagal symptoms occurred after the procedure in one saline
patient who was pretreated with fentanyl and atropine
[77]
.
b) A randomized, double-blind, placebo-controlled study (n=120) of
lidocaine spray prior to hysteroscopy also reported only limited
benefit. A total of ten metered aerosol doses of either 10% lidocaine
(equivalent to 100 milligrams lidocaine base) or placebo were
administered to the surface of the cervix, ectocervix, endocervix,
and uterus. Efficacy was similar in that 85% of lidocaine-treated
patients and 83% of placebo-treated patients required no other
analgesia to complete the procedure. Median visual analog pain
scores were also equivalent at various steps during the
hysteroscopy, with one exception: lidocaine decreased the cervical
pain associated with applying the tenaculum
[78]
.
Peripheral block anesthesia, Brachial
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Indicated for use as a peripheral nerve block
Peripheral block anesthesia, Dental
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIa; Pediatric, Class IIa
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Produces effective analgesia in adults and children
c) Adult:
1) Differing epinephrine concentrations had similar effects on
alveolar nerve block when combined with lidocaine 2%. Thirty
healthy volunteer subjects underwent dental anesthesia with 1.8
milliliters of lidocaine 2% in combination with epinephrine 1:50,000,
1:80,000, and 1:100,000, in random order on 3 separate occasions.
Using a pulp tester, no significant differences were recorded in
anesthesia of the first molar, first premolar and lateral incisor.
Subjective evaluations of lip and tongue numbness were also
equivalent between groups
[75]
.
d) Pediatric:
1) LIDOCAINE 2% has been shown to be satisfactory in producing
analgesia in 95% of routine procedures in children. Of the 5% not
experiencing analgesia, a 5% solution of LIDOCAINE may be tried,
and with careful use has been shown to be without clinical adverse
effects. A success rate of 70% has been reported with LIDOCAINE
5% in these children. LIDOCAINE 5% may be valuable in clinical
situations where analgesia is inadequate with LIDOCAINE 2% due
to the presence of inflammation
[76]
.
Peripheral block anesthesia, Intercostal
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Indicated for use as a peripheral nerve block
Peripheral block anesthesia, Paravertebral
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Indicated for use as a peripheral nerve block
Peripheral block anesthesia, Pudendal
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Indicated for use as a peripheral nerve block
Postoperative pain
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class IIa; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Reduces the severity of postoperative pain when administered by
various routes
May not be more effective than morphine alone
Topically and intravenously prevents postoperative stridor and
laryngospasm following tonsillectomy and adenoidectomy
Intraoperative administration in patients undergoing cardiac surgery
reduced the incidence of postoperative cognitive dysfunction
c) Adult:
1) POSTOPERATIVE PAIN
a) Perioperative administration of lidocaine in patients undergoing
major abdominal surgery reduced the incidence of pain and
morphine consumption following surgery. In a randomized, doubleblind, placebo- controlled study (n=40), patients undergoing major
abdominal surgery received perioperative intravenous lidocaine or
saline infusion for the prevention of postoperative pain. An
intravenous bolus injection of lidocaine 2% (1.5 milligrams/kilogram
(mg/kg)) was given at least 30 minutes prior to surgery followed by
continuous intravenous infusion of lidocaine 1.5 mg/kg/hour until 1
hour after surgery; saline infusion was administered in the same
manner. Patients given lidocaine had significantly fewer requests for
morphine as compared with those given placebo (mean number of
requests, 38 vs 68, respectively; p less than 0.05). As a result,
lidocaine-treated patients also consumed significantly less morphine
than did patients in the placebo group during the 72-hour
observation period (mean, 103.1 mg vs 159 mg, respectively; p less
than 0.05). Pain intensity at rest did not differ between groups,
however, patients in the lidocaine group reported significantly less
pain during movement as compared with patients in the placebo
group, especially during the second and third postoperative day (p
less than 0.05). Adverse events were similar between groups and
included sedation, nausea, vomiting, pruritus, and obstipation
[115]
.
b) No difference was seen with the addition of lidocaine 10
milligrams/milliliter or 20 mg/mL to morphine 1 mg/mL with patient
controlled intravenous analgesia (PCA) versus morphine 1 mg/mL
PCA alone. In a prospective, randomized, double-blind study of 200
post-intra-abdominal surgery patients, pain intensity and side effects
were evaluated on a continual basis for up to 36 hours. No statistical
difference was seen in pain requirements for all three groups, with
2% of patients overall reporting nausea
[116]
.
c) In a randomized, placebo-controlled study involving 168 patients,
wound infiltration with 15 milliliters of 1% lidocaine prior to surgical
incision was more effective than normal saline for reducing both
postoperative pain and the requirements for supplemental
analgesics following hemorrhoidectomy with spinal anesthesia
[117]
.
d) LIDOCAINE in low doses of 2 milligrams/minute (2 grams in 500
mL saline) for 24 hours was reported to significantly reduce the
severity of postoperative pain in patients undergoing elective
CHOLECYSTECTOMY
[118]
. Toxicity was not observed and effective serum levels appeared to
be 1 to 2 mcg/mL.
2) POSTOPERATIVE COMPLICATIONS
a) Administration of intraoperative lidocaine (LDC) in patients
undergoing cardiac surgery was effective in decreasing the
incidence of early postoperative cognitive dysfunction. In a
prospective, randomized, double-blind, placebo-controlled study,
patients undergoing coronary artery bypass surgery with
cardiopulmonary bypass (CPB) intraoperatively received either
placebo (n=61) or LDC 2% (n=57; administered as a bolus of 1.5
milligrams/kilogram (mg/kg) over 5 minutes at the opening of the
pericardium, followed by continuous infusion at 4 milligrams/minute
for the duration of the operation; another dose of LDC (4 mg/kg)
was administered to the priming solution of CPB). Nine days
following surgery, significantly fewer patients treated with LDC
experienced postoperative cognitive dysfunction, compared with
those given placebo (18.6% vs 40%, respectively; p=0.028). The
optimal dosing regimen and long-term effect of this treatment need
further study
[119]
.
b) Topical and intravenous (IV) lidocaine are equally effective for
prevention of postoperative stridor and laryngospasm following
TONSILLECTOMY and ADENOIDECTOMY. In this controlled,
double-blind study involving 134 patients, a group of patients
received either topical 2% lidocaine at 4 milligrams/kilogram (mg/kg)
sprayed to the subglottic, glottic, and supraglottic areas before
endotracheal intubation or topical normal saline. Another group of
patients received intravenously 1 mg/kg of 2% lidocaine before
extubation or IV normal saline. Mean plasma lidocaine levels were
1.7 and 3.4 mcg/mL after topical and IV administration, respectively.
The incidence of stridor and laryngospasm was 12.1% with topical
lidocaine compared with 21.2% with topical saline (p less than 0.05)
and 11.76% with IV lidocaine compared with 26.47% with IV saline
(p less than 0.05). There was no significant difference between
topical and IV lidocaine. However, sedation was significantly higher
in the IV lidocaine group compared with the topical lidocaine and
control groups (p less than 0.05). The authors suggest that topical
lidocaine is preferable for prevention of postoperative stridor and
laryngospasm because of the higher incidence of sedation
associated with IV lidocaine
[120]
.
d) Pediatric:
1) A combination of lidocaine and pethidine (meperidine) was more
efficacious than lidocaine alone for relief of post-tonsillectomy pain
in a study of 80 children (mean age 5 years). Subjects were
randomized to post-surgical tonsillar infiltration with 2% lidocaine (3
milliliters) combined with either saline (0.1 mL) or preservative-free
meperidine (1 milligram in 0.1 mL saline). As assessed by nurses
and patients (visual analog scale) at various time intervals over a
24-hour period, pain was significantly decreased with the addition of
meperidine (p less than 0.05). The respiratory rate was also
significantly lower for the first 3 hours with meperidine; no difference
was reported at 24 hours. No other differences in adverse effects
occurred
[121]
.
Procedure on eye - Topical local anesthetic
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
A prospective, randomized, double-blind, multicenter, phase III
clinical trial demonstrated that lidocaine hydrochloride 3.5% topical
ophthalmic gel was superior to sham-control for effective topical
ophthalmic anesthesia (n=209)
[52]
[51]
Lidocaine hydrochloride topical ophthalmic gel 3.5% is indicated for
ocular surface anesthesia during ophthalmologic procedures
[51]
.
c) Adult:
1) A prospective, randomized, double-blind, multicenter, phase III
clinical trial demonstrated that lidocaine hydrochloride 3.5% topical
ophthalmic gel was superior to sham-control for effective topical
ophthalmic anesthesia (n=209). Adult subjects were randomized on
a 1:1:1:1 ratio to 1 of 4 groups, lidocaine hydrochloride 1.5% (n=54),
2.5% (n=51), 3.5% (n=53) or sham (n=51). Patients received 2
drops to the eye of the respective study drug. The efficacy or
anesthesia was defined as the lack of pain after 2 consecutive
pinches of the conjunctiva with forceps. The primary end point was
achievement of anesthesia within 5 minutes of study drug
administration. The intent-to-treat analysis revealed that
achievement of anesthesia within 5 minutes was statistically
significant in all lidocaine groups compared to sham (p less than
0.001). The percentage of patients achieving anesthesia within 5
minutes was 92%, 89%, 88% and 22%, in lidocaine 3.5%, 2.5%,
1.5% and sham groups, respectively. The mean duration of
anesthesia in minutes (min) was 13.4 min, 11.7 min, 10.2 min and
2.8 min, respectively (p less than 0.001 lidocaine groups compared
to sham group). The most common adverse effects were
conjunctival hyperemia, corneal epithelial changes, headache, and
burning upon administration. Other adverse effects were corneal
staining, conjunctival hemorrhage and eye pain
[52]
[51]
.
Pruritus of skin
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Intravenous lidocaine may be effective for refractory pruritus
Intravenous lidocaine may be effective in the treatment of
hemodialysis pruritus
c) Adult:
1) A case of refractory pruritus in a 37-year-old male patient with
AIDS was successfully treated with intermittent intravenous bolus
lidocaine therapy. Cryptosporidium-related cholangiopathy was the
cause of this severe pruritus, which led to global excoriation.
Lidocaine 100 milligrams was administered intravenously over 5
minutes, after failure of antihistamines, bile resins, and opioids. The
patient reported complete relief, with a gradual return of symptoms
to a lesser degree after 1 to 2 weeks. This pattern was repeated
after each intermittent bolus infusion. Lidocaine's sodium channel
blocking properties may explain its beneficial effect on both
neuropathic pain and pruritus
[194]
.
2) Results of 1 study indicate that lidocaine is effective in the
treatment of pruritus in chronic hemodialysis patients. In this
placebo-controlled study involving 20 chronic hemodialysis patients,
lidocaine produced improvement in all 20 patients. Lidocaine (100 to
200 milligrams in 100 milliliters of normal saline given intravenously
over 20 minutes) was given through the arterial line of the artificial
kidney and was repeated in 1 hour if no improvement from the first
dose occurred. Out of the 20 patients, 2 episodes of hypotension
were reported and 1 patient had a seizure. The authors recommend
low doses and a slow infusion of lidocaine
[195]
.
Raised intracranial pressure
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Reduces the increase in intracranial pressure caused by
endotracheal tube suctioning
c) Adult:
1) A controlled crossover study of 10 patients with closed head
trauma demonstrated 1.5 mg/kg LIDOCAINE IV effective in reducing
the increase of intracranial pressure often caused by endotracheal
tube suctioning. There were no major changes in either
cardiorespiratory function or neurologic findings
[170]
.
Rapid sequence intubation, Preinduction
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes (2% jelly); Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class IIb; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Produces effective anesthesia for endotracheal intubation and
laryngoscopy
c) Adult:
1) ENDOTRACHEAL INTUBATION/LARYNGOSCOPY
a) SUMMARY: Lidocaine has been applied topically to the larynx
and trachea or administered intravenously prior to endotracheal
intubation. Lidocaine appears to blunt the increase in heart rate and
blood pressure associated with laryngoscopy and endotracheal
intubation. Intravenous lidocaine also prevents intracranial
hypertension in patients with brain tumors undergoing endotracheal
intubation. Intravenous administration may be the preferred
technique for administering lidocaine prior to endotracheal
intubation. The combination of lidocaine and esmolol attenuates the
heart rate and blood pressure responses associated with
laryngoscopy and tracheal intubation more effectively than either
agent alone
[110]
[111]
[112]
.
b) Tracheal lidocaine is an effective method for attenuating the
cardiovascular responses to endotracheal intubation (EI); however,
EI should be performed more than 2 minutes after tracheal
lidocaine. In this prospective study (n=75), Group A (control group)
received no tracheal lidocaine, Group B received 4 milliliters of 4%
lidocaine sprayed on the trachea followed immediately by EI, and
Group C received the same dosage of lidocaine with a 2 minute
delay to EI. Results showed that heart rate, mean arterial pressure,
and rate-pressure product (systolic arterial pressure x heart rate)
increased significantly following EI in Groups A and B but not in
group C
[110]
.
c) The results of a randomized, prospective, double-blind, placebo
controlled study indicate that only the combination of lidocaine (1.5
milligrams/kilogram) and esmolol (1 to 2 mg/kg) attenuated both the
heart rate and blood pressure responses associated with
laryngoscopy and tracheal intubation. Neither esmolol nor lidocaine,
when administered alone, affected the blood pressure response.
When administered alone, esmolol was more reliable than lidocaine
for preventing the increase in heart rate associated with tracheal
intubation
[111]
.
d) Pediatric:
1) ENDOTRACHEAL
INTUBATION/LARYNGOSCOPY/BRONCHOSCOPY
a) Nebulized 2% lidocaine at doses of 4 to 8 milligrams/kilogram
(mg/kg) provided sufficient anesthesia for 50% of children
undergoing flexible bronchoscopy (n=20). Serum lidocaine levels
following nebulization were less than or equal to 0.62 mg/liter. The
remaining 50% of subjects required supplemental lidocaine applied
directly to the mucosa during bronchoscopy, at doses up to 11.6
mg/kg. No toxic serum levels or symptoms of lidocaine toxicity
occurred in this study
[113]
.
b) The administration of intravenous lidocaine 2 milligrams/kilogram
as pretreatment for endotracheal intubation minimized autonomic
reflex responses in a placebo-controlled study of 60 children (mean
age 3.5 years) undergoing outpatient surgery. Patients received
atropine, promethazine and chloral hydrate as pre-medication (no
muscle relaxants); anesthesia was induced with inhalation of nitrous
oxide and halothane. Administration of lidocaine or placebo (saline)
preceded laryngoscopy by 90 seconds. In contrast to the placebo
group, lidocaine-treated subjects did not experience a cough reflex
or increased intraocular pressure. Although heart rate and mean
arterial pressure increased in both groups, the extent was
significantly less with lidocaine
[114]
.
Retrobulbar infiltration of local anesthetic
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Used for retrobulbar block during cataract surgery
c) Adult:
1) The results of a randomized, prospective, double-blind study
involving 60 elderly patients indicate that the addition clonidine 2
micrograms/kilogram to 3 to 4 milliliters of 2% lidocaine for
retrobulbar block during cataract surgery produces a greater
decrease in intraocular pressure (p less than 0.01) by 43% and a
small but significant reduction in blood pressure (p less than 0.01)
compared with the same dose of lidocaine without clonidine. The
median duration of analgesia (p less than 0.01) and akinesia (p less
than 0.05) was greater in patients receiving the lidocaine-clonidine
combination as compared to lidocaine alone. In addition, the
lidocaine-clonidine combination produced a greater sedative effect
than lidocaine alone (p less than 0.01)
[123]
.
Seizure
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class IIb; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective for treatment of epilepsy resistant to other drugs
Non-sedating and rarely depresses the cardiovascular or respiratory
systems
c) Adult:
1) GENERAL INFORMATION
a) LIDOCAINE seems to be a safe and effective anticonvulsant
when used with appropriate precautions. It has the benefits of being
non-sedating and it rarely depresses the cardiovascular or
respiratory systems at therapeutic levels of 2 to 5 mcg/mL (Morris,
1979)
[125]
. LIDOCAINE has been successfully used in the treatment of
STATUS EPILEPTICUS resistant to other drugs. Intravenous
lidocaine 1.5 to 2 milligrams/kilogram (mg/kg) has been
recommended for status epilepticus refractory to benzodiazepines
and phenytoin. If lidocaine terminates the episode, a continuous
infusion of 3 to 4 mg/kg/hour can be considered to prevent
recurrence
[126]
[127]
[66]
; (Morris, 1979)
[128]
[129]
[130]
[131]
.
2) Intravenous LIDOCAINE was reported effective in the treatment
of status epilepticus in an open study involving 8 patients
[127]
. LIDOCAINE was used in patients with severe obstructive lung
disease and/or convulsive status epilepticus unresponsive to IV
DIAZEPAM. PHENYTOIN IV was also given initially to all patients.
LIDOCAINE was given initially in doses of 100 milligrams (1.5 to 2
milligrams/kilogram) intravenously over 2 minutes, followed by a
repeat dose if recurrence of seizures was observed; a LIDOCAINE
infusion was initiated (3 to 4 mg/kg/hr) if required. Although transient
subsidence of seizures occurred with the initial 100 mg LIDOCAINE
dose, doses of 200 mg were required to control status effectively in
most patients. LIDOCAINE, alone or in conjunction with
PHENYTOIN, is recommended by the authors as an alternative to
DIAZEPAM in status epilepticus in patients unresponsive to IV
DIAZEPAM or in patients where respiratory depression is
undesirable.
d) Pediatric:
1) Intravenous (IV) lidocaine and lidocaine tapes were effective in
controlling intractable seizures in a 6-year-old patient with
intractable epilepsy associated with leukoencephalopathy
secondary to the treatment of central nervous system leukemia.
Following unsuccessful treatment with conventional antiepileptic
drugs, IV lidocaine (2 milligrams(mg)/kilogram(kg)/dose) was
attempted which reduced the epileptic spikes and polyspike
discharges. A continuous lidocaine infusion (1 mg/kg/hour; serum
level 0.14 mcg/mL) reduced the frequency of complex partial
seizures. IV lidocaine was substituted with lidocaine tapes to
maintain the effective serum level. Four lidocaine tapes, each
containing 18 mg of lidocaine, were used every 8 hours (12
tapes/day) which yielded a serum level of approximately 0.2
mcg/mL. After 1 month of treatment the seizures disappeared.
Subsequently, oral mexiletine (20 mg/kg/day) was substituted for
lidocaine with continued good control of seizures
[132]
.
Spinal anesthesia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIa
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Produces effective anesthesia by the spinal route of administration
c) Adult:
1) Results of a double-blind, randomized study indicate that lowdose hyperbaric 0.5% lidocaine and 5% lidocaine solution,
administered via an indwelling subarachnoid catheter, provide
equivalently effective continuous spinal anesthesia in elderly
patients undergoing urologic surgery. Patients (n=40) received an
initial 30 milligram (mg) bolus of hyperbaric lidocaine in the form of
either 6 milliliters (mL) of 0.5% solution or 0.6 mL of 5% solution.
Additional 30 mg boluses (up to a total of 90 mg) were given if
required. The median peak level of sensory anesthesia was
significantly (p=0.043) higher in patients receiving 0.5% lidocaine
compared with those given the 5% solution. However, the onset and
duration of sensory anesthesia and the time to peak sensory level
were comparable for both solutions. Hemodynamic effects were
also comparable for both solutions
[214]
.
2) The results of 1 randomized, single-blind study involving 30
women undergoing outpatient laparoscopy indicate that small-dose
hypobaric lidocaine-fentanyl spinal anesthesia is more
advantageous than conventional-dose hyperbaric lidocaine. In this
study, patients were administered either a small-dose hypobaric
solution of 1% lidocaine 25 milligrams (mg) made up to 3 milliliters
(mL) by the addition of fentanyl 25 micrograms (mcg) (group 1) or a
conventional-dose hyperbaric solution of 5% lidocaine 75 mg (in
7.5% dextrose) made up to 3 mL by the addition of 1.5 mL 10%
dextrose (group 2). Intraoperative hypotension requiring treatment
with ephedrine occurred in 54% of patients in group 2 and in 0% of
group 1 patients. Median time for full motor recovery was 50
minutes in group 1 patients compared with 90 minutes in group 2
patients (p=0.0005) and sensory recovery occurred faster in group 1
patients than in group 2 patients (p=0.0001). The incidence of
pruritus was significantly higher in group 1 patients than in group 2
patients (p less than 0.025). There was no significant difference
between the two groups in incidence of backache at any time.
