Gail K Wong1, Carolyne Pehora2, Mark W Crawford2. 1. Department of Anesthesia and Pain Medicine, The Hospital For Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. gail.wong@health.nsw.gov.au. 2. Department of Anesthesia and Pain Medicine, The Hospital For Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Abstract
BACKGROUND: The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg·kg-1 iv on susceptibility to bupivacaine-induced cardiotoxicity in rats. METHODS: In the first of two experiments, L-carnitine 100 mg·kg-1 iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg-1·min-1 iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacaine cardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg·kg-1 iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg-1, L-carnitine 100 mg·kg-1, 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation. RESULTS: In the first study, L-carnitine 100 mg·kg-1 increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01). CONCLUSION: These findings suggest that acute administration of L-carnitine 100 mg·kg-1 decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.
BACKGROUND: The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg·kg-1 iv on susceptibility to bupivacaine-induced cardiotoxicity in rats. METHODS: In the first of two experiments, L-carnitine 100 mg·kg-1 iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg-1·min-1 iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacainecardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg·kg-1 iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg-1, L-carnitine 100 mg·kg-1, 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation. RESULTS: In the first study, L-carnitine 100 mg·kg-1 increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01). CONCLUSION: These findings suggest that acute administration of L-carnitine 100 mg·kg-1 decreases susceptibility to bupivacainecardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.
Authors: Mario Bonomini; Victor Zammit; José C Divino-Filho; Simon J Davies; Lorenzo Di Liberato; Arduino Arduini; Mark Lambie Journal: J Nephrol Date: 2020-08-07 Impact factor: 3.902