Download Local anesthetics

Local and regional anesthesia
by dr. S. Bradulskis General surgery department , Kaunas
Local Anesthetic
A local anesthetic is an agent that
interrupts pain impulses in a specific
region of the body without a loss of patient
consciousness. Normally, the process is
completely reversible--the agent does not
produce any residual effect on the nerve
fiber.
Chemistry: all local anesthetics are weak
bases, classified as tertiary amines.
Characteristics
Poorly water soluble weak basic amins
(pKa 7,5-9)
Molecular weight: between 220 and 288
Lipophilic aromatic ring + tertiary hydrophilic
amin
Link: Ester (-COO-) or Amid (-NHC-) chain
Local Anesthetic Classification
Aminoesters:
 Cocaine
 Procaine
 Chloroprocaine
 Tetracaine
Aminoamids:
 Lidocaine
 Prilocaine
 Mepivacaine
 Etidocaine
 Bupivacaine
 Ropivacaine
 Levobupivacaine
Local Anesthetic Metabolism
Aminoesters (cocaine, procaine, tetracaine,
and chloroprocaine ):
Quick degradation
Hydrolysis, plasma and liver cholinesterase
Produces para-aminobenzoic acid (PABA,
allergy….)
Aminoamids (lidocaine, mepivicaine,
prilocaine, bupivacaine, and etidocaine ):
Slower degradation
Liver microsomal enzymes
Excretion (metabolites and <5% unchanged
drug) via kidneys
Prilocain (very large doses):
- Accumulation of metabolites: risk of
methemoglobinemia
Mechanism of Action
 Local anesthetics work to block nerve conduction
by reducing the influx of sodium ions into the
nerve cytoplasm.
 Sodium ions cannot flow into the neuron, thus the
potassium ions cannot flow out, thereby inhibiting
the depolarization of the nerve.
 If this process can be inhibited for just a few
Nodes of Ranvier along the way, then nerve
impulses generated downstream from the
blocked nodes cannot propagate to the ganglion.
Effect on Action
Effect of protein binding - increased
binding increases duration of action
Effect of diffusibility - increased diffusibility
= decreased time of onset (pK)
Effect of vasodilator activity - greater
vasodilator activity = decreased potency
and decreased duration of action
Vasoconstrictors
 Vasoconstrictors decrease the rate of vascular
absorption which allows more anesthetic to
reach the nerve membrane and improves the
depth of anesthesia, it .
 There is variable response between LA and the
location
of
injection
as
to
whether
vasoconstrictors increase duration of action.
1:200,000 epinephrine appears to be the best
vasoconstrictor.
Effect of lipophilicity
ANESTHETIC POTENCY
 Lipid solubility appears to be the primary
determinant of intrinsic anesthetic potency.
Chemical compounds which are highly lipophilic
tend to penetrate the nerve membrane more
easily, such that less molecules are required for
conduction blockade resulting in enhanced
potency.
 more lipophilic agents are more potent as
local anesthetics
Two forms exist simultaneously:
 Ionised kation (BH+)
 Non ionised base (B)
 Relation between the two forms
 depends on:
 pKa of the local anesthetic drug
 Tissue (and solution) pH
 Both forms necessary for the
action:
 Neutral base:
 - Penetrates the membrane
 of the nerve cell
 Kation: Active form
 - Blocks Na-channels
(intracellular)
The lower the difference
between pKa and pH
(less basic LA),
the more non ionised
molecules (base).
More non ionised molecules
= quicker onset of action
Order of sensory function block
1. pain
2. cold
3. warmth
4. touch
5. deep pressure
6. motor
Recovery in reverse order
Susceptibility to block by local
anesthetics of types of nerve fibers
In general, small nerve fibers are more
susceptible than large fibers, however:
–
–
–
–
the type of fiber
degree of myelination
fiber length and
frequency- dependence are also important in
determining susceptibility
A FIBER SIZE AND FUNCTION
• α: (dia 12-20um; cond vel 70-120m/s) largest,
afferent to and efferent from muscles and joints.
Actions: motor function, proprioception, reflex
activity.
