Interaction of intravenous diazepam and bupivacaine in conscious dogs.
The cardiac and hemodynamic effects of bupivacaine, diazepam and their coadministration were evaluated in six mongrel dogs chronically instrumented for recording of mean arterial pressure (MAP), left ventricular (LV) pressure, and cardiac output (CO, electromagnetic flow probe around the ascending aorta). LVdP/dt was derived from the LV pressure signal, and its positive peak was used as an index of myocardial contractility. Heart rate (HR), RR, PR and QT intervals were measured from ECG. At weekly intervals, each dog received in a random order one of the following treatments: (1) saline as control, (2) diazepam (0.2 mg/kg, intravenous, bolus), (3) bupivacaine (0.4 mg/kg intravenous bolus, followed by 15 micrograms/kg/minute, during 30 minutes), and (4) a combination of diazepam and bupivacaine, as in (2) and (3), respectively. Despite its intrinsic cardiodepressant effects, bupivacaine induced a delayed (30-minute) compensatory increase in HR (+ 11%, p less than 0.05) and LVdP/dt (+ 10%, p less than 0.05). Diazepam decreased systemic vascular resistance (SVR; -16%, p less than 0.05) with concomitant increases in HR and CO. After diazepam pretreatment, LVdP/dt did not rise after bupivacaine administration, whereas SVR decreased (-14%, p less than 0.05) and HR increased (+19%, p less than 0.05). The QT-RR relationship remained unchanged regardless of the treatment administered. Thus, diazepam might blunt the compensatory effects of bupivacaine on cardiac function and may decrease the margin of safety of this local anesthetic agent during major neural blockade procedure.
Gerard
J L
JL
Département de Pharmacologie et d'Anesthésiologie, Université de Paris-Sud, Hospital de Bicétre, France.
Edouard
A
A
Berdeaux
A
A
Duranteau
J
J
Ahmad
R
R
D000818:Animals; D001769:Blood; D002045:Bupivacaine / Q000008:administration & dosage*; D002245:Carbon Dioxide / Q000097:blood; D003975:Diazepam / Q000008:administration & dosage*; D004285:Dogs; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure
D004338:Drug Combinations; D002245:Carbon Dioxide; D003975:Diazepam; D010100:Oxygen; D002045:Bupivacaine