本文由小咖机器人翻译整理

期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.8772

摘要内容如下：

重要性

对乙酰氨基酚（扑热息痛）具有许多可能对脓毒症有益的药理作用，包括抑制无细胞血红蛋白诱导的脂质和其他底物的氧化。

目的

确定与安慰剂相比，对乙酰氨基酚是否增加脓毒症患者的存活天数和无器官功能障碍天数。

设计、设置和参与者

2021年10月至2023年4月进行的2B期随机、双盲临床试验，随访90天。患有败血症和呼吸或循环器官功能障碍的成人在出现症状后36小时内在40家美国学术医院的急诊科或重症监护室登记。

干预

患者随机接受每6小时静脉注射1G对乙酰氨基酚或安慰剂治疗5天。

主要成果和措施

主要终点是存活天数和无器官支持（机械通气、血管升压药和肾脏替代治疗）至第28天。通过随机分组前血浆无细胞血红蛋白水平高于10 mg/DL来评估对乙酰氨基酚的治疗效果变化。

结果

在纳入的447例患者（平均年龄64[SD，15]岁，51%为女性，平均序贯器官衰竭评估[SOFA]评分5.4[SD，2.5]）中，227例随机接受对乙酰氨基酚治疗，220例接受安慰剂治疗。对乙酰氨基酚是安全的，治疗组之间的肝酶、低血压或液体平衡没有差异。到第28天，对乙酰氨基酚的存活天数和无器官支持的天数没有显著差异（20.2天；95%CI，18.8至21.6）与安慰剂（19.6天；95%可信区间为18.2~21.0；P=.56；差值，0.6；95%置信区间，-1.4至2.6）。在15项次要转归中，对乙酰氨基酚组第2天至第4天的总SOFA评分、呼吸和凝血功能评分显著较低，7天内急性呼吸窘迫综合征的发生率也显著较低（对乙酰氨基酚组为2.2%，安慰剂组为8.5%；P=.01；差值，-6.3；95%置信区间，-10.8至-1.8）。无细胞血红蛋白水平和对乙酰氨基酚之间没有显著的相互作用。

结论和相关性

静脉注射对乙酰氨基酚是安全的，但不能显著改善危重脓毒症患者的生存天数和无器官支持。

试用注册

ClinicalTrials.gov标识符：NCT04291508。

英文原文如下：

Abstracts

Importance  Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates.

Objective  To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo.

Design, Setting, and Participants  Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation.

Intervention  Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days.

Main Outcome and Measures  The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL.

Results  Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen.

Conclusions and Relevance  Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients.

Trial Registration  ClinicalTrials.gov Identifier: NCT04291508.

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。