Download Lipid Rescue

Lipid Rescue--Its not about the nail?
LTC Peter Strube CRNA MSNA APNP ARNP DNAPc
Assistant Professor Rosalind Franklin Nurse Anesthesia Program
Cell: 608-469-1750
[email protected]
Email me: I have some great articles for you to read!
Dedicated to:
Thomas G Healey, RN, CRNA, MA
St Mary’ s University
Died January 5, 2014
Navy Corpsman Vietnam
Financial Disclosure
There is no financial conflicts with this presentation.
Lecturing about a topic does not constitute
endorsement of any product. Please take the time
to research each topic for more information.
Mentioning a product or company does NOT
represent endorsement.
Increasing Food Allergy
A kiss in 2005—Teen Dies

Peanuts – peanut oil used in Fresenius propoven

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
(a propofol product from Europe showing up in hospitals in
the U.S.)
http://www.fda.gov/downloads/Drugs/DrugSafety/Dru
gShortages/UCM207301.pdf
Mehta, 2014. Major finding: No allergic reactions were reported in patients with known food allergies
who received propofol prior to undergoing endoscopy.
Data source: A review of records from 160 food allergy patients who had endoscopies performed at
the Mount Sinai Center for Eosinophilic Disorders from November 2004 to January 2014.
Why bother with the future?

“The future belongs to the unreasonable ones, the ones
who look forward not backward, who are certain only of
uncertainty, and who have the ability and the confidence to
think completely differently.”

Charles Handy quoting Bernard Shaw

Progressives are main stream only ahead of their time!

The point is not to predict the future but to prepare
for it and to shape it
Case Study
26 year old female in labor presents for
an elective epidural----Second baby.. Hx of preterm Labor
On Fish Oil
Randomized clinical trials of fish oil supplementation in high risk
pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team
BJOG. 2000 Mar;107(3):382-95

To test the postulated preventive effects of dietary n-3 fatty
acids on pre-term delivery, intrauterine growth retardation,
and pregnancy induced hypertension

33-21% reduction in Preterm Labor

WOW… what does this have to do with a epidural….. We will see
Fish Oil- 3000mg Omega 3
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids
eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), precursors of eicosanoids that
are known to reduce inflammation throughout the body, and are thought to have many health
benefits.
Studies suggest that it is helpful with cardiovascular disease, CAD, Depression, anxiety, increased
new born outcomes and many many more……...
Some early studies are looking at using it for depression and suicide prevention… also used for
aggressive behavior, alzeimers, Parkinson's and psoriasis. This is to name a few… it is used for a
wide array of conditions
Bleeding in high doses…greater than 3 grams per day
Interacts with some anticoagulation medications and oral contraceptives.
The Ground Rules:

Recognition of Problem:
Immediate Medical Management:
Treatment:
Follow-up, after action review:

Do you know antidotes?
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Interesting thought isn’t it?
History
Very Critical to Remember! Memorize this!
Stoelting RK, Hillier SC. Pharmacology and Physiology in Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
Outcome
Dependent upon
Potency
Lipid Solubility
Onset
pKa---This is critical to
understand! Closer to
physiological Ph the more
rapid onset!
Duration
Protein Binding—must know!
IV Starts? ---Pain Theory?
Intradermal Lidocaine
PKA?
Intradermal Saline:
J Perianesth Nurs. 2012 Dec;27(6):399-407. doi:
10.1016/j.jopan.2012.08.005.

Bacteriostatic normal saline compared with
buffered 1% lidocaine when injected
intradermal as a local anesthetic to reduce pain
during intravenous catheter insertion.
The History

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
First report 1929 – 40 fatalities
Risk of modern toxicity first then
discussed in 1979
2006/2007 first treatment with Lipids.
Time Line
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1960’s-- Marcaine linked to fetal death with OB use

1970’s –Marcaine linked to cardiac arrest

1980’s – cardiac events continue even with introduction Ropivacaine
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1998—magic year….
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2006 finally hits clinical practice
Toxicity

Local anesthetics are amphipathic chemicals, meaning they have
affinity for both lipid and water environments.

This characteristic allows local anesthetics to cross plasma
membrane and intracellular membranes quickly and also to
interact with charged targets such as structural or catalytic
proteins and signaling systems.

