Nicardipine reduces the cardio-respiratory toxicity of intravenously administered bupivacaine in rats.
The purpose of our study was to examine the effect of intravenous (IV) nicardipine pretreatment (30 micrograms.kg-1), given three minutes before an IV bolus of bupivacaine to determine its effect on the incidence of fatal bupivacaine cardio-respiratory toxicity in adult male Sprague Dawley rats anaesthetized with intraperitoneal pentobarbital. Fifty rats were divided into four groups. Groups I and II (n = 10 each) received 3.5 mg.kg-1 0.5 per cent bupivacaine and Groups III and IV (n = 15 each) received 5.0 mg.kg-1, 0.5 per cent bupivacaine. Groups I and III received pretreatment with normal saline before bupivacaine, whereas Groups II and IV were given pretreatment with nicardipine, 30 mg.kg-1. There was no difference in the incidence of survival between the nicardipine pretreatment group and the saline placebo pretreatment group given 3.5 mg.kg-1, 0.5 per cent bupivacaine (no fatalities in either group). However, there was significant protection by nicardipine pretreatment in the group given 5 mg.kg-1, 0.5 per cent bupivacaine (13 of 15 survived, compared with only 4 of 15 in the saline pretreatment group, P less than 0.001). In conclusion, our data demonstrate that in rats given 0.5 per cent bupivacaine, 5 mg.kg-1, nicardipine pretreatment protected against fatal cardio-respiratory toxicity.
Matsuda
F
F
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232-2125.
Kinney
W W
WW
Wright
W
W
Kambam
J R
JR
D000704:Analysis of Variance; D000765:Anesthesia, Conduction; D000818:Animals; D001049:Apnea / Q000139:chemically induced; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology*; D010424:Pentobarbital; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D015996:Survival Rate
D009529:Nicardipine; D010424:Pentobarbital; D002045:Bupivacaine