Effects of Fentanyl and Diazepam in Dogs Deprived of Autonomic Tone

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Abstract
In contrast to reports of the untoward hemodynamic effects of fentanyl and diazepam in intact organisms, we found that neither a bolus of 100 μg/kg fentanyl nor the addition of intravenous doses of diazepam, up to and including 1 mg/kg (cumulative dose 2 mg/kg) caused cardiovascular depression in 73 anesthetized dogs after elimination of their sympathetic and parasympathetic tone. There were no significant changes in mean arterial blood pressure, cardiac output, heart rate, peak left ventricular dP/dt, cardiac filling pressures, or systemic vascular resistance. Rapid bolus injection of 3 mg/kg diazepam (cumulative dose 5 mg/kg) caused a significant (P < 0.05) but transient (time to 50% recovery less than 2 min) decrease in systemic vascular resistance, blood pressure, and dP/dt. When corrected for pressure changed (dP/dt divided by simultaneous left ventricular pressure), the decrease in dP/dt did not attain statistical significance, nor did changes in cardiac output or filling pressures, even after this large dose of diazepam. We conclude that previously reported decreases in hemodynamic function in subjects with intact autonomic function after fentanyl alone, or after the combination of fentanyl and diazepam, are indirect in nature, that is, are caused by a centrally mediated decrease in vasoregulatory (mainly sympathetic) outflow from the central nervous system.