title: Does diazepam really reduce the cardiotoxic effects of intravenous bupivacaine?
abstract: The effect of diazepam on the cardiovascular toxicity of bupivacaine was investigated in a rat model. Under chloral hydrate (400 mg/kg intraperitoneal) anesthesia, unilateral femoral venous and bilateral femoral arterial cannulae were placed for administration of drugs, for blood sampling, and for continuous qualitative monitoring of arterial blood pressure. Lead II ECG was continuously recorded and a tracheostomy performed to increase FIO2 by use of a "T-piece." Four groups of 24 to 36 rats each were studied. All rats received IV bupivacaine 2 mg/kg, within 10 seconds. Group I, the control group, received only bupivacaine. Groups II and III received IV diazepam 0.2 mg/kg, or diazepam vehicle in an equivalent volume, respectively. Five minutes after this pretreatment, groups II and III received IV bupivacaine 2 mg/kg. Group IV was given diazepam, 0.2 mg/kg, 30 seconds after injection of 2 mg/kg bupivacaine. A marked respiratory and metabolic acidosis occurred in all rats but was significantly worse in groups II and III. No rat in the study became hypoxemic. Serious arrhythmias (ventricular or supraventricular tachycardia) were noted in all groups, but the incidence was significantly higher in the group of rats given diazepam pretreatment than in the other three groups. It is concluded that IV diazepam 0.2 mg/kg given 5 minutes before administration of IV bupivacaine 2 mg/kg increases the incidence of serious cardiac arrhythmias. Second, this increase is not solely due to increased acidosis, because the rats receiving the vehicle (group III) developed equivalent acidosis but did not develop increased arrhythmias.
authors.affiliation: Department of Anesthesia, University of Cincinnati College of Medicine, OH 45267-0531.
authors.forename: R V
authors.initials: RV
authors.lastname: Gregg
authors.forename: P A
authors.initials: PA
authors.lastname: Turner
authors.forename: D D
authors.initials: DD
authors.lastname: Denson
authors.forename: R C
authors.initials: RC
authors.lastname: Stuebing
authors.forename: C S
authors.initials: CS
authors.lastname: Sehlhorst
authors.forename: T
authors.initials: T
authors.lastname: Forsberg
mesh_terms: D000142:Acidosis, Respiratory / Q000097:blood / Q000139:chemically induced; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000139:chemically induced; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000037:antagonists & inhibitors* / Q000097:blood / Q000633:toxicity; D003975:Diazepam / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D003975:Diazepam; D002045:Bupivacaine