Li Jiajing, Li Yihao, Zhong Min, Chen Hanli, Wang Ziyang, Wu Jianwei, Shi Yongyong
Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2025 Aug 25;16:1588978. doi: 10.3389/fphar.2025.1588978. eCollection 2025.
Acetaminophen, a widely used analgesic, has drawn attention for its potential to reduce oxidative stress through inhibiting lipid peroxidation and scavenging free radicals. Emerging evidence indicates that early acetaminophen administration might improve survival outcomes in surgical intensive care unit (SICU) patients. This study aims to explore the relationship between early acetaminophen use and mortality in this patient population.
We conducted a retrospective cohort analysis of adult SICU patients using the Medical Information Mart for Intensive Care (MIMIC-IV) database, which contains data on patients admitted between 2008 and 2019. The intervention cohort received acetaminophen within 48 h of ICU admission, while controls received no early acetaminophen. The primary endpoint was in-hospital mortality. We implemented 1:1 propensity score matching (PSM) to minimize selection bias and balance baseline characteristics between cohorts. Multivariable Cox regression models adjusted for residual confounding.
From 5,474 eligible patients, we generated balanced cohorts of 2,740 matched pairs. The acetaminophen group demonstrated significantly lower in-hospital mortality (11.4% vs 14.4%; adjusted HR 0.75, 95% CI 0.62-0.89, = 0.001) compared to controls. This mortality reduction persisted consistently through sensitivity analyses and subgroup evaluations. Notably, early acetaminophen administration associated with improved survival metrics across multiple timepoints: ICU mortality (adjusted HR 0.63, 0.48-0.82; = 0.001), 90-day mortality (adjusted HR 0.78, 0.66-0.92; = 0.004), and 180-day mortality (adjusted HR 0.78, 0.67-0.92; = 0.002). While no significant differences were observed in ICU or hospital length of stay between groups, early acetaminophen administration was linked to longer ICU-free days through day 28 ( = 0.71; = 0.022) and longer vasopressor-free days through day 28 ( = 0.77; = 0.012).
Early acetaminophen administration demonstrates independent associations with reduced in-hospital mortality and improved secondary clinical outcomes in surgical ICU populations. These findings highlight the need for prospective trials to confirm therapeutic efficacy and establish causal inference for this readily available pharmacologic intervention.
对乙酰氨基酚是一种广泛使用的镇痛药，因其通过抑制脂质过氧化和清除自由基来降低氧化应激的潜力而受到关注。新出现的证据表明，早期使用对乙酰氨基酚可能会改善外科重症监护病房（SICU）患者的生存结局。本研究旨在探讨该患者群体中早期使用对乙酰氨基酚与死亡率之间的关系。
我们使用重症监护医学信息集市（MIMIC-IV）数据库对成年SICU患者进行了一项回顾性队列分析，该数据库包含2008年至2019年期间入院患者的数据。干预队列在ICU入院后48小时内接受对乙酰氨基酚治疗，而对照组未早期使用对乙酰氨基酚。主要终点是住院死亡率。我们实施了1:1倾向评分匹配（PSM）以尽量减少选择偏倚并平衡队列之间的基线特征。多变量Cox回归模型对残余混杂因素进行了调整。
从5474名符合条件的患者中，我们生成了2740对匹配的平衡队列。与对照组相比，对乙酰氨基酚组的住院死亡率显著降低（11.4%对14.4%；调整后HR 0.75，95%CI 0.62 - 0.89，P = 0.001）。通过敏感性分析和亚组评估，这种死亡率降低一直持续。值得注意的是，早期使用对乙酰氨基酚与多个时间点的生存指标改善相关：ICU死亡率（调整后HR 0.63，0.48 - 0.82；P = 0.001）、90天死亡率（调整后HR 0.78，0.66 - 0.92；P = 0.004）和180天死亡率（调整后HR 0.78，0.67 - 0.92；P = 0.002）。虽然两组之间在ICU或住院时间方面未观察到显著差异，但早期使用对乙酰氨基酚与至第28天更长的无ICU天数（P = 0.71；P = 0.022）和至第28天更长的无血管活性药物天数（P = 0.77；P = 0.012）相关。
早期使用对乙酰氨基酚显示出与外科ICU患者住院死亡率降低和二级临床结局改善独立相关。这些发现凸显了进行前瞻性试验以确认治疗效果并为这种易于获得的药物干预建立因果推断的必要性。