Local anesthetics produce a variety of toxic effects in several
tissue types, mainly heart, brain and skeletal muscle.
Toxicity
The main site of both the clinically desirable and toxic effects of local anesthetics are
thought to be exerted at the voltage gated sodium channel, many alternative sites have
also been considered recently.
Notably, the most potent, toxic local anesthetics, such as bupivacaine, interrupt
practically every metabotropic and ionotropic signal transduction scheme that has
been studied.
Bupivacaine in particular has also been shown to disrupt each of the four components of
oxidative phosphorylation: substrate transport, electron transport, proton motive force
maintenance and ATP synthesis.
An interesting observation that suggests the importance of this effect in bupivacaineinduced toxicity is that the pattern of tissues affected includes those with the highest
aerobic demand and least tolerance for hypoxia
Order of CNS toxicity: Bupivacaine, tetracaine, Etidocaine, lidocaine,
mepivacaine and 2 Chloroprocaine.
Rates of Toxicity
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1:10,000 epidurals
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1:1,000 peripheral blocks
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Very unreported in
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the non-hospital setting.
Regional:
“The majority of women stated that anesthetists were the main,
and most reliable, source of their information regarding risks of
regional Anaesthesia for caesarean section” Cheng and Cyan
Anesthesia Intensive Care- Feb 2007
Stages; First stage pain is from the uterine contraction and dilation of the
cervix. Starts at T 11-12 the moves to T 11-12 to L1
The dilation of the cervix plays the key role in pain. Pain is also caused by
the uterine contractions and exceeds 25 mmHG this pain travels via
visceral afferent fibers accompanying the sympathetic nerves
Second stage: end of first stage to delivery of the baby. Pain is caused by
the pain traveling via the pudendal nerves and the distention of the
vagina, vulva and perineum trigger the sensation of pain

The onset of perineal pain indicates the beginning of the second stage
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T10-S4
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Third stage is Delivery to when the placenta is expelled
Complication rate low for CNRA lumbar
epidural injections
http://medicalxpress.com/news/2015-02-complication-cnra-lumbar-epidural.html
(Health Day)—Complication rates for fluoroscopic-guided lumbar epidural steroid injections
(LESIs) performed by certified registered nurse anesthetists (CRNAs) are similar to physician
rates cited in the literature, according to a study published online Jan. 27 in the Journal for
Healthcare Quality.
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Donald E. Beissel, D.N.P., from Southwest Interventional Pain Specialists in Albuquerque,
N.M., conducted a survey of CRNA pain practitioners. He collected data on the number of
fluoroscopic-guided LESIs performed and each of 20 complications for a six-month period.
Beissel found that participants practiced in urban (23 percent) and rural (77 percent)
settings in office/clinic (31 percent), hospital (62 percent), and mixed (7 percent)
practices. CRNAs had both master's (62 percent) and doctoral (38 percent) degrees.
Experience in performing fluoroscopic-guided LESIs ranged from one to 17 years and 50
to 12,000 procedures. For each complication, the rate of occurrence was below 1 percent,
with the highest rates for bruising and vasovagal reactions. There were no cases of
paralysis or death. There was no association between either practice setting or experience
level and complication rates.
"CRNAs were able to safely and effectively perform fluoroscopic-guided LESIs with
complication rates similar to physician rates cited in the literature," the authors write.
How did we find Lipids?
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1998……
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Rosenblatt 2006; Bupivicaine related cardiac arrest
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Litz 2006. IS-Block and Axillary block, pt arrested
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More reports followed once this case study was published.
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Concept evolved: To create a bank into which LA could be deposited from the cardiac tissue.
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Development of first protocols to treat patients.
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Interesting outcome included: Reappearance of cardiac collapse and several facilities did not have
a second dose of lipids available
http://www.lipidrescue.org
Does your Center have a plan?
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Most places do not have a plan to treat.
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Academic centers: 59% no plan, but 84% stated they had a CT surgeon within
30 if needed, 74% said the would consider using lipids.
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Old days need a CT surgeon for bypass
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Now all hospitals can treat.
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What is your plan?
The First Steps

Toxicity was the most feared complication of regional
anesthesia.

Old and new therapies have combined to reduce risks

Prevention is the key…who helps you with blocks?

