背景:对阻塞性睡眠呼吸暂停(OSA)患者使用阿片类药物存在争议,因为人们认为它们对阿片类药物更敏感。然而,缺乏阿片类药物在OSA中作用的客观数据.我们检验了以下假设:与没有OSA的受试者相比,未经治疗的OSA受试者对阿片类药物的敏感性增加。或接受持续气道正压通气(CPAP)或双水平气道正压通气(BIPAP)治疗的OSA。
方法:这是一个单中心,无OSA受试者的前瞻性队列研究(n=20),未经处理的OSA(n=33),或治疗的OSA(n=21)。使用III型(家中)多导睡眠图验证了OSA的诊断。受试者接受阶梯式剂量瑞芬太尼输注(目标效应部位浓度为0.5、1、2、3、4ng/ml-1)。主要结果是瞳孔缩小(瞳孔面积分数变化),最敏感的阿片效应。次要结果是通气率,过期的二氧化碳,镇静,和热镇痛。
结果:未经治疗的OSA受试者(平均=0.51,95%置信区间[CI]0.41-0.61)和无OSA受试者(平均=0.49,95%CI0.36-0.62)之间的瞳孔缩小没有差异(平均差异=0.02,95%CI-0.18至0.22);在接受治疗的OSA受试者之间(平均=0.56,95%CI=0.16没有OSA的受试者之间没有显着差异,未经处理的OSA,和治疗OSA的通气率,过期的二氧化碳,镇静,或瑞芬太尼的热镇痛反应。OSA严重程度与阿片类药物作用的程度之间没有关系。
结论:阻塞性睡眠呼吸暂停和阻塞性睡眠呼吸暂停治疗都不影响对缩肌症的敏感性,镇静剂,镇痛药,或阿片类药物瑞芬太尼对清醒成人的呼吸抑制作用。这些结果挑战了阻塞性睡眠呼吸暂停中阿片类药物作用的传统观念。
背景:NCT02898792(clinicaltrials.gov)。
BACKGROUND: Opioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjects with untreated OSA have increased sensitivity to opioids compared with subjects without OSA, or with OSA treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP).
METHODS: This was a single-centre, prospective cohort study in subjects without OSA (n=20), with untreated OSA (n=33), or with treated OSA (n=21). OSA diagnosis was verified using type III (in-home) polysomnography. Subjects received a stepped-dose remifentanil infusion (target effect-site concentrations of 0.5, 1, 2, 3, 4 ng ml-1). Primary outcome was miosis (pupil area fractional change), the most sensitive opioid effect. Secondary outcomes were ventilatory rate, end-expired CO2, sedation, and thermal analgesia.
RESULTS: There were no differences in miosis between untreated OSA subjects (mean=0.51, 95% confidence interval [CI] 0.41-0.61) and subjects without OSA (mean=0.49, 95% CI 0.36-0.62) (mean difference=0.02, 95% CI -0.18 to 0.22); between treated OSA subjects (mean=0.56, 95% CI 0.43-0.68) and subjects without OSA (difference=0.07, 95% CI -0.16 to 0.29); or between untreated OSA and treated OSA (difference=-0.05, 95% CI -0.25 to 0.16). There were no significant differences between subjects without OSA, untreated OSA, and treated OSA in ventilatory rate, end-expired CO2, sedation, or thermal analgesia responses to remifentanil. There was no relationship between OSA severity and magnitude of opioid effects.
CONCLUSIONS: Neither obstructive sleep apnoea nor obstructive sleep apnoea treatment affected sensitivity to the miotic, sedative, analgesic, or respiratory depressant effects of the opioid remifentanil in awake adults. These results challenge conventional notions of opioid effects in obstructive sleep apnoea.
BACKGROUND: NCT02898792 (clinicaltrials.gov).