L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats.

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.

Major complications related to epidural analgesia in children: a 15-year audit of 3,152 epidurals.

BACKGROUND: Complications associated with epidural analgesia in children have a reported incidence of 40-90 in 10,000 epidurals. We sought to determine the incidence of major complications with the use of continuous epidural analgesia that occurred in our centre over the past 15 years and to describe the nature of these complications. METHODS: The Acute Pain Service database at a tertiary care academic pediatric hospital was reviewed retrospectively over a 15-year period. Data were categorized according to patient age (neonate, infant, child one through eight years, and child > eight years), mode of insertion of the epidural (caudal, transsacral, lumbar, thoracic), complication type, and complication severity. RESULTS: Over the 15-year period, 3,152 epidurals were performed. The use of caudal-thoracic epidurals in neonates and infants has increased since 2007. Twenty-four major complications were identified (incidence, 7.6 in 1,000 epidurals). The rate of complications in neonates was 4.2% compared with 1.4% in infants, 0.5% in children aged one through eight years, and 0.8% in children over eight years of age. The two most common complications were local skin infection and drug error. CONCLUSIONS: Our incidence of major complications and our finding that complications were more common in neonates and infants are both consistent with previously published data. The two most common types of complications are potentially preventable.

Carnitine deficiency increases susceptibility to bupivacaine-induced cardiotoxicity in rats.

BACKGROUND: Anecdotal reports suggest that carnitine deficiency increases susceptibility to bupivacaine-induced cardiotoxicity. Bupivacaine inhibits lipid-based respiration in myocardial mitochondria via inhibition of acylcarnitine exchange in rats. The authors hypothesized that carnitine deficiency increases susceptibility to bupivacaine-induced asystole in rats and that acute repletion with L-carnitine reverses this effect. METHODS: Thirty male Sprague-Dawley rats were assigned to three groups. Rats assigned to the L-carnitine-deficient and L-carnitine-replete groups received subcutaneous D-carnitine on the 10 d before the experiment to induce L-carnitine deficiency. Control rats received an equal volume of subcutaneous normal saline. The rats were anesthetized and mechanically ventilated. Bupivacaine was infused intravenously at a rate of 2.0 mg · kg⁻¹ · min⁻¹ until asystole occurred. The L-carnitine-replete group received intravenous L-carnitine 100 mg · kg⁻¹ immediately before bupivacaine infusion. At asystole, blood was sampled to measure bupivacaine concentration. The primary outcome was time to asystole. RESULTS: L-carnitine deficiency significantly decreased survival duration (P < 0.0001). Time to bupivacaine-induced asystole decreased by 22% (P < 0.05) in the L-carnitine-deficient group (847 s [787-898]) (median [interquartile range]) compared with controls (1,082 s [969-1,427]). Intravenous administration of L-carnitine completely reversed the reduction in time to asystole. At asystole, the median plasma bupivacaine concentration in the L-carnitine-deficient group was 38% (P < 0.05) less than that in control animals. Plasma bupivacaine concentration was similar in L-carnitine-replete and control animals. CONCLUSIONS: Carnitine deficiency increased sensitivity to bupivacaine-induced asystole, an effect that was reversed completely by L-carnitine repletion. This study suggests that carnitine deficiency may predispose to bupivacaine-induced cardiotoxicity. L-carnitine may have a protective role against bupivacaine cardiotoxicity.

Preparation of the Dräger Fabius GS workstation for malignant hyperthermia-susceptible patients.

PURPOSE: In order to establish guidelines for the preparation of the Dräger Fabius GS premium anesthetic workstation for malignant hyperthermia-susceptible patients, the authors evaluated the effect of the workstation's exchangeable and autoclavable components on the washout of isoflurane. METHODS: A Dräger Fabius GS workstation was primed with 1.5% isoflurane, and exchangeable components were replaced as follows: Group 1: no replacement (control); Group 2: autoclaved ventilator diaphragm and ventilator hose; Group 3: flushed ventilator diaphragm and ventilator hose; Group 4: autoclaved compact breathing system. The fresh gas flow (FGF) was set at 10 L . min(-1), and the concentration of isoflurane in the inspiratory limb of the circle breathing circuit was recorded every minute until an endpoint of 5.0 parts per million (ppm) was achieved, at which time the FGF was reduced to 3 L . min(-1). Six experiments were conducted in each of the four groups. RESULTS: The time to achieve an isoflurane concentration of 5.0 ppm decreased in the following order: Group 1 (151 +/- 17 min) > Group 3 (137 +/- 7 min) > Group 4 (122 +/- 11 min) > Group 2 (42 +/- 6 min) (P < 0.01 vs control). Isoflurane concentration increased approximately fivefold when the FGF was reduced to 3 L . min(-1). CONCLUSION: Anesthetic washout from the Dräger Fabius GS is relatively slow. Although washout was accelerated when the Dräger Fabius GS was equipped with autoclaved components, the reduction in washout time may be less than that required for this technique to be accepted into clinical practice. A dedicated vapor-free workstation may be preferable for rapid turnover between cases.