Naloxone-induced and spontaneous reversal of depressed ventilatory responses to hypoxia during and after continuous infusion of remifentanil or alfentanil

Remifentanil is a new μ opioid analgesic of the synthetic phenylpiperidine class. It has an extremely short half-life (10-20 min) due to its breakdown by nonspecific estrases. We studied the effects of continuous infusion of remifentanil, compared with alfentanil, on the respiratory response to hypoxia. In addition, we examined the efficacy of naloxone to reverse remifentanil-mediated depression of respiration. Spontaneous recovery after the end of the infusion was also assessed. Twelve adult males participated in the study. On three sessions, separated by 7 to 14 days, the participants received continuous infusion over 240 min of alfentanil (0.5 μg/kg/min), remifentanil (0.025 μg/kg/min) or remifentanil (0.1 μg/kg/min). Naloxone (6 μg/kg) was given at 95 min. On a fourth session, remifentanil (0.1 μg/kg/min) was infused and placebo was given instead of naloxone. Base-line hypoxic challenge was induced at 30 min before starting the infusion. Eight hypoxic challenges were conducted at 10 min after starting the infusion and half-hourly thereafter. Two postinfusion challenges were performed at 250 and 280 min. The slope (liter/min/S(P)O₂) of the ventilatory response and the predicted ventilation at S(P)O₂ of 80% (V(E₈₀)) (liter/min) significantly decreased during the infusion with remifentanil and alfentanil. A significant difference was noted between the two doses of remifentanil. 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 associated with a prompt spontaneous recovery of the blunted hypoxic responses that was not detected with alfentanil. In conclusion, remifentanil induces significant depression in the hypoxic drive that appears to be reversed by naloxone in a dose-related fashion. In addition, spontaneous recovery after remifentanil infusion is much faster compared with alfentanil.