Department of Anesthesiology, Leiden University Medical Center, H5-Q, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Denmark.
Br J Anaesth. 2017 Dec 1;119(6):1169-1177. doi: 10.1093/bja/aex295.
There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.
Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.
All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).
In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.
目前临床上需要一些对呼吸抑制作用较小或无抑制作用的强效阿片类药物。在本研究中,我们比较了曲马多(一种μ-阿片受体激动剂和去甲肾上腺素再摄取抑制剂)和羟考酮(一种选择性μ-阿片受体激动剂)的呼吸效应。我们假设,与羟考酮 20mg 相比,曲马多 100mg 对呼吸控制的影响较小。
15 名健康志愿者被随机分为三组,分别接受口服曲马多(100mg 和 150mg)、羟考酮 20mg 或安慰剂即刻释放片的交叉双盲随机设计。研究的主要终点是治疗对呼吸性碱中毒时通气反应的影响和呼吸末二氧化碳分压(PCO2)为 7.3kPa(55mmHg,VE55)时的通气量;在药物摄入前和摄入后 6 小时评估 VE55。
三种治疗方法均对高碳酸血症的通气反应产生典型的阿片类药物效应:与反应斜率降低相关的右移。羟考酮 20mg 的呼吸抑制作用明显大于曲马多 100mg(平均差异-5.0L/min,95%置信区间:-7.1 至-2.9L/min,P<0.01),但与曲马多 150mg 相比无显著差异(羟考酮与曲马多 150mg:P>0.05)。
在这项探索性研究中,我们观察到曲马多和羟考酮均产生呼吸抑制作用。与羟考酮 20mg 相比,曲马多 100mg 但不是 150mg 具有适度的呼吸优势。需要进一步的研究来探索这些结果如何转化到临床环境中。