How Doi Introduce Lipid Therapy at Our Hospital ?

Introduction

"How doI 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 efficacysincethose experiments haven't been done yet. You'll also want some large, lueredsyringes (50-60 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 atreatmentprotocolthat 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 lipidused 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 tooldest) See the 4 case reports from the May 2008 Anesthesia and Analgesia. Also, check out Sirianni's amazing case report!

▪Liang CW, Diamond SJ, Hagg DS. Lipid rescue of massive verapamil overdose: a case report. J Med Case Reports. 2011 Aug20;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. ClinToxicol (Phila). 2011Jun;49(5):426-30.

▪Shih YH, Chen CH, Wang YM, Liu K. Successful reversal of bupivacaine and lidocaine-induced severe junctionalbradycardia by lipid emulsion following infraclavicular brachial plexus block in a uremic patient. ActaAnaesthesiol Taiwan. 2011Jun;49(2):72-4.

▪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 ofprint]

▪Mizutani K, Oda Y, Sato H. Successful treatment of ropivacaine-induced 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 Mar16.

▪Castanares-Zapatero D, Wittebole X, Huberlant V, Morunglav M, Hantson P. Lipid Emulsion as Rescue Therapy in Lamotrigine Overdose. J Emerg Med. 2011 May26.

▪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.ClinToxicol (Phila). 2011 Apr;49(4):340-4. doi:10.3109/15563650.2011.572556.

▪Boegevig S, Rothe A, Tfelt-Hansen J, Hoegberg LC. Successful reversal of life threatening cardiac effect following dosulepin overdose using intravenous lipid emulsion. ClinToxicol (Phila). 2011Apr;49(4):337-9.

▪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. 2011Apr;39(4):872-4.

▪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. 2011Apr;23(2):209-14.

▪Montiel V, Gougnard T, Hantson P. Diltiazem poisoning treated with hyperinsulinemiceuglycemia therapy and intravenous lipid emulsion. Eur J Emerg Med. 2011Apr;18(2):121-3.

▪Franxman TJ, Al-Nabhan M, Cavallazzi RS, Speak AJ.Lipid emulsion therapy for verapamil overdose. Ann Intern Med. 2011 Feb15;154(4):292.

▪Benhamou D, Mazoit JX, Zetlaoui P. [Early administration of lipid rescue after initial signs of local anesthetic-induced systemic toxicity]. Ann FrAnesthReanim. 2010 Nov;29(11):826. Epub 2010 Nov 3. [Article inFrench]

▪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? 2010Dec Please see Uncles, et al. reply in editorials

▪Lin EP, Aronson LA.Successful resuscitation of bupivacaine-induced cardiotoxicity in a neonate. PaediatrAnaesth. 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 Dec15;237(12):1455-8.

▪Man D, Podichetty VK. Lipid rescue in resuscitation of local anesthetic-induced cardiac arrest in aesthetic surgery. PlastReconstr Surg. 2010Jun;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. ClinToxicol (Phila). 2010Mar;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. 2010Jan;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 Oct22.

▪Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest. AnesthAnalg. 2009Apr;108(4):1344-6.

▪Young AC, Velez LI, KleinschmidtKC.Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose. Resuscitation. 2009 May;80(5):591-3. Epub 2009 Mar17.

▪Weinberg G, Di Gregorio G, Hiller D, Hewett A, SirianniA.Reversal of haloperidol-induced cardiac arrest by using lipid emulsion. Ann Intern Med. 2009 May19;150(10):737-8.

▪Finn SD, Uncles DR, Willers J, Sable N. Early treatment of a quetiapine and sertraline overdose with Intralipid.Anaesthesia. 2009Feb;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 bupivacaine-associated cardiac arrest. RegAnesth 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. AnesthAnalg. 2008May;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 anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. AnesthAnalg. 2008May;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. AnesthAnalg. 2008May;106(5):1575-7 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. AnesthAnalg. 2008May;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. 2007May;62(5):516-8. 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. Anaesthesist2007 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 EmergM 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. 2007Sep;107(3):516-7 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.

