Anesthesiology
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Randomized Controlled Trial Clinical Trial
Prolonged antagonism of opioid action with intravenous nalmefene in man.
To identify the opioid antagonist activity of nalmefene and to determine its duration in man, six healthy male subjects were pretreated on separate days with a saline placebo, 0.5 mg, 1 mg, or 2 mg nalmefene intravenously in a randomized double-blind fashion. Opioid challenges with fentanyl, 2 micrograms/kg, then were administered 1, 2, 4, 6, and 8 h afterward. Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 rebreathing, while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test. ⋯ The antagonist effects of the lowest nalmefene dose, 0.5 mg, persisted for about 4 h, at which time VE60 was 64% of control. Fentanyl administration produced consistent increases in pain tolerance (44-55% above control) throughout the experiment. Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly.(ABSTRACT TRUNCATED AT 250 WORDS)