Postoperative headache occurred in 38% of all patients
[215]
. The results of a related study involving 64 women undergoing
outpatient laparoscopy indicate that 25 mcg appears to be the
optimal dose of fentanyl (compared with 0 mcg and 10 mcg
fentanyl) to be added to small-dose hypobaric lidocaine (20 mg)
spinal anesthesia for outpatient laparoscopy
[216]
.
3) Lidocaine 1.5% in 7.5% dextrose provided equivalent spinal
anesthesia to hyperbaric lidocaine 5% in a study of 51 male
subjects undergoing lower abdominal surgery (hernia repair). For
both sensory and motor blockade, no significant differences in
onset, degree and duration of anesthesia occurred. Although further
study is required, the lower lidocaine concentration may be
preferred as having less neurotoxic potential
[217]
.
4) As a "top-up" agent for combined spinal epidural anesthesia in 8
healthy volunteers, lidocaine was more efficacious than saline in
terms of prolonging sensory and motor block. Following epidural
injection of 50 milligrams lidocaine, an additional "top-up" agent (10
mL saline, 10 mL lidocaine 1.5%, or 2.5 mL saline as control) was
administered at the time of two-segment dermatomal regression to
pinprick, in a randomized, double-blind, triple crossover design.
Lidocaine significantly extended sensory block by an average 28
minutes and prolonged motor blockade of the quadriceps. Saline, in
contrast, had no effect on sensory or motor block and actually
decreased tolerance to transcutaneous electrical stimulation
[218]
.
Tinnitus
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Can temporarily improve or abolish tinnitus in most patients
See Drug Consult reference:
DRUG THERAPY OF TINNITUS
c) Adult:
1) In a report spanning a 24-year period, use of intravenous (IV)
lidocaine was found to be effective in most patients with subjective
tinnitus of various etiologies. In this study, patients (n=103 (117
ears); mean age 55 years, range 23 to 83 years) with tinnitus were
administered either 60 or 100 milligrams (mg) of IV lidocaine. Within
5 minutes of treatment, lidocaine was completely or partially
effective in 83 ears (70.9%). Overall response in the group as a
whole, tinnitus was absent in 36 ears (30.8%), reduced in 47 ears
(40.2%), unchanged in 26 ears (22.2%), and worse in 8 ears (6.8%).
The best response to treatment was in those with presbycusis
(84.2%) and the worst was in those with acoustic trauma (55.6%).
The 100 mg dose was more effective than the 60 mg dose in
eliminating tinnitus. Following the 100 mg dose, tinnitus was absent
in 29 ears (34.9%) and reduced in 30 ears (36.1%) and following the
60 mg dose, tinnitus was absent in 7 ears (20.6%) and reduced in
17 ears (50.0%); however, when absent and reduced results were
combined, the improvement rates were similar (71.1% vs 70.6%,
respectively). Ears with low- to middle-tone tinnitus (less than 4,000
Hz) had a better response than those with a high-frequency pitch
tinnitus (overall improvement rate, 85.7% vs 64.1%, respectively).
Ears with a hearing level of 40 dB or more had a significantly better
response (p=0.0067) than those with a lower level (overall
improvement rate, 90.3% vs 64.7%, respectively). Patients who
were 60 years or older experienced a significantly better response
(p=0.026) than patients who were younger than 60 years (overall
improvement rate, 82.6% vs 63.4%, respectively). Lidocaine only
provided temporary (several minutes) relief in most cases, but two
patients reported lasting (several months) relief. No significant
adverse effects were reported with either dose
[196]
.
2) In a double-blind crossover study, results demonstrate
improvement or abolishment of tinnitus in 19 of 20 patients with
tinnitus aurium following therapy with LIDOCAINE 1.5
milligram/kilogram intravenously
[197]
.
Topical local anesthetic to mucous membrane
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Viscous lidocaine hydrochloride 2% is indicated to provide topical
anesthesia to irritated or inflamed mucous membranes of the mouth
and pharynx
[53]
Topical local anesthetic to skin
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes (age 3 to 18 years and
older)
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIb; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
The lidocaine tape was effective in decreasing pain associated with
needle insertion
[29]
and with propofol injection
[35]
c) Adult:
1) Patch
a) The results of a double-blind, randomized, placebo-controlled
study involving 101 patients indicate that intraoral 10% (23
milligrams) and 20% (46 milligrams) lidocaine patches are safe and
more effective than placebo for reducing needle insertion pain in the
maxillary and mandibular premolar mucosa of adults. Onset of
analgesia was evident within 2.5 to 5 minutes after placement in the
mandibular arch and within 5 minutes after placement in the
maxillary arch. Maximum analgesic effects occurred between 5 and
15 minutes after placement of the lidocaine patch. Analgesic effects
were evident 30 minutes after patch removal. Analgesia was dose
related with the 20% patch producing analgesia that was more
profound and of longer duration than the 10% patch. Systemic blood
levels of lidocaine following application of the patches were lower
(16 to 22 nanograms/milliliter) than levels reported following
infiltration injection of a single cartridge of 2% lidocaine with
1:100,000 epinephrine (average 220 nanograms/milliliter). There
were no differences in the incidence of adverse effects between the
lidocaine and placebo patches
[22]
.
2) Powder intradermal injection
a) In a randomized, double-blind, parallel-arm, sham-placebo
controlled study of 693 adult patients, less pain was experienced
from venipuncture at the antecubital fossa but not at the back of the
hand following intradermal use of lidocaine hydrochloride powder
injection (Zingo(TM)) compared with placebo. Patients were treated
1 to 3 minutes prior to venipuncture with lidocaine hydrochloride
(n=345) or placebo (n=348) via intradermal application to the back
of the hand or antecubital fossa. Pain measurement was using a
continuous 100 mm visual analogue scale ranging from 0 (no pain)
to 100 (worst possible pain). The adjusted least square mean of the
visual analog scale score was 11.61 in the active treatment group
versus 16.23 in the placebo group (difference -4.62 (standard error
1.55), 95% confidence interval (CI), -7.67 to -1.57)
[56]
. Zingo(TM) has been withdrawn from the U.S. market in 2008.
3) Tape
a) A self-adhesive lidocaine tape available in Japan (Penles(R))
provided relief of pain associated with needle insertion for stellate
ganglion block in a crossover study (n=30). Chronic pain patients
received each of the following in random order, as pretreatment for
a series of stellate ganglion blocks: placebo tape, lidocaine tape (18
milligrams in a controlled-release polymer matrix) administered for 7
minutes, 15 minutes, 30 minutes, and 60 minutes prior to needle
insertion. Visual analog and verbal rating scores for pain were
significantly reduced with lidocaine tape for all time durations as
compared with placebo. Transient skin erythema occurred more
frequently with lidocaine tape (50% with 7 minutes contact, up to
83% with 30 minutes contact)
[29]
.
b) In a placebo-controlled study (n=90), a 60% lidocaine tape
(Penles(R), Japan) successfully decreased the pain associated with
propofol injection when applied for 120 minutes. Pain reduction was
statistically similar to that achieved by mixing lidocaine 40 milligrams
with propofol for intravenous injection
[35]
.
d) Pediatric:
1) Powder intradermal injection
a) In two randomized, double-blind, parallel-arm, placebo-controlled
trials of 1114 pediatric patients ages 3 to 18 years, less pain was
experienced from venipuncture or peripheral cannulation following
intradermal use of lidocaine hydrochloride powder injection
compared with placebo. Patients were treated 1 to 3 minutes prior to
venipuncture or peripheral cannulation with lidocaine hydrochloride
(n=561) or placebo (n=553) via intradermal application to the back
of the hand or antecubital fossa. Pain measurement was evaluated
using the 6-point Wong-Baker FACES pain rating scale, 0 (no hurt)
to 5 (hurts worst). A modified intent-to-treat analysis demonstrated
an adjusted least square mean of the pain rating scale in study one
of 1.77 active treatment vs 2.1 placebo (95% confidence interval
(CI), -0.58 to -0.08), and in study two of 1.38 active treatment vs
1.77 placebo (95% CI, -0.65 to -0.13)
[57]
. Zingo(TM) has been withdrawn from the U.S. market in 2008.
Topical local anesthetic to wound
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIa; Pediatric, Class IIa
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective as a topical local anesthetic
c) Adult:
1) SOLUTION
a) The use of topical anesthetic solutions containing tetracaine,
adrenaline, and cocaine (TAC or TEC), lidocaine and adrenaline
(LE), or tetracaine, lidocaine, and adrenaline (TLE or LET) are
effective methods for providing local anesthesia when treating minor
lacerations. These solutions should not be used on mucous
membranes, large abrasions, digits, pinna of the ear, penis, over
burned or denuded areas, or in other conditions which would
increase the potential for systemic adverse effects
[23]
[24]
[25]
[26]
[27]
.
2) INFILTRATION
a) Buffered lidocaine significantly reduces the pain associated with
local anesthetic infiltration without affecting the wound infection rate
of traumatic wounds. Retrospective analysis of 2711 patients
prospectively enrolled in a wound registry for treatment of traumatic
wounds revealed similar infection rates for patients anesthetized
with plain lidocaine 1% and those anesthetized with lidocaine 1%
with sodium bicarbonate 8.4% in a ratio of 10:1
[58]
.
b) Topical application of lidocaine 4%, epinephrine 1:2000, and
tetracaine 0.5%, compounded into a gel formulation with a final
volume of 3 milliliters, elicited less pain than injection of a buffered
lidocaine epinephrine solution prior to laceration repair in an openlabel study (n=66). Both the gel and injection provided equivalent
anesthesia during suturing
[59]
.
d) Pediatric:
1) GEL/SOLUTION
a) GENERAL
1) The use of topical anesthetic solutions and gels containing
tetracaine, epinephrine (adrenaline), and cocaine (TEC or TAC) or
tetracaine, lidocaine, and epinephrine (TLE or LET) are effective for
topical anesthesia for the repair (suturing) of minor dermal
lacerations of the face and scalp in children
[36]
[37]
[38]
. However, application of topical aqueous 1% lidocaine alone, when
placed on a laceration for 10 minutes, does not decrease pain from
the subsequent lidocaine injection in children with simple lacerations
[39]
.
b) Topical anesthetic solutions or gels containing lidocaine (4%),
epinephrine (0.1%), and tetracaine (0.5%) (LET) are equally
effective for providing local anesthesia during suturing of
uncomplicated lacerations of the face and scalp in children. The gel
may be preferred because it is easier to apply and it tends to remain
where it is placed, therefore it has less potential to drain out of the
laceration and onto mucous membranes and ocular surfaces
[36]
.
c) The combination solution of lidocaine, epinephrine, and
tetracaine (LET) is as effective as the combination of tetracaine,
epinephrine, and cocaine (TEC) for topical anesthesia during
suturing of uncomplicated lacerations on the face and scalp in
children. A double-blind, randomized, controlled study involving 171
children with lacerations on the face and scalp requiring suturing
found that LET is an effective alternative to TEC in children. There
was no difference between LET and TEC in adequacy of anesthesia
or duration of anesthesia before or during suturing
[38]
.
Ventricular arrhythmia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class IIb; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Effective for the treatment of serious ventricular arrhythmias
Lidocaine is a second-line agent for monomorphic ventricular
tachycardia (VT); lidocaine is less effective than procainamide,
sotalol, and amiodarone in terminating VT and when administered to
patients with or without a history of myocardial infarction with
spontaneous sustained stable VT in the hospital setting
[85]
.
Effective for treatment of ventricular arrhythmias secondary to
digitalis toxicity
c) Adult:
1) GENERAL
a) Lidocaine is effective for the treatment of serious ventricular
arrhythmias. Lidocaine is considered the drug of choice for the
acute treatment of ventricular tachycardia (VT), ventricular fibrillation
(VF), and digitalis-induced ventricular tachyarrhythmias. Lidocaine is
effective for the control of ventricular arrhythmias that occur during
cardiac surgery or catheterization. Routine prophylactic use of
lidocaine for the treatment of acute myocardial infarction (AMI) is
NOT recommended, with the possible exception being situations in
which a defibrillator is unavailable. Studies have shown that
prophylaxis with lidocaine significantly reduces the incidence of
primary VF in the pre- hospital and early hospital settings; however,
prophylactic use of lidocaine has been associated with a trend
toward increased mortality, most likely from fatal episodes of
bradycardia, asystole, and electromechanical dissociation. Episodes
of VF and monomorphic VT associated with angina, pulmonary
congestion, or hypotension should be treated with immediate directcurrent countershock. Monomorphic VT not associated with angina,
pulmonary congestion, or hypotension should be treated with
intravenous lidocaine, procainamide, or amiodarone. Lidocaine is
the drug of choice for AMI when episodes of VF/VT are not easily
converted by defibrillation and epinephrine (ie, resistant VF/VT).
Ideally, if a lidocaine infusion is initiated, it should be maintained for
only 6 to 24 hours and then discontinued so that the patient's need
for antiarrhythmic therapy can be reassessed
[86]
[87]
[88]
[89]
[90]
[66]
[91]
[92]
[93]
[94]
[95]
[96]
[97]
[98]
.
b) Ventricular arrhythmias uncommonly are resistant to LIDOCAINE
(Aldeman et al, 1974). Most cases of lidocaine resistance are
probably due to errors in applying pharmacokinetic principles in
dosing the drug. True LIDOCAINE resistance can be documented
by the presence of LIDOCAINE levels of 8 to 9 mcg/mL without
adequate ventricular arrhythmia suppression.
2) ISOFLURANE-INDUCED TACHYCARDIA
a) Pre-treatment with endotracheal 0.4 milliliter lidocaine 8% spray,
but not intravenous (IV) administration of lidocaine (32 milligrams),
reduces isoflurane induced tachycardia which typically follows a
rapid increase in isoflurane concentration. In this randomized study,
patients (n=72) were initially stabilized with oxygen and isoflurane
1%. Following a rapid increase to 3% isoflurane, the increase in
heart rate was significantly less (p less than 0.05) in patients that
received pre-treatment with endotracheal lidocaine compared with
those that received pre-treatment with IV lidocaine or did not receive
any pre-treatment. Heart rate increased similarly in the IV lidocaine
group and the no pre-treatment group. The plasma lidocaine
concentration was lower in the endotracheal group (0.4 mcg/mL)
than in the IV group (1.5 mcg/mL) (p less than 0.05)
[31]
.
3) OUT-OF-HOSPITAL USE
a) Although unavailable in the United States, intramuscular
administration of lidocaine (300 milligrams; 3 milliliters of a 10%
solution) has been effective in the treatment of ventricular
arrhythmias based on limited studies
[99]
[100]
[101]
.
b) Self-administration of lidocaine via intramuscular auto-injector
has been safely used for documented ventricular tachyarrhythmias.
A medical organization in Israel monitored the cardiac rhythms of its
patients via portable transtelephonic electrocardiographic (ECG)
transmitters. Symptomatic patients were instructed to self-inject
lidocaine 300 milligrams (3 milliliters of 10%, LidoPen(R)) into the
quadriceps muscle if the ECG showed sustained wide-QRS
tachycardia of ventricular origin with rate over 100 beats per minute,
or multiple premature ventricular complexes (PVCs) with chest
discomfort. A mobile intensive care unit was simultaneously
dispatched to the scene. A total of 112 patients received 137
injections with no complications reported. Of 76 cases of sustained
ventricular tachycardia, 34 (45%) either converted to sinus rhythm
or experienced rate slowing greater than 30%. Of 30 cases of
multiple PVCs and/or nonsustained ventricular tachycardia, 37%
achieved similar outcomes. A wide QRS-tachycardia, subsequently
determined to be of supraventricular origin, accounted for the
remaining 31 self-injections
[99]
.
c) Patients found in ventricular fibrillation following out-of-hospital
cardiac arrest have a return of spontaneous circulation (ROSC)
more frequently and are hospitalized alive more frequently when
treated with lidocaine prior to hospital admission when compared
with patients not treated with lidocaine. However, there was no
significant difference in the rate of hospital discharge between the
groups
[102]
.
d) Available data indicates that because of adverse reactions and
inadequate blood levels, ORAL lidocaine has limited value in the
treatment of ventricular arrhythmias. Adverse effects such as
dizziness, light-headedness, and numbness of the tongue have
been reported with 500 milligram oral doses of lidocaine.
Therapeutic blood levels have not been consistently achieved
following oral dosing
[103]
[104]
[105]
.
Ventricular fibrillation
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors
efficacy
Recommendation: Adult, Class IIb; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
b) Summary:
Lidocaine hydrochloride monohydrate powder intradermal injection
system (Zingo(TM)) was recalled on November 11, 2008 due to
nonsafety-related regulatory compliance issues which could affect
product shelf life. Anesiva has no plans to distribute Zingo(TM) in
the future
[254]
.
Lidocaine is considered an alternative to amiodarone for the
treatment of ventricular fibrillation/pulseless ventricular tachycardia
associated with cardiac arrest
[85]
c) Adult:
1) General Information
a) According to the American Heart Association Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular
Care, lidocaine is considered an alternative to amiodarone for the
treatment of ventricular fibrillation/pulseless ventricular tachycardia
associated with cardiac arrest
[85]
.
2) In patients with out-of-hospital shock-resistant ventricular
fibrillation (VF), amiodarone was significantly more effective than
lidocaine. In this double-blind controlled study (Amiodarone versus
Lidocaine in Prehospital Ventricular Fibrillation Evaluation (ALIVE)),
patients (n=347) with multiple shocks and epinephrine-resistant VF
received placebo and amiodarone (5 milligrams/kilogram (mg/kg)) or
lidocaine (1.5 mg/kg) by rapid infusion. Patients received additional
defibrillator shocks as necessary and if VF persisted, a second dose
of study drug (1.5 mg/kg lidocaine or 2.5 mg/kg amiodarone) was
given. The mean time interval from paramedic dispatch to arrival on
scene and dispatch to drug administration was 7 and 25 minutes,
respectively. Significantly more patients survived to hospital
admission following treatment with amiodarone compared with
lidocaine (22.8% vs 12%; p=0.009). Shorter time intervals from
paramedic dispatch to drug administration and transient return of
spontaneous circulation prior to drug administration were associated
with increased survival to hospital admission. Among patients for
whom the time from dispatch to drug administration was equal to or
less than the median (24 minutes), 27.7% of patients given
amiodarone and 15.3% of patients given lidocaine survived to
hospital admission (p=0.05). Amiodarone-treated patients had a
better outcome than lidocaine-treated patients at all measured time
intervals, and the benefit was consistent whether the drug was given
early or late during the course of resuscitation. However, the
percentage of patients who survived to hospital discharge was not
significantly different between the two groups
[106]
.
Comparative Efficacy / Evaluation With Other Therapies
Ajmaline
Ventricular tachycardia
a) In a prospective, non-blinded, randomized study of ajmaline (50
milligrams (mg) injected intravenously (IV) over 3 minutes) and
lidocaine (100 mg injected IV over 3 minutes), ajmaline was
effective in terminating sustained ventricular tachycardia in 19 of 30
hemodynamically stable patients, while lidocaine was effective in
only 4 of 31 patients. Ajmaline prolonged QRS and RR intervals
from 164 to 214 milliseconds and from 371 to 479 milliseconds,
respectively, while lidocaine had no effect on these parameters.
Ajmaline also statistically significantly increased cardiac output from
3.5 liters per minute to 5.5 liters per minute, whereas lidocaine did
not. The authors conclude that ajmaline is more effective than
lidocaine in treatment of sustained ventricular tachycardia in
hemodynamically stable patients
[541]
.