▪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. Anesthesiology2006;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. Anaesthesia2006;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 andCommentary For discussion of the recent letters in Anesthesiology see the link to Blog and News in thenavigator

▪Bet 2: intralipid/lipid emulsion in Beta-blocker overdose. [No authors listed] Emerg Med J. 2011Nov;28(11):991-3

▪Kawaraguchi Y, Roth DM, Patel HH. From Local to Global: Intralipid Makes a Move. Anesthesiology. 2011 Jun 8. [Epub ahead ofprint]

▪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. 2011May;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. 2011Mar;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 reply284.

▪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. 2010Nov;38(11):2268-9.

▪Woehlck HJ, El-OrbanyM.Anesthetic effects and lipid resuscitation protocols. Anesthesiology. 2010Feb;112(2):499-500

▪McKevith J, Banks A. Lipid resuscitation. Resuscitation. 2009 Dec;80(12):1448. Epub 2009 Oct4.

▪Isherwood P. Lipid rescue: small trials and animal research. Anaesthesia. 2009Dec;64(12):1380

▪Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review. Anesthesiology. 2009Sep;111(3):498-505.

▪Picard J, Harrop-Griffiths W. Lipid emulsion to treat drug overdose: past, present and future. Anaesthesia. 2009Feb;64(2):119-21.

▪Picard J, Ward S, Meek T. Antidotes to anesthetic catastrophe: lipid emulsion and dantrolene. AnesthAnalg. 2007Jul;105(1):283-4 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. AnesthAnalg. 2008May;106(5):1337-9 Excellent editorial on LipidRescue method.

▪Rowlingson JC. Lipid rescue: a step forward in patient safety? Likely so! AnesthAnalg. 2008May;106(5):1333-6 An editorial by my mentor, John Rowlingson.

▪Lipid infusion therapy: translation to clinical practice. AnesthAnalg. 2008May;106(5):1340-2 My editorial on the current state-of-the-art.

▪Picard J, Meek T. Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia2006;61:107-9.

▪Weinberg GL.Indefence of lipid resuscitation.Anaesthesia. 2006Aug;61(8):807-8

▪Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity: proof of clinical efficacy. Anesthesiology2006;105:7-8.

▪Groban L, Butterworth J. Lipid reversal of bupivacaine toxicity: has the silver bullet been identified? RegAnesth Pain Med2003;28:167-9.

▪Research Articles (LipidRescueResuscitation)

▪Mauch J, Martin Jurado O, Spielmann N, Bettschart-Wolfensberger R, Weiss M. PaediatrAnaesth. 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

▪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. ClinToxOct2011

▪Mauch J, Martin Jurado O, Spielmann N, Bettschart-Wolfensberger R, Weiss M. PaediatrAnaesth. Resuscitation strategies from bupivacaine-induced cardiac arrest. doi: 10.1111/j.1460-9592.2011.03688.x. 2011 Aug 29. [Epub ahead ofprint] 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 Intralipid-induced Cardioprotection against Ischemia/Reperfusion Injury. Anesthesiology. 2011 Jun 17. [Epub ahead ofprint]

▪Bushey BA, Auld VH, Volk JE, Vacchiano CA. Combined lipid emulsion and ACLS resuscitation following bupivacaine- and hypoxia-induced cardiovascular collapse in unanesthetized swine. AANA J. 2011Apr;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 Mar31

▪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 2011Mar

▪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):515-22.Epu

▪Harvey M, Cave G, Prince G, Lahner D. Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. AnesthAnalg. 2010Sep;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. AnesthAnalg. 2010 May 1; 110(5):1473-9

▪Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). RegAnesth Pain Med. 2010Mar-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 infusion: a first approximation of LD50 in rats. RegAnesth Pain Med. 2010Mar-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. 2009Sep;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 Sep27.

▪Harvey M, Cave G, Kazemi A. Intralipid infusion diminishes return of spontaneous circulation after hypoxic cardiac arrest in rabbits. AnesthAnalg. 2009Apr;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 toxin-induced cardiac arrest. Crit Care Med. 2009Mar;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. 2009Feb;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. 2008Dec;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. AcadEmerg Med. 2008 Oct 25. [Epub ahead ofprint] 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. 2008May;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. 2008Apr;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.