Circulation 84,122 • Volume 24, No. 1 • Spring 2009   Issue PDF

Intralipid Treatment of Bupicavaine Toxicity

Pete Stiles, BA; Richard C. Prielipp MD, MBA, FCCM


Cardiac toxicity associated with overdose of intravascular injection of local anesthetic is characterized by hypotension, atrioventricular conduction delay, idioventricular rhythms, and eventual cardiovascular collapse. Although all local anesthetics potentially shorten the myocardial refractory period, bupivacaine avidly blocks the cardiac sodium channels, thereby making it most likely to precipitate malignant arrhythmias. Even levobupivacaine and ropivacaine (single-enantiomer derivatives), developed to ameliorate cardiovascular side effects, still harbor the potential to disrupt cardiac function.

Data suggest up to 20 out of 10,000 peripheral nerve blocks and 4 per 10,000 epidural blocks result in systemic local anesthetic toxicity. As current practice often favors the addition of regional anesthesia and major plexus blocks to supplement or substitute for general anesthesia, all anesthesia professionals must be familiar with signs of local anesthetic cardiotoxicity—and current treatment options.

Lipid to the Rescue?

While pretreatment with a lipid infusion in rats was found to increase the dose of i.v. bupivacaine required to induce asystole, subsequent studies examined resuscitation in dogs with lipid emulsion after an intravenous dose of bupivacaine. Researchers found substantially improved hemodynamics and myocardial metabolism.1 Thus, by 2006, many touted “lipid rescue” for local anesthetic cardiotoxicty and suggested that anesthesiologists routinely stock lipid emulsions wherever regional anesthesia was practiced. Some challenged these conclusions on grounds that severe systemic toxicity from local anesthetics occurs with far greater frequency than is published in medical literature, and that the most appropriate way to limit the hazards of local anesthetics is to prevent complications with proper injection techniques and careful dosing.

Case Reports Document Lipid Rescue

One case report describes a 58-year-old man who, 30 seconds after an interscalene injection, developed a tonic-clonic seizure and cardiac arrest. Prolonged ACLS failed to restore a perfusing rhythm, so 100 mL of 20% Intralipid was rapidly infused while maintaining cardiac compressions and preparing for cardiopulmonary bypass. Remarkably, the first defibrillation after lipid administration restored a sinus rhythm, and cardiovascular performance now responded to inotropes and vasopressors. Intralipid 0.5 mL/kg/min was infused for 2 hours, during which time the patient regained full consciousness and recovered without neurological sequelae.2 While this case suggests lipids might be routinely stocked in areas in which peripheral nerve blocks are performed2, the high-dose safely profile of Intralipid is unknown, and other questions also remain:

  1. What is the mechanism of action of lipid rescue?
  2. Is the beneficial effect of Intralipid promoted or hindered by concurrent drug therapy administered via ACLS protocol?

Currently, 12 published cases support lipid rescue in the setting of local anesthetic cardiotoxicity, where early administration of Intralipid is emphasized. Fortunately, it appears that the beneficial effect of Intralipid administration also includes local anesthetics other than bupivacaine.3

Proposed Mechanisms

The mechanism by which lipids reverse local anesthetic cardiotoxicity may be increasing clearance from cardiac tissue. This nonspecific, observed extraction of local anesthetics from aqueous plasma or cardiac tissues is termed a “lipid sink.”4 Another proposed mechanism is that lipids counteract local anesthetic inhibition of myocardial fatty acid oxidation, thereby enabling energy production and reversing cardiac depression.

Caution is Still Prudent

The ultimate role of lipid rescue is still debated as some suggest that successful resuscitation could be due to spontaneous clearance of the instigating local anesthetic within 20 minutes of routine ACLS. Others caution that prevention is always more appropriate—and the concept of a “remedy” could make some practitioners less careful.5 Moreover, while lipid rescue may be the driving force behind successful cardiac resuscitation, the risk to the brain from prolonged circulatory collapse remains.5 Thus we emphasize that primary therapy remains adherence to proven guidelines—cardiac and SpO2 monitoring, proper availability and dosing of all local anesthetics, immediate means to support ventilation, proper cardiac compressions during CPR, and application of proven advanced life support techniques. Only then should lipid rescue be considered in the therapeutic algorithm.

