Introduction
"How do I introduce lipid therapy at our hospital"?.
We often encounter this question from people who've just
heard of lipidrescue and want to know what to do at the
outset. The first thing to do is contact your hospital's
pharmacy and request they stock 20% lipid emulsion at sites
where regional anesthesia is used. This could be kept in a
drug (Pyxis) or equipment (Omnicell) dispensor in the
recovery room, or block room.....anywhere with rapid access
from where you do your injections. It will often help if you've
figured out the best logistical location before contacting the
pharmacist. Similarly, the pharmacist is likely not to have
heard of the technique, so it will help if you come armed
with a couple of articles (see attached Literature). A case
report (e.g., Dr. Rosenblatt's or Dr. Litz's), letter or editorial
will probably help, too. If you're at a very academic location,
go with an animal study for something that has a little
scientific bite to it. You will probably want to have at least
500 mL and in all probability, Intralipid brand, only because
this is the stuff all the studies were done with. We're not
sure at this point if the other lipid emulsion preps have equal
or superior efficacy since those experiments haven't been
done yet. You'll also want some large, luered syringes (5060 mL) and an infusion kit (macrodrip). It also makes sense
to attach some laminated instructions (see attached).
Treatment Regimens
FIRST, A WARNING:
There are no standard methods for lipid emulsion therapy.
In fact, there are many more questions than answers:
Should the lipid dose be titrated, by patient weight, local
anesthetic dose, or the symptoms/signs/severity of toxicity?
What is the best rate and total dose of the following
infusion? Is there a safe upper limit of lipid dosing? What are
the possible complications or adverse effects of lipid
infusion? Should lipid be used alone or in combination with
epinephrine, and other components of standard resuscitative
cocktails? What is better, 20% or 30% lipid? What
formulation is best? Intralipid has been used predominantly
so far, but is there a better choice? Do the other available
lipid emulsions work as well?
Obviously, a great deal of research in this area is required to
determine a treatment protocol that optimizes outcome.
What is known about dosing?
In animal studies, large doses of local anesthetic were used
in order to make the most stringent possible tests for
methods of treatment. Hence the doses of lipid used in rats
and dogs (mL/kg) are probably excessive compared to what
should work in humans who, by weight, have generally
much smaller doses introduced into their circulation.
Data from humans are limited to two case reports (see
News) and no prospective epidemiologic study is possible
since numbers are too small; and ethical considerations rule
out experiments on volunteers. So these data are very
limited as well. Both patients received bolus injections of
100 mL 20% Intralipid followed by continuous infusions at
either 0.5 mL/kg/min for 2 hours, or 10 mL/min for 10
minutes. In both cases, the same general approach was
used as in the animal experiments, namely a bolus followed
by a continuous infusion.
Given an understanding of these limitations in our method
an Example Protocol follows; this should be used only after
standard resuscitation methods fail to re-establish sufficient
circulatory stability:
20% Intralipid:
1.5 mL/kg as an initial bolus, followed by
0.25 mL/kg/min for 30-60 minutes
Bolus could be repeated 1-2 times for persistent asystole
Literature
▪ Case Reports - (newest to oldest)
See the 4 case reports from the
May 2008 Anesthesia and Analgesia. Also, check out Sirianni's amazing
case report!
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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
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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.
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Shih YH, Chen CH, Wang YM, Liu K. Successful reversal of
bupivacaine and lidocaine-induced severe junctional bradycardia
by lipid emulsion following infraclavicular brachial plexus block
in a uremic patient. Acta Anaesthesiol Taiwan.
2011 Jun;49(2):72-4.
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McAllister RK, Tutt CD, Colvin CS. Lipid 20% emulsion ameliorates
the symptoms of olanzapine toxicity in a 4-year-old. Am J
Emerg Med. 2011 Jun 2. [Epub ahead of print]
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Mizutani K, Oda Y, Sato H. Successful treatment of ropivacaineinduced central nervous system toxicity by use of lipid emulsion:
effect on total and unbound plasma fractions. J Anesth. 2011
Jun;25(3):442-5. Epub 2011 Mar 16.
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Castanares-Zapatero D, Wittebole X, Huberlant V, Morunglav M,
Hantson P. Lipid Emulsion as Rescue Therapy in Lamotrigine
Overdose. J Emerg Med. 2011 May 26.