Alfentanil
Injection site pain - Propofol adverse reaction
a) In a randomized, double-blind, placebo-controlled study involving
89 patients undergoing elective surgery, the use of lidocaine 40
milligrams added to 180 mg of propofol or alfentanil 1 mg 30
seconds prior to propofol are both equally effective for reducing pain
during injection of propofol
[633]
.
Amiodarone
Cardiac arrest - Ventricular fibrillation
a) In patients with out-of-hospital shock-resistant ventricular
fibrillation (VF), amiodarone is significantly more effective than
lidocaine. In this double-blind controlled study (Amiodarone versus
Lidocaine in Prehospital Ventricular Fibrillation Evaluation (ALIVE)),
patients (n=347) with multiple shocks- and epinephrine-resistant VF
received placebo and amiodarone (5 milligrams/kilogram (mg/kg)) or
lidocaine (1.5 mg/kg) by rapid infusion. Patients received additional
defibrillator shocks as necessary and if VF persisted, a second dose
of study drug (1.5 mg/kg lidocaine or 2.5 mg/kg amiodarone) was
given. The mean time interval from paramedic dispatch to arrival on
scene and dispatch to drug administration was 7 and 25 minutes,
respectively. Significantly more patients survived to hospital
admission following treatment with amiodarone compared with
lidocaine (22.8% vs 12%; p=0.009). Shorter time intervals from
paramedic dispatch to drug administration and transient return of
spontaneous circulation prior to drug administration were associated
with increased survival to hospital admission. Among patients for
whom the time from dispatch to drug administration was equal to or
less than the median (24 minutes), 27.7% of patients given
amiodarone and 15.3% of patients given lidocaine survived to
hospital admission (p=0.05). Amiodarone-treated patients had a
better outcome than lidocaine-treated patients at all measured time
intervals, and the benefit was consistent whether the drug was given
early or late during the course of resuscitation. However, the
percentage of patients who survived to hospital discharge was not
significantly different between the two groups
[648]
.
Ventricular tachycardia
a) Intravenous (IV) amiodarone is significantly more effective than
IV lidocaine in the treatment of shock-resistant ventricular
tachycardia (VT). In this double-blind, parallel design study, patients
(n=29) with shock-resistant VT were randomized to receive up to 2
IV boluses over 2 minutes of either amiodarone 150 milligrams (mg)
(aqueous formulation; "Amio-Aqueous") or lidocaine 100 mg. Bolus
doses were followed by a 24- hour infusion of the assigned drug
(amiodarone 600 mg over 24 hr or lidocaine 2 mg/min over 24 hr).
Patients received an additional bolus followed by a doubling of the
infusion rate if breakthrough VT occurred during the infusion. If the
first assigned drug did not terminate VT, the patient was crossedover to the alternate therapy. Immediate VT termination was
achieved in 78% of patients given amiodarone compared with 27%
of those given lidocaine (p less than 0.05). At 1 hour after the initial
bolus, 67% of patients on amiodarone and 9% of patients on
lidocaine were alive and free of VT (p less than 0.01). At 24 hours,
the success rate (ie, alive and free of VT) was 39% vs 9% for
amiodarone and lidocaine, respectively (p less than 0.01). Due to
treatment failure, 8 patients were crossed over from lidocaine to
amiodarone and 4 patients from amiodarone to lidocaine (p less
than 0.05). Among the 8 patients who crossed over to amiodarone,
5 (63%) had their VT terminated and all 5 survived the 24-hr study
period. Three patients failed to respond to amiodarone and were
discontinued from the study. Among the 4 patients who crossed
over to lidocaine, 3 (75%) experienced VT conversion and 1 of them
survived the 24-hr study period. Hypotension occurred more
frequently with lidocaine than with amiodarone. The incidence of
bradyarrhythmias and asystole was similar between both drugs
[649]
.
Articaine Hydrochloride/Epinephrine
Anesthesia for intraoral procedure, Dental
a) Nerve block or infiltration anesthesia was comparable with
lidocaine 2% with epinephrine 1:80,000 and articaine 4% with
epinephrine 1:200,000 in adult patients undergoing tooth extraction
(type unspecified) and in healthy adult subjects in randomized
studies
[604]
[605]
. Mean times to onset of anesthesia and anesthesia duration were
similar with each agent.
b) A faster onset and more prolonged duration has been observed
with articaine compared to lidocaine in some studies using solutions
containing equal concentrations of epinephrine
[604]
; however, the 1:80,000 concentration is most often used with
lidocaine in the clinical setting.
c) In a double-blind study, mean times to onset of anesthesia were
187 seconds and 201 seconds following maxillary infiltration with
0.6-milliliter (mL) doses of articaine 4% (epinephrine 1:200,000) and
lidocaine 2% (epinephrine 1:80,000), respectively, in healthy
subjects; durations of anesthesia were also similar (about 25
minutes)
[604]
.
Brachial plexus block by axillary approach
a) Limited data suggest the comparable efficacy of articaine 1.5%
and lidocaine 1.5%, each with epinephrine 5 micrograms/milliliter
(mcg/mL)), in patients undergoing axillary brachial plexus
anesthesia for hand or forearm surgery. Onset of surgical analgesia
was approximately 10 minutes after each agent. No adverse events
were observed
[603]
.
Epidural anesthesia
a) Epidural articaine 2% and epidural lidocaine 2% (each with
epinephrine 1:200,000) were comparable with respect to onset,
spread of anesthesia, duration, and motor blockade in male patients
undergoing transurethral surgery in a double-blind comparison
[606]
. Anesthesia onset and duration in this study were 16 and 60
minutes with articaine and 15 and 64 minutes with lidocaine,
respectively. Adverse effects were comparable in severity and
incidence.
Intravenous anesthesia, Regional
a) Articaine 0.5% and lidocaine 0.5% (each without epinephrine)
have been similarly effective for providing intravenous regional
anesthesia in small randomized studies
[607]
[608]
. In these investigations, 40 milliliters (mL) anesthetic was given
over 30 seconds; onset of surgical analgesia (loss of pinprick
sensation) was faster with articaine (2.5 versus 11 minutes).
However, only small numbers of patients were evaluated, and a
larger study investigating various injection rates is warranted; there
is some evidence of a more rapid onset of articaine with higher
doses.
Spinal anesthesia
a) In a double-blind study involving elderly male patients undergoing
spinal anesthesia for urological procedures, onset of analgesia in
the inguinal region was similar with intraspinal lidocaine and
articaine (about 2 minutes), whereas motor block occurred
significantly faster in the articaine group (mean, 2.3 versus 3.1
minutes); loss of tactile sensation in the inguinal region was also
faster with articaine (3.5 versus 4.5 minutes). Duration of analgesia
was similar between groups (total duration, approximately 110
minutes). Lidocaine and articaine were administered as 5%
hyperbaric solutions (10% glucose), each in a dose of 0.025
milliliter/kilogram (mL/kg)
[609]
. Despite achieving statistical significance, the differences in favor of
articaine in this study are not clinically significant, and both agents
should be considered virtually comparable with regard to quality and
duration of analgesia, motor block, and adverse effects (mainly
hypotension; similar incidence of adverse effects in each group).
Benoxinate
Anesthesia for procedures on eye
a) A significant reduction in pain caused by needle insertion during
regional anesthesia of the eye was observed with both topical
benoxinate 0.4% and topical lidocaine 4% in a randomized, doubleblind study of 90 patients (p less than 0.05). The eye drops were
instilled into the conjunctiva 5 minutes before needle insertion and
results were compared with a balanced salt solution. Visual
analogue scale pain scores were significantly lower with anesthetic
pre-treatment. Patient comfort and the anesthetic effect of
benoxinate eye drops were significantly improved when cotton tip
sticks soaked with benoxinate solution were placed on the
conjunctiva
[595]
.
b) Sub-Tenon's infiltration with lidocaine solution demonstrated
superior anesthetic effects to benoxinate in a randomized study of
35 patients undergoing small incision self-sealing
phacoemulsification cataract surgery. Patients either received
surface anesthesia with 0.4% benoxinate solution instilled into the
cornea or conjunctiva, or a subconjunctival injection of 2% lidocaine
with 1:200000 adrenaline. Pre-treatment for the sub-Tenon's
technique consisted of topical anesthesia with benoxinate drops.
Pain assessment was performed by a visual analogue pain score
chart. Seven patients in the benoxinate group and three patients in
the lidocaine group experienced pain during surgery. The median
pain score was significantly lower in the lidocaine group (p = 0.004)
[596]
.
Benzocaine
Topical local anesthetic
a) Both topical lidocaine and topical benzocaine are effective
anesthetics. One study has reported the similar efficacy of topical
benzocaine (Cetacaine(R) and Hurricaine(R)) and 10%
Xylocaine(R) spray as topical anesthetics prior to upper
gastrointestinal endoscopy
[567]
.
b) Lidocaine has a spectrum of current use which is similar to that of
benzocaine (surface anesthesia of ear, nose, throat, urethra and
skin). However, benzocaine appears to be a common sensitizer
which can produce allergic dermatitis
[568]
, whereas lidocaine produces little sensitization
[569]
[570]
. On this basis, lidocaine may be preferable to benzocaine for
topical anesthesia.
c) Lidocaine is also a useful alternative agent for topical anesthesia
in benzocaine-sensitive subjects. Lidocaine is an amide type
anesthetic whereas benzocaine is an ester. Ester-type local
anesthetics do not cross-react with amides
[571]
[572]
.
Bretylium
Ventricular fibrillation
a) Bretylium tosylate and lidocaine hydrochloride appear to equally
effective in the initial management of ventricular fibrillation (or
equally ineffective). Patients received either bretylium tosylate 500milligram or lidocaine 100-milligram boluses. An organized rhythm
was achieved in 89% and 93% and a stable perfusing rhythm was
obtained in 58% and 60% of the patients treated with bretylium and
lidocaine, respectively. The organized rhythm was first established
after an average of 10.4 minutes and 10.6 minutes, respectively,
following the initiation of advanced life support. Patients receiving
bretylium required an average of 2.8 defibrillatory shocks and
patients receiving lidocaine required an average of 2.4 defibrillatory
shocks. In no case was chemical defibrillation observed. Bretylium
did not offer any advantages or disadvantages when compared to
lidocaine in the initial management of ventricular fibrillation
[583]
.
b) One study compared the efficacy of bretylium and lidocaine in
preventing post-infarction arrhythmias in 31 consecutive patients
[584]
. Bretylium was administered in 5 milligram/kilogram doses
intramuscularly every 6 hours. Lidocaine 2 mg/minute via
continuous infusion after a loading dose of 2 milligram/kilogram.
Both drugs were administered for 48 hours after admission.
Incidence of arrhythmias was similar in both groups. Neither
bretylium nor lidocaine caused significant changes in heart rate, but
bretylium tosylate did shorten left ventricular ejection time and lower
systolic arterial blood pressure. Bretylium was discontinued in 7
patients because of hypotension, 2 of whom developed signs of
impending circulatory shock (mental changes, decrease in urine
flow, metabolic acidosis, cold clammy skin). Both drugs were
equally effective in preventing cardiac arrhythmias during the 48
hours of the trial. However, the substantial and unpredictable
circulatory effects of bretylium in acute myocardial infarction
contraindicates its routine use as the drug of choice in the
prophylaxis of malignant arrhythmias.
Bupivacaine
Anesthesia
a) One study compared the analgesic effects of lidocaine with
bupivacaine in 335 patients during labor administered via extradural
blockade
[525]
. Complete pain relief was obtained in 80% of patients receiving
bupivacaine and 56% of patients receiving lidocaine. Similar results
were obtained with the addition of epinephrine. In a similar
comparative study, a continuous extradural infusion of lidocaine did
not provide adequate analgesia during labor and delivery
[526]
. Bupivacaine provided a significantly better quality of analgesia
during both the first and second stages of labor and required fewer
additional boluses. However, patients receiving lidocaine
experienced a low incidence of motor block, a shorter duration of
second stage, a higher rate of spontaneous vaginal delivery, and a
decreased requirement for oxytocin augmentation.
b) One study compared 0.5% bupivacaine plus epinephrine
1/200,000 with 1% lidocaine plus epinephrine 1/200,000 in facial
plastic surgery. The 2 mixtures had comparable potency, however,
patients receiving bupivacaine required fewer postoperative
analgesics and experienced a longer duration of anesthesia
[527]
.
c) In a prospective, randomized, double-blind trial, bupivacaine
0.25% was superior to lidocaine 1% in producing analgesia during
and after suturing of minor lacerations
[528]
. The mean time to onset of analgesia following lidocaine injection
was 3 minutes; with bupivacaine the onset was 3.5 minutes. The
degree of pain experienced prior to treatment, as rated by patients,
was similar between groups. Following suturing, patients receiving
bupivacaine (n=54) rated themselves as having less pain than those
receiving lidocaine (n=50). The difference between groups was
significant between 1 and 6 hours after suturing; at 30 minutes, and
12, 18, and 24 hours no difference in pain scores was observed.
None of the patients in either group experienced adverse effects.
Another study also reports a significantly longer duration of action
with bupivacaine when compared with lidocaine
[529]
.
d) In a randomized, double-blind, prospective study, the
combination of 1% LIDOCAINE/0.25% BUPIVACAINE achieved no
significant difference with respect to pain on injection site or onset of
local anesthesia, when compared to 0.25% BUPIVACAINE alone
[530]
.
e) Spinal anesthesia with 0.5% bupivacaine 3 milliliters (mL) at L3-4,
was similarly effective and tolerable as a combined peripheral nerve
block with 1.33% lidocaine and epinephrine (1:240,000) 30 mL
(lumbar) plus 10 mL (sacral) and 5 mL of 1% lidocaine (iliac crest) in
a study of 29 elderly subjects (mean age 85 years) undergoing
surgical reduction of hip fracture. The average decreases in mean
arterial pressure were 27.5% and 37.8% in the nerve block and
spinal anesthesia groups, respectively (p=NS). Age over 85 was
positively related to the extent of blood pressure decline. The
average ephedrine requirement was significantly higher in the spinal
anesthesia group (13 versus 3 milligrams, p=0.015). All
bupivacaine-treated patients experienced complete anesthesia (no
pain), while 4 lidocaine-treated patients had incomplete or
unsatisfactory anesthesia (required extra alfentanil or sedation).
Both techniques were free of complications
[531]
.
Anesthesia for intraoral procedure, Dental
a) When 0.5% bupivacaine with epinephrine (1/200,000) was
compared to 2% lidocaine with epinephrine (1/100,000) to evaluate
postoperative pain following periodontal surgery, the patients
receiving bupivacaine experienced less postoperative pain, a longer
duration of anesthesia, and required fewer postoperative analgesics
[533]
.
b) Bupivacaine and lidocaine were similarly safe and effective when
used for dental anesthesia during bilateral third molar extraction in a
crossover trial (n=23). Each patient received bupivacaine 0.5% with
1:200,000 epinephrine on one side and, on another occasion
separated by at least 1 month, lidocaine 2% with 1:100,000
epinephrine on the contralateral side. Visual analogue pain scores
were statistically similar at 0, 4, 16 and 24 hours after the
procedure. The 8-hour pain scores were significantly lower in the
bupivacaine group (19 versus 34, p = 0.01). Analgesic requirements
did not differ between groups. The only notable cardiovascular
parameter was an equivalent decrease in heart rate between 15 and
30 minutes. No toxicity or adverse effects occurred with either agent
(Bouloux et al, 1999).
Anesthesia for procedures on eye, Corneal, topical
a) Lidocaine, alone or in combination with tetracaine, provided
analgesia of longer duration than did tetracaine alone, bupivacaine
alone, or combined tetracaine and bupivacaine when applied
topically to the cornea. The 34 eyes of 17 healthy subjects were
randomly assigned to one of 5 groups: 0.5% tetracaine
hydrochloride, 4% lidocaine hydrochloride, 0.75% bupivacaine,
tetracaine followed by lidocaine, or tetracaine followed by
bupivacaine. Two-drop doses of topical anesthesia were instilled
into eyes from a 23-gauge hypodermic needle. At 10 minutes after
application, corneal sensitivity, measured by a mechanical stimulus,
was significantly less in eyes treated with lidocaine than in eyes
treated with other agents (p less than 0.005). When tetracaine
preceded lidocaine administration, the subjects did not experience
the pain associated with lidocaine alone
[532]
.
b) Lidocaine, alone or in combination with tetracaine hydrochloride,
provided analgesia of longer duration than did tetracaine
hydrochloride alone, bupivacaine alone, or combined tetracaine
hydrochloride and bupivacaine when applied topically to the cornea.
The 34 eyes of 17 healthy subjects were randomly assigned to one
of 5 groups: 0.5% tetracaine hydrochloride, 4% lidocaine
hydrochloride, 0.75% bupivacaine, tetracaine hydrochloride followed
by lidocaine, or tetracaine hydrochloride followed by bupivacaine.
Two-drop doses of topical anesthesia were instilled into eyes from a
23-gauge hypodermic needle. At 10 minutes after application,
corneal sensitivity, measured by a mechanical stimulus, was
significantly less in eyes treated with lidocaine than in eyes treated
with other agents (p less than 0.005). When tetracaine
hydrochloride preceded lidocaine administration, the subjects did
not experience the pain associated with lidocaine alone
[616]
.
Local anesthetic intercostal nerve block, Extrapleural
a) As a continuous extrapleural intercostal nerve block to alleviate
thoracotomy pain, lidocaine 1% and bupivacaine 0.5%
demonstrated equivalent efficacy in a controlled trial (n=46).
Patients received a loading dose of 10 milliliters (mL), then 0.1
mL/kilogram/hour of either drug. Visual analogue pain scores and
patient-controlled analgesia (morphine) usage were statistically
similar with both drugs. Because lidocaine is shorter acting and
carries less risk of toxicity as utilized in this setting, the authors
recommend lidocaine over bupivacaine for continuous extrapleural
intercostal nerve block (Watson et al, 1999).
Chloroprocaine
Anesthesia for procedure on perineum
a) Chloroprocaine may be preferable to lidocaine for local infiltration
anesthesia of the perineum for episiotomy due to the considerable
fetal exposure following lidocaine administration compared to
chloroprocaine. Investigators determined the amount of
chloroprocaine detectable in the fetus of 17 normal term females
following chloroprocaine local infiltration for episiotomy, and little if
any fetal exposure to the pharmacologically active drug was evident
[640]
.
Intravenous anesthesia, Regional
a) Alkalinized chloroprocaine (ACP) was similar to lidocaine in
producing effective intravenous regional anesthesia (IVRA; Bier
block) of the upper extremity, whereas patients receiving nonalkalinized chloroprocaine (NACP) required significantly more
intraoperative rescue analgesia. In 2 parallel, double-blind clinical
trials, patients undergoing distal upper extremity surgery received
intravenous regional anesthetic block with either 40 milliliters (mL)
lidocaine 0.5% (n=20, each study), 40 mL plain chloroprocaine 0.5%
(n=20, NACP study) or 40 mL alkalinized chloroprocaine 0.5%
(n=20, ACP study; pH adjusted from 4 to 7.6). Fentanyl (NACP
study) or alfentanil (ACP study) was administered as supplemental
analgesia for intraoperative breakthrough pain. Times to sensory
block onset and duration times were similar among all groups.
Significantly more patients in the NACP group required
supplemental analgesia compared with lidocaine (p less than
0.003); the NACP group also exhibited a significantly higher
incidence of injection-region hives (p=0.017) and metallic taste
anomalies (p=0.014) compared with lidocaine. There were no
significant differences observed between ACP and lidocaine groups
with regard either to quantities of supplemental analgesia required,
or number and type of adverse events reported
[635]
.
