Effects of intrathecal morphine on the ventilatory response to hypoxia.

Background: Intrathecal administration of morphine produces intense analges ia, but it depresses respiration, an effect that can be life-threatening. W hether intrathecal morphine affects the ventilatory response to hypoxia, ho wever, is not known. Methods: We randomly assigned 30 men to receive one of three study treatmen ts in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected d oses of intravenous and intrathecal morphine produce similar degrees of ana lgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pre ssures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma leve ls of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug adminis tration. Results: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation du ring the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minut e in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-mo rphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area unde r the curve) was significantly lower after either intravenous morphine (20. 2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=0.003). Twelv e hours after treatment, the ventilatory response to hypoxia in the intrath ecal-morphine group (19.9+/-8.9 liters per minute), but not in the intraven ous-morphine group (30.5+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 l iters per minute) (P=0.02 for intrathecal morphine vs. placebo). Plasma con centrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine t han after intravenous morphine. Conclusions: Depression of the ventilatory response to hypoxia after the ad ministration of intrathecal morphine is similar in magnitude to, but longer -lasting than, that after the administration of an equianalgesic dose of in travenous morphine.