EFFECT OF NALBUPHINE HYDROCHLORIDE ON THE VENTILATORY AND OCCLUSION PRESSURE RESPONSES TO CARBON DIOXIDE IN VOLUNTEERS

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We studied the effect of nalbuphine on the ventilatory and occlusion pressure responses to carbon dioxide rebreathing in six healthy male volunteers (mean age 25.5 yr) in a single-blind laboratory study. On four separate days volunteers were assigned randomly to receive either placebo (0.9% sodium chloride) or three i.v. doses of nalbuphine (15, 30 and 60 mg 70 kg-1), followed 90 min later by naloxone 0.4 mg 70 kg-1. Duplicate rebreathing tests were performed and the mean intercept at PE'CO2 7 kPa and the slopes of the linear relationship between inspiratory minute ventilation (Vl) or occlusion pressure (P0.1) with PE'CO2 were measured. Nalbuphine significantly decreased the mean intercept of the Vl (P less than 0.01) and P0.1 (P less than 0.05) responses, but caused no changes in the slopes. No significant difference between the doses was noted, suggesting that an Effect maximum (E'max) for respiratory depression was reached with a dose of approximately 15 mg 70 kg-1. Naloxone was less effective in antagonizing the depression in Vl at the higher dose of nalbuphine. Similar P0.1 values were associated with the same inspiratory flow rate (1 litre s-1) before and after drug treatment, suggesting that nalbuphine acts centrally to depress ventilation. Sedation increased significantly following each dose of nalbuphine (P less than 0.001). No demonstrable difference between the doses was shown, suggesting an Effect maximum (E'max) for sedation was reached at about 15 mg 70 kg-1. Administration of nalbuphine was associated with pain at the injection site, dizziness, dreaming, nausea and vomiting. Cardiovascular stability was maintained in all subjects.