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French D, Armenian P, Ruan W, Wong A, Drasner K, Olson KR, Wu
AH. Serum verapamil concentrations before and after
Intralipid® therapy during treatment of an overdose.Clin Toxicol
(Phila). 2011 Apr;49(4):340-4.
doi: 10.3109/15563650.2011.572556.
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Boegevig S, Rothe A, Tfelt-Hansen J, Hoegberg LC. Successful
reversal of life threatening cardiac effect following dosulepin
overdose using intravenous lipid emulsion. Clin Toxicol (Phila).
2011 Apr;49(4):337-9.
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Dix SK, Rosner GF, Nayar M, Harris JJ, Guglin ME, Winterfield JR,
Xiong Z, Mudge GH Jr. Intractable cardiac arrest due to
lidocaine toxicity successfully resuscitated with lipid emulsion.
Crit Care Med. 2011 Apr;39(4):872-4.
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Harvey M, Cave G, Chanwai G, Nicholson T. Successful resuscitation
from bupivacaine-induced cardiovascular collapse with
intravenous lipid emulsion following femoral nerve block in an
emergency department. Emerg Med Australas.
2011 Apr;23(2):209-14.
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Montiel V, Gougnard T, Hantson P. Diltiazem poisoning treated with
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hyperinsulinemic euglycemia therapy and intravenous lipid
emulsion. Eur J Emerg Med. 2011 Apr;18(2):121-3.
Franxman TJ, Al-Nabhan M, Cavallazzi RS, Speak AJ.Lipid emulsion
therapy for verapamil overdose. Ann Intern Med. 2011
Feb 15;154(4):292.
Benhamou D, Mazoit JX, Zetlaoui P. [Early administration of lipid
rescue after initial signs of local anesthetic-induced systemic
toxicity]. Ann Fr Anesth Reanim. 2010 Nov;29(11):826. Epub
2010 Nov 3. [Article in French]
Aveline C, et al. Ineffectiveness of intralipid infusion for central
nervous toxicity following ultrasound-guided sciatic nerve block
with lidocaine-ropivacaine solution: interaction between
carbamazepine, local anaesthetic and intralipid?
2010 Dec
Please see Uncles, et al. reply in editorials
Lin EP, Aronson LA.Successful resuscitation of bupivacaine-induced
cardiotoxicity in a neonate. Paediatr Anaesth. 2010
Oct;20(10):955-7. doi: 10.1111/j.
O'Brien TQ, Clark-Price SC, Evans EE, Di Fazio R, McMichael MA.
Infusion of a lipid emulsion to treat lidocaine intoxication in a
cat. J Am Vet Med Assoc. 2010 Dec 15;237(12):1455-8.
Man D, Podichetty VK. Lipid rescue in resuscitation of local
anesthetic-induced cardiac arrest in aesthetic surgery. Plast
Reconstr Surg. 2010 Jun;125(6):257e-9e.
Stellpflug SJ, Harris CR, Engebretsen KM, Cole JB, Holger JS.
Intentional overdose with cardiac arrest treated with
intravenous fat emulsion and high-dose insulin. Clin Toxicol
(Phila). 2010 Mar;48(3):227-9.
Cordell CL, Schubkegel T, Light TR, Ahmad F.Lipid infusion rescue for
bupivacaine-induced cardiac arrest after axillary block. J Hand
Surg Am. 2010 Jan;35(1):144-6.
Wong GK, Joo DT, McDonnell C.Lipid resuscitation in a carnitine
deficient child following intravascular migration of an epidural
catheter*Anaesthesia. 2009 Oct 22.
Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after
lipid rescue from bupivacaine-induced cardiac arrest. Anesth
Analg. 2009 Apr;108(4):1344-6.
Young AC, Velez LI, Kleinschmidt KC.Intravenous fat emulsion
therapy for intentional sustained-release verapamil overdose.
Resuscitation. 2009 May;80(5):591-3. Epub 2009 Mar 17.
Weinberg G, Di Gregorio G, Hiller D, Hewett A, Sirianni A.Reversal of
haloperidol-induced cardiac arrest by using lipid emulsion. Ann
Intern Med. 2009 May 19;150(10):737-8.
Finn SD, Uncles DR, Willers J, Sable N. Early treatment of a
quetiapine and sertraline overdose with Intralipid.Anaesthesia.
2009 Feb;64(2):191-4
A very interesting case of reversing
deep coma with lipidrescue. Saved the pt intubation and a night
in the ICU.
