PDF(Pubmed)
Abstract：
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.
To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo.
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.
Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days.
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.
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.
Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients.
ClinicalTrials.gov Identifier: NCT04291508.
To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo.
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.
Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days.
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.
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.
Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients.
ClinicalTrials.gov Identifier: NCT04291508.
摘要：
■对乙酰氨基酚（扑热息痛）具有许多药理作用，可能对败血症有益，包括抑制无细胞血红蛋白诱导的脂质和其他底物的氧化。
■确定与安慰剂相比，对乙酰氨基酚在脓毒症中是否能增加存活和无器官功能障碍的天数。
■第2b阶段随机化，双盲,临床试验于2021年10月至2023年4月进行，随访90天。败血症和呼吸或循环器官功能障碍的成年人在36小时内被纳入40家美国学术医院的急诊科或重症监护病房。
■患者被随机分配给每6小时静脉注射1克对乙酰氨基酚或安慰剂治疗5天。
■主要终点是无器官支持的存活天数（机械通气，血管升压药,和肾脏替代疗法）至第28天。通过随机化前血浆无细胞血红蛋白水平高于10mg/dL来评估对乙酰氨基酚的治疗效果改变。
■纳入的447名患者(平均年龄，64[SD,15]年，51%女性,平均序贯器官衰竭评估[SOFA]评分，5.4[SD，2.5]),227人随机分配给对乙酰氨基酚，220人随机分配给安慰剂。对乙酰氨基酚是安全的，肝酶没有差异，低血压,或治疗臂之间的液体平衡。对乙酰氨基酚（20.2天；95％CI，18.8至21.6）与安慰剂（19.6天；95％CI，18.2至21.0；P=.56；差异，0.6；95%CI，-1.4至2.6）。在15个次要结果中，total,呼吸,对乙酰氨基酚组的凝血SOFA评分在第2天至第4天显著降低，7天内急性呼吸窘迫综合征的发生率也显著降低(2.2%vs8.5%对乙酰氨基酚vs安慰剂；P=0.01；差异，-6.3；95%CI，-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。
■静脉注射对乙酰氨基酚是安全的，但不能显著改善重症脓毒症患者的存活天数和无器官支持的天数。
■ClinicalTrials.gov标识符：NCT04291508。
■确定与安慰剂相比，对乙酰氨基酚在脓毒症中是否能增加存活和无器官功能障碍的天数。
■第2b阶段随机化，双盲,临床试验于2021年10月至2023年4月进行，随访90天。败血症和呼吸或循环器官功能障碍的成年人在36小时内被纳入40家美国学术医院的急诊科或重症监护病房。
■患者被随机分配给每6小时静脉注射1克对乙酰氨基酚或安慰剂治疗5天。
■主要终点是无器官支持的存活天数（机械通气，血管升压药,和肾脏替代疗法）至第28天。通过随机化前血浆无细胞血红蛋白水平高于10mg/dL来评估对乙酰氨基酚的治疗效果改变。
■纳入的447名患者(平均年龄，64[SD,15]年，51%女性,平均序贯器官衰竭评估[SOFA]评分，5.4[SD，2.5]),227人随机分配给对乙酰氨基酚，220人随机分配给安慰剂。对乙酰氨基酚是安全的，肝酶没有差异，低血压,或治疗臂之间的液体平衡。对乙酰氨基酚（20.2天；95％CI，18.8至21.6）与安慰剂（19.6天；95％CI，18.2至21.0；P=.56；差异，0.6；95%CI，-1.4至2.6）。在15个次要结果中，total,呼吸,对乙酰氨基酚组的凝血SOFA评分在第2天至第4天显著降低，7天内急性呼吸窘迫综合征的发生率也显著降低(2.2%vs8.5%对乙酰氨基酚vs安慰剂；P=0.01；差异，-6.3；95%CI，-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。
■静脉注射对乙酰氨基酚是安全的，但不能显著改善重症脓毒症患者的存活天数和无器官支持的天数。
■ClinicalTrials.gov标识符：NCT04291508。
