NALOXONE-INDUCED AND SPONTANEOUS REVERSAL OF DEPRESSED VENTILATORY RESPONSES TO HYPOXIA DURING AND AFTER CONTINUOUS-INFUSION OF REMIFENTANIL OR ALFENTANIL

Remifentanil is a new mu opioid analgesic of the synthetic phenylpiper idine class. It has an extremely short half-life (10-20 min) due to it s breakdown by nonspecific estrases. We studied the effects of continu ous infusion of remifentanil, compared with alfentanil, on the respira tory response to hypoxia. In addition, we examined the efficacy of nal oxone to reverse remifentanil-mediated depression of respiration. Spon taneous recovery after the end of the infusion was also assessed. Twel ve adult males participated in the study. On three sessions, separated by 7 to 14 days, the participants received continuous infusion over 2 40 min of alfentanil (0.5 mu g/kg/min), remifentanil (0.025 mu g/kg/mi n) or remifentanil (0.1 mu g/kg/min). Naloxone (6 mu g/kg) was given a t 95 min. On a fourth session, remifentanil (0.1 mu g/kg/min) was infu sed and placebo was given instead of naloxone. Base-line hypoxic chall enge was induced at 30 min before starting the infusion. Eight hypoxic challenges were conducted at 10 min after starting the infusion and h alf-hourly thereafter. Two postinfusion challenges were performed at 2 50 and 280 min. The slope (liter/min/SPO2) of the ventilatory response and the predicted ventilation at SPO2 of 80% (VE(80)) (liter/min) sig nificantly decreased during the infusion with remifentanil acid alfent anil, A significant difference was noted between the two doses of remi fentanil. Naloxone administration was associated with reversal of the depressed hypoxic responses during the infusion of alfentanil and the low dose of remifentanil. Termination of remifentanil infusion was ass ociated with a prompt spontaneous recovery of the blunted hypoxic resp onses that was not detected with alfentanil. In conclusion, remifentan il induces significant depression in the hypoxic drive that appears to be reversed by naloxone in a dose-related fashion. In addition, spont aneous recovery after remifentanil infusion is much faster compared wi th alfentanil.