McCutchen G, Gerancher JC. Early lipid therapy may have prevented
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bupivacaine-associated cardiac arrest. Reg Anesth Pain Med.
2008; 33(2):178-180
A nice case report of patient with
seizures and ventricular tachycardia responding to lipid +
countershock. Patient did well.
Smith HM, Jacob AK, Segura LG, Dilger JA, Torsher LC. Simulation
education in anesthesia training: a case report of successful
resuscitation of bupivacaine-induced cardiac arrest linked to
recent simulation training. Anesth Analg.
2008 May;106(5):1581-4
A fascinating case that illustrates the
value in educating physicians in LipidRescue methodology. A
training session resulted in a clean save several months later.
Warren JA, Thoma RB, Georgescu A, Shah SJ. Intravenous lipid
infusion in the successful resuscitation of local anestheticinduced cardiovascular collapse after supraclavicular brachial
plexus block. Anesth Analg. 2008 May;106(5):1578-80
An
impressive save with lipid. Good ECG traces.
Litz RJ, Roessel T, Heller AR, Stehr SN. Reversal of central nervous
system and cardiac toxicity after local anesthetic intoxication by
lipid emulsion injection. Anesth Analg. 2008 May;106(5):15757
Another great save with a very thought provoking discussion.
Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM.
Successful resuscitation after ropivacaine and lidocaine-induced
ventricular arrhythmia following posterior lumbar plexus block in
a child. Anesth Analg. 2008 May;106(5):1572-4
The first
report of LIpidRescue in a child.
Foxall G, McCahon R, Lamb J, Hardman JG, Bedforth NM.
Levobupivacaine-induced seizures and cardiovascular collapse
treated with Intralipid. Anaesthesia. 2007 May;62(5):5168.
Excellent case report of lipid reversing CNS and
cardiovascular signs of toxicity.
Zimmer C, Piepenbrink K, Riest G, Peters J. Cardiotoxic and
neurotoxic effects after intravascular bupivacaine
administration: therapy with lidocaine, propofol and lipid
emulsion. Anaesthesist 2007
This is a chance to test your
German. A very interesting case of toxicity presenting as
agitation and SVT. They used clonidine first, then lidocaine, then
propofol without success. All symptoms resolved after lipid
infusion. Only one case but instructive.
Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR,
Goodkin MB, Weinberg GL, Henretig FM. Use of Lipid Emulsion in
the Resuscitation of a Patient With Prolonged Cardiovascular
Collapse After Overdose of Bupropion and Lamotrigine. Ann
Emerg M
See the Blog and News of 9-13-07. This is an
absolutely amazing case.
Spence AG. Lipid reversal of central nervous system symptoms of
bupivacaine toxicity. Anesthesiology. 2007 Sep;107(3):5167
This may be the first example of purely CNS symptoms
reversed by lipidrescue. Very well written case report as letter
to the editor with good commentary.
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Rosenblatt MA, Abel M, Fischer GW et al. Successful Use of a 20%
Lipid Emulsion to Resuscitate a Patient after a Presumed
Bupivacaine-related Cardiac Arrest.
Anesthesiology 2006;105:217-8.
The first case report of
successful resuscitation of a patient in prolonged cardiac arrest
from presumed systemic local anesthetic toxicity. The patient
recovered with no neurological sequelae after ~20 minutes of
asystole and no response to ACLS. <s
Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a
patient with ropivacaine-induced asystole after axillary plexus
block using lipid infusion. Anaesthesia 2006;61:800-1.
The
second case report of lipid emulsion infusion successfully
resuscitating a patient from apparently intractable cardiac
arrest. This case involved ropivacaine.
Editorials and Commentary
For discussion of the recent letters in
Anesthesiology see the link to Blog and News in the navigator
Bet 2: intralipid/lipid emulsion in Beta-blocker overdose. [No authors
listed] Emerg Med J. 2011 Nov;28(11):991-3
Kawaraguchi Y, Roth DM, Patel HH. From Local to Global: Intralipid
Makes a Move. Anesthesiology. 2011 Jun 8. [Epub ahead
of print]
Uncles DR, Willers JW, Samuels TL, Chaklader A. Local anaesthetic
systemic toxicity treated with intravenous lipid emulsion:
ineffective treatment or selection of an inadequate lipid rescue
dose? Eur J Anaesthesiol. 2011 May;28(5):390-1.
Reply to
Aveline C. See in case reports
Weinberg GL. Intravenous lipid emulsion: why wait to save a life?