Ultrasound!!!!
New Ultrasound?--”Another tool to distinguish us from the CRNA”
Ultrasound and Anesthesia
Ultrasound speeds up safety and how well and effective your block is…
Increase Public Relations and Productivity..
Spinal and Epidural Placement
Ultrasound Cheap?--Interson
We continue to revolutionize imaging devices
U-blok----See More Software….
Nanomaxx-Sonosite
Bupivacaine Toxicity

Blocks Nerve impulses…well isn’t that our goal? Not in the cardiac tissues!!!!

It is more cardiotoxic because it enters sodium channels rapidly and leaves them very slowly

Diffuses during diastole, depresses conduction and inducing reentrant-type ventricular arrhythmias.
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Results in Systolic dysfunction, especially involving right ventricle, which precedes the occurrence
of arrhythmias
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Blocks CNS impulses at lower doses…
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Indirect cardiac initially followed by depression and then direct effects:
Initial arrhythmias, negative inotropy and chronotropy
Early Identification is the Key
Prompt attention to detail……tube the goose…??
Avoid Benadryl because it works on sodium channels also
Hypoventilation……………………
Expand volume and consider ?
ACLS protocols to include all pressers. ?
Seizures?
Things to think about?
End-tidal CO2 (ETCO2) is the measurement of CO2 at the
very end of expiration. It is the maximum concentration of
expired CO2
Hyperventilation or low CO2 in the brain leads to
spontaneous and asynchronous firing of neurons
Not Everything is it appears?
Tattoos

Based on the limited information available it is
possible that inserting an epidural or spinal
needle through a tattoo could cause long-term
problems such as arachnoiditis or a neuropathy
secondary to an inflammatory reaction, but we
don’t know.

Canadian Journal of Anesthesia 49:1057-1060
(2002)

Professional inks may be made from iron
oxides

AANA--2010

Lumbar Epidural Catheter Placement in the
Presence of Low Back Tattoos: A Review of the
Safety Concerns

Dawn Welliver, CRNA, MS Mark Welliver,
CRNA, DNP Tammy Carroll, CRNA, MSN
Peggy James, MD
LAST
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Key considerations:
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
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Atypical presentations
40% of time
Delay of onset: 1
minute with some
reports 60 minutes later
CV toxicity can occur
without CNS toxicity
Lipid Sink

LA love the lipids..

Bind them with...sink
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Initial increase in plasma levels

Then Lipids rapidly decrease in serum

It partitions the local away from receptors
A lot of case reports

They all have a single resounding tone
with them?
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Can you guess what?
Mistakes!
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Intravascular injection
Volume: 40 cc 1% Ropivacaine = 400mg
Not aspirating
Not assessing for signs of toxicity
Giving Lidocaine for ectopy after collapse?
Not monitoring patient after
IV administration of Bupivacaine
Not admitting to problem of toxicity
Multiple dosing routes
Mistakes!


How Many Die From Medical Mistakes in
U.S. Hospitals?
http://www.propublica.org/article/how-many-die-from-medicalmistakes-in-us-hospitals
Deaths Per Year!


1999, the Institute of Medicine published the famous “To Err Is Human”
report, which dropped a bombshell on the medical community by reporting
that up to 98,000 people a year die because of mistakes in hospitals
(2014) A study in the current issue of the Journal of Patient Safety that says the
numbers may be much higher — between 210,000 and 440,000 patients
Lipid Registry
1997 young student accidently overdosed
22 year old instructed to apply
10%lidocaine/10% tetracaine mix
prior to hair removal—died.
EMLA

EMLA = Eutectic (equal) mixture of local anesthetic. 5% Lidocaine
and 5% prilocaine

Contact time of at least 45 min-1 hour is required under an occlusive dressing.
Absorption depends upon contact time, local tissue blood flow, keratin
thickness, and total dose.

Several types of surgery can be performed with EMLA, including laser
removal of port-wine stains, lithotripsy, skin grafting, and circumcision

Side effects of EMLA include: skin blanching, edema, erythema. It should
not be used on mucous membranes, broken skin, infants less than 1 month
old, or patients with methemoglobinemia.


