TY - JOUR
T1 - The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats
AU - Srinivasa, Venkatesh
AU - Gerner, Peter
AU - Haderer, Anna
AU - Abdi, Salahadin
AU - Jarolim, Petr
AU - Wang, Ging Kuo
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Intravascular injection of local anesthetics carries the risk of cardiovascular (CV) and central nervous system (CNS) toxicity. Amitriptyline, a tricyclic antidepressant, has local anesthetic potency that is more than that of bupivacaine. In this study, we compared the CV and CNS toxicity of the local anesthetics bupivacaine and levobupivacaine with that of amitriptyline. Twenty-nine Sprague-Dawley rats had their right external jugular vein and carotid artery cannulated under general anesthesia. On Day 2, rats were sedated with midazolam (0.375 mg/kg intraperitoneally) and received rapid infusions of either 1) bupivacaine, levobupivacaine, or amitriptyline at 2 mg·kg-1 min-1 (5 mg/mL concentration) or 2) normal saline (400 μL·kg-1·min-1) through an external jugular vein cannula. Electrocardiogram and arterial blood pressure were measured until the dose to cause impending death was reached (heart rate 50 bpm/asystole or apnea for >30 s). The mean dose required to cause apnea and impending death was significantly larger for amitriptyline (74.0 ± 21 mg/kg and 74.5 ± 21 mg/kg, respectively) than for levobupivacaine (32.2 ± 20 mg/kg and 33.9 ± 22 mg/ kg, respectively) or bupivacaine (21.5 ± 7 mg/kg and 22.7 ± 7 mg/kg, respectively) (P < 0.05). A significantly larger dose of amitriptyline, given by rapid infusion, is required to cause CV and CNS toxicity in rats, when compared with bupivacaine and levobupivacaine.
AB - Intravascular injection of local anesthetics carries the risk of cardiovascular (CV) and central nervous system (CNS) toxicity. Amitriptyline, a tricyclic antidepressant, has local anesthetic potency that is more than that of bupivacaine. In this study, we compared the CV and CNS toxicity of the local anesthetics bupivacaine and levobupivacaine with that of amitriptyline. Twenty-nine Sprague-Dawley rats had their right external jugular vein and carotid artery cannulated under general anesthesia. On Day 2, rats were sedated with midazolam (0.375 mg/kg intraperitoneally) and received rapid infusions of either 1) bupivacaine, levobupivacaine, or amitriptyline at 2 mg·kg-1 min-1 (5 mg/mL concentration) or 2) normal saline (400 μL·kg-1·min-1) through an external jugular vein cannula. Electrocardiogram and arterial blood pressure were measured until the dose to cause impending death was reached (heart rate 50 bpm/asystole or apnea for >30 s). The mean dose required to cause apnea and impending death was significantly larger for amitriptyline (74.0 ± 21 mg/kg and 74.5 ± 21 mg/kg, respectively) than for levobupivacaine (32.2 ± 20 mg/kg and 33.9 ± 22 mg/ kg, respectively) or bupivacaine (21.5 ± 7 mg/kg and 22.7 ± 7 mg/kg, respectively) (P < 0.05). A significantly larger dose of amitriptyline, given by rapid infusion, is required to cause CV and CNS toxicity in rats, when compared with bupivacaine and levobupivacaine.
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U2 - 10.1213/01.ANE.0000065600.15574.AB
DO - 10.1213/01.ANE.0000065600.15574.AB
M3 - Article
C2 - 12818949
AN - SCOPUS:0038311803
SN - 0003-2999
VL - 97
SP - 91
EP - 95
JO - Anesthesia and analgesia
JF - Anesthesia and analgesia
IS - 1
ER -