Emerg Med Australas. 2011 Apr;23(2):113-5.
doi: 10.1111/j.1742-6723.2011.01400.x
Cave G, Harvey M. Intravenous lipid emulsion as antidote: How
should we chew the fat in 2011? Crit Care Med 2011 Apr;
39(4): 919-20.
Murray DB, Bateman DN.Use of intravenous lipids. Not yet in all
overdoses with failed resuscitation.BMJ. 2011 Apr 8;342:d2265.
doi: 10.1136/bmj.d2265.
Samuels TL, Uncles DR, Willers JW, Monteiro R, Halloran C. Logging
the potential for intravenous lipid emulsion in propranolol and
other lipophilic drug overdoses. Anaesthesia.
2011 Mar;66(3):221-2.
Davis W. Factors related to recovery in a cat treated for lidocaine
intoxication. J Am Vet Med Assoc. 2011 Feb 1;238(3):284;
author reply 284.
Weinberg G, Lin B, Zheng S, Di Gregorio G, Hiller D, Ripper R,
Edelman L, Kelly K, Feinstein D. Partitioning effect in lipid
resuscitation: further evidence for the lipid sink. Crit Care Med.
2010 Nov;38(11):2268-9.
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Woehlck HJ, El-Orbany M.Anesthetic effects and lipid resuscitation
protocols. Anesthesiology. 2010 Feb;112(2):499-500
McKevith J, Banks A. Lipid resuscitation. Resuscitation. 2009
Dec;80(12):1448. Epub 2009 Oct 4.
Isherwood P. Lipid rescue: small trials and animal research.
Anaesthesia. 2009 Dec;64(12):1380
Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond
local anesthetic toxicity: a systematic review. Anesthesiology.
2009 Sep;111(3):498-505.
Picard J, Harrop-Griffiths W. Lipid emulsion to treat drug overdose:
past, present and future. Anaesthesia. 2009 Feb;64(2):11921.
Picard J, Ward S, Meek T. Antidotes to anesthetic catastrophe: lipid
emulsion and dantrolene. Anesth Analg. 2007 Jul;105(1):2834
This is a very interesting comment, pointing out the
similarities in terms of progress in acceptance of lipid for local
anesthetic toxicity and dantrolene for MH.
Brull SJ. Lipid emulsion for the treatment of local anesthetic toxicity:
patient safety implications. Anesth Analg.
2008 May;106(5):1337-9
Excellent editorial on LipidRescue
method.
Rowlingson JC. Lipid rescue: a step forward in patient safety? Likely
so! Anesth Analg. 2008 May;106(5):1333-6
An editorial by my
mentor, John Rowlingson.
Lipid infusion therapy: translation to clinical practice. Anesth Analg.
2008 May;106(5):1340-2
My editorial on the current state-ofthe-art.
Picard J, Meek T. Lipid emulsion to treat overdose of local
anaesthetic: the gift of the glob. Anaesthesia 2006;61:107-9.
Weinberg GL.In defence of lipid resuscitation.Anaesthesia.
2006 Aug;61(8):807-8
Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity:
proof of clinical efficacy. Anesthesiology 2006;105:7-8.
Groban L, Butterworth J. Lipid reversal of bupivacaine toxicity: has
the silver bullet been identified? Reg Anesth Pain
Med 2003;28:167-9.
▪ Research Articles (LipidRescue Resuscitation)
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Mauch J, Martin Jurado O, Spielmann N, Bettschart-Wolfensberger R,
Weiss M. Paediatr Anaesth. Comparison of epinephrine vs lipid
rescue to treat severe local anesthetic toxicity - an experimental
study in piglets. 2011 Nov;21(11):1103-8.
doi: 10.1111/j.14
NOTE PIGS ARE ALLERGIC TO LIPID
EMULSION AND THEREFORE NOT A SUITABLE MODEL OF LIPID
RESCUE
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French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH.Partition
constant and volume of distribution as predictors of clinical
efficacy of lipid rescue for toxicological emergencies.French D,
Smollin C, Ruan W, Wong A, Drasner K, Wu AH. Clin Tox
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Oct 2011
Mauch J, Martin Jurado O, Spielmann N, Bettschart-Wolfensberger R,
Weiss M. Paediatr Anaesth. Resuscitation strategies from
bupivacaine-induced cardiac arrest. doi: 10.1111/j.14609592.2011.03688.x. 2011 Aug 29. [Epub ahead of print]
Note:
Pigs are allergic to lipid emulsion and therefore not a suitable
model of lipid rescue
Rahman S, Li J, Bopassa JC, Umar S, Iorga A, Partownavid P,
Eghbali M. Phosphorylation of GSK-3β Mediates Intralipidinduced Cardioprotection against Ischemia/Reperfusion Injury.
