Answer this question: When was the first report published describing lipid emulsion for treating human local anesthetic toxicity? I'll make it easier with some choices: 1976, 1986, 1996, or 2006? The answer is 2006, less than a decade ago. Frankly, this surprised me. It seems we've been talking about lipid rescue therapy forever.
Rosenblatt et al. in that paper described a 58-year-old man who suffered a seizure and cardiac arrest after receiving a local injection of bupivacaine and mepivacaine for rotator cuff repair. (Anesthesiology 2006;105:217.) He received 20 minutes of Advanced Cardiac Life Support and progressed through several ventricular dysrhythmias, but he was still asystolic and about to be put on cardiopulmonary bypass.
Then a member of the team recalled animal studies on bupivacaine and lipid emulsion, and administered 100 mL Intralipid. The paper describes what followed: “Within seconds, a single sinus beat appeared on the electrocardiogram, and 1 mg atropine and 1 mg epinephrine were administered. Within 15 s, while external chest compressions were continued, the cardiac rhythm returned to sinus at a rate of 90 beats/minute.”
The patient's vital signs continued to be stable, and he recovered without any neurological sequelae.
Lipid emulsion has since become first-line therapy for acute local anesthetic cardiotoxicity, and the antidote is stocked and readily available at most, if not all, centers that perform regional anesthesia. Shortly after that case was published, reports appeared in which lipid emulsion was used to treat severe cardiotoxicity from ingestion of lipophilic cardiotoxic drugs such as amitriptyline, bupropion, quetiapine, and calcium channel blockers. The data are somewhat anecdotal, but these publications reflected impressive though nonconclusive results.
Many cases of enteral overdoses treated with lipid emulsion use a protocol similar to one by the American Society of Regional Anesthesia and Pain Medicine for treating local anesthetic toxicity. (Table 1.) The pharmacokinetics of local anesthetic toxicity is rather different from that of enteral overdose. When, say, bupivacaine is injected into a vessel, the systemic level builds quickly and declines rapidly. Giving a bolus of lipid emulsion followed by an aggressive but short-lived infusion conceptually matches this time course.
Absorption is often slow and can continue for hours with enteral overdose, and a bolus followed by a short infusion may not be optimal. Guy Weinberg, MD, and his group at the University of Illinois recently addressed this. (Ann Emerg Med 28 Feb 2015; doi: 10.1016/j.annemergmed.2015.01.020.) The authors noted that the American College of Medical Toxicology adopted interim guidelines for lipid resuscitation therapy that were based on the ASRA dosing for local anesthetic toxicity. (J Med Toxicol 2011;7:81.) These did not mention a specific maximum total dose, however. In fact, a number of cases have been reported in which patients received remarkably high volumes of lipid emulsion, sometimes far in excess of the 12.5 mL/kg that the Food and Drug Administration recommends as the maximum daily dosage in adults when using lipid emulsion for nutritional support.
Giving extremely high does of lipid emulsion involves the possibility of precipitating fat overload syndrome. This condition, associated with markedly elevated triglyceride levels, manifests with fever, coagulopathy, and injury to organs such as the liver and lungs. Fat overload syndrome is potentially fatal, but appears to be rare among patients treated with lipid emulsion for enteral overdose.
The authors suggest that an extended infusion should aim at maintaining lipemic serum, which would accomplish the goals of lipid emulsion therapy: accelerating redistribution of toxic drug from key organs to buffer areas such as liver and skeletal muscle and providing a direct inotropic substrate to improve myocardial function.
These considerations and using pharmacokinetic data and computer modeling led the authors to make provisional recommendations for treating enteral overdose with lipid emulsion. (Table 2.) All dose calculations (mL/kg) are based on ideal weight (lean body mass), not actual weight. The authors also recommend not exceeding the maximum FDA nutritional limit of 12.5 mL/kg/day, and aiming for a serum triglyceride level of approximately 1,000 mg/dL.
It's impossible to know at this point if this is the optimal dose schedule for treating enteral overdose, and certainly more data are required before the issue is sorted out. But it is important to realize that the requirements for treating toxic ingestions may be somewhat different from those established for local anesthetic toxicity.
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