Intervention Review

Interventions for paracetamol (acetaminophen) overdose

  1. Jesper Brok1,*,
  2. Nick Buckley2,
  3. Christian Gluud1

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 19 APR 2006

Assessed as up-to-date: 21 FEB 2006

DOI: 10.1002/14651858.CD003328.pub2


How to Cite

Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003328. DOI: 10.1002/14651858.CD003328.pub2.

Author Information

  1. 1

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  2. 2

    University of NSW, Professorial Medicine Unit, POWH Clinical School, Randwick, NSW, Australia

*Jesper Brok, Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. jbrok@ctu.rh.dk. jesperb5@hotmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 APR 2006

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning.

Objectives

To assess the benefits and harms of interventions for paracetamol overdose.

Search methods

We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until December 2005.

Selection criteria

Randomised clinical trials and observational studies were included.

Data collection and analysis

The primary outcome measure was all-cause mortality plus liver transplantation. Secondary outcome measures were clinical symptoms, (eg, hepatic encephalopathy, fulminant hepatic failure), hepatotoxicity, adverse events, and plasma paracetamol concentration. We used Peto odds ratios and odds ratios with 95% confidence intervals (CI) for analysis of outcomes. Random- and fixed-effects meta-analyses were performed.

Main results

Ten small and low-methodological quality randomised trials, one quasi-randomised study, and 48 observational studies were identified. It was not possible to perform relevant meta-analyses of randomised trials that have addressed our outcome measures. Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the absorption of paracetamol, but the clinical benefit is unclear. Of these, activated charcoal seems to have the best risk-benefit ratio. N-acetylcysteine seems preferable to placebo/supportive treatment, dimercaprol, and cysteamine, but N-acetylcysteine's superiority to methionine is unproven. It is not clear which N-acetylcysteine treatment protocol offers the best efficacy. No strong evidence supports other interventions for paracetamol overdose. N-acetylcysteine may reduce mortality in patients with fulminant hepatic failure (Peto OR 0.26, 95% CI 0.09 to 0.94, one trial). Liver transplantation has the potential to be life saving in fulminant hepatic failure, but refinement of selection criteria for transplantation and long-term outcome reporting are required.

Authors' conclusions

Our results highlight a paucity of randomised trials on interventions for paracetamol overdose. Activated charcoal seems the best choice to reduce absorption. N-acetylcysteine should be given to patients with overdose but the selection criteria are not clear. No N-acetylcysteine regime has been shown to be more effective than any other. It is a delicate balance when to proceed to liver transplantation, which may be life-saving for patients with poor prognosis.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Evidence on interventions for paracetamol (acetaminophen) overdose patients is weak

Poisoning with paracetamol (acetaminophen) is a common cause of hepatic injury. The evidence for all interventions for paracetamol overdose is weak. Activated charcoal, gastric lavage, and ipecacuanha are able to reduce absorption of paracetamol if started within one to two hours of paracetamol ingestion, but the clinical benefit is unclear. Activated charcoal seems to be the best choice if the patient is compliant. N-acetylcysteine seems superior to no intervention and other antidotes (dimercaprol, cysteamine) and should be administered to patients at significant risk of hepatic damage. However, N-acetylcysteine superiority to methionine is unclear. Liver transplantation will clearly benefit patients with irreversible hepatic failure. However, identifying such patients early is problematic and the long-term outcomes in this group of patients have not been reported. Other interventions have not shown any clinical benefit for paracetamol overdose.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

Paracetamol(acetaminophen)過量的治療

paracetamol中毒在西方世界是一個造成肝臟毒性常見的原因。治療paraceTamol的方式有吸收的抑制,自血循系統的移除,解毒藥和肝臟移植。

目標

評估paracetamol過量各種治療的好處和害處。

搜尋策略

我們搜尋2005年12月以前的電子資料庫、手工尋找的書目和雜誌、試驗的作者、和醫藥公司的試驗。

選擇標準

包括隨機臨床試驗和觀察性研究。

資料收集與分析

主要結果的評估是所有的死亡原因和肝臟移植的情形。次要結果的評估是臨床的症狀,(例如,肝昏迷,猛暴性肝衰竭),肝臟毒性,不良事件和血漿paracetamol的濃度。我們使用Peto勝算比(odds ratio;OR)和其95%信賴區間(CI)來分析結果,然後做隨機和固定影響下的統合分析(metaanalyses)。

主要結論

我們找到10個小規模和低品質方法學的隨機試驗,一個類似隨機的研究,以及48個觀察性研究。此結果難以執行我們所要評量的隨機試驗統合分析。活性碳、胃洗滌、和ipecacuanha能降低paracetamol的吸收,但是臨床的好處並不清楚。在這些方法中,活性碳似乎有最好益害比(riskbenefit ratio)。Nacetylcysteine似乎優於安慰劑(支持性療法)、dimercaprol、和cysteamine,但是未能證實Nacetylcysteine是否優於methionine,也不清楚那一種Nacetylcysteine處理的療程會有最好的療效。沒有強烈的證據支持其他的方法可用於治療paracetamol過量。Nacetylcysteine可降低猛暴性肝衰竭病患的死亡率(Peto OR 0.26,95% CI 0.09 to 0.94,1個試驗)。肝臟移植有潛能成為猛暴性肝衰竭病患救命的方法,但是須要慎重考量肝臟移植病患的選擇標準和進一步評估長期的預後結果。

作者結論

我們的結果突顯了paracetamol過量的隨機試驗治療研究是稀少的。活性碳似乎是降低吸收最好的選擇。Nacetylcysteine 應該使用於paracetamol過量的病患,但是選擇標準並不清楚。沒有那一種Nacetylcysteine的處方療程被證明較有效。什麼時候著手肝臟移植來解救預後不佳的病患需要仔細的衡量。

翻譯人

本摘要由臺中榮民總醫院王建得翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

對於paracetamol (acetaminophen)過量的治療的證據是微弱的。paracetamol中毒是一個造成肝臟損傷常見的原因。對於所有paracetamol過量的治療的證據都是微弱的。假使在paracetamol食入1到2小時內使用活性碳,胃洗滌和ipecacuanha是能降低paracetamol的吸收,但是臨床的好處是不清楚的。假使病患順從良好,活性碳似乎是最好的選擇。Nacetylcysteine似乎優於無治療和其他的解毒劑(dimercaprol 和cysteamine),並且應給予有明顯風險會肝臟損傷的病患。但是Nacetylcysteine是否優於methionine並不清楚。很明確地肝臟移植將可以助益不可逆性肝衰竭的病人。然而,早期選擇出如此的病人是有困難的而且這群病人的長期預後還未被報告。其他的處置並沒有顯示對於paracetamol過量有任何臨床益處。