• β: (dia 5-12um; 30-70m/s) large as A-alpha,
afferent to and efferent from muscles and joints.
Actions: motor proprioception, touch, pressure,
touch and pressure.
• γ: (dia 3-6um; 15-30m/s) muscle spindle tone.
• δ: (dia 2-5um; 12-30m/s) thinnest, pain and
temperature. Signal tissue damage.
B FIBER SIZE AND FUNCTION
B fibers: (dia – 2-5um) Myelinated
preganglionic autonomic. Innervate
vascular smooth muscle. Though
myelinated, they are more readily blocked
by LA than C fibers.
C FIBER SIZE AND FUNCTION
C fibers: (dia 0.4-1.2 um) Nonmyelinated,
very small nerves. Smallest nerve fibers,
slow transmission. Transmit dull pain and
temperature, post-ganglionic autonomic.
* Both A-d and C fibers transmit pain and
are blocked by the same concentration of
LA.
TOXICITIES OF LA
 Essentially all systemic toxic reactions
associated with local anesthetics are the
result of over-dosage leading to high blood
levels of the agent given. Therefore, to avoid
a systemic toxic reaction to a local
anesthetic, the smallest amount of the most
dilute solution that effectively blocks pain
should be administered.
Toxicity of LA
Signs of toxicity occur on a continuum. From
early to late stages of toxicity, these signs
are: circum-oral and tongue numbness,
lightheadedness,
tinnitus,
visual
disturbances,
muscular
twitching,
convulsions,
unconsciousness,
coma,
respiratory arrest, then cardiovascular
collapse.
Toxicity of LA
 Hypersensitivity.
Some
patients
are
hypersensitive
(allergic)
to
some
local
anesthetics. Although such allergies are very
rare, a careful patient history should be taken in
an attempt to identify the presence of an allergy.
There are two basic types of local anesthetics
(the amide type and the ester type). A patient
who is allergic to one type may or may not be
allergic to the other type.
Toxicity of LA
Central Nervous System Toxicities.
 Local
anesthetics,
if
absorbed
systematically in excessive amounts, can
cause central nervous system (CNS)
excitement or, if absorbed in even higher
amounts, can cause CNS depression.
Toxicity of LA to CNS
Excitement. Tremors, shivering, and
convulsions characterize the CNS
excitement.
Depression. The CNS depression is
characterized by respiratory depression
and, if enough drug is absorbed,
respiratory arrest.
Toxicity of LA to Cardiovascular
system
 Cardiovascular Toxicities. Local anesthetics if
absorbed systematically in excessive amounts
can cause depression of the cardiovascular
system.
 Peripheral vascular action arteriolar dilation
(except cocaine which is vasoconstrictive
 Hypotension and a certain type of abnormal
heartbeat (atrioventricular block) characterize
such depression. These may ultimately result in
both cardiac and respiratory arrest.
Systemic toxicity: prevention
IV access secured before injection of the LA
 Chose least toxic drug suitable
 Consider block type and patient specific max. dose ranges
Start with a „typical dose“
 Consider adding a vasoconstrictive adjuvant (epinephrine)
Careful aspiration during injection
 Observe clinical reactions:
Talk to the patient and monitor ECG/blood pressure to realize
early symptoms of central-nervous and cardiovascular toxicity
 Stop injection immediately when early symptoms are realized
 Consider the time course for development of toxic signs
(5-10 min. after correct injection….)
Systemic toxicity: treatment
Stop injection immediately
Treat:
Give oxygen, (hyperventilate - mask or airway device)
Stop cerebral excitation (Benzodiazepines, Barbiturates, Propofol
(Midazolam 2-5 mg,Thiopental 50-150 mg,Propofol 50-100 mg)
Correct hypotension and arrhythmias
(crystalloids, vasopressors, antiarrhythmic drugs (Ephedrin 5-10 mg, Epinephrine 10-100 μg )
Cardiopulmonary resuscitation for cardiac arrest / VF
Avoid / treat aggravating factors: Hypoxia and acidosis (respiratory
and metabolic)
Influencing factors: patientrelated
Age:
Old age (> 70 yr): elimination prolonged
- 10-20% dose reduction for continuous applications
Newborns (< 4 months): elimination of amid LA prolonged
- 15% dose reduction per kg
Renal dysfunction:
Excretion reduced:
- 10-20% dose reductions relative to degree of dysfuncion
Hepatic dysfunction:
Low liver blood flow or poor liver function:
- Higher blood levels of amid local anesthetics
- 10-50% dose reduction for repeated or continuous applications
Influencing factors: patient-related
Body size:
In very small adults, the dose for blocks requiring large
doses (brachial plexus, IVRA) should be reduced.
