Mogri Mohammed, Desai Himanshu, Webster Lynn, Grant Brydon J B, Mador M Jeffery
Department of Medicine, State University of New York at Buffalo, Buffalo, NY 14215, USA.
Sleep Breath. 2009 Mar;13(1):49-57. doi: 10.1007/s11325-008-0208-4. Epub 2008 Aug 6.
Animal models have shown a quantal slowing of respiratory pattern when exposed to opioid agonist, in a pattern similar to that observed in central sleep apnea. We postulated that opioid-induced hypoventilation is more likely to be associated with sleep apnea rather than hypoventilation alone. Since we did not have a direct measure of hypoventilation we used hypoxemia as an indirect measure reasoning that significant hypoventilation would not occur in the absence of hypoxemia.
We conducted a retrospective analysis of 98 consecutive patients on chronic opioid medications who were referred for overnight polysomnography. All patients on chronic opioids seen in the chronic pain clinic were referred for a sleep study regardless of whether they had sleep symptoms or not. Sleep-related hypoxemia was defined as arterial oxyhemoglobin saturation of less than 90% for more than 5 min with a nadir of <or=85%, or greater than 30% of total sleep time at an oxyhemoglobin saturation of less than 90%.
Of the 98 patients, 36% (95% CI 26-46%) had obstructive sleep apnea, 24%, (95% CI 16-33%) had central sleep apnea, 21% (95% CI 14-31%) had combined obstructive and central sleep apnea, in 4% (95% CI 0-10%) sleep apnea was classified as indeterminate, and 15% (95% CI 9-24%) had no sleep apnea. Opioids were potentially responsible for hypoxemia during wakefulness in 10% of patients (95% CI 5-18%) and for hypoxemia during sleep not clearly associated with apneas/hypopneas in 8% of patients (95% CI 4-15%). Two patients (2%, 95% CI 0-7%) had sleep-related hypoxemia in the absence of sleep apnea or hypoxemia during wakefulness.
Patients on chronic opiate therapy for chronic pain have an extremely high prevalence of sleep apnea and nocturnal hypoxemia. Hypoxemia can occur during quiet wakefulness in patients on chronic opioid medications with and without sleep apnea. In patients on chronic opioid therapy, isolated nocturnal hypoxemia without coexisting sleep apnea or daytime hypoxemia is very uncommon.
动物模型显示，暴露于阿片类激动剂时呼吸模式会出现量子性减慢，其模式类似于中枢性睡眠呼吸暂停中观察到的模式。我们推测，阿片类药物引起的通气不足更可能与睡眠呼吸暂停相关，而非单纯的通气不足。由于我们没有直接测量通气不足的方法，因此我们使用低氧血症作为间接测量指标，理由是在没有低氧血症的情况下不会发生明显的通气不足。
我们对98例连续接受慢性阿片类药物治疗并被转诊进行夜间多导睡眠图检查的患者进行了回顾性分析。慢性疼痛诊所中所有接受慢性阿片类药物治疗的患者，无论是否有睡眠症状，均被转诊进行睡眠研究。与睡眠相关的低氧血症定义为动脉血氧血红蛋白饱和度低于90%持续超过5分钟，最低点≤85%，或在血氧血红蛋白饱和度低于90%时占总睡眠时间的30%以上。
98例患者中，36%（95%可信区间26 - 46%）患有阻塞性睡眠呼吸暂停，24%（95%可信区间16 - 33%）患有中枢性睡眠呼吸暂停，21%（95%可信区间14 - 31%）患有阻塞性和中枢性混合性睡眠呼吸暂停，4%（95%可信区间0 - 10%）的睡眠呼吸暂停分类不明确，15%（95%可信区间9 - 24%）没有睡眠呼吸暂停。阿片类药物可能导致10%的患者（95%可信区间5 - 18%）清醒时出现低氧血症，8%的患者（95%可信区间4 - 15%）睡眠时出现与呼吸暂停/低通气无明显关联的低氧血症。两名患者（2%，95%可信区间0 - 7%）在没有睡眠呼吸暂停或清醒时低氧血症的情况下出现了与睡眠相关的低氧血症。
接受慢性阿片类药物治疗慢性疼痛的患者睡眠呼吸暂停和夜间低氧血症的患病率极高。在有或没有睡眠呼吸暂停的慢性阿片类药物治疗患者中，安静清醒时可能会出现低氧血症。在接受慢性阿片类药物治疗的患者中，孤立的夜间低氧血症且无并存的睡眠呼吸暂停或白天低氧血症非常罕见。