Hepatic metabolism of Prilocaine…. Methemoglobinemia…
Methemoglobinemia inducing drugs: phenytoin, phenobarbital,
acetaminophen, sulfonamides.
Prior to Block
• Standard monitoring with audible oxygen saturation tone.
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Oxygen supplementation. Airway Equipment to include suction……
Monitor Patient, before, during and up to 30 minutes post block
Slow, incremental injection (5 mL every 10–15 seconds).********
Gentle aspiration for blood before injection and every 5 mL thereafter.******
Initial injection of local anesthetic test dose containing at least 5–15 μg epinephrine with
observation for heart rate change > 10 beats/min, blood pressure changes > 15 mmHg, or lead II Twave amplitude decrease of 25%.
Pretreatment with benzodiazepines to increase the seizure threshold to local anesthetic toxicity.
Patient either awake or sedated, but still able to maintain meaningful communication.
Resuscitation equipment and medications readily available at all times.
If seizures occur, patient care includes airway maintenance, supplemental oxygen, and termination
of the seizure with propofol (25–50 mg) or thiopental (50 mg).
Know Signs:
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CNS: excitation, agitation, confusion, twitching, seizures
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Depression, sedation, coma, apnea
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Metallic taste, circumoral numbness, diplopia, tinnitus, dizzy
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Cardiac: initial hyper dynamic, then hypo dynamic
Local Anesthetic Toxicity
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Systemic toxic effects are related to blood levels and are most commonly seen in the
CNS and CV systems
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CNS: tinnitus, perioral peristhesias, dizziness, lightheadedness progressing to grand
mal seizure. (Benzodiazepines and Barbiturates are useful in prevention and
treatment of local anesthetic-induced seizures.)
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CV: At less than 5 mcg/ml of lidocaine, no symptoms. At 5-10 mcg/ml there are EKG
changes including prolonged PR interval and widened QRS as well as decreased CO
and peripheral vasodilation. At > 10 mcg/ml, asystole and circulatory collapse can be
seen.
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Patients with atypical pseudocholinesterase are more likely to develop toxicity to ester
local anesthetics because they cannot metabolize them adequately
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Bupivicaine>Etidocaine>Ropivicaine
Local Anesthetic Toxicity
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Bupivicaine dissociates slowly from cardiac sodium channels and has
the most persistent depressant effects (most cardiotoxic)
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Echothiopate (irreversibly), Neostigmine, Pyridostigmine, and
Edrophonium can prolong duration of ester local anesthetics
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Pregnancy, liver disease, neonates, and atypical pseudocholinesterase
can prolong ester local anesthetics
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Volatile anesthetics, propranolol, and cimetidine decrease clearance of
amide local anesthetics by inhibiting CP450
http://nerveblocks.coma.media-net.de/tutorium/?lang=en_EN&main=1&sub=3&section=content
Drug
Onset
Maximum Dose
(with epinephrine);
Max mg dose
Duration
(with Epinephrine)
Lidocaine
Rapid
4.5 mg/kg (7 mg/kg)
300mg (500 mg)
120 min (240 min)
Cocaine
Rapid
200mg
Mepivacaine
Rapid
5 mg/kg (7 mg/kg)
300mg (500mg)
180 min (360 min)
Bupivacaine
Slow
2.5 mg/kg (3 mg/kg)
175mg (225mg)
4 hours (8 h)
Procaine
Slow
8 mg/kg (10 mg/kg)
1000mg
45 min (90 min)
Chloroprocaine
Rapid
10 mg/kg (15 mg/kg)
800mg (1000mg)
30 min (90 min)
Etidocaine
Rapid
2.5 mg/kg (4 mg/kg)
300mg(400mg)
4 hours (8 h)
Prilocaine
Medium
5 mg/kg (7.5 mg/kg)
400mg (600mg)
90 min (360 min)
Ropivicaine
Rapid
2.5 -3 mg/kg
300mg
Tetracaine
Slow
1.5 mg/kg (2.5 mg/kg)
200mg
3 hours (10 h)

You must know your doses…Extrapolation of lab experiments, clinical
studies and case reports.

Recommendations from the 1940’s ????
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Max….
Lidocaine:
Chloroprocaine:
Tetracaine:
Ropivacaine:
Procaine:
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Trick to calculating the mcg/cc epi?
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Marcaine 2-3 mg/kg with or without
4-7 mg/kg with or without (less IV)
8-12mg/kg—1000mg max
3mg/kg—200 mg max
3mg/kg—300 mg max
8mg/kg – 800 mg max
Initiate Treatment

