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Correspondence  |   February 2010
Anesthetic Effects and Lipid Resuscitation Protocols
Author Affiliations & Notes
  • Harvey J. Woehlck, M.D.
    *
  • *Medical College of Wisconsin, Milwaukee, Wisconsin.
Article Information
Correspondence
Correspondence   |   February 2010
Anesthetic Effects and Lipid Resuscitation Protocols
Anesthesiology 2 2010, Vol.112, 499-500. doi:10.1097/ALN.0b013e3181c91ed0
Anesthesiology 2 2010, Vol.112, 499-500. doi:10.1097/ALN.0b013e3181c91ed0
To the Editor:
Hicks et al.  1 studied 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.  2 used 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.2 Azaperone also blocks α-adrenergic receptors, producing hypotension, impaired thermoregulation,3,4 and probably causing the extreme hypotension in the absence of epinephrine in the study of Mayr et al.  2 Hicks et al.  1 used α-chloralose, an anesthetic that was historically used as a rodenticide.5 α-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.6 Drugs that decrease cardiac conduction velocity will enhance bupivacaine arrhythmias,7 and α-chloralose has also been shown to be proarrhythmic toward the ischemic porcine heart.8 One 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.
References
Hicks SD, Salcido DD, Logue ES, Suffoletto BP, Empey PE, Poloyec SM, Miller DR, Callaway CW, Menegazzi JJ: Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a swine model of bupivacaine induced cardiac arrest. Anesthesiology 2009; 111:138–46Hicks, SD Salcido, DD Logue, ES Suffoletto, BP Empey, PE Poloyec, SM Miller, DR Callaway, CW Menegazzi, JJ
Mayr VD, Mitterschiffthaler L, Neurauter A, Gritsch C, Wenzel V, Mueller T, Luckner G, Lindner KH, Strohmenger HU: A comparison of the combination of epinephrine and vasopressin with lipid emulsion in a porcine model of asphyxial cardiac arrest after intravenous injection of bupivacaine. Anesth Analg 2008; 106:1566–71Mayr, VD Mitterschiffthaler, L Neurauter, A Gritsch, C Wenzel, V Mueller, T Luckner, G Lindner, KH Strohmenger, HU
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Bardaji A, Cinca J, Worner F, Schoenenberger A: Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ. Cardiovasc Res 1990; 24:227–31Bardaji, A Cinca, J Worner, F Schoenenberger, A