对乙酰氨基酚减轻严重脓毒症氧化损伤的随机、安慰剂对照试验：减轻严重脓毒症氧化损伤的对乙酰氨基酚试验
Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial.
作者信息
Janz David R, Bastarache Julie A, Rice Todd W, Bernard Gordon R, Warren Melissa A, Wickersham Nancy, Sills Gillian, Oates John A, Roberts L Jackson, Ware Lorraine B
机构信息
1Section of Pulmonary and Critical Care Medicine, Department of Medicine, Louisiana State University School of Medicine, New Orleans, LA. 2Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN. 3Division of Clinical Pharmacology, Department of Internal Medicine, Vanderbilt University School of Medicine, Nashville, TN. 4Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN.
出版信息
Crit Care Med. 2015 Mar;43(3):534-41. doi: 10.1097/CCM.0000000000000718.
OBJECTIVES
This trial evaluated the efficacy of acetaminophen in reducing oxidative injury, as measured by plasma F2-isoprostanes, in adult patients with severe sepsis and detectable plasma cell-free hemoglobin.
DESIGN
Single-center, randomized, double-blind, placebo-controlled phase II trial.
SETTING
Medical ICU in a tertiary, academic medical center.
PATIENTS
Critically ill patients 18 years old or older with severe sepsis and detectable plasma cell-free hemoglobin.
INTERVENTIONS
Patients were randomized 1:1 to enteral acetaminophen 1 g every 6 hours for 3 days (n = 18) or placebo (n = 22) with the same dosing schedule and duration.
MEASUREMENTS AND MAIN RESULTS
F2-Isoprostanes on study day 3, the primary outcome, did not differ between acetaminophen (30 pg/mL; interquartile range, 24-41) and placebo (36 pg/mL; interquartile range, 25-80; p = 0.35). However, F2-isoprostanes were significantly reduced on study day 2 in the acetaminophen group (24 pg/mL; interquartile range, 19-36) when compared with placebo (36 pg/mL; interquartile range, 23-55; p = 0.047). Creatinine on study day 3, a secondary outcome, was significantly lower in the acetaminophen group (1.0 mg/dL; interquartile range, 0.6-1.4) when compared with that in the placebo (1.3 mg/dL; interquartile range, 0.83-2.0; p = 0.039). There was no statistically significant difference in hospital mortality (acetaminophen 5.6% vs placebo 18.2%; p = 0.355) or adverse events (aspartate aminotransferase or alanine aminotransferase > 400; acetaminophen 9.5% vs placebo 4.3%; p = 0.599).
CONCLUSIONS
In adults with severe sepsis and detectable plasma cell-free hemoglobin, treatment with acetaminophen within 24 hours of ICU admission may reduce oxidative injury and improve renal function. Additional study is needed to confirm these findings and determine the effect of acetaminophen on patient-centered outcomes.
目的
本试验评估了对乙酰氨基酚在降低氧化损伤方面的疗效，氧化损伤通过血浆F2-异前列腺素进行测量，研究对象为患有严重脓毒症且血浆中可检测到游离血红蛋白的成年患者。
设计
单中心、随机、双盲、安慰剂对照的II期试验。
地点
一家三级学术医疗中心的医学重症监护病房。
患者
年龄在18岁及以上、患有严重脓毒症且血浆中可检测到游离血红蛋白的重症患者。
干预措施
患者按1:1随机分组，一组每6小时口服1克对乙酰氨基酚，共3天（n = 18），另一组服用安慰剂（n = 22），给药方案和疗程相同。
测量指标及主要结果
主要结局指标为研究第3天的F2-异前列腺素水平，对乙酰氨基酚组（30 pg/mL；四分位间距，24 - 41）与安慰剂组（36 pg/mL；四分位间距，25 - 80；p = 0.35）之间无差异。然而，与安慰剂组（36 pg/mL；四分位间距，23 - 55；p = 0.047）相比，对乙酰氨基酚组在研究第2天F2-异前列腺素水平显著降低（24 pg/mL；四分位间距，19 - 36）。次要结局指标为研究第3天的肌酐水平，对乙酰氨基酚组（1.0 mg/dL；四分位间距，0.6 - 1.4）显著低于安慰剂组（1.3 mg/dL；四分位间距，0.83 - 2.0；p = 0.039）。住院死亡率（对乙酰氨基酚组5.6% vs安慰剂组18.2%；p = 0.355）或不良事件（天冬氨酸转氨酶或丙氨酸转氨酶>400；对乙酰氨基酚组9.5% vs安慰剂组4.3%；p = 0.599）无统计学显著差异。
结论
对于患有严重脓毒症且血浆中可检测到游离血红蛋白的成年人，在入住重症监护病房24小时内使用对乙酰氨基酚治疗可能会降低氧化损伤并改善肾功能。需要进一步研究以证实这些发现，并确定对乙酰氨基酚对以患者为中心的结局的影响。
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