Paracervical block anesthesia
a) In parturients with preexisting epidural catheters and a baseline
epidural infusion to maintain a T10 sensory level, both lignocaine
with epinephrine and bicarbonate and chloroprocaine with
bicarbonate administered epidurally are able to produce excellent
surgical anesthesia rapidly for urgent cesarean section without
adverse effects on the newborn. Although onset of anesthesia (T4
sensory level) was faster with chloroprocaine than lignocaine (3.1 vs
4.4 min, respectively), the difference may not be clinically
significant. In this study, all patients had preexisting epidural
catheters and were receiving epidural infusions of 0.125%
bupivacaine and 1:400,000 epinephrine to maintain a T10 sensory
level. Patients then received 2 milliliters (mL) of 8.4% sodium
bicarbonate and either 23 mL of 1.5% lignocaine with 1:200,000
epinephrine or 23 mL of 3% chloroprocaine administered in divided
doses over 2 minutes. There were no differences in neonatal
outcomes between lignocaine and chloroprocaine
[636]
.
b) Lidocaine (10 mL of a 1% solution) was reported as effective as
chloroprocaine (10 mL of a 2% solution) in paracervical block for
labor pain. There was no change in uterine activity with either drug
and no side effects were observed
[637]
.
c) One study reported a higher incidence of moderate and severe
backache following epidural injections of chloroprocaine 3% with or
without epinephrine in 54 patients undergoing knee arthroscopy as
compared to lidocaine 2% with or without epinephrine
[638]
. Another study also found that more back pain occurred with
epidural chloroprocaine (Nesacaine-CE(R) was used) than with
epidural lidocaine
[639]
.
Clonidine
Hypertension, Perioperative
a) Clonidine 0.3 milligram orally pre-operatively successfully
attenuated the rise in systolic pressure associated with ketamine
induction anesthesia. Lidocaine 1.5 milligrams/kilogram prior to
induction had no effect
[536]
.
Pain
a) The combination of epidural clonidine 150 micrograms plus
lidocaine 40 milligrams injected in total volume of 3 mL was rated
superior to either drug alone in those dosages for subjective pain
relief assessed 3 hours after injection. Each of the 20 patients had
previously responded to either clonidine or lidocaine; pain was
secondary to a variety of conditions including neuropathy, back, leg,
or pelvic pain, or Wegner's granulomatosis. Twelve of 17 patients
who received all 3 treatments preferred the combination; 4 preferred
clonidine alone, while 1 preferred lidocaine. Evidence of either
sensory (6) or motor (11) block was evident in all 17 patients
receiving the combination, while clonidine alone produced evidence
of blocks in 6 and lidocaine monotherapy 14
[537]
.
b) Combined use of clonidine plus lidocaine for epidural anesthesia
provides for prolonged pain relief with a lower potential for adverse
reactions due to excessive lidocaine serum levels. Epidural
administration of clonidine 300 micrograms plus lidocaine 2% 20 mL
resulted in greater than 50% reduction of peak serum lidocaine
concentrations at 30 minutes following injection. Clonidine-induced
reduction in local blood flow was suggested to result in a reduced
rate of lidocaine systemic absorption. Twenty-four ASA physical
status 1 patients were randomized to receive 20 mL of 2% epidural
lidocaine alone or in combination with either clonidine 300
micrograms, epinephrine 1:200000, or both clonidine and
epinephrine. The only significant change in lidocaine
pharmacokinetic parameters over the following 360 minutes was
reduction of peak serum concentrations by 37% to 54% measured
at 20 to 30 minutes following administration; the combination of
lidocaine, clonidine, and epinephrine did not result in additive
effects. No patient experienced a drop in systemic blood pressure
greater than 25%. Lower clonidine doses (90 to 150 micrograms)
have previously been shown to have no effect on lidocaine
pharmacokinetics
[538]
.
Cocaine
Topical local anesthetic
a) When topical anesthetics are applied at their maximal effective
concentration (MEC) on the tip of the tongue, cocaine (with a MEC
of 20%) exhibits a shorter latent period, an equal or longer duration
of action, and a larger topical dose limit than tetracaine (MEC 1%),
dibucaine (MEC 0.5%) and lidocaine (MEC 4%)
[663]
. Specifically, cocaine has a latent period of 0.3 minutes as
compared to tetracaine, dibucaine, and lidocaine with latent periods
of 1.1, 1.2, and 2 minutes, respectively. The duration of action of
cocaine is 54.5 minutes, as compared to tetracaine, dibucaine, and
lidocaine with durations of 5.5, 46.5 and 15.2 minutes, respectively.
Cocaine has a topical dose limit of 0.2 gram to 0.3 gram as
compared to tetracaine, dibucaine, and lidocaine, with dose limits of
0.025 gram to 0.04 gram, 0.1 gram to 0.2 gram and 0.25 gram,
respectively.
b) When used for topical anesthesia of the larynx, one study found
no significant difference between cocaine and lidocaine in terms of
cardiovascular effects, absorption profile, and efficacy
[664]
.
c) In one clinical trial, nasal inhalation of lidocaine mixed with
adrenaline was similar in efficacy to cocaine in patients undergoing
NASOENDOSCOPY. Patients (n=20) with symptoms of nasal
obstruction were randomized to a total dose of 0.5 milliliter per
nostril (seven puffs for each nostril) of cocaine 10% or 4% lidocaine
with adrenaline 1:1000. Following the anterior RHINOSCOPY
procedure, the degree of discomfort was measured for each patient.
A comparison group of healthy patients (ie, without a history of
nasal obstruction) was also randomized to the two drug treatment
groups for control purposes. The degree of discomfort for both
treatment groups was similar with a majority of patients reporting
mild discomfort (85% for both subject groups). One patient with
nasal obstruction in the lidocaine/cocaine group reported severe
discomfort as opposed to none in the cocaine group. All of the
control patients (100%) reported mild discomfort following
rhinoscopy. Nasal airway resistance (Rn) was significantly reduced
(p less than 0.05) in the patient group for both treatment modalities
AFTER administration of drug. Analysis between the two drug
regimens for difference in Rn was not performed
[665]
.
Dibucaine
Local anesthesia
a) In one study, the anesthetic efficacy of aerosol formulations of
lidocaine 5%, dibucaine 2%, and placebo in 76 primiparous women
with post-episiotomy pain were compared
[534]
. Lidocaine and dibucaine preparations produced significant pain
relief when compared to placebo as evaluated by the patients;
however, lidocaine proved to be more effective than dibucaine. Side
effects only consisted of slight stinging following the application of
lidocaine in 2 patients.
b) In one study, enrolling 150 subjects, the efficacy of a dibucaine
preparation (Nupercainal(R) ointment) to block the sensations of
itch, burning, and pain in normal and sunburned subjects was
compared to other commonly applied topical anesthetic
preparations (benzocaine and lidocaine)
[535]
. Subjects graded their own relief of discomfort secondary to
sunburn induced by a ultraviolet light and electrical stimulation. The
authors concluded that the ability of a local anesthetic to block
sensations of itch, burning, and pain is dependent on whether the
agent is in the salt form, or base form. These investigators found
that local anesthetic agents in concentrated base form are effective,
whereas, the salt forms are ineffective.
Diclofenac
Myofascial pain
a) Diclofenac IM injections were reported superior to lidocaine IM in
the treatment of myofascial pain in a single-blind study involving 24
patients
[634]
. Diclofenac was given in doses of 50 mg in the trigger-point, with
lidocaine being given in doses of 2 mL of a 1% solution.
Dihydroergotamine
Migraine
a) One study compared multiple dose therapy (chlorpromazine 12.5
mg intravenously given at 20-minute intervals, up to 37.5 mg;
dihydroergotamine 1 mg intravenously, repeated if necessary; or
lidocaine 50 mg intravenously given at 20-minute intervals, up to
150 mg) in patients seen in an emergency department for acute
migraine
[629]
. Reduction in mean headache intensity was greatest among
chlorpromazine-treated patients, and more patients experienced
headache relief persisting through the 24-hour follow-up period in
this group relative to the other treatments.
Diltiazem
Extubation of trachea - Hypertension
a) Diltiazem in combination with lidocaine was more effective than
either diltiazem or lidocaine alone in suppressing the hyperhemodynamic response associated with tracheal extubation in
hypertensive patients, in a randomized, double-blind, clinical study.
Patients undergoing elective extremity orthopedic surgery were
given one of the following intravenous regimens 3 minutes after
reversal of anesthesia and 1 minute prior to tracheal extubation:
diltiazem 0.2 milligrams (mg)/kilogram (n=20), lidocaine 1.0 mg/kg
(n=20), or diltiazem 0.2 mg/kg with lidocaine 1.0 mg/kg (n=20).
Heart rate (HR), mean arterial pressure (MAP), and rate-pressure
product (HR multiplied by MAP; RPP) were monitored in postextubation sequential measurements. HR increased in the diltiazem
and lidocaine groups immediately after extubation compared with
baseline (p less than 0.05). MAP and HR increased significantly in
the lidocaine group compared with baseline and the diltiazem group,
and remained elevated after 3 minutes (p less than 0.05). The RPP
increased immediately after extubation in the diltiazem and lidocaine
groups, remaining elevated at 3 minutes post-extubation (p less
than 0.05). The group receiving the combined diltiazem-lidocaine
regimen did not exhibit increases in HR, MAP, or RPP anytime after
tracheal extubation. There were no adverse events reported
[650]
.
Dimethindene
Local anesthesia
a) Using laser algesimetry in healthy volunteers, it was
demonstrated that dimethindene 0.1% gel under occlusion for 45
minutes had more local anesthetic activity than lidocaine 2% gel
occluded for 45 minutes
[524]
. Maximal effects of dimethindene were observed at 2 hours and
persisted for more than 4 hours.
Diphenhydramine
Local anesthesia
a) A clinical trial in healthy volunteers (n=30) reports that 1%
diphenhydramine (DH) was not as effective as 0.9% benzyl alcohol
with 1:100,000 epinephrine (BE) or 0.9% buffered lidocaine (BL). A
volume of 0.5 milliliter of each solution was injected in 3 sites along
the volar aspect of 1 forearm. The main endpoints were pain on
injection and duration of anesthesia. Using a visual analog scoring
system (a score of 100 millimeters (mm) is the maximum), the
scores for DH, BE, and BL were as follows: 55 mm, 12.5 mm, and 5
mm, respectively. DH was not as effective as the 3 other solutions.
BE had the best response (p=0.022). Pain sensation, as determined
by a 20-gauge needle stick, returned within the 45-minute study
period for the following: DH, 63%; BE, 37%; and BL 10%. BL was
significantly better (p less than 0.05) than the 2 other solutions;
however, no difference was noted between DH and BE in terms of
duration of anesthesia. None of the patients reported any serious
adverse effects. The investigators suggests that BE appears to be a
better choice than DE in lidocaine allergic patients. The clinical
application of these results, including larger injectable volumes of
solution, required additional study (Bartfield et al, 1998).
b) In patients with simple lacerations, both buffered and plain 1%
LIDOCAINE with EPINEPHRINE were more effective than either
buffered lidocaine alone or DIPHENHYDRAMINE with epinephrine.
Among the 180 patients in the double-blind study, 45 were
randomized to buffered lidocaine (BL) alone, 46 received buffered
lidocaine with epinephrine (BLE), 47 received lidocaine with
epinephrine (LE), and 42 received diphenhydramine with
epinephrine (DE). Pain on injection and during suturing occurred
less often with BL and BLE. There were no between-group
differences in wound complications or need for additional
anesthesia. Because of several study limitations (small sample size,
unchecked solution pH, uncontrolled rate of injection), statistical
significance of treatment outcomes could not be determined
[627]
.
Dyclonine
Stomatitis
a) A prospective, double-blind study compared viscous lidocaine
plus 1% cocaine, dyclonine 1%, kaolin-pectin solution with
diphenhydramine plus saline, and placebo solution in the treatment
of radiation- and chemotherapy-induced stomatitis in 18 patients.
Based on patient self-evaluation, dyclonine provided the most pain
relief; dyclonine and viscous lidocaine plus cocaine provided the
longest duration of pain relief, which averaged 50 minutes
[628]
.
Ephedrine
Pain following administration of agent - Propofol adverse reaction
a) Ephedrine was as effective as lidocaine in reducing the pain from
intravenous injection of propofol during anesthesia induction;
ephedrine was superior to lidocaine in preventing the reduction in
mean arterial pressure and heart rate commonly associated with
propofol administration. In a randomized, double-blind, placebocontrolled trial, 176 patients undergoing elective surgery were given
an injection of isotonic saline 2 milliliters (mL) (placebo), 2%
lidocaine in 2 mL, or ephedrine 30, 70, 110, or 150
micrograms/kilogram in 2 mL isotonic saline. Thirty seconds after
administration of the test solution, all patients were given
intravenous propofol 2.5 mg/kg. The incidence of pain was 87% in
the placebo group and about 39% +/-4% in all other groups.
Lidocaine and ephedrine were significantly better than placebo for
pain prevention but not different from each other. Mean arterial
pressure (MAP) was decreased in the placebo and lidocaine groups
(compared to pre-induction values) but was maintained in all
ephedrine groups. The authors recommended a small dose of
ephedrine (30 or 70 micrograms/kilogram) prior to anesthesia
induction with propofol
[632]
.
Esmolol
Rapid sequence intubation, Preinduction
a) In randomized single center study comparing the effectiveness of
esmolol, lidocaine, fentanyl and placebo in blunting the sympathetic
response to laryngoscopy and tracheal intubation, esmolol was
significantly more effective than lidocaine and placebo in decreasing
both heart rate and systolic blood pressure, and significantly more
effective than fentanyl in decreasing tachardia. Patients undergoing
elective, noncardiac procedures were randomized to receive
esmolol 2 milligrams/kilogram (mg/kg) (n=20), lidocaine 2 mg/kg
(n=20), fentanyl 3 micrograms/kg (n=20), or normal saline (n=20)
three minutes prior to laryngoscopy and intubation. Patients were
premedicated with diazepam and received thiopental and
succinylcholine to facilitate the intubation. After intubation, systolic
arterial blood pressure (BP) and heart rate were recorded every
minute for 10 minutes. The incidence of post-intubation tachycardia
(heart rate greater than 100 beats per minute) was significantly
lower in esmolol-treated patients at 15% (3/20) compared to
placebo-, lidocaine- and fentanyl-treated patients at 85% (17/20),
75% (15/20), and 55% (11/20), respectively (p less than 0.05).
Esmolol-treated patients had a 20% (4/20) incidence of postintubation hypertension (systolic BP over 180 mmHg) compared to
80% (16/20) and 70% (14/20), in placebo- and lidocaine-treated
patients, respectively (p less than 0.05)). The incidence of
hypertension in fentanyl-treated patients was 40% (8/20)(not
statistically significant)
[565]
.
b) In a double-blind, randomized fixed dose study comparing the
effectiveness of esmolol, lidocaine, fentanyl, and placebo in blunting
the sympathetic response to laryngoscopy and tracheal intubation,
esmolol was the only medication to protect against both the heart
rate and systolic blood pressure increases that accompany
laryngoscopy and tracheal intubation. Patients (46 to 53 years; 78 to
82 kilograms) undergoing noncardiac surgery were randomly
assigned to receive fixed pre-intubation doses of placebo, lidocaine
200 milligrams (mg), fentanyl 200 micrograms, or esmolol 150 mg
two minutes prior to intubation. Patient were pre-medicated with
glycopyrrolate and midazolam and received thiopental and
succinylcholine prior to intubation. After intubation, heart rate and
systolic blood pressure were monitored for 10 minutes. Maximum
percent increases in heart rate were 44% +/- 6% in the placebo
group, 51% +/- 10% in the lidocaine group, 37% +/- 5% in the
fentanyl group, and 18% +/- 5% in the esmolol group (p less than
0.05 compared to placebo). Maximum systolic blood pressure
percent increases were 20% +/- 6% in the lidocaine group, 12% +/3% in the fentanyl group, 19% +/- 4% in the esmolol group, and
36% +/- 5% in the placebo group (p less than 0.05). Esmolol was
the only medication to protect against both increases in heart rate
and blood pressure. Lidocaine and fentanyl provided protection
against systolic blood pressure, but not heart rate
[566]
.
c) In patients with isolated head trauma, there was no difference in
the effectiveness of esmolol and lidocaine in blunting the
sympathetic response to intubation in a prospective double-blind,
randomized study. Patients (mean age 44.1 years; range 20 to 82
years) entering the emergency room with isolated head trauma
requiring intubation were randomized to receive esmolol 2
milligrams/kilogram (mg/kg) (n=16) or lidocaine 2 mg/kg (n=14)
three minutes prior to intubation. Patients were premedicated with
midazolam, and received vecuronium and succinylcholine prior to
intubation. Heart rate and blood pressure measurements were
recorded for 8 minutes following intubation. The study had 90%
power to detect a 20 beat/minute difference in heart rate and a 35
mmHg difference in systolic blood pressure and a 20 mmHg
difference in diastolic blood pressure. No significant difference
within or between groups for changes in heart rate or diastolic blood
pressure were observed. A significant difference was found within
group for changes in systolic blood pressure, but there no difference
between groups was detected
[651]
.
d) The results of a randomized, prospective, double-blind, placebo
controlled study indicate that only the combination of lidocaine (1.5
milligrams/kilogram) and esmolol (1 to 2 mg/kg) attenuated both the
heart rate and blood pressure responses associated with
laryngoscopy and tracheal intubation. Neither esmolol nor lidocaine,
when administered alone, affected the blood pressure response.
When administered alone, esmolol was more reliable than lidocaine
for preventing the increase in heart rate associated with tracheal
intubation
[111]
.
Ethyl Chloride
Backache
a) SUMMARY: ETHYL CHLORIDE spray and LIDOCAINE injection
were comparable for relief of back pain.
b) Ethyl chloride spray was no better than an injection of lidocaine
for the control of low back pain
[631]
. A double-blind clinical trial randomized 63 individuals with low back
pain to receive any one of the following: injection of 1.5 milliliters of
1% lidocaine, injection of 0.75 milliliter of 1% lidocaine and 0.75
milliliter of triamcinolone (Aristospan(R)), acupuncture, or a 10second spray of ethyl chloride followed by a 20-second acupressure
[631]
. Although not statistically significant, patients who received
vapocoolant spray with acupressure reported a 67% subjective
improvement in pain compared to the rates of 40% to 61% reported
in the other 3 groups. When the attrition rates are considered, this
group had a 50% improvement rate compared to the 31% to 55%
rates cited in the other groups.
Etidocaine
Anesthesia for intraoral procedure, Dental
a) SUMMARY: Several investigators have compared the clinical
efficacy of etidocaine and lidocaine in oral surgery
[618]
; (Jensen et al, 1981, Danielsson et al, 1986). Although the literature
is conflicting, it appears that etidocaine produces a similar onset and
intensity of anesthesia, and its duration of action far outlasts that of
lidocaine. Some clinicians have suggested that this property may
decrease the need for postoperative analgesics
[619]
[620]
, but this notion has been challenged by other authors
[621]
[622]
.
b) In a double-blind, split-mouth study, 28 patients received
lidocaine and etidocaine via inferior alveolar nerve block for
impacted third molar extraction. While the mean time to onset of
anesthesia was similar (1.8 minutes for lidocaine versus 2 minutes
for etidocaine), regression of anesthesia, defined as the time from
injection of the anesthetic to the start of postoperative pain, was
267.6 minutes with lidocaine, whereas with etidocaine it was 460.6
minutes
[618]
.
c) Similarly, another study found a similar onset of anesthesia (65
seconds for lidocaine versus 75 seconds for etidocaine), but
regression time was 138.8 minutes for lidocaine, and 245.6 minutes
for etidocaine
[621]
.
d) In other studies, the onset and quality of anesthesia produced by
etidocaine was found to be similar to that of lidocaine. However, the
degree of postoperative blood loss was found to be greater with
etidocaine. Etidocaine may have more potent vasodilatory
properties than lidocaine
[623]
[624]
.
