Dose-dependent effects of nalbuphine in canine hemorrhagic shock

We noted the effects of the mixed opiate agonist/antagonist nalbuphine on cardiovascular function and survival in canine hemorrhagic shock. Anesthetized adult mongrel dogs were bled to a mean arterial pressure (MAP) of 45 mmHg, which was maintained with a reservoir for 1 hr before the reservoir was clamped and the animals treated with 0.9% NaCl as a control or nalbuphine at various doses. Shed blood was reinfused 1 hr after the reservoir was clamped, and survival was followed for three days. Nalbuphine at 1-4 mg/kg bolus plus 1-4 mg/kg hr infusion intravenously for 3.5 hr increased MAP, cardiac output, left ventricular contractility, heart rate, and survival. At doses above 8 mg/kg plus 8 mg/kg hr nalbuphine had deleterious effects on these parameters and survival. These effects were dose-dependent and support the hypothesis that endorphins acting on opiate receptors contribute to the cardiovascular pathophysiology of canine hemorrhagic shock. Nalbuphine, furthermore, may be a logical alternative to naloxone, since its analgesic properties obviate the theoretical objection of enhanced pain perception with the use of naloxone in shock.