Pregnancy:
Hormonally increased sensitivity of the CNS to LA:
Reduced requirements
Risk for toxicity ↑:
Reduced protein binding of bupivacaine
Increased cardiac output, perfusion ↑ and uptake ↑
Anatomic and physiologic changes - 10% dose
reduction
Influencing factors: patient-related
Infected tissue:
Low tissue pH:
More ionised kations
Less uncharged base available for
penetration
Vasodilation:
Uptake into circulating blood ↑
Reduced effect of the injected local
anesthetic
Influencing factors: not patientrelated
Alkalinization (pH ↑ with sodium bicarbonate):
Uncharged base↑, diffusion rate through nerve membrane ↑
- Time to onset ↓
And: Injection is less painful ! (higher pH)
But: Duration of action ↓
Recipe:
9 ml LA (lidocaine, mepivacaine) +1 ml NaBic 8.4%
Adjuvant (Epinephrine 1 : 200‘000 (5 μg/ml))
Vasoconstriction: Intravascular uptake ↓
- Duration of action 30-50%↑
only in combination with short acting LA (Lido-, Prilo-, Mepivacaine!)
- Toxicity ↓ (all LA)
Recipe:
20 ml LA + 0.1 mg Epinephrine
Contraindication for epinephrine:
Local anesthesia around
end arteries (finger, ear, penis)!
Types of Local Anesthesia
• Surface Anesthesia. This type of
anesthesia is accomplished by the
application of a local anesthetic to skin or
mucous membranes. Surface anesthesia is
used to relieve itching, burning, and surface
pain (for example, as seen in minor
sunburns).
• Lidocaine
– 5% ointment, 2% gel,
4% solution, 10%
aerosol, 100 mg
suppository
– Onset 3-5 min
• Bensocain
– 14-20% solution, gel,
– Onset 30 s
Types of Local Anesthesia
• Local Infiltration Local infiltration occurs
when the nerve endings in the skin and
subcutaneous tissues are blocked by direct
contact with a local anesthetic, which is
injected into the tissue. Local infiltration is
used primarily for surgical procedures
involving a small area of tissue (for
example, suturing a cut).
Intravenous regional anesthesiaBier anesthesia
 How does it work?
 Injection into a previously
exsanguinated and occluded limb
 Retrograde spread of the distally
injected local anesthetic agent
 Very rapid onset
 For arm/leg procedures < 1hour
 Can be performed with:
Prilocaine, Chloroprocaine,
Lidocaine (0.5% solution, 40-60 ml)
 Possible complications:
LA intoxication when tourniquet
is insufficient or released less
than 15 - 20 minutes after injection
Types of Local Anesthesia
• Peripherial Nerve Block. In this type of
anesthesia, a local anesthetic is injected around
a nerve that leads to the operative site. Usually
more concentrated forms of local anesthetic
solutions are used for this type of anesthesia.