Some controversy of timing, but based on clinical exam sooner is better.
Current Recommendation is SOONER!!!!
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Epi may impair treatment, limit epi use less than 1 mcg/kg
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Propofol is not a substitute. Will address later
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ICU monitoring for 24-48 hours
Lets recap the highlights
Get your pen ready, these are the highlights
LIPID Rescue
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
How does this work?
School of thought is that LA interfere with fatty acid transport into the
mitochondria of the cardiac cells which inhibits the heart from
performing oxidative phosphorylation and this is what leads to cardiac
dysrhythmias

Most (and current???) thought pattern is that LIPIDS act as a SINK

The sink – the lipids provide a alternative binding site for the LA

Cheap and found by accident – when it is cheap what drug company
will fund research?
Theories:

Positive effect on oxidative metabolism may explain the swift cardiotoxic
effect lipid treatment

Bupivacaine potentially inhibits fatty acid transport at the inner mitochondrial
membrane

Lipid could act by countering the brake on the oxidation of the hearts preferred
energy source
The brand of the lipid emulsion doesn’t influence the outcome—just need lipids.

Basically, we really don’t know!
Test Question?
Which Blade is Better?
There are 14 main variants of blades, but
which one is the best?
LIPID rescue
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Cardiac toxicity related to the overdose or intravascular injection of
local anesthetics has long been a concern of anesthesia
Overdose is characterized by seizures, hypotension, atrioventricular
conduction delay, idioventricular rhythms, and eventual cardiovascular
collapse
Think about who is helping you with the block
All local anesthetics potentially shorten the myocardial refractory
period, Marcaine has the highest affinity for cardiac tissues (cardiac
sodium channels) making Marcaine the most likely to participate
malignant arrhythmias.
Remember B E E R
OK B E R
Lipid Rescue

First line of defense is to be conservative!!!!

If the surgeon asks you what the dose is – go under!!—Minimum
effective doses should be used
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Aspirate prior to injection
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Check of HEME
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Who is helping you? Incremental dosing…… we need to do it correct
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Ultrasound!!!!! (Regional, Airway, Venous
Arterial, Spinal, Epidural……pneumo?)
Evidence suggests peripheral blocks
are performed using significantly larger
doses than are necessary
Lipid Rescue

Consider extremes of Age: (4 and under and greater than 70)

History of Cardiac conduction defects
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Ischemic heart disease
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Renal Dysfunction
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Hepatic Dysfunction
Lipid Rescue

Goal is to prevent complications; with proper injection techniques
and careful dosing
•
Remember Madison OB patient a few years ago…
The major failure was not identifying the problem

Current treatments ACLS, BYPASS, LIPID rescue

Lateral—Work Place Bully
Definition
Bullying is deliberate or intentional behavior using words or actions, intended to
cause fear, intimidation or harm. Bullying is a repeated behavior and involves
an imbalance of power. The behavior may be motivated by an actual or
perceived distinguishing characteristic, such as, but not limited to: age;
national origin; race; ethnicity; religion; gender; gender identity; sexual
orientation; physical attributes; physical or mental ability or disability; and
social, economic or family status.
Bullying behavior can be:
1. Physical (e.g. assault, hitting or punching, kicking, theft, threatening behavior)
2. Verbal (e.g. threatening or intimidating language, teasing or name-calling,
racist remarks)
3. Indirect (e.g. spreading cruel rumors
, intimidation through gestures, social exclusion and sending insulting messages
or pictures by mobile phone or using the internet – also known as cyber
bullying)
Lateral Violence
57% report verbal abuse
43% experience threatening body language
53% put down by supervisor
40% of abused victims forced to ignore errors or
medication errors
Shortage can be related to lateral violence
Lipid Rescue
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2006 lipid rescue was touted as the new Local Anesthetic toxicity
rescue treatment
Current suggestion includes LIPID available at all facilities
Will we ever know more? Lipids are cheap; drug companies
don’t want to pay when there will be little if any profit
Mechanism of action: several suggested reasonsMost agree it is a LIPID sink: meaning, lipids reverse local anesthetic
cardio toxicity may be increasing cardiac clearance. This nonspecific,
observed extraction of local anesthetics from aqueous plasma or
cardiac tissue is the lipid sink
First step of resuscitation for
lipids rescue!
First Step.. Stay Calm
Lipid Rescue



20% lipid solution
1.5 ml/kg over 1 minute
Follow immediately by a infusion at rate of
0.25ml/kg/min
(17.5 ml/min for a 70 kg adult)



Repeat dose if no improvement – and double the
infusion rate
Max of 10 ml/kg???
www.lipidrescue.org

Airway Management
TX seizures
ACLS------limit epi----Weinberg work!

