Do Formulation and Dose of Long-Term Opioid Therapy Contribute to Risk of Adverse Events among Older Adults?
Do Formulation and Dose of Long-Term Opioid Therapy Contribute to Risk of Adverse Events among Older Adults?
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长期阿片类药物治疗的配方和剂量是否会增加老年人发生不良事件的风险？
DOI：
10.1007/s11606-021-06792-8
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发表时间：
2022
影响因子：
5.7
通讯作者：
Yang,Yi
中科院分区：
文献类型：
--
作者：
Salkar,Monika;Ramachandran,Sujith;Bentley,JohnP;Eriator,Ike;McGwin,Gerald;Twyner,ChanningC;Yang,Yi
慢性非癌性疼痛（CNCP）在老年人中非常普遍，长期阿片类药物治疗（LTOT）已被用于治疗慢性疼痛。然而，LTOT在老年CNCP患者中的安全性尚不明确，有必要确定老年人阿片类药物相关不良事件的治疗相关危险因素。目的评价符合医疗保险条件的老年人LTOT阿片类药物剂量和处方与阿片类药物相关不良事件风险的关系。设计巢式病例对照研究。参与者为2012年至2016年期间在CNCP的90天内接受了bb30张阿片类药物处方的医疗保险受益人（N=35,189），总天数为>45天。本研究利用医疗保险5%的医疗和处方索赔数据。结局指标包括阿片类药物引起的呼吸抑制（OIRD）、阿片类药物过量、全因死亡率和复合结局（定义为前三种事件中任何一种的首次发生）。关键的独立变量是LTOT期间处方的阿片类药物配方和阿片类药物剂量（以吗啡毫克当量（MME）计量）。随访期间共观察到74例OIRD、133例用药过量、982例全因死亡和1122例复合结局事件。在未经调整的分析中，与短效（SA）阿片类药物相比，联合阿片类药物的使用（OR: 4.52 [95%CI: 1.51-13.47]）与OIRD显著相关。在校正分析中，与SA阿片类药物相比，阿片类药物相关不良事件与LA（过量OR: 13.00 [95%CI: 1.30-130.16]）和联合阿片类药物（过量OR: 6.27 [95%CI: 1.91-20.55]；死亡率OR: 2.75 [95%CI: 1.87-4.04]；复合OR: 2.82 [95%CI: 2.01-3.96]）的使用显著相关。与低于20 MME的平均剂量相比，结果与20 - 50 MME剂量（死亡率OR: 1.61 [95%CI: 1.24-2.10]；复合OR: 1.59 [95%CI: 1.26-2.01]）和50 MME剂量（死亡率OR: 1.99 [95%CI: 1.28-3.10]；复合OR: 2.09 [95%CI: 1.43-3.04]）显著相关。结论接受高剂量阿片类药物治疗的成人以及同时使用LA和SA阿片类药物的成人发生阿片类药物相关不良事件的风险增加，需要对患者进行密切监督。
BackgroundChronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults.ObjectiveTo evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT.DesignNested case-control study.ParticipantsOlder Medicare beneficiaries (N=35,189) who received>3 opioid prescriptions with a total days-supply of>45 days within a 90-day period for CNCP between 2012 and 2016.Main MeasuresThis study utilized Medicare 5% medical and prescription claims data. Outcome measures included opioid-induced respiratory depression (OIRD), opioid overdose, all-cause mortality, and a composite outcome, defined as the first occurrence of any of the previous three events. Key independent variables were opioid formulation and opioid dose (measured in morphine milligram equivalents (MME)) prescribed during LTOT.Key ResultsSeventy-four OIRD, 133 overdose, 982 all-cause mortality, and 1122 composite outcome events were observed during follow-up. In unadjusted analyses, the use of combination opioids (OR: 4.52 [95%CI: 1.51–13.47]) was significantly associated with OIRD compared to short-acting (SA) opioids. In adjusted analyses, opioid-related adverse events were significantly associated with the use of LA (overdose OR: 13.00 [95%CI: 1.30–130.16] and combination opioids (overdose OR: 6.27 [95%CI: 1.91–20.55]; mortality OR: 2.75 [95%CI: 1.87–4.04]; composite OR: 2.82 [95%CI: 2.01–3.96]) when compared to SA opioids. When compared to an average dose of less than 20 MME, outcomes were significantly associated with doses of 20–50 MME (mortality OR: 1.61 [95%CI: 1.24–2.10]; composite OR: 1.59 [95%CI: 1.26–2.01]) and >50 MME (mortality OR: 1.99 [95%CI: 1.28–3.10]; composite OR: 2.09 [95%CI: 1.43–3.04]).ConclusionsOlder adults receiving medically prescribed opioids at higher doses and those using LA and combination of LA and SA opioids are at increased risks for opioid-related adverse events, highlighting the need for close patient supervision.