• Major nerve block - (plexus brachialis)
• Minor nerve block - (n. radialis)
Peripheral nerve blocks
Choice of agent:
Most local anesthetics can be used. Choice depends on
intended duration of the block
Dose / concentration:
Lidocaine, Mepivacaine, Prilocaine (1 % solutions)
Bupivacaine (0.5 % solution), Ropivacaine (0.75% solution)
(10 –) 20 – 40 (– 50) ml (depending on nerve or plexus type)
Onset of action and duration:
Onset is rapid for Lido/Mepi/Prilocaine and slow for
Bupi/Ropi. Time to onset and duration with considerable
variations (depending on distance of LA deposit to nerves…)
Epinephrine prolongs duration of Lido/Mepi/Prilocaine,
but is less effective with Bupivacaine
Brachial plexus block
Block possible at different sites:
 Interscalene: Supraclavicular,
Infraclavicular
 Axillary
Chosen site:
Depends on planned surgical
procedure
Injected volume: 30 – 50 ml
Time to onset: < 10 min (Lido,
Mepi, Prilo) up to 25 min
(Bupi, Ropi)
Spinal and epidural anesthesia
Main indications:
•
•
•
•
•
Spinal:
Surgery below the
umbilicus
lower abdomen
lower extremities
transurethral and
vaginal procedures
Cesarean section
•
•
•
•
•
•
Epidural:
Indications as for
spinal, +:
- Thoracic approach in
combination with
general anesthesia:
abdominal and thoracic
surgery
Obstetric analgesia
Treatment of acute and
chronic pain
Spinal and epidural anesthesia
Contraindications:
• Sepsis
• (Severe) Coagulopathies
• Shock, severe hypovolemia
• Infection at/near puncture site
• Refusal
• Certain neurologic diseases
• Severe aortic valve stenosis
• Communication problems
• Elevated intracranial pressure
• Anatomical abnormalities
Spinal and epidural anesthesia:
effects
Main effects:
Anesthesia and analgesia
Cardiovascular system:
Hypotension (related to: extent of sympathetic block,
volemia)
Bradycardia (blocked sympathetic cardioaccelerator
fibers;Young males: more frequent)
Both effects more pronounced with spinal than with
epidural anesth.
Respiratory system:
Reduced active exhalation with high block level:
- Caution in patients with severe COPD!
Spinal and epidural anesthesia:
effects
•
•
•
•
•
•
•
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Gastrointestinal and urogenital:
Unopposed parasympathetic activity:
Nausea (associated with high block level)
Increased secretions, relaxed sphincters, bowel constriction
Long lasting block of sacral parasympathetic nerves:
Postoperative urinary retention possible
Endocrine-metabolic:
Less perioperative stress-response:
Reduction of: protein catabolism, hyperglycemia, sodium and
water retention, fever, tachycardia, increased minute ventilation
Coagulation:
Reduced hypercoagulability, reduced thromboembolic events
• Spinal Anesthesia. In spinal anesthesia,
the local anesthetic is injected into the
subarachnoid space of the spinal cord
Spinal anesthesia
• Only use drugs without
preservatives!
• Commonly used: 0.5%
Bupivacaine (long
action)
• hyperbaric (with 8%
glucose) or plain
(isobaric) solution
• No hyperbaric (=heavy)
lidocaine (transient neural
symptoms)!
• Rapid onset (injection
close to nerve roots)
Epidural Anesthesia. This type of anesthesia is
accomplished by injecting a local anesthetic into
the epidural space
• Lido-, Mepiva-, Prilo-, Bupiva, Ropivacaine
• Onset 5-15 min
(Lido/Mepi/Prilo) to 20-30 min
(Bupi/Ropi)
• Anesthesia:
• high concentration: 2%
Lido/0.5% (L-)Bupi/0.75% Ropi
• Analgesia postoperative
without motor deficit:
• 0.125-0.25% (L-)Bupi/0.2%
Ropi
Postoperative Analgesia
Local anesthetics for postoperative
analgesia:
Thoracic Epidural analgesia
Continuous peripheral nerve blocks
(Shoulder, Arm, Leg)
Continuous wound infiltration
(Shoulder, Tram-Flap, ….)
Postoperative epidural analgesia
Advantages compared with systemic opioid-based analgesia:
Decreased postoperative pain
Better analgesic effect
Reduced opioid related side-effects (Nausea/Vomiting, Pruritus,
Sedation)
Also suitable for some outpatients (elastomere pumps)
Less sedation, less postoperative fatigue
Higher „Health related quality of life“
Earlier mobilization
Better respiratory function, better exercise capacity,better bowel
function, earlier oral nutrition
Earlier ready for discharge (not done, other factors….)
No difference: incidence of postoperative surgical complications
But:
Method-specific side effects (similar to regional anesthesia