What about Propofol? (Propofol is 1%)


LipidRescue™
TREATMENT FOR LOCAL ANESTHETICINDUCED
CARDIAC ARREST
PLEASE KEEP THIS PROTOCOL ATTACHED TO
THE INTRALIPID BAG
In the event of local anesthetic-induced cardiac arrest that is unresponsive
to
standard
therapy,
in
addition
to
standard
cardio-pulmonary
resuscitation, Intralipid 20% should be given i.v. in the following dose
regime:
– Intralipid 20% 1.5 mL/kg over 1 minute
– Follow immediately with an infusion at a rate of 0.25 mL/kg/min,
– Continue chest compressions (lipid must circulate)
– Repeat bolus every 3-5 minutes up to 3 mL/kg total dose until
circulation is restored
– Continue infusion until hemodynamic stability is restored. Increase
the rate to 0.5 mL/kg/min if BP declines
– A maximum total dose of 8 mL/kg is recommended
In practice, in resuscitating an adult weighing 70kg:
– Take a 500ml bag of Intralipid 20% and a 50ml syringe.
– Draw up 50ml and give stat i.v., X2
– Then attach the Intralipid bag to an iv administration set
(macrodrip) and run it .i.v over the next 15 minutes
– Repeat the initial bolus up to twice more – if spontaneous
circulation has not returned.
If you use Intralipid to treat a case of local anaesthetic
toxicity, please report it at www.lipidrescue.org. Remember
to restock
the lipid.
Ver 7/06
Other Things to Remember!


Ask the question…. What about other
treatments?
What did Larry Say?
The Saving Grace!



Wellbutrin 7.95 gms, Lamotrigine 4
grams
Wellbutrin 100mg/TID
Lamotrigine 300mg/QD
Many classes of compounds bind and
inhibit Na channels
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Local anesthetics
General anesthetics
Ca channel blockers
2 agonists
Tricyclic antidepressants
Substance P antagonists
Many nerve toxins
Benadryl
Droperidol ????
Harvey M, Cave G.Case report: successful lipid resuscitation in multi-drug overdose with
predominant tricyclic antidepressant toxidrome. Int J Emerg Med. 2012 Feb 2;5(1):8. [Epub
ahead of print]
◾Blaber MS, Khan JN, Brebner JA, McColm R.J "Lipid Rescue" for Tricyclic Antidepressant
Cardiotoxicity. Emerg Med. 2012 Jan 11. [Epub ahead of print]
◾Jakkala-Saibaba R, Morgan PG, Morton GL. Treatment of cocaine overdose with lipid
emulsion. Anaesthesia. 2011 Dec;66(12):1168-70. doi: 10.1111/j.1365-2044.2011.06895.x.
◾Liang CW, Diamond SJ, Hagg DS. Lipid rescue of massive verapamil overdose: a case report. J
Med Case Reports. 2011 Aug 20;5(1):399
◾Jovic-Stosic J, Gligic B, Putic V, Brajkovic G, Spasic R. Severe propranolol and ethanol
overdose with wide complex tachycardia treated with intravenous lipid emulsion: a case report.
Clin Toxicol (Phila). 2011 Jun;49(5):426-30.
◾Shih YH, Chen CH, Wang YM, Liu K. Successful reversal of bupivacaine and lidocaineinduced severe junctional bradycardia by lipid emulsion following infraclavicular brachial plexus
block in a uremic patient. Acta Anaesthesiol Taiwan. 2011 Jun;49(2):72-4.
Droperidol
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Prophylactic doses (<1 mg) are effective against PONV
FDA issued a ‘black box’ warning:
 Droperidol may cause death or life-threatening events
associated with QT prolongation and torsade's de pointes
 Labeling changes based on 100 unique spontaneous
cardiovascular adverse events
Addition of black box warning has restricted use
Droperidol:
The FDA Box Warning
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Droperidol has been used for over 40 years
Why a problem now?
No evidence of adverse events in published trials
No published case reports
An association does not prove cause and effect
If prolonged QTc is an issue then 5HT3 antagonists should
also carry the same warning
At least 3 cases of VT associated with 5HT3 administration
No “denominator” provided (or available)
Allergic Reactions

Esters are derivatives of para-aminobenzoic acid. Para-aminobenzoic acid
is responsible for most of the allergic phenomenon associated with use of
ester local anesthetics.