Retrobulbar infiltration of local anesthetic
a) In a double-blind comparison of 2% lidocaine with 1:200,000
epinephrine and 1% etidocaine without epinephrine, 50 patients
underwent retrobulbar block for cataract surgery (N=25 in each
group)
[619]
. They found that while both groups had a similar onset of sensory
and motor block (3 minutes), etidocaine produced a significantly
longer duration of sensory anesthesia (301 minutes) than did
lidocaine (199 minutes). The etidocaine group also required less
postoperative medication (48%) than the lidocaine group (75%).
b) In another double-blind study, 62 patients received either a) 2%
lidocaine with 1:200,000 epinephrine, b) etidocaine 1% without
epinephrine, or c) etidocaine 1% with 1:200,000 epinephrine for
retrobulbar anesthesia prior to cataract surgery
[625]
. The onset of both sensory and motor blockade was similar for all
three groups. However, the duration of motor nerve block was much
longer in the etidocaine groups, and a smaller number of these
patients reported pain after cataract removal (17/21 with lidocaine,
9/20 with plain etidocaine, and 9/21 with etidocaine plus
epinephrine). No differences were noted between the etidocaine
groups. Etidocaine was superior to lidocaine because of its longer
duration of action, and also to bupivacaine because of its more rapid
onset of action.
c) One double-blind study evaluated the comparative efficacy of 1%
etidocaine with a 1% lidocaine plus 0.375% bupivacaine
combination in patients undergoing cataract removal. The onset of
action was 0.3 to 10 minutes with either treatment, but a longer
duration of action was observed in the lidocaine/bupivacaine group.
Either choice would be an equivalent alternative in this setting
[626]
.
Adverse Effects
a) Etidocaine may cause considerable pain on injection. When compared
to 0.5% bupivacaine, 2% chloroprocaine, 1% lidocaine, and 1%
mepivacaine in a double-blind fashion, 1% etidocaine produced a
considerably greater amount of pain upon subcutaneous or intradermal
injection than did the other preparations
[617]
.
Fentanyl
Cataract surgery - Pain
a) In a prospective, randomized, double-blinded study (n=96),
topical lidocaine gel provided effective intraoperative analgesia
compared with intravenous fentanyl in pediatric patients (ages 3 to
12 years) undergoing cataract surgery. Children weighing more than
10 kilograms (kg) and scheduled for elective cataract surgery were
randomized to receive 2% topical lidocaine gel (group G; n=48) to
cover the cornea surface (left in contact with cornea for 5 minutes)
or intravenous (IV) fentanyl 2 micrograms (mcg)/kg (group F; n=48)
after anesthesia induction. All children were given intramuscular
ketorolac (1 milligram/kg) for postoperative pain relief; IV boluses of
0.5 mcg/kg of fentanyl were given intraoperatively if supplementary
analgesia was required (increase of more than 20% in baseline
heart rate or mean arterial pressure). Postoperatively, the time to
recovery was evaluated by recording the time needed to achieve a
maximum Aldrete score of 10. Pain was assessed using the
objective pain score (OPS) with IV boluses of fentanyl 0.5 to 1
mcg/kg given for inadequate pain control. After discharge from the
post anesthesia care unit (PACU), oral ibuprofen (10 mg/kg in syrup
form) was given on the nursing unit for pain relief. Intraoperative
fentanyl was needed in 8 patients in group F compared with 1
patient in group G (p=0.0291). Time to reach Aldrete 10 in the
PACU was significantly longer in group F compared with group G
(15.53 +/- 16.21 minutes versus 7.81 +/- 6.82 minutes; p=0.01).
OPS was similar between the 2 groups; supplemental IV fentanyl
was needed in 5 children (10.4%) in group F and 7 children (14.6%)
in group G (p=0.54). In the remaining observation period on the
nursing unit, ibuprofen use was similar between the 2 groups (12
children (25%) in group F and 17 children (35.4%) in group G
received ibuprofen; p=0.27)
[667]
.
Limb stump pain
a) In a crossover study, intrathecal fentanyl 25 mcg was superior to
intrathecal lidocaine 70 mg in providing a quicker onset, better
quality, and longer duration of analgesia in 8 patients with
established lower limb postamputation stump pain. Fentanyl
analgesic effects were evident within 1 to 2.5 minutes and complete
by 5 to 10 minutes with a median duration of 8 hours. Lidocaine
provided good stump relief, with optimal effects occurring at 30
minutes. Unlike fentanyl, lidocaine did not completely relieve pain in
all the patients; 3 of 8 men experienced a lower degree, but
persistent, pain. Both agents were generally well tolerated, however
pruritus, involving the trunk and legs, was the only unique side effect
that occurred in the fentanyl-treated group
[668]
.
Rapid sequence intubation, Preinduction
a) In randomized single center study comparing the effectiveness of
esmolol, lidocaine, fentanyl and placebo in blunting the sympathetic
response to laryngoscopy and tracheal intubation, esmolol was
significantly more effective than lidocaine and placebo in decreasing
both heart rate and systolic blood pressure, and significantly more
effective than fentanyl in decreasing tachardia. Patients undergoing
elective, noncardiac procedures were randomized to receive
esmolol 2 milligrams/kilogram (mg/kg) (n=20), lidocaine 2 mg/kg
(n=20), fentanyl 3 micrograms/kg (n=20), or normal saline (n=20)
three minutes prior to laryngoscopy and intubation. Patients were
premedicated with diazepam and received thiopental and
succinylcholine to facilitate the intubation. After intubation, systolic
arterial blood pressure (BP) and heart rate were recorded every
minute for 10 minutes. The incidence of post-intubation tachycardia
(heart rate greater than 100 beats per minute) was significantly
lower in esmolol-treated patients at 15% (3/20) compared to
placebo-, lidocaine- and fentanyl-treated patients at 85% (17/20),
75% (15/20), and 55% (11/20), respectively (p less than 0.05).
Esmolol-treated patients had a 20% (4/20) incidence of postintubation hypertension (systolic BP over 180 mmHg) compared to
80% (16/20) and 70% (14/20), in placebo- and lidocaine-treated
patients, respectively (p less than 0.05)). The incidence of
hypertension in fentanyl-treated patients was 40% (8/20)(not
statistically significant)
[565]
.
b) In a double-blind, randomized fixed dose study comparing the
effectiveness of esmolol, lidocaine, fentanyl, and placebo in blunting
the sympathetic response to laryngoscopy and tracheal intubation,
esmolol was the only medication to protect against both the heart
rate and systolic blood pressure increases that accompany
laryngoscopy and tracheal intubation. Patients (46 to 53 years; 78 to
82 kilograms) undergoing noncardiac surgery were randomly
assigned to receive fixed pre-intubation doses of placebo, lidocaine
200 milligrams (mg), fentanyl 200 micrograms, or esmolol 150 mg
two minutes prior to intubation. Patient were pre-medicated with
glycopyrrolate and midazolam and received thiopental and
succinylcholine prior to intubation. After intubation, heart rate and
systolic blood pressure were monitored for 10 minutes. Maximum
percent increases in heart rate were 44% +/- 6% in the placebo
group, 51% +/- 10% in the lidocaine group, 37% +/- 5% in the
fentanyl group, and 18% +/- 5% in the esmolol group (p less than
0.05 compared to placebo). Maximum systolic blood pressure
percent increases were 20% +/- 6% in the lidocaine group, 12% +/3% in the fentanyl group, 19% +/- 4% in the esmolol group, and
36% +/- 5% in the placebo group (p less than 0.05). Esmolol was
the only medication to protect against both increases in heart rate
and blood pressure. Lidocaine and fentanyl provided protection
against systolic blood pressure, but not heart rate
[566]
.
Granisetron
Injection site pain - Propofol adverse reaction
a) Granisetron was as effective as lidocaine for the prevention of
pain associated with intravenous propofol injection. In a
randomized, double-blind, placebo controlled study, patients
(n=150) undergoing laparoscopic procedures under general
anesthesia received 5 milliliters (mL) of an intravenous pretreatment
solution into the hand while a tourniquet was applied to the upper
arm. The pretreatment solution contained 1 of 3 solutions; saline
(n=50), 40 milligrams (mg) lidocaine in saline (n=50), or 2 mg
granisetron in saline (n=50). After 2 minutes, the tourniquet was
released and one-fourth of the total propofol dose (2.5 milligrams
per kilogram (mg/kg)) was administered over 5 seconds. The level
of pain on propofol injection was assessed by a clinician blinded to
pretreatment group allocation. Overall incidence of pain was 62%,
18%, and 22% in the saline, lidocaine, and granisetron groups,
respectively. Mild or moderate pain was reported in 16, 7, and 8
patients and severe pain was reported in 15, 2, and 3 patients in the
saline, lidocaine, and granisetron groups, respectively (p less than
0.001 for lidocaine and granisetron groups compared to saline).
Headache in the postoperative period occurred in 2 granisetron
patients; no other adverse events were reported
[630]
.
Guanethidine
Posttraumatic osteoporosis
a) Guanethidine 20 mg in 20 mL of sodium chloride 0.9%
administered distal to a cuff was as effective as a stellate ganglion
block performed with 7 mL of lidocaine 2% combined with 7 mL of
bupivacaine 0.5% via paratracheal route. Eighteen patients suffering
from Sudeck's atrophy were divided into 2 equal groups and treated
with either drug regimen. Although the results of both therapies
were not significantly different, guanethidine was easier to perform
and the blockade lasted longer than the stellate ganglion technique
[564]
.
Lidocaine/Prilocaine
Anal fissure
a) Lidocaine 10% ointment applied twice daily was less effective
than prilocaine 5%/lidocaine 5% eutectic mixture, each applied twice
daily, in the treatment of anal fissures in children (average age, 3
years) in a placebo-controlled study
[554]
. After 8 weeks of treatment, complete fissure healing was observed
in 64% and 29% of children in the lidocaine/prilocaine and lidocaine
groups, respectively.
Catheterization of vein
a) In a randomized, crossover study, dermal analgesia produced by
lidocaine iontophoresis (delivery electrode saturated with 1 milliliter
(mL) of lidocaine 2% with epinephrine) was as effective as topical
application of 2.5 grams (g) lidocaine/prilocaine cream (EMLA(R))
with occlusive dressing in providing pain relief for intravenous
catheter insertion in children (7 to 16 years of age)
[555]
.
Venipuncture
a) Topical liposomal lidocaine 4% (ELA-Max(R)) applied for 30
minutes (no occlusion) and topical lidocaine/prilocaine (EMLA(R))
cream with occlusion applied for 60 minutes were similarly effective
in reducing venipuncture pain in pediatric patients in a randomized,
double-blind study
[556]
.
b) In European studies (n=200), application of EMLA(R) cream for
at least 1 hour was superior to placebo or ethyl chloride in providing
dermal analgesia prior to venipuncture or intravenous cannulation.
The efficacy of EMLA(R) was less than that of intradermal lidocaine,
but similar to that of subcutaneous lidocaine
[557]
.
c) In a double-blind, randomized study, a topical formulation of
tetracaine and lidocaine had a shorter latency period than lidocaineprilocaine cream (EMLA(R)) and fewer adverse events than a more
concentrated tetracaine cream. Patients were children ages 3
months to 10 years undergoing minor elective surgery. One of 3
anesthetic creams was applied to the dorsum of both hands on
venous puncture sites. Group I (n=100) received eutectic 2.5%
lidocaine and 2.5% prilocaine mixture (EMLA(R)), Group II (n=100)
received 4% tetracaine, and Group III (n=100) received a 2.5%
lidocaine and 2.5% tetracaine mixture (AMLI). In children younger
than 1 year, 2 grams (g) per 10 square centimeters (cm(2)) of AMLI
and EMLA(R) cream and 0.5 g/10 cm(2) of 4% tetracaine cream
were applied over a maximum 16 cm(2); for children over 1 year of
age, 2.5 g/10 cm(2) of AMLI and EMLA(R) cream and 1 g/10 cm(2)
of 4% tetracaine cream were applied over a maximum of 32 cm(2).
Within each treatment group, 5 subgroups (n=20 for each subgroup)
were formed based on time before removal of the anesthetic cream.
Sedation state after 0.375 milligram per kilogram (mg/kg)
midazolam premedication and an observational pain score were
recorded before and during venipuncture. Frequency of pain during
puncture was significantly higher in Group I than the other groups
when duration of cream application was 30 minutes or less;
percentage of patients with pain was 85% for Group I and 40% for
Group II and Group III (p less than 0.01). Increasing application time
significantly increased percentage of patients without pain when
compared to the shortest time period (30 minutes or less) in all 3
groups (p less than 0.001 for Groups I, p less than 0.01 for Groups
II and III). AMLI cream showed the greatest efficacy when compared
to the other 2 anesthetic creams at the longest application period
(120 minutes or more). Patients in Group II experienced the greatest
number of adverse events; this difference was significant for the 60
to 90 minute application period subgroup (p less then 0.05). Overall,
EMLA(R) cream had a longer latency period and 4% tetracaine
cream and EMLA(R) both had a higher incidence of adverse events
compared to AMLI cream
[558]
.
Lorcainide
Ventricular arrhythmia
a) In a randomized trial involving 30 patients with frequent
ventricular premature beats (more than 30 per hour) unassociated
with acute infarction, intravenous lorcainide (2 milligrams/kilogram,
then 200 milligrams/24 hours) and lidocaine (1 milligram/kilogram,
then 2 milligrams/minute) were similarly effective in suppressing
repetitive ventricular premature beats
[657]
. Adverse effects were also similar. Another study has reported that
lorcainide and lidocaine decrease the severity of ventricular
premature beats with equal efficacy
[658]
.
b) Lorcainide was reported to be more effective than either lidocaine
or procainamide in preventing ventricular tachycardia induction by
electrophysiological testing. Of 100 patients with symptomatic
ventricular tachycardia, lorcainide was 69% effective, lidocaine 30%
effective and procainamide 50% effective in preventing induced
ventricular tachycardia
[659]
.
c) Twenty-one of 28 patients who had had a myocardial infarction
were protected from ventricular tachycardia by lorcainide
(intravenous bolus 10 milligrams (mg) every 5 minutes to 100 to 200
mg total) on programmed electrical stimulation testing, while only 5
of 21 patients given lidocaine (1 mg/kg of body weight intravenous
bolus once or twice) were protected
[660]
.
d) The effects of lorcainide appear to be longer-lasting than those of
lidocaine. In a double-blind, two-period, cross-over trial, 19 patients
with stable, regularly occurring ventricular premature beats were
randomly given either a lorcainide-placebo-lidocaine or a placebolorcainide-lidocaine sequence. Each dose was administered at
twenty-four hour intervals. Lorcainide was given intravenously at 2
milligrams (mg)/kg at a rate of 5 to 10 mg/minute. Lidocaine was
administered at 100 mg over one minute. Lorcainide decreased the
ventricular premature beats maximally at 30 to 45 minutes by 98%
and 74%, which was prolonged for at least two hours, while
lidocaine produced only a temporary reduction at 30 minutes of 41%
to 86%
[661]
.
e) In a study of thirty patients with complex ventricular arrhythmias
who were randomized to receive either lorcainide 2.0 milligrams
(mg)/kg intravenously at a rate of 2 mg/minute (with subsequent
maintenance infusion of 200 to 300 mg/24 hours) or lidocaine at 1
mg/kg at an infusion rate of 25 mg/minute (with a maintenance
infusion following at a rate of 2 mg/minute for up to 24 hours),
lorcainide was more effective in suppressing arrhythmia. In the
lorcainide group, the mean premature ventricular complex frequency
decreased 87%, while on lidocaine, it was 35%, in the two-hour
period following administration. Lorcainide was also more effective
in suppressing ventricular ectopic beats and ventricular couplets.
Patients who did not respond to a drug were switched to the other
drug. Crossover to lorcainide gave variable results, while crossover
to lidocaine increased arrhythmia frequency in each of the seven
trials
[662]
.
Meperidine
Administration of analgesic - Postoperative pain
a) In a randomized, single blind study, preemptive peribulbar block
with bupivacaine/lidocaine provided better analgesia and less
postoperative nausea and vomiting than meperidine in pediatric
patients undergoing vitreoretinal (VR) or retinal detachment (RD)
surgery. Pediatric patients ages 6 to 13 years received general
anesthesia and either peribulbar block (n=42) with 0.25 milliliter per
kilogram (mL/kg) of a 1:1 mixture of 0.5% bupivacaine and 2%
lidocaine containing hyaluronidase (500 International Units) or 1
milligram (mg) per kilogram (mg/kg) intravenous meperidine (n=43).
Analgesia was assessed using a visual analog scale (VAS),
increase in hemodynamic variables during surgery, number of
episodes of oculocardiac reflex (OCR) during surgery, supplemental
analgesic requirements, and a modified Children's Hospital of
Eastern Ontario Pain Score (CHEOPS). Ratings on the VAS and
CHEOPS determined supplemental analgesic requirements. The
peribulbar block group had significantly better intraoperative
analgesia (p=0.0001), better postoperative analgesia (p=0.0002),
lower use of supplemental analgesics (p=0.02 for NSAIDs, p=0.008
for opioids), and lower incidence of postoperative emesis (p=0.001)
compared to the meperidine group. Parent satisfaction with the
child's postoperative status was also significantly better in the
peribulbar block group (p=0.0001). No adverse events were
reported for either group
[548]
.
Spinal anesthesia
a) Meperidine was reported to have no significant advantage over
lidocaine/glucose as a spinal anesthetic in patients undergoing
surgery of the lower abdomen or the lower extremities
[549]
[550]
. Patients received either 2 mL of 5% lidocaine in 7.5% glucose
(Xylocaine 5% Heavy) or 2 mL of 5% meperidine in water. The
frequency of complications was greater with meperidine as
compared to lidocaine-glucose and consisted of intraoperative
nausea, vomiting and drowsiness and postoperative urinary
retention, itching, nausea, and vomiting. However, meperidine may
have a greater duration of postoperative analgesia
[549]
[551]
.
b) LIDOCAINE was similar to MEPERIDINE in anesthetic effect but
had a shorter duration of analgesia in patients undergoing
postpartum tubal ligation (n=20). The need for analgesic relief of
pain occurred significantly earlier in patients receiving lidocaine
when compared with patients receiving meperidine (83 vs 448
minutes; p less than 0.001)
[549]
.
c) In a comparison of lidocaine alone or combined with meperidine
for continuous spinal anesthesia in elderly patients (mean, 80.7
years), the addition of meperidine significantly reduced the initial
dose of lidocaine required, and prolonged time to reinjection.
However, ephedrine was required more frequently in the meperidine
group than in the lidocaine/meperidine group (47% vs 11%)
[552]
.
d) Lower doses (0.5 milligram/kilogram) of meperidine compared to
0.5 milligram/kilogram doses of lidocaine/glucose produced similar
therapeutic response and adverse effects. Ten of 22 meperidine
patients failed to achieve motor block compared to 0 of 20 lidocaine
patients
[553]
.
Mepivacaine
Injection of anesthetic agent into pudendal nerve
a) Both lidocaine and mepivacaine are effective local anesthetics
when used in recommended doses for both paracervical and
pudendal nerve blocks. Excessive dosage can result in fetal
bradycardia and acidosis as well as maternal adverse effects such
as paresthesias, hypotension, or convulsions
[643]
[644]
.
Intraosseous anesthesia for dental surgery
a) Primary intraosseous injection of 2% LIGNOCAINE with
1:100,000 epinephrine is more effective than 3% MEPIVACAINE
and results in a longer duration of pulpal anesthesia in noninflamed
mandibular first molars
[642]
.
Local anesthesia
a) Mepivanor(R) generally provides less effective analgesia during
laceration repair in children than 1% lignocaine infiltration. Seventyone patients aged 2 to 16 years were included in a blinded trial
comparing the effectiveness of Mepivanor(R) (topical anesthetic
preparation of 2% mepivacaine and 1:100,000 norepinephrine); a
topical solution of 1% tetracaine, 1:4,000 adrenaline, and 4%
cocaine (TAC); and 1% lignocaine infiltration. Facial lacerations
were involved in 61% of the cases and scalp lacerations in the
remaining 39%. Pharmacologic sedation was not used and a
restraint was utilized in 15% of the children. A parent remained in
the room throughout the procedure in all but one of the cases. A
Visual Analogue Scale was utilized. Additionally, a seven-point
Likert scale was used to measure pain perceptions of parents and
suture technicians. Non-cocaine-containing Mepivanor(R) caused
less wound blanching than TAC which indicates a weaker
vasoconstrictive effect and may explain the lower efficacy of
Mepivanor(R) compared with TAC. The authors of the study
acknowledge that the findings may have underestimated overall
comparative performance of Mepivanor(R) and TAC relative to
lignocaine since comparisons of pain scores did not consider the
pain associated with initial lignocaine injection
[641]
.
