Simpson Scott A, Zaccagni Hayden, Bichell David P, Christian Karla G, Mettler Bret A, Donahue Brian S, Roberts L Jackson, Pretorius Mias
1Department of Pediatrics, Vanderbilt University Medical School, Nashville, TN. 2Department of Cardiac Surgery, Vanderbilt University Medical School, Nashville, TN. 3Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN. 4Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN. 5Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Nashville, TN.
Pediatr Crit Care Med. 2014 Jul;15(6):503-10. doi: 10.1097/PCC.0000000000000149.
Hemolysis, occurring during cardiopulmonary bypass, is associated with lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass.
Single-center prospective randomized double-blinded study.
University-affiliated pediatric hospital.
Thirty children undergoing elective surgical correction of a congenital heart defect.
Patients were randomized to acetaminophen (OFIRMEV [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass.
Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes), and acute kidney injury were measured throughout the perioperative period. Cardiopulmonary bypass was associated with a significant increase in free hemoglobin (from a prebypass level of 9.8 ± 6.2 mg/dL to a peak of 201.5 ± 42.6 mg/dL postbypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans compared with placebo (p = 0.02 for effect of study drug). There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation. Acetaminophen did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney injury.
Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary bypass.
体外循环期间发生的溶血与脂质过氧化及术后急性肾损伤相关。对乙酰氨基酚可抑制血红素蛋白催化的脂质过氧化，在动物模型中可减轻横纹肌溶解诱导的急性肾损伤。这项初步研究检验了对乙酰氨基酚可减轻接受体外循环的儿童脂质过氧化这一假设。
单中心前瞻性随机双盲研究。
大学附属医院。
30名接受先天性心脏病择期手术矫正的儿童。
患者被随机分为每6小时接受一次对乙酰氨基酚（奥施康定[对乙酰氨基酚]注射液；加利福尼亚州圣地亚哥市凯登斯制药公司）或安慰剂治疗，共四剂，在体外循环开始前开始给药。
在围手术期全程测量溶血、脂质过氧化（异呋喃和F2-异前列腺素）及急性肾损伤的标志物。体外循环与游离血红蛋白显著增加相关（从体外循环前的9.8±6.2mg/dL水平升至体外循环后的峰值201.5±42.6mg/dL）。手术期间血浆和尿液中的异呋喃及F2-异前列腺素浓度显著增加。血浆异呋喃的增加幅度大于血浆F2-异前列腺素的增加幅度。与安慰剂相比，对乙酰氨基酚减轻了血浆异呋喃的增加（研究药物的效应p=0.02）。对乙酰氨基酚对血浆F2-异前列腺素或脂质过氧化的尿液标志物无显著影响。对乙酰氨基酚不影响术后肌酐、尿中性粒细胞明胶酶相关脂质运载蛋白或急性肾损伤的发生率。
儿童体外循环与溶血和脂质过氧化相关。对乙酰氨基酚减轻了血浆异呋喃浓度的增加。需要进一步研究以确定其他减轻或预防游离血红蛋白作用的疗法是否能更有效地抑制接受体外循环患者的脂质过氧化。
