Hicks et al.  1studied the effect of lipid emulsion, epinephrine, and vasopressin on survival rate after bupivacaine-induced cardiac arrest in a porcine model. The results of the authors demonstrated a completely different and unexpected outcome when compared with previous studies that used rodent and canine models. Although species difference may partially explain the different outcomes, one must acknowledge that the anesthetics used in these studies were also markedly different. It is possible to study conscious animals in a canine model because dogs are easily trained. This closely mimics the human clinical scenario when bupivacaine is inadvertently injected intravenously during an attempted regional anesthetic with minimal sedation. Conversely, swine are more difficult to handle without heavy sedation or general anesthesia. Governmental regulations may sometimes disallow animal experimentation in the conscious state. Hicks et al.  used ketamine, xylazine, and α-chloralose to induce general anesthesia. These drugs are known to work well in large animals such as swine. In a similar porcine study, Mayr et al.  2used azaperone, atropine, ketamine, and piritramid followed by isoflurane after intubation. These anesthetic regimens produce hemodynamic and cardiac electrophysiologic effects, which may explain the failure of lipid rescue protocols in these studies.

Azaperone is a butyrophenone that, like droperidol, may have detrimental electrophysiologic effects at the high doses used in animals.2Azaperone also blocks α-adrenergic receptors, producing hypotension, impaired thermoregulation,3,4and probably causing the extreme hypotension in the absence of epinephrine in the study of Mayr et al.  2Hicks et al.  1used α-chloralose, an anesthetic that was historically used as a rodenticide.5α-Chloralose decreases cardiac conduction velocity in the cardiac muscle and atrioventricular node, prolongs the QTc interval, delays atrioventricular conduction, increases the ventricular refractory period, and exacerbates atrioventricular block caused by verapamil.6Drugs that decrease cardiac conduction velocity will enhance bupivacaine arrhythmias,7and α-chloralose has also been shown to be proarrhythmic toward the ischemic porcine heart.8One can speculate that even if lipid rescue could partially reverse the effects of lipophilic drugs such as bupivacaine, one would not expect this for hydrophilic drugs such as α-chloralose. Through multiple hemodynamic and electrophysiologic effects, the anesthetics, as used in these porcine studies of bupivacaine-induced cardiac arrest, may have contributed to the failure of lipid rescue. For animal studies to optimally contribute to our understanding of resuscitation from inadvertent bupivacaine toxicity, studies should incorporate anesthetic and sedative techniques as that used in humans.

*Medical College of Wisconsin, Milwaukee, Wisconsin. hwoehlck@mcw.edu

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