Regional anesthesia
a) Mepivacaine provided better analgesia than did lidocaine when
used for intravenous regional anesthesia (IVRA). In a randomized,
double-blind study, 42 patients undergoing forearm or hand surgery
were given either lidocaine 0.5%, 3 milligrams/kilogram (mg/kg), or
mepivacaine 0.5% to 1%, 5 mg/kg, to a maximal dose of 400 mg
and maximal volume of 40 milliliters (mL). The anesthetic was
administered via a catheter after inflation of a tourniquet. Forty-five
percent of patients receiving lidocaine and 9% receiving
mepivacaine required supplementary analgesia with fentanyl
(p=0.02). Five minutes after the tourniquet was released, plasma
concentrations of the two drugs were similar, but the concentration
of lidocaine then decreased and was much lower at 60 minutes than
the concentration of mepivacaine (p less than 0.001). The
concentration of mepivacaine did not change during the 60-minute
observation period. There were no adverse reactions associated
with mepivacaine during the observation period. In the lidocaine
group, transient bradycardia and dizziness were experienced by 1
patient each within 5 minutes of tourniquet release. Possible
adverse effects associated with the prolonged increase of systemic
mepivacaine concentration were not examined
[645]
.
Spinal anesthesia
a) A greater frequency of transient neurologic symptoms occurred
after spinal anesthesia with LIDOCAINE (22%) than with
MEPIVACAINE (0%) in patients receiving outpatient arthroscopic
knee surgery (p equal 0.008)
[646]
. Transient neurologic symptoms were defined as back pain or
dysesthesia that began within 24 hours of surgery and radiated to
the buttocks, hips, thighs, or calves. In a randomized, double-blind
fashion, 30 patients were given 1.5% mepivacaine 3 milliliters (mL)
(45 milligrams) and 27 patients, 2% lidocaine 3 mL (60 mg). Times
to regression to L5 sensory level, to resolution of motor block, and
to discharge milestones were similar between groups.
Metoprolol
Pain following administration of agent - Propofol adverse reaction
a) Intravenous (IV) metoprolol is as effective as IV lidocaine in
reducing infusion-related pain associated with propofol injection.
Patients (n=90) undergoing elective surgery with general anesthesia
were randomized to receive either metoprolol 2 milligrams (mg),
lidocaine 20 mg, or saline 2 milliliters prior to propofol injection. One
of these agents was administered IV on the dorsum of the hand
while venous drainage was occluded for 45 seconds. After releasing
the occlusion, propofol (2 to 2.5 mg/kg) at room temperature was
injected at 2 mL (20 mg) every 4 seconds. At 16 seconds, the
incidence of severe pain was significantly higher in the saline group
(56.7%) than in the metoprolol (16.6%) and lidocaine (10%) groups
(both p less than 0.05 compared with saline). Compared with the
saline group, there were significantly more pain-free patients in the
metoprolol and lidocaine groups at all times (p less than 0.05). At 8
seconds, the incidence of pain in the metoprolol group was higher
than in the lidocaine group (p less than 0.05), but there was no
significant difference between metoprolol and lidocaine groups at 16
seconds
[669]
.
Mexiletine
Ventricular arrhythmia
a) SUMMARY: Intravenous administration of mexiletine has been
demonstrated to be at least as effective as intravenous lidocaine in
the treatment of ventricular arrhythmias, with the advantage of being
effective in lidocaine-resistant cases
[652]
[653]
[654]
.
b) Mexiletine was found to be superior to lidocaine in the
prophylactic treatment of arrhythmias following acute myocardial
infarctions
[653]
. Twenty-four patients who developed ventricular tachyarrhythmias
within 48 hours of acute myocardial infarction randomly received
mexiletine 200 mg bolus, followed by an infusion of 1 mg/minute
reduced to 0.5 mg/minute after one hour, or lidocaine 100 mg bolus,
followed by an infusion of 3 mg/minute reduced to 2 mg/minute after
one hour. The mexiletine patients experienced significantly fewer
complex ventricular tachyarrhythmias and also had fewer ventricular
extrasystoles. This difference was especially marked during the
second 24 hours of treatment. Differences were not statistically
significant and further evaluation is required.
c) Intravenous mexiletine has been reported to be an effective
alternative to lidocaine for the management of ventricular
arrhythmias
[654]
. In a randomized parallel study 22 patients (17 men and 5 women)
with symptomatic ventricular ectopy received either intravenous
lidocaine or mexiletine. Following a loading dose, 12 patients
received mexiletine 5 to 10 milligrams/minute until greater than or
equal to 95% suppression of premature ventricular beats or a dose
of 450 milligrams was attained. Ten patients received lidocaine 1
milligram/kilogram over 3 minutes, with a second bolus dose given if
needed. Eleven (92%) of patients receiving mexiletine responded
completely and 1 patient was a partial responder (suppression
between 75% and 95%). Five (50%) patients receiving lidocaine
responded fully, 3 (30%) were partial responders, and 2 failed to
respond. Adverse effects were transient in both patient groups.
d) In a study of 17 patients with ventricular tachycardia (VT) the
inefficacy of lidocaine was predictive of the inefficacy of oral
mexiletine and oral tocainide
[655]
. Nonresponders to lidocaine are very likely to fail suppression of
ventricular ectopy with mexiletine
[656]
.
Nifedipine
Anal fissure
a) A randomized, double-blind trial demonstrated superior efficacy
with topical nifedipine 0.2% gel every 12 hours as compared to
topical lidocaine 1% plus hydrocortisone acetate 1% in the
treatment of acute anal fissures (n=283). Complete healing occurred
within 21 days of therapy in 95% and 50% of the nifedipine and
lidocaine groups, respectively (p less than 0.01). Between baseline
and day 21, nifedipine-treated patients experienced a mean 30%
reduction in maximum resting anal pressure (from 72.5 to 50.5
millimeters of mercury (mmHg)), and a mean 17% decline in
maximum squeeze anal pressure (from 130.5 to 108.5 mmHg). No
such anal pressure changes were observed in lidocaine-treated
patients (p less than 0.01 between groups). The only adverse effect
was local hyperemia in 2% of nifedipine recipients
[601]
. Follow-up commentary noted that results for acute versus chronic
anal fissure may not be similar, nor can these data be extrapolated
to other rectal disorders. Further study is required (Cook &
Mortensen, 2000; Antropoli & Perrotti, 2000).
Thrombosed external hemorrhoids
a) More rapid complete pain relief, reduced need for supplemental
analgesics, and greater healing of external thrombosed hemorrhoids
was demonstrated in a group of 50 patients treated with both topical
nifedipine 0.3% and 1.5% lidocaine ointment when compared to 48
control patients treated with topical lidocaine alone, applied every 12
hours for 2 weeks. Other conservative therapy included high-fiber
diets, bulk laxatives, and sitz baths. At 7 days, 86% of nifedipine
patients and 50% of controls were pain-free (16% of controls had
persistent pain and 33% reported only mild pain, while the
remaining nifedipine patients reported only mild pain). Only 8% of
nifedipine versus 54% of control patients required continuous oral
analgesics throughout the first week. Complete remission of
hemorrhoids (clot dissolution without ulceration; absence of pain
and swelling) at 14 days was achieved in twice as many nifedipine
users (46 versus 22; 92% versus 46%). Of the remaining 4 patients
in the nifedipine group, one healed at 28 days, and 3 progressed to
hemorrhoidectomy. With lidocaine alone, and additional 7 patients
healed after 28 days, another 4 after 6 weeks, and 15 required
surgery
[602]
.
Nitroglycerin
Anal fissure
a) NITROGLYCERIN ointment or combination LIDOCAINEPRILOCAINE ointment were both more effective for symptomatic
relief and healing of anal fissures than were lidocaine only ointment
or vaseline (placebo) in children with anal fissures (n=102, mean 3
years of age). Subjects were randomized to 1 of 4 ointments:
vaseline (placebo, n=20), lidocaine 10% (L, n=24), a eutectic
mixture of lidocaine 5%-prilocaine 5% (LP, n=25), or nitroglycerin
0.2% (glyceryl trinitrate-GTN, n=22). The ointment was applied to
the distal anal canal twice daily for 8 weeks. Progress was
measured at 10 days and 8 weeks, using scales for relief of
symptoms (0=no relief; 1=some relief; 2=complete relief) and fissure
healing (0=deep fissures with bleeding; 1=pale, shallow fissures
without bleeding, and 3=complete healing). On day 10, proportions
of patients with scores of 0 (no progress) in symptom relief and
fissure healing were significantly higher in the placebo and L groups
compared with the LP and GTN groups (both p less than 0.05). After
8 weeks, the highest number of patients with scores of 0 were in the
control group (50%), followed by the L group (12%) (p less than
0.05, L group versus placebo); no one in the LP and GTN groups
had a zero score at 8 weeks. Ten-day rates of complete
symptomatic relief and complete healing were 45% and 4%,
respectively, for GTN-treated subjects compared with 20% and 0%,
respectively, for LP-treated subjects. Percentages with complete
relief and healing at 8 weeks were 91% and 82%, respectively, for
the GTN group and 76% and 64%, respectively, for the LP group
(no significant difference LP vs GTN)
[597]
.
b) Nitroglycerin ointment 0.2% applied to the anus and anal canal 3
times daily resulted in faster and more complete healing of anal
fissures than lidocaine 2% anesthetic gel among patients with both
acute and chronic disease. While 90% of acute disease and 12% of
chronic disease patients (60% overall) showed healing with
nitroglycerin within 14 days, no patients healed with lidocaine. After
1 month, overall healing rate among nitroglycerin users was up to
80%, while only 40% of lidocaine users had healed fissures. Serial
anal sphincter manometry (day 0, 14, 28) demonstrated a mean
20% reduction in maximum resting pressure for the rapid
nitroglycerin responders, but no change for the slower-healing
chronic disease patients treated with nitroglycerin or for any of the
patients given lidocaine
[598]
.
Catheterization - Venipuncture
a) Addition of lidocaine to propofol was more effective than use of
topical nitroglycerin over the injection site in reducing the perception
of pain during propofol injection from 65% (with no lidocaine) to 35%
(with lidocaine)
[599]
. Four groups of 31 patients scheduled for elective ambulatory
surgery were compared. Either nitroglycerin or placebo ointment
was applied to the skin over the cannula tip followed by injection of
propofol alone (10 milligram/milliliter (mg/mL)) or mixed with 2 mL of
1% lidocaine. Patients were queried regarding the presence,
intensity and character of any pain experienced during injection, and
any recall of pain at induction following the surgical procedure. Use
of lidocaine or the combination of lidocaine plus topical nitroglycerin
was associated with pain-free injection in 52% to 58% of the
patients. Use of nitroglycerin only and plain propofol resulted in
pain-free injection in only 8 patients (26%), fewer than with placebo
ointment (11 patients; 35%). Gender did not influence response, but
age over 50 years old was always associated with less perceived
pain than reported by younger patients
[599]
.
Nitrous Oxide
Adverse reaction to drug - Injection site pain
a) Nitrous oxide and a lidocaine-propofol mixture were equally
effective for reducing the incidence and intensity of propofol-induced
injection pain. In this controlled, observer-blinded study, patients
undergoing general anesthesia for elective surgery were randomly
assigned to receive 100% oxygen (control; n=45), 50% nitrous oxide
in oxygen (n=45), or a lidocaine-propofol mixture (n=45). Breathing
gas mixtures were administered for 120 seconds followed by
injection of propofol. The lidocaine-propofol mixture was prepared
by adding 2 milliliters (mL) of 1% lidocaine (20 milligrams (mg)) to
18 mL propofol (concentration 10 mg/mL), for a 1 mg/mL lidocaine
concentration. Pain scores were assessed after a 5 second propofol
injection (injection rate 1 mL per second) using observation of the
patients' verbal response and behavioral signs. The number of
patients with pain on injection were 26 (58%), 11 (24%; p=0.001
compared to control), and 11 (24%; p=0.001 compared to control)
for the control, nitrous oxide, and lidocaine groups, respectively. The
severity of pain was also less in the treatment groups; the number of
patients reporting moderate or severe pain were 15 (33%), 6 (13%;
p=0.04) and 2 (4%; p=0.0007) for the control, nitrous oxide, and
lidocaine groups, respectively. Frequency and severity of pain was
not significantly different between the nitrous oxide and lidocaine
groups
[542]
.
Catheterization of vein
a) EMLA(R) cream (lidocaine/prilocaine) and nitrous oxide are
equally effective for providing pain relief for venous cannulation in
pediatric patients; however, nitrous oxide was associated with more
adverse effects than EMLA(R) cream. A prospective, double-blind
study involving 40 children (ages 6 to 11) compared the efficacy of
EMLA(R) cream (2.5 grams) applied at least 1-hour before catheter
insertion and inhaled nitrous oxide (70% N2O and 30% O2) for pain
relief during venous cannulation. Patients who received N2O also
received a placebo cream and those receiving EMLA(R) were
administered 30% O2. Efficacy was assessed by the children using
the 0 to100 mm Visual Analog Scale (VAS). Two blinded
investigators subjectively measured ease of cannulation and the
efficacy of the technique. Patient's pain was assessed with the
Objective Pain Scale (OPS). Results showed no difference in pain
between the two groups. Median pain assessment ratings were low
in both groups. There were significantly more adverse effects in the
N2O group, but they were mild
[543]
.
OnabotulinumtoxinA
Anal fissure
a) Botulinum toxin type A (BTX-A) was more effective than lidocaine
5% ointment for the treatment of chronic anal fissure. Patients
(n=62) were randomized to receive either topical lidocaine 5% or
BTX-A (Botox(R)). The lidocaine group (n=28) applied the topical
ointment twice daily and after each defecation for at least 4 weeks
to the anus and anal canal. The BTX-A group (n=34) received 25
Units injected into the internal anal sphincter on either side of the
fissure. Effectiveness was measured by clinical evaluation,
anoscopy, and anorectal manometry 2 months after baseline
assessment. Treatment was considered successful if the fissure
healed; symptomatic improvement was defined as persistence of
the fissure in the absence of symptoms. Epithelialization was
significantly higher in the BTX-A group (70.58%) than the lidocaine
group (21.42%; p=0.006). Baseline maximum anal resting pressures
were 83 millimeters of mercury (mmHg) and 86 mmHg,
posttreatment pressures were 81 mmHg and 71 mmHg (p=0.0001
compared to baseline) in the lidocaine and BTX-A groups,
respectively. Maximum voluntary squeeze pressures were 81
mmHg and 105 mmHg at baseline and 80 mmHg and 95 mmHg
(p=0.003 compared to baseline) posttreatment in the lidocaine and
BTX-A groups, respectively. No significant differences were
reported between the groups in relief of nocturnal and
postdefecatory pain
[573]
.
Ondansetron
Anesthesia - Preventing pain
a) Pretreatment with ondansetron reduced the pain associated with
propofol and rocuronium injections during the induction of general
anesthesia, but was not as effective as lidocaine. In this
randomized, controlled, double-blind trial, 60 patients undergoing
elective orthopedic and gastrointestinal procedures received
ondansetron 4 milligrams (mg), lidocaine 50 mg, or saline placebo
by intravenous (IV) injection, followed by rocuronium 0.6 mg per
kilogram (/kg) IV and propofol 2.5 mg/kg IV. A blinded anesthetist
assessed pain at baseline and after rocuronium and propofol
injections, using a scale of 0 to 3, where 0=no pain, 1=mild pain,
2=moderate pain, and 3=severe pain. Both lidocaine and
ondansetron significantly reduced the pain associated with
rocuronium over placebo (scores 0,1,2, respectively), but
ondansetron was not more effective than lidocaine as an analgesic.
Following propofol administration, pain was similar between
placebo- and ondansetron- treated patients (score of 1 in each
group), but eliminated in lidocaine-treated patients. No differences in
intubating conditions were observed between treatment groups, as
determined by an intubating score assessing jaw relaxation, ease of
laryngoscopy, vocal chord status, presence and severity of cough,
and limb movement
[561]
.
Pirmenol
Ventricular premature complex
a) Intravenous pirmenol (150 milligrams) was superior to
intravenous lidocaine (250 milligrams) in the treatment of chronic
premature ventricular complexes (frequency of greater than
60/hour) in a small controlled study (n=12). Response rates of 88%
and 25%, respectively, were reported. Adverse effects occurred
more frequently with lidocaine, necessitating discontinuance in 2
patients (drowsiness, paresthesias)
[540]
. A larger comparison of lidocaine and pirmenol is needed to confirm
these findings.
Efficacy
a) In a double-blind, placebo-controlled study, 3 groups of 10 patients each
received either pirmenol (50 milligrams intravenously (IV), then 2.5
milligrams/minute IV infusion), lidocaine (75 milligrams IV, then 3
milligrams/minute IV infusion), or placebo. Compared to baseline, pirmenol
increased heart rate (p less than 0.001), increased mean arterial pressure
(p less than 0.001), increased systemic vascular resistance (p less than
0.05), and pulmonary artery resistance (p less than 0.01). Left ventricular
end-diastolic pressure (LVEDP), cardiac index, and left ventricular work
index were not significantly affected. Similarly, lidocaine increased mean
arterial pressure (p less than 0.001); however, lidocaine increased LVEDP
(p less than 0.05). Left ventricular ejection fraction was reduced more by
pirmenol than by lidocaine
[539]
.
Prajmaline
Cardiac dysrhythmia
a) The effects of intravenous lidocaine 2.1 milligrams/minute (3
grams/day) were compared to oral prajmaline 20 milligrams every 4
hours (60 milligrams/day) in the treatment of 35 patients with acute
myocardial infarction and premature ventricular complexes (PVCs)
[647]
. In both groups frequency of PVCs decreased significantly as
compared to the control group. Six hours after onset of therapy,
prajmaline reduced PVCs to 37% and lidocaine to 51% and they
increased 169% in the control group. Prajmaline reduced PVCs to
5% of initial value and lidocaine to 20% 10 hours later when peak
effect of prajmaline was reached. This was the only significant
difference in drug effect. Prajmaline was significantly more effective
than lidocaine in reducing runs of PVCs. Runs of PVCs were almost
completely suppressed with prajmaline and only moderately and not
significantly reduced with lidocaine. Eight hours after starting
therapy, prajmaline reduced runs to 8% and lidocaine to 79% of the
initial value. The authors suggest that prajmaline may be an
effective alternative to lidocaine in treating ventricular arrhythmias
after acute myocardial infarction.
Pregabalin
Diabetic neuropathy
a) In an open-label, randomized, multicenter, non-inferiority study in
patients with postherpetic neuralgia (PHN) and diabetic peripheral
neuropathy (DPN), non-inferiority was not established for 5%
lidocaine medicated plaster compared with pregabalin in providing
effective analgesia with fewer adverse events at 4 weeks of therapy.
In this two-stage adaptive study, patients with PHN or DPN and
average pain intensity of greater than 4 on an 11-point numerical
rating scale (NRS) were randomized to receive 5% lidocaine
medicated plaster (n=144, mean age 62.6 years old) applied to the
area of maximal pain for up to 12 hour (hr) within each 24-hr period,
or pregabalin (n=137, mean age 61.8 years old) twice daily. The
dose of lidocaine was a maximum of 3 plasters in PHN patients and
4 in DPN patients. The pregabalin dosage was 150 milligrams (mg)
per day the first week, 300 mg per day the second week, and further
increased to 600 mg per day if NPS score remained 4 or greater
after 2 weeks. Lidocaine patients used a mean of 1.71 (PHN) and
2.83 (DPN) plasters. Mean pregabalin dose was not reported,
however 86 patients required doses of 600 mg per day. Response
to therapy (primary endpoint), defined as reduction of 2 or more
points in NRS score from baseline or overall score less than 4, was
met in 65.3% of lidocaine patients and 62% of pregabalin patients
(per-protocol analysis). Based upon per-protocol analysis, treatment
with lidocaine did not meet the pre-specified non-inferiority margin of
8% and p less than 0.0038, as the lower limit of the confidence
interval (CI) was -9.15 and p=0.00656. Based upon intention-to-treat
analysis, lidocaine was determined to be non-inferior to pregabalin
(p=0.00229, lower limit CI, 7.03). Stratifying response by indication,
62.2% of PHN patients on lidocaine responded to treatment,
compared with 46.5% of pregabalin patients. In patients with DPN,
66.7% of lidocaine patients and 69.1% of pregabalin patients were
responders. Drug-related adverse events occurred in 29 lidocaine
patients and in 71 pregabalin patients. The most frequently reported
adverse events in the pregabalin group were gastrointestinal
(15.5%), fatigue (13%), dizziness (11.8%), and vertigo (7.8%), while
for the lidocaine group headache and application site irritation were
reported in 1.3% of patients each. Adverse events leading to drug
discontinuation occurred in 9 (5.8%) of lidocaine patients and 39
(25.5%) of pregabalin patients
[562]
Postherpetic neuralgia
a) In an open-label, randomized, multicenter, non-inferiority study in
patients with postherpetic neuralgia (PHN) and diabetic peripheral
neuropathy (DPN), non-inferiority was not established for 5%
lidocaine medicated plaster compared with pregabalin in providing
effective analgesia with fewer adverse events at 4 weeks of therapy.