Allergic reactions to amides are extremely rare. Methylparaben (a
derivative of para-aminobenzoic acid) found in multi-dose vials may cause
some allergic reactions

Cross sensitivity to esters and amides does not occur

History is key to making the diagnosis. Many local anesthetic preparations
often contain epinephrine which causes palpitations that may be reported as
an allergy.
Systemic Pharmacologic and Toxicological
Effects

Allergic Reactions

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

More common with ester-type local anesthetics. No cross reactivity with amide type.
Manifested as contact dermatitis, bronchospasm, hives.
Allergic reactions to amide-type local anesthetics is possible but rare.
In patients who claim allergy to all local anesthetics, diphenhydramine (1%) has been
used as an alternative with some success.
Methemoglobinemia (hemoglobin in Fe3+ oxidation state)

Amide-type agents (lidocaine, prilocaine)

Toxic metabolite (aromatic amine)

Cyanosis (brown blood, blue skin color)

Antidote: methylene blue
Methylene Blue




This is a age old drug; Traditionally used for
Methemoglobinemia and as a tissue marker
Recent evidence (mostly in cardiac surgery) shows that it
may be a benefit for refractory hypotension
Has been used with liver transplant for hypotension
Reports of being used for patients on ACE inhibitors for
refractory hypotension
Exparel
Posidur

New product just like Exparel

Except Clear…. Could this be trouble?
Boronicaine May 8, 2015
http://www.painnewsnetwork.org/stories/2015/5/8/researchers-develop-new-painkiller-from-lidocaine
“MU researchers synthesized Boronicaine as a derivative of lidocaine by changing its chemical structure.
They found that Boronicaine provided pain relief that lasted five times longer than lidocaine. In preclinical, early stage studies, Boronicaine provided about 25 minutes of relief, compared to about five
minutes of pain relief with lidocaine.”
"Boronicaine could have distinct advantages over existing painkilling medications," said M. Frederick
Hawthorne, PhD, director of MU's International Institute of Nano and Molecular Medicine and a pioneer
in the field of boron chemistry. "We're conducting more research into the side effects of the compound,
but in time it could very well become a useful material to use as an anesthetic."
The cornea is the clear, dome-shaped outer area of the eye. It lies in front of the colored part of the
eye (iris) and the black hole in the iris (pupil). The outermost layer of the eyeball consists of the
cornea and the white part of the eye (sclera). A corneal abrasion is basically a superficial cut or
scrape on the cornea. A corneal abrasion is not as serious as a corneal ulcer, which is generally
deeper and more severe than an abrasion
To diagnose a corneal abrasion, a topical anesthetic with a yellow dye called fluorescein is placed
into the eye. Under blue cobalt light, the part of the cornea abraded will be stained by the dye and is
easily seen by the examiner. The area and depth of the abrasion can be easily seen under a special
microscope called a slit lamp biomicroscope. If a microscope is not available, then a blue light called
a Burton lamp may be used
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Voltaren) and ketorolac
(Acular) are modestly useful in reducing pain from corneal abrasions
If antibiotics are used, ointment (e.g., bacitracin [AK-Tracin], erythromycin, gentamycin [Garamycin])
is more lubricating than drops and is considered first-line treatment. In patients who wear contact
lenses, an antipseudomonal antibiotic (e.g., ciprofloxacin [Ciloxan], gentamycin, ofloxacin [Ocuflox])
should be used, and contact lens use should be discontinued. Clinical trial data are lacking, but it is
recommended that contact lenses be avoided until the abrasion is healed and the antibiotic course
completed.
Proparacaine:
DO NOT USE TETRACAINE
Dry Eyes?
Where do you put your pulse ox?
Things to never forget!

Remember that local anesthetic toxicity is additive, i.e., there is no
advantage to mixing drugs in combination thinking that you will lessen the
likelihood of toxicity.


Additive effect:
50% Lidocaine+50% dose
Marcaine
= 100% of toxic effects
Know all routes and duration of actions!
Have you thought about all
the locations of local?

What could we have missed?
Tumescent Liposuction


High volume low dose lidocaine mixed with
epi for liposuction.
Is this best practice? Increased mortality?
Can I be excused?
… my brain is full !
Thanks, Peter:
[email protected]