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Interaction of Intravenous Diazepam and Bupivacaine in Conscious Dogs
  1. Jean-Louis Gerard, M.D.,
  2. Jacques Duranteau, M.D.,
  3. Alain Edouard, M.D.,
  4. Riaz Ahmad, M.D. and
  5. Alain Berdeaux, M.D., PH.D.
  1. From the Département de Pharmacologie et d'Anesthésiologie, Université de Paris-Sud, Hopital de Bicétre, Le Kremlin Bicétre cedex, France.


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 μg/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 < 0.05) and LVdP/dt (+ 10%, p < 0.05). Diazepam decreased systemic vascular resistance (SVR; −16%, p < 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 < 0.05) and HR increased (+19%, p < 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.

  • Anesthetics
  • local
  • bupivacaine
  • toxicity
  • bupivacaine
  • benzodiazepines
  • diazepam

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