Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats
Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats
复制标题
DOI：
10.1093/bja/aei145
复制
发表时间：
2005-06-01
影响因子：
9.8
通讯作者：
Danhof, M
中科院分区：
文献类型：
--
作者：
Dahan, A;Yassen, A;Danhof, M
背景。有来自动物研究的证据表明，丁丙诺啡引起的呼吸抑制存在天花板效应。为了研究丁丙诺啡诱导的呼吸抑制是否存在明显的天花板效应，我们比较了丁丙诺啡和芬太尼对人体和大鼠的呼吸作用。健康志愿者在90 s内静脉注射阿片类药物，并在7 kPa的固定潮末Pco(2)下测量7 h的分钟通气量。丁丙诺啡剂量分别为0.7、1.4、4.3和8.6 μ g kg(-1) (n=20)，芬太尼剂量分别为1.1、2.1、2.9、4.3和7.1 μ g kg(-1) （n=21）。7名受试者接受安慰剂。大鼠分别静脉注射两种阿片类药物20 min，分别于芬太尼开始输注后5、10、15、20 min和丁丙诺啡开始输注后30、150、270、390 min测定动脉Pco(2)。试验剂量分别为丁丙诺啡0、100、300、1000、3000 μ g kg（-1）和芬太尼0、50、68、90 μ g kg（-1）。在人类中，芬太尼在剂量≥2.9 μ g kg（-1）时，对呼吸暂停的分钟通气产生剂量依赖性抑制；丁丙诺啡引起的分钟通气量下降，在剂量≥3.0 μ g kg（-1）时趋于稳定，约为基线的50%。大鼠动脉Pco(2)与芬太尼剂量呈线性关系，在20 min时出现最大呼吸抑制（最大Pa-co2 8.0 kPa）。无论何时获得测量结果，丁丙诺啡对Pa-co2的影响呈非线性，在剂量>时呈天花板效应；1.4 μ g kg（-1）。对Pa-co2的影响不大（测得最大值为5.5 kPa）。我们的数据证实了丁丙诺啡对呼吸抑制的天花板效应，而不是芬太尼。
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.