Nunes Anthony P, Jung Heeyoon, Yuan Yiyang, Baek Jonggyu, Pawasauskas Jayne, Hume Anne L, Liu Shao-Hsien, Lapane Kate L
Department of Population and Quantitative Health Sciences, Division of Epidemiology, UMass Chan Medical School, Worcester, Massachusetts, USA.
Department of Population and Quantitative Health Sciences, Division of Biostatistics and Health Services Research, UMass Chan Medical School, Worcester, Massachusetts, USA.
J Am Geriatr Soc. 2025 May;73(5):1517-1527. doi: 10.1111/jgs.19417. Epub 2025 Mar 28.
For patients with continued pain while receiving an initial course of a short-acting opioid (SAO), clinicians may intensify the opioid regimen by escalating the SAO dose or initiating a long-acting opioid (LAO). The objective of this study was to assess the comparative safety of opioid intensification regimens in nursing home residents with nonmalignant pain.
We conducted a retrospective cohort analysis of US long-stay nursing home residents identified from the national Minimum Data Set (MDS) 3.0 and linked Medicare data, 2011-2016. Opioid regimen changes were assessed using Part D claims to identify dose escalation of SAO, adding LAO to SAO, or a switch from SAO to LAO. The outcomes of interest were hospitalized falls/fractures and delirium identified in the MDS or hospitalization. Resident attributes were described by opioid regimen. Hazard ratios of study outcomes were quantified using as-treated (primary analysis) and intent-to-treat (secondary analysis) doubly robust inverse probability of treatment (IPT) weighted Fine & Gray regression models with a competing risk of death.
In the as-treated analysis, relative to residents in the SAO escalation cohort, the hazard of delirium was elevated in the LAO cohorts (aHR [LAO switch]: 2.05, 95% CI: 1.57-2.67; aHR [LAO add-on]: 1.55, 95% CI: 1.23-1.96). Results for falls and fractures were inconclusive. We did not observe evidence of an association with falls and fractures in the primary as-treated analysis; however, the intent-to-treat analysis observed increased hazards in the LAO switch cohort relative to the SAO escalation cohort (aHR 2.86, 95% CI:1.64-4.99).
There is limited evidence to inform the clinical judgment between escalating the SAO dose or incorporating a LAO. Our study suggests increased risks of delirium in nursing home residents with nonmalignant pain when switching or adding an LAO to the opioid regimen relative to increasing the dose of SAOs.
对于在接受短效阿片类药物（SAO）初始疗程时仍持续疼痛的患者，临床医生可通过提高SAO剂量或开始使用长效阿片类药物（LAO）来强化阿片类药物治疗方案。本研究的目的是评估阿片类药物强化治疗方案在患有非恶性疼痛的养老院居民中的相对安全性。
我们对2011 - 2016年从国家最低数据集（MDS）3.0和相关医疗保险数据中识别出的美国长期居住养老院居民进行了回顾性队列分析。使用D部分索赔评估阿片类药物治疗方案的变化，以确定SAO剂量增加、SAO添加LAO或从SAO转换为LAO。感兴趣的结局是在MDS或住院治疗中确定的住院跌倒/骨折和谵妄。通过阿片类药物治疗方案描述居民特征。使用治疗后（主要分析）和意向性治疗（次要分析）双重稳健的逆概率治疗（IPT）加权Fine & Gray回归模型对研究结局的风险比进行量化，并考虑死亡的竞争风险。
在治疗后分析中，相对于SAO剂量增加队列中的居民，LAO队列中谵妄的风险升高（调整后风险比[LAO转换]：2.05，95%置信区间：1.57 - 2.67；调整后风险比[LAO添加]：1.55，95%置信区间：1.23 - 1.96）。跌倒和骨折的结果尚无定论。在主要的治疗后分析中，我们未观察到与跌倒和骨折相关的证据；然而，意向性治疗分析观察到LAO转换队列相对于SAO剂量增加队列的风险增加（调整后风险比2.86，95%置信区间：1.64 - 4.99）。
关于在提高SAO剂量或加入LAO之间进行临床判断的证据有限。我们的研究表明，与增加SAO剂量相比，在阿片类药物治疗方案中转换或添加LAO时，患有非恶性疼痛的养老院居民谵妄风险增加。