Anesthesiology. 2011 Jun 17. [Epub ahead of print]
Bushey BA, Auld VH, Volk JE, Vacchiano CA. Combined lipid emulsion
and ACLS resuscitation following bupivacaine- and hypoxiainduced cardiovascular collapse in unanesthetized swine. AANA
J. 2011 Apr;79(2):129-38.
Harvey M, Cave G, Lahner D, Desmet J, Prince G, Hopgood G.
Insulin versus Lipid Emulsion in a Rabbit Model of Severe
Propranolol Toxicity: A Pilot Study. Crit Care Res Pract.
2011;2011:361737. Epub 2011 Mar 31
Samuels TL, Uncles DR, Willers JW, Monteiro R, Halloran C. Logging
the potential for intravenous lipid emulsion in propranolol and
other lipophilic drug overdoses. Anaesthesia. 2011
Mar;66(3):221-2. doi: 10.1111/j.1365-2044.2011.06635
Kazemi A, Harvey M, Cave G, Lahner D. The effect of lipid emulsion
on depth of anaesthesia following thiopental administration to
rabbits. Anaesthesia. 2011 May;66(5):373-8. doi:
10.1111/j.1365-2044.2011.06690.x. Epub 2011 Mar
Jensen-Gadegaard P, Skjønnemand M, Damgaard-Jensen J,
Gottschau B. Limited knowledge of lipid rescue therapy in local
anaesthetic systemic toxicity. Dan Med Bull 2011 Jan;
58(1): A4226
Lokajová J, Pukkila J, Holopainen JM, Wiedmer SK. In vitro capturing
of various lipophilic illicit drugs by lipid dispersions. An
electrokinetic capillary chromatography and fluorescence
polarization study. Eur J Pharm Sci. 2010 Nov 20;41(3-4):51522. Epu
Harvey M, Cave G, Prince G, Lahner D. Epinephrine injection in lipidbased resuscitation from bupivacaine-induced cardiac arrest:
transient circulatory return in rabbits. Anesth Analg.
2010 Sep;111(3):791-6.
Candela D, et al. Reversal of bupivacaine-induced cardiac
electrophysiologic changes by two lipid emulsions in
anesthetized and mechanically ventilated piglets. Anesth Analg.
2010 May 1; 110(5): 1473-9
Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST).
Reg Anesth Pain Med. 2010 Mar-Apr;35(2):188-93.
Hiller DB, Di Gregorio G, Kelly K, Ripper R, Edelman L, Boumendjel
R, Drasner K, Weinberg GL. Safety of high volume lipid emulsion
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infusion: a first approximation of LD50 in rats. Reg Anesth Pain
Med. 2010 Mar-Apr;35(2):140-4.
Hiller DB, Gregorio GD, Ripper R, Kelly K, Massad M, Edelman L,
Edelman G, Feinstein DL, Weinberg GL. Epinephrine impairs lipid
resuscitation from bupivacaine overdose: a threshold effect.
Anesthesiology. 2009 Sep;111(3):498-505.
Zhou Y, Zhan C, Li Y, Zhong Q, Pan H, Yang G. Intravenous lipid
emulsions combine extracorporeal blood purification: a novel
therapeutic strategy for severe organophosphate poisoning. Med
Hypotheses. 2010 Feb;74(2):309-11. Epub 2009 Sep 27.
Harvey M, Cave G, Kazemi A. Intralipid infusion diminishes return of
spontaneous circulation after hypoxic cardiac arrest in rabbits.
Anesth Analg. 2009 Apr;108(4):1163-8.
Di Gregorio G, Schwartz D, Ripper R, Kelly K, Feinstein DL, Minshall
RD, Massad M, Ori C, Weinberg GL.Lipid emulsion is superior to
vasopressin in a rodent model of resuscitation from toxininduced cardiac arrest. Crit Care Med. 2009 Mar;37(3):993-9
Picard J, Ward SC, Zumpe R, Meek T, Barlow J, Harrop-Griffiths W
Guidelines and the adoption of 'lipid rescue' therapy for local
anaesthetic toxicity. Anaesthesia. 2009 Feb;64(2):122-5
A
survey investigating the rate of adoption of AAGBI guidelines in
the UK.