What Should Clinicians Conclude?

Assertion of a unique role for Intralipid with new ACLS protocol guidelines6 must be tempered by awareness that the appropriate dose of Intralipid for resuscitation remains unknown and that excess lipid may interfere with lipophilic ACLS drugs. Current doses vary widely, and pediatric dosing recommendations are even more elusive. Nonetheless, in a survey completed in 2006, respondents from 90 academic anesthesiology departments revealed that 26% would consider using lipid rescue in the setting of local anesthetic toxicity—and that the more major nerve blocks performed at an institution, the more likely they were to use lipid rescue.7 Thirty-nine percent of institutions stored Intralipid in the OR pharmacy, 35% in the hospital pharmacy, 22% in the “code box,” and 4% in a drug-dispensing device in the OR. More than half of the centers specified that the drug was accessible in less than 10 minutes. The Association of Anaesthetists of Great Britain and Ireland recently provided members with protocols to treat local anesthetic cardiotoxicity that include an infusion of lipid emulsion.8 In an editorial published in Anesthesia & Analgesia, Brull explains, “based on the available data, it would seem reasonable to have a [lipid] rescue kit available in any setting in which regional anesthesia is practiced—and, in fact, in any location where local anesthetics are administered by any professional, by any route, and in almost any dose.”9 Moreover, it will be critical to support further investigation of lipid rescue.

Thus, anesthesia professionals should consider this alternative when a patient shows signs and symptoms of local anesthetic toxicity with, or even before, failing CPR. A useful website,, is dedicated to the discussion and promotion of lipid emulsion reversal of local anesthetic systemic toxicity. Here, the latest data and case reports are synthesized. Readers are cautioned that human prospective studies have not yet been reported, so a registry of local anesthetic-associated cardiac arrests is being planned. Indeed, acknowledging the limited understanding of lipid therapy, many questions remain:

  • Should the lipid dose be titrated, by patient weight, local anesthet
    ic dose, or the symptoms/ signs/severity of toxicity?
  • What is the best rate and total dose of the infusion that follows bolus dosing? Is there a safe upper limit of lipid dosing?
  • How long should the patient receive the lipid infusion?
  • What is the risk of reoccurrence of toxicity once the lipid infusion is stopped?
  • Should lipid emulsion be used for patients exhibiting signs of CNS toxicity, or should intralipid only be used for cardiac toxicity?
  • 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 measures?
  • 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?

With all the limitations noted above, one plausible dosing application to consider after “all standard resuscitation methods fail to re-establish sufficient circulatory stability” would be as follows:

20% Intralipid:

  1. Administer 1.5 mL/kg as an initial bolus; the bolus can be repeated 1- 2 times for persistent asystole.
  2. Start an infusion at 0.25 mL/kg/min for 30-60 minutes; increase infusion rate up to 0.50 mL/kg/min for refractory hypotension.3,10

Pete Stiles, BA, is a senior medical student at the University of Minnesota Medical School. He is expecting to be awarded his medical degree in May 2009. Dr. Prielipp is the JJ Buckley Professor and Chair of the Department of Anesthesiology at the University of Minnesota Medical School, Minneapolis, MN.


  1. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med 2003;28:198-202.
  2. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006;105:217-8.
  3. Weinberg G. Lipid rescue in the literature. Available at: Accessed April 3, 2009.
  4. 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;31:296-303.
  5. de Jong RH. Lipid infusion for cardiotoxicity: promise? Yes—panacea? Not. Anesthesiology 2007;106:635-6.
  6. Corman SL, Skledar SJ. Use of lipid emulsion to reverse local anesthetic-induced toxicity. Ann Pharmacother 2007;41:1873-7.
  7. 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;103:1322-6.
  8. Weinberg GL. Lipid infusion therapy: translation to clinical practice. Anesth Analg 2008;106:1340-2.
  9. Brull SJ. Lipid emulsion for the treatment of local anesthetic toxicity: patient safety implications. Anesth Analg 2008;106:1337-9.
  10. Weinberg G. Treatment regimens. Available at: Accessed April 3, 2009.
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