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Excerpt
In the editorial accompanying our article1,2 in Regional Anesthesia and Pain Medicine, Dr. Butterworth and Dr. Groban consider whether lipid rescue from bupivacaine toxicity may represent a “silver bullet” in treatment of this potentially catastrophic anesthetic complication. I would like to thank them for their supportive comments and offer a few caveats before we take the final leap to embracing this novel therapy.
Several colleagues have recently asked me for a specific dosing recommendation in lipid rescue from bupivacaine-associated cardiac arrest. While our reported (and unpublished) data validate the efficacy of lipid rescue, the safety of high-dose rapid lipid infusion is not established. Therefore, we are studying dose-response data to determine an optimal dosing regimen. We seek to achieve desired results while minimizing potential adverse effects of lipid overdose. Nevertheless, in the scenario of bupivacaine-induced cardiac arrest that is unresponsive to standard therapy, I recommend intravenous bolus infusion of 20% lipid emulsion, 1 mL/kg over 1 minute, while continuing chest compressions. I would repeat this increment every 3 to 5 minutes to a maximum of 3 mL/kg, converting at that point, or earlier with evidence of recovery, to a continuous infusion of 20% lipid at a rate of 0.25 mL/kg/min, given until hemodynamic recovery. Dose limits are not yet established, but total doses greater than 8 mL/kg are unlikely to be required in those who do recover, nor of additional benefit in those who do not.
I do not recommend using propofol in the treatment of bupivacaine-induced cardiac arrest. We did not use propofol during resuscitation in any of the reported studies. Further, the standard formulation of propofol, (10 mg/mL in 10% lipid) implies that a massive overdose of propofol would be delivered along with the large volumes that are likely to be needed in refractory cardiac arrest (200-1,000 mL of propofol!). Propofol may be helpful in seizure suppression following bupivacaine overdose, but for cardiac arrest, 20% lipid is preferable. Moreover, we have not addressed whether propofol infusion during regional anesthesia with lipid soluble local anesthetics improves their safety profile, or lowers the risk of adverse events during regional anesthesia. Such a recommendation awaits experimental substantiation.
I appreciate the letter from Dr. Goor. Although the publication of Dr. Krieglestein3 indicates that pretreatment with lipid infusion prevents toxicity, it does not address the more clinically relevant question of whether lipid can save an animal already near death from the offending drug. We showed previously that lipid infusion does improve success in resuscitating rats from bupivacaine-induced asystole.4 Our current study further showed that resuscitation can be successful in a larger animal (dog), after long “down” times, and with improved myocardial metabolic indices. Goor et al.5 compare 24-hour survival in rats following injection of clomipramine dissolved in lipid with that after injection of clomipramine alone. This is essentially a bioassay for the effect of in vitro lipid compounding on toxin bioavailability. The mechanism of death was not studied.
Dr. Goor further comments that neither I, Dr. Groban, nor Dr. Butterworth “…could offer a well-defined mechanism for this effect,…” later implying the moniker “silver bullet” is premature. I agree that more work is needed to understand how lipid infusion reverses otherwise fatal bupivacaine toxicity. In the meantime, I am pleased that Dr. Groban and Dr. Butterworth have validated the importance of our finding. After all, 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.
