Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats

Background. There is evidence from animal studies suggesting the existence of a ceiling effect for buprenorphine-induced respiratory depression. To study whether an apparent ceiling effect exists for respiratory depression induced by buprenorphine, we compared the respiratory effects of buprenorphine and fentanyl in humans and rats. Methods. In healthy volunteers, the opioids were infused i.v. over 90 s and measurements of minute ventilation at a fixed end-tidal Pco(2) of 7 kPa were obtained for 7 h. Buprenorphine doses were 0.7, 1.4, 4.3 and 8.6 μ g kg(-1) (n=20 subjects) and fentanyl doses 1.1, 2.1, 2.9, 4.3 and 7.1 μ g kg(-1) (n=21). Seven subjects received placebo. In rats, both opioids were infused i.v. over 20 min, and arterial Pco(2) was measured 5, 10, 15 and 20 min after the start of fentanyl infusion and 30, 150, 270 and 390 min after the start of buprenorphine infusion. Doses tested were buprenorphine 0, 100, 300, 1000 and 3000 μ g kg(-1) and fentanyl 0, 50, 68 and 90 μ g kg(-1). Results. In humans, fentanyl produced a dose-dependent depression of minute ventilation with apnoea at doses ≥ 2.9 μ g kg(-1); buprenorphine caused depression of minute ventilation which levelled off at doses ≥ 3.0 μ g kg(-1) to about 50% of baseline. In rats, the relationship of arterial Pco(2) and fentanyl dose was linear, with maximum respiratory depression at 20 min (maximum Pa-co2 8.0 kPa). Irrespective of the time at which measurements were obtained, buprenorphine showed a non-linear effect on Pa-co2, with a ceiling effect at doses > 1.4 μ g kg(-1). The effect on Pa-co2 was modest (maximum value measured, 5.5 kPa). Conclusions. Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.