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EFFECT OF NALBUPHINE HYDROCHLORIDE ON THE VENTILATORY AND OCCLUSION PRESSURE RESPONSES TO CARBON DIOXIDE IN VOLUNTEERS
Authors:PUGH  G C; BROWN  D T; DRUMMOND  G B
Institution:Department of Anaesthetics, Royal Infirmary of Edinburgh Lauriston Place, Edinburgh EH3 9YW
Abstract:We studied the effect of nalbuphine on the ventilatory and occlusionpressure reponses to carbon dioxide rebreathing in six healthymale volunteers (mean age 25.5 yr) in a single-blind laboratorystudy. On four separate days volunteers were assigned randomlyto receive either placebo (0.9% sodium chloride) or three i.v.doses of nalbuphine (15, 30 and 60 mg 70 kg–1), followed90 min later by naloxone 0.4 mg 70 kg–1. Duplicate rebreathingtests were performed and the mean intercept at PE'co2 7 kPaand the slopes of the linear relationship between inspiratoryminute ventilation (Vl) or occlusion pressure (P0.1) with PE'co2were measured. Nalbuphine significantly decreased the mean interceptof the Vl (P < 0.01) and P0.1 (P < 0.05) responses, butcaused no changes in the slopes. No significant difference betweenthe doses was noted, suggesting that an Effect maximum (E'max)for respiratory depression was reached with a dose of approximately15 mg 70 kg–1. Naloxone was less effective in antagonizingthe depression in Vl at the higher dose of nalbuphine. SimilarP0.1 values were associated with the same inspiratory flow rate(1 litre s–1) before and after drug treatment, suggestingthat nalbuphine acts centrally to depress ventilation. Sedationincreased significantly following each dose of nalbuphine (P< 0.001). No demonstrable difference between the doses wasshown, suggesting an Effect maximum (E'max) for sedation wasreached at about 15 mg 70 kg–1. Administration of nalbuphinewas associated with pain at the injection site, dizziness, dreaming,nausea and vomiting. Cardiovascular stability was maintainedin all subjects.
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