Harvey M, Cave G. Survey of the availability of lipid emulsion
infusion in Australasian emergency departments. Emerg Med
Australas. 2008 Dec;20(6):531-3.
A survey of general
awareness among an Australian medical community of lipid
rescue.
Perez E, Bania TC, Medlej K, Chu J. Determining the Optimal Dose of
Intravenous Fat Emulsion for the Treatment of Severe Verapamil
Toxicity in a Rodent Model. Acad Emerg Med. 2008 Oct 25.
[Epub ahead of print]
These studies find the optimal dose of
20% lipid emulsion for resuscitating rats in verapimil overdose
was 18mL/kg. Interestingly, we've found the optimal dose of
30% lipid emulsion for bupivacaine overdose is 12 mL/kg:
exactly the same mass of lipid!
Weinberg GL, Di Gregorio G, Ripper R, Kelly K, Massad M, Edelman
L, Schwartz D, Shah N, Zheng S, Feinstein DL.Resuscitation with
lipid versus epinephrine in a rat model of bupivacaine overdose.
Anesthesiology. 2008 May;108(5):907-13
Epinephrine is
shown in a rodent model of bupivacaine overdose to have
adverse effects on hemodynamics and metabolic profile c/w
lipid.
Williamson RM, Haines J.Availability of lipid emulsion in obstetric
anaesthesia in the UK: a national questionnaire survey.
Anaesthesia. 2008 Apr;63(4):385-8
A survey of obstetric
departments in the UK
Bania T, Chu J, Perez E, Su M, Hahn I. Hemodynamic effects of
intravenous fat emulsion in an animal model of verapamil
toxicity resuscitated with atropine, calcium and saline. Acad.
Emerg. Med. 2007; 14:105-11
A study in dogs shows that lipid
infusion resuced subjects from high dose verapamil. In one
limb, 14% survival in controls compared with 100% survival in
the treated group. We hope this study will increase awareness
of lipid rescue among toxicologists.
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Harvey M, Cave G. Intralipid Outperforms Sodium Bicarbonate in a
Rabbit Model of Clomipramine Toxicity. Ann Emerg Med. 2006
Nov 9; [Epub ahead of print]
This study shows that lipid
infusion rescues rabbits given an overdose of clomipramine.
Very similar to the dog bupivacaine studies, no animals given
bicarb survived; all lipid-treated animals did (n=4 in each
group).
Corcoran W, Butterworth J, Weller RS, Beck JC, Gerancher JC, Houle
TT, Groban L.Local anesthetic-induced cardiac toxicity: a survey
of contemporary practice strategies among academic
anesthesiology departments. Anesth Analg.
2006 Nov;103(5):1322-6.
A excellent paper, the authors
performed a survey of academic US anesthesiology depts on
their preparation for local anesthetic systemic toxicity. They
show a lack of general agreement on an approach to treating LA
toxicity.
Weinberg GL, Ripper R, Murphy P, Edelman LB, Hoffman W,
Strichartz G, Feinstein DL. Lipid infusion accelerates removal of
bupivacaine and recovery from bupivacaine toxicity in the
isolated rat heart. Reg Anesth Pain Med. 2006 JulAug;31(4):296-303.
Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion
infusion rescues dogs from bupivacaine-induced cardiac toxicity.
Reg Anesth Pain Med. 2003 May-Jun;28(3):198-202.
Studies
in a dog model of acute bupivacaine toxicity find that all
subjects treated with lipid exhibit return of normal
hemodynamics while no controls recover.
Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF,
Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts
the dose-response to bupivacaine-induced asystole in rats.
Anesthesiology. 1998 Apr;88(4):1071-5
This paper reports the
original observation in rats that lipid prevents (pretreatment)
and treats bupivacaine overdose.
▪ Research (Bupivacaine Cardiac Preservation)
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Ross JD, Ripper R, Law WR, Massad M, Murphy P, Edelman L, Conlon
B,Adding bupivacaine to high-potassium cardioplegia improves
function and reduces cellular damage of rat isolated hearts after
prolonged, cold storage.Anesthesiology. 2006 Oct;105(4):74652.
Ironically, bupivacaine is a good cardioprotectant. This
suggests that bupivacaine toxicity should be entirely reversible,
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with no permanent cardiac damage.
