初用阿片类药物的痴呆患者与非初用阿片类药物的痴呆患者起始使用阿片类药物后的短期死亡率：一项回顾性队列研究
Short-term mortality after opioid initiation among opioid-naïve and non-naïve patients with dementia: a retrospective cohort study.
作者信息
Hwang Yeon-Mi, Hah Jennifer M, Bramen Jennifer E, Hadlock Jennifer J, Hernandez-Boussard Tina
机构信息
Department of Medicine, School of Medicine, Stanford University, Palo Alto, CA, USA.
Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
出版信息
BMC Med. 2025 Jun 9;23(1):340. doi: 10.1186/s12916-025-04172-1.
BACKGROUND
In the ongoing opioid epidemic, the mortality risk of opioid initiation in patients with dementia or mild cognitive impairment (MCI) remains understudied despite their vulnerability. This study evaluates mortality risks associated with opioid exposure in patients diagnosed with dementia or MCI by comparing outcomes between the initiation and continuation groups.
METHODS
We conducted a retrospective cohort study using data from a Northern California academic healthcare system (Stanford Health Care Alliance; 2015/01/01-2024/07/31), including 27,757 patients aged 50-100 with dementia or MCI. Of these, 14,105 received opioids after diagnosis and were classified as initiation (opioid-naïve; n=9443) or continuation (non-naïve; n=4662) groups. Cox regression assessed 14-day mortality risk. Aalen's additive model examined time-varying impact up to 180 days. Potential causes of death were extracted from clinical notes using GPT-3.5-Turbo. We also analyzed an independent community healthcare system cohort (Providence Health & Service; n=208,306) from western US states (2015/01/01-2023/05/31) as a replication cohort.
RESULTS
In the primary cohort, 4.1% (572/14,105) of patients died within 14 days of opioid exposure. The initiation group had a significantly higher 14-day mortality risk than the continuation group (adjusted hazard ratio (aHR), 2.00 (1.59-2.52); P<0.0001). The replication cohort had a 14-day mortality rate of 6.2% (7022/113,343) with a smaller difference between the initiation (n=77,168) and continuation (n=36,175) groups (aHR 1.22 (1.16-1.30); P<0.0001). In both cohorts, elevated risk stabilized after day 30. In the primary cohort, respiratory conditions (62% vs. 48%, P<0.1), particularly pneumonia (38% vs. 19%, P<0.05), were more prevalent among the initiation group who died early.
CONCLUSIONS
Starting opioids in patients with dementia or MCI is associated with elevated short-term mortality risks, with the initiation group having twice the 14-day mortality risk in academic settings and a smaller but significant increase in community healthcare systems. The first 30 days after initiation represent a critical risk window, likely due to a lack of tolerance to opioid adverse effects. These findings underscore the need for cautious initiation, tailored follow-up protocols accounting for healthcare setting characteristics, and close monitoring during the first month in this vulnerable population.
背景
在持续的阿片类药物流行中，尽管痴呆症或轻度认知障碍（MCI）患者易受伤害，但开始使用阿片类药物对其死亡风险的研究仍不足。本研究通过比较起始组和持续组的结果，评估被诊断为痴呆症或MCI的患者使用阿片类药物后的死亡风险。
方法
我们进行了一项回顾性队列研究，使用来自北加利福尼亚学术医疗系统（斯坦福医疗联盟；2015年1月1日至2024年7月31日）的数据，包括27757名年龄在50至100岁之间患有痴呆症或MCI的患者。其中，14105名患者在诊断后使用了阿片类药物，并被分为起始组（未使用过阿片类药物；n = 9443）或持续组（曾使用过阿片类药物；n = 4662）。Cox回归评估14天的死亡风险。Aalen加法模型检查长达180天的时变影响。使用GPT-3.5-Turbo从临床记录中提取潜在死因。我们还分析了来自美国西部各州的一个独立社区医疗系统队列（普罗维登斯健康与服务；n = 208306）（2015年1月1日至2023年5月31日）作为复制队列。
结果
在主要队列中，4.1%（572/14105）的患者在使用阿片类药物后的14天内死亡。起始组的14天死亡风险显著高于持续组（调整后的风险比（aHR），2.00（1.59 - 2.52）；P < 0.0001）。复制队列的14天死亡率为6.2%（7022/113343），起始组（n = 77168）和持续组（n = 36175）之间的差异较小（aHR 1.22（1.16 - 1.30）；P < 0.0001）。在两个队列中，风险在第30天后趋于稳定。在主要队列中，呼吸系统疾病（62%对48%，P < 0.1），特别是肺炎（38%对19%，P < 0.05），在早期死亡的起始组中更为普遍。
结论
在痴呆症或MCI患者中开始使用阿片类药物与短期死亡风险升高相关，在学术环境中起始组的14天死亡风险是持续组的两倍，在社区医疗系统中虽差异较小但仍显著增加。开始使用阿片类药物后的前30天是关键的风险窗口期，可能是由于对阿片类药物不良反应缺乏耐受性。这些发现强调了在这一脆弱人群中谨慎起始、根据医疗环境特征制定个性化随访方案以及在第一个月密切监测的必要性。
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