EFFICACY OF ORAL N-ACETYLCYSTEINE IN THE TREATMENT OF ACETAMINOPHEN OVERDOSE - ANALYSIS OF THE NATIONAL MULTICENTER STUDY (1976 TO 1985)
EFFICACY OF ORAL N-ACETYLCYSTEINE IN THE TREATMENT OF ACETAMINOPHEN OVERDOSE - ANALYSIS OF THE NATIONAL MULTICENTER STUDY (1976 TO 1985)
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DOI：
10.1056/nejm198812153192401
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发表时间：
1988-12-15
影响因子：
158.5
通讯作者：
RUMACK, BH
中科院分区：
文献类型：
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作者：
SMILKSTEIN, MJ;KNAPP, GL;RUMACK, BH
在口服n -乙酰半胱氨酸作为对乙酰氨基酚中毒解毒剂的研究中，报告了11195例疑似对乙酰氨基酚过量的病例。我们描述了2540例对乙酰氨基酚摄入患者的结果，每公斤体重口服140毫克n -乙酰半胱氨酸，4小时后每公斤口服70毫克，每4小时增加17次剂量。根据患者的初始血浆对乙酰氨基酚浓度和摄入与治疗之间的时间间隔对患者进行分类分析。当n -乙酰半胱氨酸在摄入对乙酰氨基酚后10小时内开始治疗时，有可能存在肝毒性的患者中有6.1%发生肝毒性，而在摄入对乙酰氨基酚后10至24小时开始治疗的患者中有26.4%发生肝毒性。在服用过量对乙酰氨基酚16至24小时后接受治疗的高危患者中，41%的人出现肝毒性，这一比例低于历史对照组。在对乙酰氨基酚摄入后8小时内给予n -乙酰半胱氨酸，无论初始血浆对乙酰氨基酚浓度如何，都具有保护作用。n -乙酰半胱氨酸在摄入后0至4小时或4至8小时开始治疗，结果没有差异，但疗效随着进一步延迟而下降。2540例患者中有11例死亡（0.43%）；在治疗前检测转氨酶的9例死亡病例中，在n -乙酰半胱氨酸开始治疗前，转氨酶升高。n -乙酰半胱氨酸在16小时内开始治疗的患者中，没有明显因对乙酰氨基酚引起的死亡。我们的结论是，n -乙酰半胱氨酸治疗应在对乙酰氨基酚过量后8小时内开始，但至少在摄入后24小时仍需要治疗。根据现有数据，72小时口服n -乙酰半胱氨酸方案与之前描述的20小时静脉注射方案一样有效，并且在延迟治疗时可能更优。
During the investigational use of oral N-acetylcysteine as an antidote for poisoning with acetaminophen, 11,195 cases of suspected acetaminophen overdose were reported. We describe the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Patients were categorized for analysis on the basis of initial plasma acetaminophen concentrations and the interval between ingestion and treatment. Hepatotoxicity developed in 6.1 percent of patients at probable risk when N-acetylcysteine was started within 10 hours of acetaminophen ingestion and in 26.4 percent of such patients when therapy was begun 10 to 24 hours after ingestion. Among patients at high risk who were treated 16 to 24 hours after an acetaminophen overdose, hepatotoxicity developed in 41 percent-a rate lower than that among historical controls. When given within eight hours of acetaminophen ingestion, N-acetylcysteine was protective regardless of the initial plasma acetaminophen concentration. There was no difference in outcome whether N-acetylcysteine was started zero to four or four to eight hours after ingestion, but efficacy decreased with further delay. There were 11 deaths among the 2540 patients (0.43 percent); in the nine fatal cases in which aminotransferase was measured before treatment, values were elevated before N-acetylcysteine was started. No deaths were clearly caused by acetaminophen among patients in whom N-acetylcysteine therapy was begun within 16 hours. We conclude that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion. On the basis of available data, the 72-hour regimen of oral N-acetylcysteine is as effective as the 20-hour intravenous regimen described previously, and it may be superior when treatment is delayed.