Weinberg G, Paisanthasan C, Feinstein D, Hoffman W. The effect of
bupivacaine on myocardial tissue hypoxia and acidosis during
ventricular fibrillation.Anesth Analg. 2004 Mar;98(3):7905,
This paper reports that bupivacaine protects the heart
against the tissue acidosis in 'no flow' states. This might explain
successful lipid resuscitation in animals and case reports after
long 'downtimes'.
▪ Reviews
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Mercado P, Weinberg GL. Local anesthetic systemic toxicity:
prevention and treatment. Anesthesiol Clin.
2011 Jun;29(2):233-4
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Ciechanowicz S, Patil V. Lipid emulsion for local anesthetic systemic
toxicity. Anesthesiol Res Pract. 2012;2012:131784. Epub 2011
Sep 29
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Fernandez, A et al. The use of intravenous lipid emulsion as an
antidote in veterinary toxicology. J Vet Emerg Crit Care. 2011
June 3.
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Cave G, Harvey M, Graudins A. Intravenous lipid emulsion as
antidote: a summary of published human experience. Emerg
Med Australas. 2011 Apr;23(2):123-41
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Bern S, Weinberg G. Local anesthetic toxicity and lipid resuscitation
in pregnancy. Curr Opin Anaesthesiol. 2011 Apr 13.
▪
Bern S, Akpa BS, Kuo I, Weinberg G. Lipid resuscitation: a lifesaving antidote for local anesthetic toxicity. Curr Pharm
Biotechnol. 2011 Feb 1;12(2):313-9.
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Skjønnemand M, Damgaard-Jensen J, Gottschau B. [Intravenous
administration of lipids in poisoning caused by local analgesics].
Ugeskr Laeger. 2011 Jan 10;173(2):120-3. Danish.
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Toledo P. The role of lipid emulsion during advanced cardiac life
support for local anesthetic toxicity.J Obstet Anesth. 2011
Jan;20(1):60-3. Epub 2010 Nov 26.
▪
Burch MS, McAllister RK, Meyer TA. Treatment of local-anesthetic
toxicity with lipid emulsion therapy. Am J Health Syst Pharm.
2011 Jan 15;68(2):125-9.
▪
Sandlin-Leming DC. Resuscitation of local anesthesia-induced cardiac
arrest: lipids to the rescue. J Perianesth Nurs.
2010 Dec;25(6):418-20.
▪
Lui KC, Chow YF. Safe use of local anaesthetics: prevention and
management of systemic toxicity. Hong Kong Med J.
2010 Dec;16(6):470-5
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Rothschild L, Bern S, Oswald S, Weinberg G.Intravenous lipid
emulsion in clinical toxicology. Scand J Trauma Resusc Emerg
Med. 2010 Oct 5;18:51.
▪
Dillane D, Finucane BT.Local anesthetic systemic toxicity. Can J
Anaesth. 2010 Apr;57(4):368-80
▪
Bourne E, Wright C, Royse C. A review of local anesthetic
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▪
▪
▪
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cardiotoxicity and treatment with lipid emulsion. Local and
Regional Anesthesia. Feb 2010:3 11-19
Jamaty C, Bailey B, Larocque A, Notebaert E, Sanogo K, Chauny
JM.Lipid emulsions in the treatment of acute poisoning: a
systematic review of human and animal studies. Clin Toxicol
(Phila). 2010 Jan;48(1):1-27.
Leskiw U, Weinberg GL.Lipid resuscitation for local anesthetic
toxicity: is it really lifesaving? Curr Opin Anaesthesiol.
2009 Oct;22(5):667-71
Weinberg, G. Lipid Rescue Resuscitation from Local Anaesthetic
Cardiac Toxicity. Toxicological Reviews, Volume 25, Number 3,
2006, pp. 139-145(7)
A summary of state-of-the-art as of
December 2006. Includes lab background, some mechanism
data and information on the first two cases. And you can buy it
on the Ingentaconnect site for only $54.
Guy L Weinberg, Malek G Massad, Metabolic modulation for cardiac
protection.Expert Review of Cardiovascular Therapy, March
2007, Vol. 5, No. 2, Pages 135-138
A review of this promising
approach to myocardial preservation.
