Nimodipine reduces the toxicity of intravenous bupivacaine in rats.
We examined nimodipine modification of bupivacaine toxicity in anesthetized male rats. Three minutes after pretreatment, group 1 (n = 11), group 3 (n = 10), and their respective control groups (n = 11 and n = 9) received intravenous bupivacaine LD50 (median lethal dose). After pretreatment, group 2 (n = 10), group 4 (n = 8), and their respective control groups (n = 10 and n = 8) received intravenous bupivacaine LD90 (90% lethal dose). Pretreatment was 200 micrograms/kg intravenous nimodipine in groups 1 and 2 and 500 micrograms/kg in groups 3 and 4. Control animals were pretreated with intravenous saline solution. Data were analyzed by chi 2-analysis and analysis of variance. Survival increased after 200 micrograms/kg nimodipine (P less than 0.05). In group 1, 9 (81%) of 11 survived compared with control animals (4 [36%] of 11). In group 2, 8 (80%) of 10 survived compared with control animals (2 [20%] of 10). Survival was not increased after 500-micrograms/kg nimodipine pretreatment. In group 3, 2 (22%) of 9 survived compared with control animals (4 [40%] of 10). In group 4, 4 (50%) of 8 survived compared with control animals (2 [25%] of 8). We conclude that nimodipine pretreatment with 200 micrograms/kg protects against fatal toxicity from LD50 and LD90 bupivacaine, but 500 micrograms/kg does not.
Hyman
S A
SA
Department of Anesthesiology, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232-2125.
Kinney
W W
WW
Horn
J L
JL
Skelley
C C
CC
Kambam
J R
JR
D000818:Animals; D001049:Apnea / Q000139:chemically induced; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D002045:Bupivacaine / Q000633:toxicity*; D002319:Cardiovascular System / Q000187:drug effects; D004347:Drug Interactions; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012137:Respiratory System / Q000187:drug effects; D013997:Time Factors
D009553:Nimodipine; D010424:Pentobarbital; D002045:Bupivacaine