VOLUME 29, Issue 1
Lipid Emulsion for Treatment of Local Anesthetic Systemic Toxicity:
The evolution from experimental model to standard treatment
Russell K. McAllister
TSA Editor
As a mid-career physician, there sometimes seems to be very few groundbreaking changes in medicine where a new treatment emerges for a clinical problem that previously had very limited treatment options. It is rare that we get to witness the full evolution of this new treatment becoming standard of care. I have had such an opportunity in seeing lipid emulsion therapy become accepted as the treatment for local anesthetic systemic toxicity (LAST).
Although this seems like a new development, the groundwork for it was laid over 20 years ago in Dr. Guy Weinberg’s lab in Chicago, when he discovered that pretreatment or resuscitation with a lipid infusion caused a shift in the dose-response to bupivacaine-induced asystole in rats.1 His work continued and led to the 2003 publication of, what I consider a landmark paper for my generation, “Lipid emulsion infusion rescues dogs from bupivacaine-induced toxicity.”2 This is the paper that caught my attention and led to my interest in the subject many years ago. Simply put, it was a 12 dog study where all dogs were given lethal doses of bupivacaine intravenously. As expected, in the control group treated with saline, all of the dogs developed asystole and died. However, in the lipid emulsion treated group, all dogs developed asystole, but then returned to normal sinus rhythm after lipid emulsion infusion. I vividly recall thumbing through the journal in 2003 and being intrigued by the title and reading this article from start to finish. I had a sense at the time that, if this study was correct, this would be a game changer for how we manage LAST. Human case reports would follow in 2006.3 Research would also later show efficacy of lipid emulsion therapy in treatment of certain lipid soluble oral ingestion medications culminating with an impressive human case report of the lipid emulsion rescue of a young female who had overdosed on lamotrigine and bupropion and had a complete, neurologically intact, survival after an hour of cardiopulmonary resuscitation.4
These published reports led to a gradual implementation of lipid emulsion therapy into most sites where local anesthesia is used, as well as emergency departments where patients who have ingested toxic lipid soluble drugs may be treated. The process, though it has seemed quite rapid, has evolved over a couple of decades. It started with an idea that was tested in small animals in a lab in the 90’s, was verified in larger animals in the early 2000’s, confirmed in humans in the mid to late 2000’s, and slowly adopted and refined as standard of care over the past few years. This is one of those rare situations where human efficacy studies will likely never be done due to the lethal effects of intravenous bupivacaine.
Research into the exact mechanism of how lipid emulsion exerts its effects is ongoing in multiple labs and appears to be promising. The effects appear to be very complex and seem to involve cell signaling and many other mechanisms that have positive effects on the cardiopulmonary system that are far too complex to tackle in this setting. The ongoing research is exciting and I believe that we will gain much more insight into the mechanisms of how this treatment exerts its effects, as well as discovering other situations where it may be used effectively to rescue patients. As Dr. Weinberg has noted, “anesthesiologists have shown for over 150 years that they are comfortable using agents better known for their efficacy than for their precise mechanism of action.”
References:
- Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 1998; 88: 1071–1075.
- 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.
- 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: 217–218.
- Sirianni AJ, Osterhoudt KC, Calello DP, et al. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med 2008; 51: 412–415.
Management of Local Anesthetic Systemic Toxicity-Guidelines of the American Society of Regional Anesthesia
- Get Help
- Initial Focus
- Airway management: ventilate with 100% oxygen
- Seizure suppression: benzodiazepines are preferred; AVOID propofol in patients having signs of cardiovascular instability
- Alert the nearest facility having cardiopulmonary bypass capability
- Management of Cardiac Arrhythmias
- Basic and Advanced Cardiac Life Support (ACLS) will require adjustment of medications and perhaps prolonged effort
- AVOID vasopressin, calcium channel blockers, beta blockers, or local anesthetic
- REDUCE individual epinephrine doses to <1 mcg/kg
- Lipid Emulsion (20%) Therapy (values in parenthesis are for 70kg patient)
- Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (~100mL)
- Continuous infusion 0.25 mL/kg/min (~18 mL/min; adjust by roller clamp)
- Repeat bolus once or twice for persistent cardiovascular collapse
- Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low
- Continue infusion for at least 10 minutes after attaining circulatory stability
- Recommended upper limit: Approximately 10 mL/kg lipid emulsion over the first 30 minutes