Malinovsky JM, Mazoit JX, Sztark F, Estèbe JP, Capdevila X, Samii K,
Eledjam JJ, Benhamou D, Bonnet F, Bouaziz H, Weinberg G; Le
Comité douleur-anesthésie locorégionale de Sfar. [Systemic
toxicity of local anaesthetics and lipid emulsions:
an interesting
A very nice review of lipid emulsion therapy...in
French
▪ Research: Metabolic Mechanisms of Bupivacaine Toxicity
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Weinberg GL, Palmer JW, VadeBoncouer TR, Zuechner MB, Edelman
G, Hoppel CL.Weinberg GL, Palmer JW, VadeBoncouer TR,
Zuechner MB, Edelman G, Hoppel CL.
Bupivacaine inhibits
mitochondrial transport of the heart's preferred fuel.
▪
Edelman LB, Ripper R, Kelly K, Di Gregorio G, Weinberg GL.Metabolic
context affects hemodynamic response to bupivacaine in the
isolated rat heart. Chem Biol Interact. 2008 Mar 10;172(1):4853. Epub 2007 Nov 13.
This study in isolated heart indicates
that hearts using lipid substrate are more sensitive to
bupivacaine toxicity than those burning carbohydrate.
▪
Weinberg G, VadeBoncouer T.Improved energetics may explain the
favorable effect of insulin infusion on bupivacaine
cardiotoxicity.Anesth Analg. 2001 Apr;92(4):1075-6.
A letter
in reply to a study showing that insulin-glucose attenuates
bupivacaine toxicity. We provide an alternate explanation.
▪
Weinberg GL, Laurito CE, Geldner P, Pygon BH, Burton BK.Malignant
ventricular dysrhythmias in a patient with isovaleric acidemia
receiving general and local anesthesia for suction lipectomy.J
Clin Anesth. 1997 Dec;9(8):668-70
This is the index case for
my interest in local anesthetic toxicity. This event led indirectly
to the discovery of an antidote for this life-threatening
▪
condition.
Onyüksel H, Sethi V, Weinberg GL, Dudeja PK, Rubinstein
I.Bupivacaine, but not lidocaine, disrupts cardiolipin-containing
small biomimetic unilamellar liposomes.
Experiments
supporting my theory that interaction with cardiolipin can
explain bupivacaine's metabolic affects.
▪ Guidelines
▪
ACMT position statement: interim guidance for the use of lipid
resuscitation therapy. American College of Medical Toxicology. J
Med Toxicol. 2011 Mar;7(1):81-2
▪
Neal JM, Bernards CM, Butterworth JF 4th, Di Gregorio G, Drasner K,
Hejtmanek MR, Mulroy MF, Rosenquist RW, Weinberg GL. ASRA
practice advisory on local anesthetic systemic toxicity. Reg
Anesth Pain Med. 2010 Mar-Apr;35(2):152-61.
▪
Picard J, Ward SC, Zumpe R, Meek T, Barlow J, Harrop-Griffiths W.
Guidelines and the adoption of 'lipid rescue' therapy for local
anaesthetic toxicity. Anaesthesia. 2009 Feb;64(2):122-5.
▪ News
Poisoning cure - give fat a chance.
Poisoning cure - give fat a chance
AMY CORDEROY
July 12, 2011
IT may mean death for your diet but it turns out fat could save your
life. An injection of fat could prove the antidote for some serious
poisons, emergency doctors say.
The fat solution is made from simple ingredients that could be bought
at a supermarket - eggs and soybean oil - and has already been used
to help save patients' lives.
Medical records for 42 poisoned patients who received the treatment
for cardiovascular or severe central nervous system problems
showed some came back from the brink of death, and most showed
improvement in their condition.
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Grant Cave, an emergency physician and intensivist at Tamworth
Hospital, said the treatment was in its early days but held great
potential as an antidote for poisonings from highly fat soluble
medications such as local anaesthetic and some heart medications
and antidepressants.
The fat worked by helping the blood filter the poison from the body. It
was already used occasionally as a last resort.
"We call it 'lipid rescue' because you are rescuing people when all
other methods have failed but they are still alive," he said.
Dr Cave, who presented his findings at the Australasian College for
Emergency Medicine winter symposium in New Zealand this week,
has also compiled the first study of reports of the treatment.
His research, published in Emergency Medicine Australasia, found 42
good quality reports of fat injection treatments, out of which 39
patients showed improvement ranging from minor to almost
immediate resolution of their symptoms.
But the study could not show how much of the improvement was due
to the fat injection rather than other factors, Dr Cave said.