In this two-stage adaptive study, patients with PHN or DPN and
average pain intensity of greater than 4 on an 11-point numerical
rating scale (NRS) were randomized to receive 5% lidocaine
medicated plaster (n=144, mean age 62.6 years old) applied to the
area of maximal pain for up to 12 hour (hr) within each 24-hr period,
or pregabalin (n=137, mean age 61.8 years old) twice daily. The
dose of lidocaine was a maximum of 3 plasters in PHN patients and
4 in DPN patients. The pregabalin dosage was 150 milligrams (mg)
per day the first week, 300 mg per day the second week, and further
increased to 600 mg per day if NPS score remained 4 or greater
after 2 weeks. Lidocaine patients used a mean of 1.71 (PHN) and
2.83 (DPN) plasters. Mean pregabalin dose was not reported,
however 86 patients required doses of 600 mg per day. Response
to therapy (primary endpoint), defined as reduction of 2 or more
points in NRS score from baseline or overall score less than 4, was
met in 65.3% of lidocaine patients and 62% of pregabalin patients
(per-protocol analysis). Based upon per-protocol analysis, treatment
with lidocaine did not meet the pre-specified non-inferiority margin of
8% and p less than 0.0038, as the lower limit of the confidence
interval (CI) was -9.15 and p=0.00656. Based upon intention-to-treat
analysis, lidocaine was determined to be non-inferior to pregabalin
(p=0.00229, lower limit CI, 7.03). Stratifying response by indication,
62.2% of PHN patients on lidocaine responded to treatment,
compared with 46.5% of pregabalin patients. In patients with DPN,
66.7% of lidocaine patients and 69.1% of pregabalin patients were
responders. Drug-related adverse events occurred in 29 lidocaine
patients and in 71 pregabalin patients. The most frequently reported
adverse events in the pregabalin group were gastrointestinal
(15.5%), fatigue (13%), dizziness (11.8%), and vertigo (7.8%), while
for the lidocaine group headache and application site irritation were
reported in 1.3% of patients each. Adverse events leading to drug
discontinuation occurred in 9 (5.8%) of lidocaine patients and 39
(25.5%) of pregabalin patients
[562]
Prilocaine
Anal fissure
a) NITROGLYCERIN ointment or combination LIDOCAINEPRILOCAINE ointment were both more effective for symptomatic
relief and healing of anal fissures than were lidocaine only ointment
or vaseline (placebo) in children with anal fissures (n=102, mean 3
years of age). Subjects were randomized to 1 of 4 ointments:
vaseline (placebo, n=20), lidocaine 10% (L, n=24), a eutectic
mixture of lidocaine 5%-prilocaine 5% (LP, n=25), or nitroglycerin
0.2% (glyceryl trinitrate-GTN, n=22). The ointment was applied to
the distal anal canal twice daily for 8 weeks. Progress was
measured at 10 days and 8 weeks, using scales for relief of
symptoms (0=no relief; 1=some relief; 2=complete relief) and fissure
healing (0=deep fissures with bleeding; 1=pale, shallow fissures
without bleeding, and 3=complete healing). On day 10, proportions
of patients with scores of 0 (no progress) in symptom relief and
fissure healing were significantly higher in the placebo and L groups
compared with the LP and GTN groups (both p less than 0.05). After
8 weeks, the highest number of patients with scores of 0 were in the
control group (50%), followed by the L group (12%) (p less than
0.05, L group versus placebo); no one in the LP and GTN groups
had a zero score at 8 weeks. Ten-day rates of complete
symptomatic relief and complete healing were 45% and 4%,
respectively, for GTN-treated subjects compared with 20% and 0%,
respectively, for LP-treated subjects. Percentages with complete
relief and healing at 8 weeks were 91% and 82%, respectively, for
the GTN group and 76% and 64%, respectively, for the LP group
(no significant difference LP vs GTN)
[575]
. ANESTHESIA
b) As spinal anesthesia for short surgical procedures of the lower
body, isobaric lidocaine 80 milligrams (mg) was associated with a
significantly higher incidence of transient neurological symptoms
(TNS) than isobaric prilocaine 80 mg in a randomized, double-blind
trial (n=70). When interviewed on the first postoperative day, 20%
and 0% of lidocaine and prilocaine recipients, respectively, reported
TNS (pain and/or dyesthesia of the buttocks or lower extremities)
(p=0.006), with an average pain rating of 5.3 on a scale of zero to
ten. All cases of TNS resolved by the fourth postoperative day.
Efficacy parameters such as duration of and maximum sensory
block as well as maximum motor block did not differ between
groups. However, prilocaine produced a significantly longer duration
of motor block (mean 166 versus 130 minutes, p=0.004)
[576]
.
c) Prilocaine and lidocaine were comparable in terms of onset,
duration, and quality of anesthesia in a randomized, double-blind
study of 21 adult patients undergoing hand surgery following
intravenous regional anesthesia. Utilizing a proximal cuff double
tourniquet, the patients received an intravenous injection of either
50 mL of prilocaine 0.5% or lidocaine 0.5%. Side effects were
minimal with both agents; however, a significant increase in
methemoglobin serum concentrations from 0.5% to approximately
3% was noted in patients receiving prilocaine. No signs of cyanosis
were noted in these patients, and this methemoglobin level would
not be expected to be clinically significant. Prilocaine produced
significantly lower serum concentrations than lidocaine following
tourniquet deflation, which may demonstrate a greater margin of
safety with this prilocaine in terms of potential systemic toxicity
[577]
.
d) Prilocaine 3% provided better ocular akinesia than a mixture of
lidocaine 2% and bupivacaine 0.75% in patients undergoing
cataract surgery. Patients were randomized to 3% prilocaine with
felypressin and hyaluronidase or 2% lidocaine and 0.75%
bupivacaine with hyaluronidase mixture. Prior to injection of study
drug, the conjunctiva and cornea was anesthestized with topical
amethocaine. The injection site was along the medial wall of the
orbit to a depth of 20 to 25 millimeters. Major clinical endpoints
included time to block and globe ocular movement scores. The
major goal of peribulbar block is to minimize ocular movement
during surgery. Eight minutes following the injection for peribulbar
block, the median ocular movement score (maximum score for each
direction tested is 3) was 1 for the prilocaine group as compared to
3 for the lidocaine/bupivacaine group (p=0.0163). The median time
to block considered sufficient for the operation was 10 minutes for
the prilocaine group and 12 minutes for the lidocaine/bupivacaine
group (p=0.091). Some patients did experience complications (eg,
mild discomfort, conjunctival chemosis, subcutaneous hematoma,
and intraoperative pain); however, none were considered serious
and the incidences between treatment groups were not statistically
different
[578]
.
Pain relief
a) PEDIATRIC: Liposomal LIDOCAINE 4% cream (ELA-MAX(R))
showed comparable safety and efficacy to a eutectic cream mixture
of LIDOCAINE 2.5% and PRILOCAINE 2.5% (EMLA(R)) for
reduction of pain in children undergoing venipuncture. This finding
emanated from a double- randomized, blinded, cross-over trial in
120 children aged 5 to 16 years of age (mean 9 years). Children
were randomized to 1 of 2 regimens: (1)30-minute (min) application
of both lidocaine 4% (L4%) and lidocaine 2.5%-prilocaine 2.5% (LP2.5%) cream in randomized order OR (2)60-minute application of
both L4% and LP-2.5% cream in randomized order. A dose of 2.5
grams of cream was used for all applications; occlusion was applied
with the 30-minute LP-2.5% application and both 60-minute
applications. Subject-rated pain scores on a 100-point visual analog
scale were 10.9 and 10.8 for L4% and LP-2.5% when duration of
application was 30 min (p=0.412). Pain scores were 11.9 and 8.2 for
L4% and LP-2.5%, respectively, applied for 60 minutes (p=0.83).
Parents and a blinded research-observer were present at the time of
the venipunctures and completed Observed Behavioral Distress
(OBD) scoring tools. No statistically significant differences were
found between scores of either parents or research-observers for
the venipuncture anticipatory, insertion, or recovery periods related
to any of the regimens. No serious adverse events occurred, and
over 84% of study participants had no skin reaction to the
medication. Three events that were considered probably related to
treatment included tingling and numbness (1), significant pruritus
(1), and mild itching and redness (1). Lidocaine serum
concentrations were measured in a sub-group of 10 who received
L4% as a 60-min application; no clinically significant systemic
absorption of lidocaine occurred
[581]
.
b) PEDIATRIC: LIDOCAINE 2% transdermal iontophoresis and a
eutectic cream mixture of LIDOCAINE 2.5% and PRILOCAINE 2.5%
(EMLA(R)) showed similar efficacy for reduction of pain in children
(7 to 16 years) undergoing intravenous (IV) cannulation, according
to a randomized, cross-over trial (n=22). During an EMLA session, 2
sites for venipuncture were covered with a thick paste of 2.5 grams
of EMLA cream followed by an occlusive dressing for at least 60
minutes. During a lidocaine iontophoresis session, the reservoir of a
positively charged delivery electrode was saturated with 1 milliliter of
lidocaine hydrochloride 2% with epinephrine 1:100,000; the
iontophoresis device (PM-800 Iomed) produced an electric current
which carried ionized lidocaine through the stratum corneum to a
depth of 10 millimeters (mm). Comparing the 2 treatments, there
was no significant difference in number of successful IV
cannulations on the first attempt, total number of attempts, or ease
of IV catheter insertion. Pain, as measured on a 100 mm visual
analog scale (VAS), did not differ between iontophoresis or EMLA
as rated by subjects or parents, although parents' scores were
significantly lower than subjects' scores. A blinded independent
observer rated pain on the Children's Hospital of Eastern Ontario
Pain Scale, resulting in no observed differences between the 2
treatments. After completing both iontophoresis and EMLA, subjects
could pick whichever one they preferred for the third cannulation
session. Overall, 11 subjects (50%) chose iontophoresis, 5 (23%)
chose EMLA, and 6 (27%) had no preference. No severe adverse
events were noted during the study. Two subjects aborted
iontophoresis procedures due to intolerable tingling, itching, and
discomfort
[582]
.
Procedure on eyelid, Minor
a) Discomfort associated with injection of anesthetic for minor eyelid
procedures was significantly less with prilocaine than with
lignocaine. One hundred twenty five patients randomly received 1
milliliter of either 2% lignocaine plain or 2% prilocaine plain in a
double-blind manner. On a 10-point scale, the mean pain score (for
the injection itself and not the transdermal insertion of the needle)
was 1.82 for prilocaine and 3.19 for lignocaine (p less than 0.001 by
Mann-Whitney U-test). One third of patients receiving prilocaine felt
no pain, compared to only 15% of those receiving lignocaine
[579]
.
Topical local anesthetic
a) In a double-blind, randomized study, a topical formulation of
tetracaine and lidocaine had a shorter latency period than lidocaineprilocaine cream (EMLA(R)) and fewer adverse events than a more
concentrated tetracaine cream. Patients were children ages 3
months to 10 years undergoing minor elective surgery. One of 3
anesthetic creams was applied to the dorsum of both hands on
venous puncture sites. Group I (n=100) received eutectic 2.5%
lidocaine and 2.5% prilocaine mixture (EMLA(R)), Group II (n=100)
received 4% tetracaine, and Group III (n=100) received a 2.5%
lidocaine and 2.5% tetracaine mixture (AMLI). In children younger
than 1 year, 2 grams (g) per 10 square centimeters (cm(2)) of AMLI
and EMLA cream and 0.5 g/10 cm(2) of 4% tetracaine cream were
applied over a maximum 16 cm(2); for children over 1 year of age,
2.5 g/10 cm(2) of AMLI and EMLA cream and 1 g/10 cm(2) of 4%
tetracaine cream were applied over a maximum of 32 cm(2). Within
each treatment group, 5 subgroups (n=20 for each subgroup) were
formed based on time before removal of the anesthetic cream.
Sedation state after 0.375 milligram per kilogram (mg/kg)
midazolam premedication and an observational pain score were
recorded before and during venopuncture. Frequency of pain during
puncture was significantly higher in Group I than the other groups
when duration of cream application was 30 minutes or less;
percentage of patients with pain was 85% for Group I and 40% for
Group II and Group III (p less than 0.01). Increasing application time
significantly increased percentage of patients without pain when
compared to the shortest time period (30 minutes or less) in all 3
groups (p less than 0.001 for Groups I, p less than 0.01 for Groups
II and III). AMLI cream showed the greatest efficacy when compared
to the other 2 anesthetic creams at the longest application period
(120 minutes or more). Patients in Group II experienced the greatest
number of adverse events; this difference was significant for the 60
to 90 minute application period subgroup (p less then 0.05). Overall,
EMLA cream had a longer latency period and 4% tetracaine cream
and EMLA both had a higher incidence of adverse events compared
to AMLI cream
[580]
.
Procainamide
Ventricular arrhythmia
a) The results of a randomized parallel study involving 29 patients
indicate that procainamide is more effective than lidocaine for
terminating spontaneous monomorphic ventricular tachycardia. In
this study 15 patients received procainamide 10 mg/kg
intravenously administered at a rate of 100 mg/min and 14 patients
received intravenous lidocaine 1.5 mg/kg over 2 minutes.
Ventricular tachycardia (VT) was terminated in 3 of 14 patients
receiving lidocaine and in 12 of 15 patients receiving procainamide.
Procainamide terminated 8 of 11 episodes of VT not responding to
lidocaine and lidocaine terminated 1 of 1 episodes of VT not
responding to procainamide. In the cases of VT recurrence involving
16 patients, with the drugs given in reversed order, lidocaine
terminated 6 of 31 VT recurrences and procainamide 38 of 48
recurrences. QRS width and QT interval were significantly
lengthened after procainamide but no change in these values was
observed after lidocaine
[559]
.
Procaine
Spinal anesthesia
a) Patients receiving spinal anesthesia with procaine experienced
significantly fewer postoperative transient neurologic symptoms
(TNS) compared with patients receiving lidocaine spinal anesthesia,
in a randomized, double-blind, clinical study; however, the incidence
of anesthesia inadequacy was substantially higher in the procaine
group compared with patients receiving lidocaine. Patients
undergoing arthroscopic knee surgery received spinal anesthesia
with equipotent doses of either hyperbaric procaine 100 milligrams
(mg; n=35) or hyperbaric lidocaine 50 mg (n=35) prior to the start of
the procedure. Adequacy of spinal anesthesia was assessed by the
need for sedation or general anesthesia in order to eliminate patient
discomfort at any time during surgery. Sensory blockade levels were
similar between the groups at 10 and 20 minutes postinfusion,
whereas motor block was significantly lower at 10 minutes in the
procaine group. There were identical trends toward increased
incidences of anesthesia inadequacy and intraoperative nausea in
the procaine group compared with patients receiving lidocaine (17%
versus 3%, respectively), and a significantly increased time to
hospital discharge required by the procaine group compared with
the lidocaine group (p less than 0.05). Procaine-anesthetized
patients did experience a significantly lower incidence of TNS
compared with lidocaine-anesthetized patients (6% versus 31%,
respectively; p=0.007). The concurrent findings of increased
incidence of nausea, extended time to discharge, and trend toward
an increased rate of anesthesia failure would suggest a need to
evaluate whether the lower incidence of TNS justifies the risks
inherent in an increased frequency of anesthetic failure and
intraoperative nausea
[563]
.
Promethazine
Anesthesia
a) Promethazine appears to be as effective as lidocaine for
providing LOCAL ANESTHESIA. In this study, 20 eligible patients
undergoing inguinal hernia repair were randomized to either
promethazine (50 milligrams) or lidocaine (1%). Clinical outcomes
indicate that the two drugs are similar in terms of pain control and
duration of anesthesia. With regards to vital signs, promethazine
was associated with a lower PREOPERATIVE pulse rate; however,
there were no differences in pulse rate or blood pressure at any
OTHER time points (ie, up to skin closure following hernia repair). In
addition, no adverse effects were reported in either group
[560]
.
Propafenone
Myocardial infarction
a) In a placebo-controlled study, propafenone was compared with
lidocaine as an antiarrhythmic agent during the first 24 hours
following acute myocardial infarction (MI)
[544]
. One hundred twelve patients were randomly assigned to either
placebo, intravenous lidocaine 100 mg initially, followed by an
infusion of 2 mg/minute, or intravenous propafenone 105 mg
initially, followed by 300 mg orally every 8 hours for a total dose of
900 mg. Twenty-three patients were excluded due to defective
Holter monitor readings or inability to document myocardial
infarction. There was a trend towards a decrease in the number of
premature ventricular contractions only with lidocaine. Similarly,
during the first 8 hours, there was a trend towards the superiority of
lidocaine in suppressing complex arrhythmias, couplets, and
ventricular tachycardia. However, statistical significance was never
reached with either agent as compared to placebo. The study did
not support the use of propafenone as an alternative to lidocaine
therapy during the acute phase of MI. However, the marginal
efficacy of lidocaine in this study limits interpretation of results. The
relatively small number of patients employed (89) may have been
too low to determine significant differences between treatments.
Larger studies are required to compare these 2 agents in acute MI
prophylaxis.
b) In a case report of a patient with acute myocardial infarction
complicated by atrial and ventricular arrhythmias, propafenone 1
mg/kg by intravenous bolus, followed by an 11 mcg/kg/min infusion,
was superior to mexiletine and lidocaine
[545]
.
Ventricular arrhythmia
a) Twenty consecutive patients admitted with chest pain suggestive
of a myocardial infarction randomly received intravenous lidocaine
75 mg by bolus injection, followed by a 2 to 3 mg/min infusion, or
propafenone 1 mg/kg bolus (up to 70 mg), followed by 150 mg orally
after one hour
[546]
. Propafenone reduced the mean number of premature ventricular
contractions (PVCs) during a 24-hour period by 75%, compared to
73% with lidocaine, and high grade ventricular arrhythmias were
similarly reduced with both drugs. Further studies using larger
numbers of patients, longer-term therapy, and a larger propafenone
dose are needed to adequately evaluate the comparative efficacy of
the 2 drugs.
Quinidine
Ventricular arrhythmia
a) One study compared the effects of IV lidocaine and oral quinidine
in the prevention of ventricular extrasystoles
[666]
. Quinidine was administered in doses of 200 to 500 mg orally. No
significant decreases in the incidence of ectopic contractions were
observed when quinidine placebo was administered alone, but
lidocaine IV significantly decreased the frequency of the ventricular
ectopic beats.
Remifentanil
Injection site pain - Propofol adverse reaction
a) Remifentanil was comparable to lidocaine in the prevention of
propofol- induced injection pain. In this double blind, randomized,
placebo- controlled study, 155 patients undergoing elective surgery
were premedicated with 7.5 milligrams (mg) of oral midazolam 45 to
60 minutes (min) prior to induction of anesthesia. Before
intravenous (IV) propofol (1.5 to 2 mg per kilogram (mg/kg)) was
administered, patients were randomized to 1 of 3 groups. The
remifentanil group (n=53) received IV remifentanil at a dosage of
0.25 micrograms per kilogram per minute (mcg/kg/min) over 60
seconds (sec) via a syringe pump; the lidocaine group (n=52)
received 40 mg (2 mL) of lidocaine IV; the placebo group (n=50)
received 0.9% saline IV. All were administered 60 sec before
propofol. Upon administration of propofol, patients were repeatedly
assessed using a 4-point pain scale. Remifentanil and lidocaine
significantly reduced the incidence and severity of injection pain.
Incidence of pain was 30.2%, 32.7%, and 62% for remifentanil (p
less than 0.0015 versus placebo), lidocaine (p less than 0.005
versus placebo), and placebo, respectively. Severity of pain was
also less in the remifentanil (p less the 0.00005 versus placebo) and
lidocaine groups (p less than 0.0002 versus placebo). There were
no significant differences in incidence or severity of pain between
the remifentanil and lidocaine groups. Remifentanil may be an
effective alternative to lidocaine in the prevention of propofolinduced injection pain
[547]
.
Ropivacaine
Intravenous anesthesia, Regional
a) Ropivacaine provided superior postoperative analgesia and a
faster return of motor function versus lidocaine in a randomized,
double-blind study of 40 patients undergoing open should surgery.
Patients received an interscalene brachial plexus block with either
30 milliliters (mL) of 1.5% lidocaine or 0.5% ropivacaine followed by
an continuous patient-controlled interscalene analgesia with 1%
lidocaine or 0.2% ropivacaine, respectively. Postoperative pain
intensity measured on a 0 to 100 millimeter visual analog scale was
significantly higher in the lidocaine group for the first 8 hours of
infusion (p=0.05). Rescue analgesia was required in 16/20 (84%) of
the lidocaine group versus 8/20 (46%) of the ropivacaine group
(p=0.05). At 16 and 24 hours of observation, a larger proportion
(70% and 95%) of the ropivacaine group had complete regression of
motor block versus the lidocaine group (50% and 55%; p=0.05 and
0.013, respectively). Nausea had a higher incidence in the lidocaine
group (5/20 versus 0/20; p=0.046). While lidocaine 1% can be used
for postoperative pain control, this study showed that ropivacaine
was superior
[589]
.
b) Lidocaine and ropivacaine provided similar results on intravenous
regional anesthesia in volunteers. In a cross-over study, 10
volunteers received 40 milliliters each of lidocaine 0.5% and
ropivacaine 0.2% injected intravenously into the dorsal surface area
of the hand on 2 separate occasions. A double-cuff tourniquet was
placed on the upper arm and then the anesthetic was injected over
1 minute. Time to complete loss of pinprick sensation and loss to
tetanic stimulation occurred at similar times with the anesthetics.
Decreased pinprick sensation (p=0.0002) and decreased grip
strength (p=0.02) persisted significantly longer with ropivacaine after
tourniquet release than with lidocaine. After tourniquet release with
ropivacaine therapy, the volunteers reported less dizziness
(p=0.01), tinnitus (p=0.003), metallic taste (p=0.01), and
lightheadedness (p=0.001) than when they received lidocaine.
Ropivacaine appears appropriate for use in intravenous regional
anesthesia but further studies under surgical conditions are needed
[590]
.
c) Ropivacaine appeared to provide comparable but longer lasting
intravenous residual anesthesia as compared to lidocaine in 15
volunteers. Volunteers (5 in each group) randomly received either
ropivacaine 1.2 milligrams/kilogram (mg/kg), ropivacaine 1.8 mg/kg,
or lidocaine 3 mg/kg. The anesthetic was injected as a 40-mL bolus
over 2 minutes. Before therapy a tourniquet was applied to the
upper arm. The onset to complete sensory and motor block was
similar in all treatment groups (within 30 minutes. Anesthesia to
pinprick and transcutaneous electric stimulation was also sustained
significantly longer in the high-dose ropivacaine group as compared
to the lidocaine group (p=0.008). Time to partial recovery of pinprick
sensation was also longer in the high-dose ropivacaine group as
compared to the low dose (p less than 0.05). Light-headedness and
hearing disturbances during cuff deflation was reported in all 5
volunteers receiving lidocaine, in 1 receiving high-dose ropivacaine,
and none receiving low-dose ropivacaine
[591]
.
Peribulbar infiltration of local anesthetic - Retrobulbar infiltration of
local anesthetic
a) Ropivacaine 0.2% provided ocular surgical analgesia that was
comparable in efficacy to lidocaine 1%, in a randomized, doubleblind, comparative trial. Patients undergoing cyclophotocoagulation
or panphotocoagulation surgery received peribulbar/retrobulbar
anesthetic blocks with hyaluronidase 3.75 International
units/milliliter, administered concurrently with either ropivacaine
0.2% solution (n=37) or lidocaine 1% solution (n=37). The total
volume of anesthetic administered was determined by lean body
weight. Analgesia effectiveness was determined by the presence or
absence of supplemental intraoperative anesthetic required for
surgery completion. The need for supplementary block was similar
between the ropivacaine and lidocaine treatment cohorts (11% and
14%, respectively). Ropivacaine produced significantly less motor
blockade at the end of treatment compared with lidocaine (p=0.02);
however, approximately 2 hours after surgery, significantly more
ropivacaine-treated patients required eye patching due to impaired
eye movements compared with the lidocaine group (p=0.035)
[592]
.
Topical local anesthetic
a) CATARACTS: ROPIVACAINE 1% eyedrops showed similar
efficacy to LIDOCAINE 4% eyedrops as topical anesthesia in
cataract surgery, with ropivacaine achieving slightly better ratings on
subjective pain scores, based on a randomized, double-blind trial
(n=64). The eyedrops were given every 5 minutes starting 30
minutes before cataract surgery. Supplemental anesthesia was
required by 5 ropivacaine-treated patients and 4 lidocaine-treated
patients (not significant). Mean pain scores were 1.843 and 2.406
for the ropivacaine and lidocaine groups, respectively (p=0.179). No
significant between-group differences occurred related to duration of
surgery or intraoperative complications. On postoperative day 1,
corneal edema was observed in 12 eyes and 6 eyes of those given
ropivacaine and lidocaine, respectively (p=0.150). Although
endothelial cell density decreased significantly in both groups, mean
endothelial cell loss over the 2 months after surgery was
significantly less in the ropivacaine group (p=0.031)
[593]
.
Sotalol
Ventricular tachycardia
a) In a study involving 33 patients, most of whose underlying heart
disease was old myocardial infarction, sotalol (100 mg IV over 5
min) was significantly more effective than lidocaine(100 mg IV over
5 min), 69% vs 18% respectively, for the acute termination of
sustained ventricular tachycardia (VT). The arrhythmic events were
well-organized sustained monomorphic VT primarily based on old
myocardial infarction. This type of sustained VT is usually re-entrant
in mechanism and arise in areas of myocardial scarring.
Tachycardia was terminated in 50% (n=7) of patients that were
unresponsive to lidocaine and crossed over to sotalol and 25% of
patients (n=1) that were unresponsive to sotalol and crossed over to
lidocaine. There was no significant difference in the numbers of
deaths or the incidence of adverse effects between the 2 drugs
[600]
.
Sufentanil
Extracorporeal shockwave lithotripsy
a) Intrathecal sufentanil at a dose of 20 micrograms used for
extracorporeal shock wave lithotripsy (ESWL) was shown to allow
earlier discharge of outpatients following the procedure as
compared to varying doses of intrathecal lidocaine depending on the
level of spinal induction desired. It was proposed that the earlier
discharge of ESWL patients receiving intrathecal sufentanil would
be due to the maintenance of motor and sensory function. Twentytwo patients were randomized evenly and completed the study
protocol. There were no significant differences between the study
groups in the variables of stone size, number of shocks, or utilized
voltage. Initial verbal analogue pain scale (VAPS), postoperative
VAPS, and fentanyl requirement for post-op pain management were
not different between groups. The patients who received intrathecal
sufentanil could ambulate, tolerate oral intake, and void
spontaneously (p less than 0.05) earlier than the lidocaine
randomized counterparts and could be discharged home earlier.
Discharge data revealed that those sufentanil-treated patients who
experienced pruritus (3 of 11) were discharged an average of 30
minutes later than those who did not experience this side effect in
the sufentanil group. Another study evaluating the costeffectiveness of intrathecal sufentanil for outpatient ESWL has been
suggested
[585]
.
Tetracaine Hydrochloride
Anesthesia for procedures on eye, Corneal, topical
a) Lidocaine, alone or in combination with tetracaine hydrochloride,
provided analgesia of longer duration than did tetracaine
hydrochloride alone, bupivacaine alone, or combined tetracaine
hydrochloride and bupivacaine when applied topically to the cornea.
The 34 eyes of 17 healthy subjects were randomly assigned to one
of 5 groups: 0.5% tetracaine hydrochloride, 4% lidocaine
hydrochloride, 0.75% bupivacaine, tetracaine hydrochloride followed
by lidocaine, or tetracaine hydrochloride followed by bupivacaine.
Two-drop doses of topical anesthesia were instilled into eyes from a
23-gauge hypodermic needle. At 10 minutes after application,
corneal sensitivity, measured by a mechanical stimulus, was
significantly less in eyes treated with lidocaine than in eyes treated
with other agents (p less than 0.005). When tetracaine
hydrochloride preceded lidocaine administration, the subjects did
not experience the pain associated with lidocaine alone
[616]
.
Anesthesia for procedures on eye - Operation on pterygium
a) Both lidocaine 2% gel and tetracaine hydrochloride 1% solution
provided effective anesthesia as the sole topical anesthetic agent
for patients undergoing primary pterygium surgical excision and
mitomycin C; however, lidocaine gel appeared superior according to
the operating physician and its application was more convenient. In
this prospective, randomized, double-blind study, patients (mean
age 60.8 +/- 11.97 years) undergoing primary pterygium surgery
were randomized to receive tetracaine hydrochloride 1% drops with
a placebo gel (n=21) or lidocaine 2% gel with normal saline eye
drops (n=19). One drop of the allocated eye drop was applied 3
times every 5 minutes for the first 15 minutes followed by
administration of 1 mL of allocated eye gel once 5 minutes before
surgery. The allocated eye drop and gel were administered again at
the beginning of surgery and when the pterygium was excised.
Mitomycin C was applied to the undersurface of the conjunctival
edge after the pterygium was removed. If patients experienced pain
during the procedure, they could request a drop of tetracaine 1%
solution be administered. Pain was assessed on a 10-point (0=no
pain; 10-worst pain ever) scale separately by the patient and the
operating physician at 4 stages during surgery (1) upon first incision,
(2) upon excision of the pterygium body, (3) during conjunctival
suturing, and (4) immediately following surgery. Additional
tetracaine drops were requested by 11 patients in the tetracaine
group (with 3 patients requiring 2 doses), and 3 patients in the
lidocaine group. Mean surgical duration was 25.33 +/- 5.29 and
24.21 +/- 4.85 minutes in the tetracaine and lidocaine groups,
respectively. Patient reported pain showed no difference in pain
reported during stages 1, 2, and 4 of the surgical procedure, but a
statistically significant difference in favor of lidocaine was observed
during stage 3 (1.43 vs 0.47; p=0.03). Physician rated pain scores
were statistically significant in favor of lidocaine for each stage of
the surgical procedure: stage 1 (1.76 vs 1.11; p=0.039), stage 2
(4.52 vs 2.84; p=0.0005), stage 3 (2.24 vs 1.11; p=0.0005), stage 4
(1.14 vs 0.32; p= 0.0005). There were no corneal epithelial or ocular
surface complications reported in either group
[588]
.
Anesthesia for procedures on eye - Strabismus surgery
a) Lidocaine 2% gel is a more effective topical anesthetic than
tetracaine hydrochloride 1% solution for one-stage adjustable suture
strabismus surgery. In this prospective, double-blind study, each
patient (n=14) undergoing bilateral and symmetrical strabismus
surgery received lidocaine 2% gel (1 milliliter) in one eye and
tetracaine hydrochloride 1% solution (3 drops 5 minutes apart) in
the other eye. The results of a 10-cm visual analog scale indicate
that mean subjective pain and discomfort scores during surgery
were significantly higher for tetracaine hydrochloride than for
lidocaine (p=0.01). In addition, the mean number of additional drops
required by eyes was significantly higher following tetracaine
hydrochloride than after lidocaine (p=0.02)
[587]
.
Topical local anesthetic to skin
a) One study reports that topical-lidocaine (5%)epinephrine(1:2000)(TLE) is similar in efficacy to a tetracaine
hydrochloride(0.5%)-adrenaline(epinephrine, 1:2000)cocaine(10.4%)(TAC) solution when evaluated in patients with facial
or scalp lacerations
[586]
. In this pilot study, 35 patients with facial or scalp laceration were
randomized to receive either a TLE or TAC application prior to
suturing. Upon wound closure, pain relief was measured by using a
standardized visual pain scale (1 to 4, complete anesthesia; 5 to 6,
partial anesthesia; 7 to 9, inadequate anesthesia). The mean pain
score for both TLE and TAC was 2.66 and 3.29, respectively
(p=0.33). Assuming equal efficacy, it would appear that there are
other important advantages of the TLE solution that would favor its
use over TAC solutions. TLE provides topical anesthesia without the
potential toxicities that have been associated with tetracaine
hydrochloride and cocaine used in TAC solutions. In addition, TAC
costs substantially more than TLE. In this study, the projected
annual savings for the institution was $59,998 if TLE was switched
for TAC in all patients presenting with a laceration suitable for
topical anesthesia. Additional studies are encouraged to fully
evaluate the comparative efficacy of TAC solutions to alternative
topical anesthetic agents.
Thiopental
Raised intracranial pressure
a) Intravenous lidocaine is as effective as thiopental for rapid
reduction of intraoperative intracranial hypertension and causes less
cardiovascular depression, as demonstrated in 20 patients with
brain tumors undergoing craniotomy
[574]
.
Tocainide
Myocardial infarction
a) Prophylactic administration of tocainide has been reported at
least as effective as prophylactic lidocaine for arrhythmias
associated with acute myocardial infarction
[610]
.
Tinnitus
a) One study evaluated the effectiveness of single intravenous
doses of lidocaine versus tocainide (open-label) and oral tocainide
versus placebo in a selected group of 24 patients with relatively
constant, unilateral tinnitus
[611]
. In the first part, patients were administered a single intravenous
dose of lidocaine 100 mg over 1.5 minutes, then 2 hours later
intravenous tocainide 250 mg over 2 minutes. Tinnitus was
assessed subjectively by the patient and with masking, pure tone,
and speech audiometry. The authors did not present specific data,
but indicated that there was no significant difference in suppression
of tinnitus between intravenous lidocaine or tocainide; however, the
effect on tinnitus was significantly improved with both compared to
control values. The second part of the study was an open-label, oral
dose titration trial in which patients received oral tocainide 400 mg
daily, with the dosage increased weekly to 400 mg four times daily.
Thereafter, patients were randomly administered placebo or oral
tocainide for 2 weeks. Patients received the tocainide dose that
produced a greater than 50% decrease in tinnitus during the dose
titration trial or a maximum of 600 mg three times daily if there was
less than a 50% decrease in tinnitus at 400 mg four times a day. No
significant difference between tocainide and placebo was detected.
During the trials, 4 patients dropped out because of severe side
effects (urticaria, paresthesia, drowsiness, central nervous system
or gastrointestinal symptoms) while on an oral tocainide dose of 400
mg three to four times daily.
Ventricular arrhythmia
a) Patients who respond to lidocaine are likely to respond to
tocainide, but this is not absolute
[612]
.
b) One study showed comparable effects of intravenous lidocaine
and oral tocainide in an open label study in patients with an acute
myocardial infarction and exhibiting PVCs
[613]
. With response defined as a 70% reduction in PVCs within 24
hours, 14 patients responded to tocainide versus 13 for lidocaine.
Adverse reactions were reported in 50% of the patients on tocainide
versus 70% for the lidocaine group.
c) In 99 patients with ventricular arrhythmias occurring following
cardiac surgery, intravenous tocainide and lidocaine were similarly
effective in producing an 80% or greater reduction in PVCs or
complete resolution of ventricular couplets or tachycardia
[614]
. Another study found similar results in a study of similar design with
25 patients
[615]
.
Verapamil
Hypertension, Perioperative
a) In a study comparing the efficacy of verapamil, lidocaine, and a
verapamil-lidocaine combination for attenuation of cardiovascular
responses to tracheal extubation, the verapamil-lidocaine
combination was the most effective. In this study, 100 patients
undergoing minor elective surgery were randomized to receive
saline plus saline, verapamil 0.1 milligram (mg) per kilogram (kg)
plus saline, lidocaine 1 mg/kg plus saline, or verapamil 0.1 mg/kg
plus lidocaine 1 mg/kg intravenously after surgery. Tracheal
extubation was performed 2 minutes after infusion of the study
drugs. After extubation, systolic arterial blood pressure, diastolic
arterial blood pressure, and heart rate values all significantly
increased in the control group. Verapamil, lidocaine, and the
combination of these 2 drugs successfully attenuated these
physiologic responses. Maximal attenuation was observed in the
group receiving verapamil plus lidocaine
[594]
.
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359. Product Information: STRIBILD(TM) oral tablets, elvitegravir cobicistat
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388. Product Information: INVIRASE(R) oral capsules, tablets, saquinavir mesylate oral
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402. Product Information: KALETRA(R) oral capsule, oral solution, lopinavir/ritonavir
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417. Product Information: Wydase(R), hyaluronidase. Wyeth Laboratories, Philadelphia,
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plasma lidocaine clearance. Clin Pharmacol Ther 1984; 36:584-587.
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metoprolol and of propranolol. Clin Pharmacol Ther 1983; 33:133-138.
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continuous infusion and by coadministration of propranolol. N Engl J Med 1980;
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Pharmacol 1984; 18:853-860.
432. Bax ND, Tucker GT, Lennard MS, et al: The impairment of lidocaine clearance by
propranolol-major contribution from enzyme inhibition. Br J Clin Pharmacol 1985;
19:597-603.
433. Schneck DW, Luderer JR, Davis D, et al: Effects of nadolol and propranolol on
plasma lidocaine clearance. Clin Pharmacol Ther 1984; 36:584-587.
434. Conrad KA, Byers MJ III, Finley PR, et al: Lidocaine elimination: effects of
metoprolol and of propranolol. Clin Pharmacol Ther 1983; 33:133-138.
435. Product Information: PREZISTA(TM) oral tablets, darunavir oral tablets. Tibotec
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clinical importance. Anesth Analg 1980; 59:678-682.
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plasma lidocaine clearance. Clin Pharmacol Ther 1984; 36:584-587.
441. Conrad KA, Byers MJ III, Finley PR, et al: Lidocaine elimination: effects of
metoprolol and of propranolol. Clin Pharmacol Ther 1983; 33:133-138.
442. Bax ND, Tucker GT, Lennard MS, et al: The impairment of lidocaine clearance by
propranolol-major contribution from enzyme inhibition. Br J Clin Pharmacol 1985;
19:597-603.
443. Ochs HR, Carstens G, & Greenblatt DJ: Reduction in lidocaine clearance during
continuous infusion and by coadministration of propranolol. N Engl J Med 1980;
303:373-378.
444. Graham CF, Turner WM, & Jones JK: Lidocaine-propranolol interactions (letter). N
Engl J Med 1981; 304:1301.
445. Miners JO, Wing LM, Lillywhite KJ, et al: Failure of 'therapeutic' doses of beta-
adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine. Br J Clin
Pharmacol 1984; 18:853-860.
446. Schneck DW, Luderer JR, Davis D, et al: Effects of nadolol and propranolol on
plasma lidocaine clearance. Clin Pharmacol Ther 1984; 36:584-587.
447. Conrad KA, Byers MJ III, Finley PR, et al: Lidocaine elimination: effects of
metoprolol and of propranolol. Clin Pharmacol Ther 1983; 33:133-138.
448. Product Information: NORVIR(R), ritonavir capsules, ritonavir oral solution. Abbott
Laboratories, Abbott Park, IL, 2005.
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