Paracetamol (acetaminophen) poisoning.
PubMedPublished 1 June 2002
Nicholas A. Buckley, Michael Eddleston
Citations52
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TL;DR
A systematic review of treatments for acute paracetamol poisoning finds information relating to the effectiveness and safety of the following interventions: activated charcoal, gastric lavage, ipecacuanha, liver transplant, methionine, N-acetylcysteine, and so on.
Abstract
In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal (single or multiple dose), gastric lavage, ipecacuanha, liver transplant, methionine, N-acetylcysteine.
Keywords
MedicinePharmacology, Toxicology and Pharmaceutics
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1,107 Citations1988Martin J. Smilkstein, Gary L. Knapp +2 more
It is concluded 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, and it may be superior when treatment is delayed.
HepatologyAASLD position paper
974 Citations2005Julie Polson, William M. Lee
These recommendations provide a data-supported approach based on formal review and analysis of recently-published world literature on the topic and the experience of the authors in the topic.
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Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose, and rates of deterioration and recovery of liver function were similar in the two groups.
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415 Citations1983L.F. Prescott
Cysteamine, methionine and N-acetylcysteine prevent liver damage, renal failure and death following paracetamol overdosage if given within 8 to 10 hours; treatment after 15 hours is of no benefit.
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390 Citations1999American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists
The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based.
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382 Citations1997Peter A. Chyka, Donna Seger
Single-dose activated charcoal should not be administered routinely in the management of poisoned patients and unless a patient has an intact or protected airway, the administration of charcoal is contraindicated.
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Gastric lavage should not be employed routinely in the management of poisoned patients unless a patient has ingested a potentially life-threatening amount of a poison and the procedure can be undertaken within 60 minutes of ingestion.
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248 Citations1973Russell Clark, V. Borirakchanyavat +5 more
Of a series of sixty patients admitted after paracetamol overdose, forty-nine developed liver damage, and twelve of these died from fulminant hepatic failure, and it is likely that the liver damage can be prevented only in the first 24 hours.
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244 Citations2003Laura P. James
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228 Citations2006Jesper Brok, Nicholas A. Buckley +1 more
A paucity of randomised trials on interventions for paracetamol overdose highlights the potential to be life saving in fulminant hepatic failure, but refinement of selection criteria for transplantation and long-term outcome reporting are required.
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Different prognostic criteria used to determine need for liver transplantation in patients with fulminant hepatic failure secondary to acetaminophen poisoning are compared to evaluate the efficacy of the APACHE II criteria.
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To test the hypothesis that administration of activated charcoal is as efficacious and safe as the combination regimen of gastric emptying plus charcoal in adults after acute oral overdose, a large number of patients receive treatment with activated charcoal.
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167 Citations1997D. Gunnell, Keith Hawton +5 more
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166 Citations2005Fergus Kerr, Andrew Dawson +6 more
This study confirmed that early treatment with N -acetylcysteine (within 8 hours of ingestion) is more effective than later treatment and demonstrated a reduction of drug-related adverse outcomes with the 60-minute infusion.
HepatologyUse and outcome of liver transplantation in acetaminophen-induced acute liver failure
165 Citations1998William Bernal, Julia Wendon +3 more
Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen‐induced hepatotoxicity, and for a substantial proportion of patients, transplantation was never an option because of the rapidity of clinical deterioration.
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146 Citations1996Keith Hawton, Christopher J. G. Ware +5 more
Establishing a maximum number of tablets (e.g. 25) that can be available in individual preparations is likely to reduce the dangers of paracetamol self-poisoning.
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130 Citations2001Lars E. Schmidt, Kim Dalhoff
Asthma must be considered a risk factor in the development of side-effects to N-acetylcysteine and there is no reason to withhold NAC from any patient with paracetamol poisoning.
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124 Citations1999Nicholas A. Buckley, Nicholas A. Buckley +3 more
A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N- acetylcysteine by charcoal and vomiting make intravenous N-acetylcy Steine preferable for most patients with acetaminophen poisoning.
Archives of Disease in ChildhoodParacetamol induced hepatotoxicity
109 Citations2005S. B. K. Mahadevan
Delayed presentation and/or delay in treatment, and hepatic encephalopathy ⩾grade III were significant risk factors, implying poor prognosis and need for OLT.
Journal of Toxicology Clinical ToxicologyActivated Charcoal Reduces the Need for<i>N</i>-Acetylcysteine Treatment After Acetaminophen (Paracetamol) Overdose
107 Citations1999Nicholas A. Buckley, Nicholas Buckley +3 more
In patients ingesting more, activated charcoal appears to reduce the number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for treatment and hospital stay.
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106 Citations2000Olga F. Woo, Paula D. Mueller +3 more
It is suggested that a shorter course of oral NAC therapy in patients who do not show evidence of hepatotoxicity within 36 hours of an acute acetaminophen overdose is safe and effective.
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99 Citations2003Louise Kao, Mark A. Kirk +4 more
Intravenous administration of an oral solution of N-acetylcysteine by the intravenous route is associated with a low rate of adverse events and should be considered for selected patients with suspected acetaminophen poisoning.
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97 Citations2000E. Martin Caravati
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It is indicated that 52 hours of intravenous NAC is as effective as 72 hours of oral NAC in treating acetaminophen poisoning.
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79 Citations2002Frank Vinholt Schiødt, Peter Ott +2 more
A plasma acetaminophen (INN, paracetamol) half‐life of more than 4 hours has been correlated with hepatotoxicity in acetaminphen overdosing not treated with an antidote.
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75 Citations2005Marco L.A. Sivilotti, Mark Yarema +3 more
The risk prediction instrument identifies a large group of low-risk patients for whom 20-hour intravenous N-acetylcysteine therapy is sufficient, and suggests that acute and chronic ethanol use dramatically influences acetaminophen toxicity.
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74 Citations2003Catherine L. Dorrington, David W. Johnson +1 more
Clinically significant complications associated with the use of multiple-dose activated charcoal occur infrequently and are judged to have had clinically significant pulmonary aspiration and gastrointestinal obstruction.
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71 Citations2005Griselda Cooper, David G. Le Couteur +2 more
Routine administration of charcoal following oral overdose did not significantly influence length of stay or other patient outcomes following oral drug overdose, and this does not exclude a role in patients who present shortly after ingestion of highly lethal drugs.
Liver TransplantationGc-Globulin and Prognosis in Acute Liver Failure
66 Citations2005Frank Vinholt Schiødt, Lorenzo Rossaro +4 more
It is demonstrated that Gc‐globulin has prognostic value in patients with non‐acetaminophen‐induced ALF, in the same range as the King's College criteria.
Journal of Public HealthImpact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study
64 Citations2005Oliver Morgan, Clare Griffiths +1 more
Between 1993 and 2002, mortality rates and hospital admissions due to paracetamol poisoning declined, however, the contribution of the 1998 regulations to this decline is not clear.
Journal of Public HealthRestricting paracetamol in the United Kingdom to reduce poisoning: a systematic review
64 Citations2004Oliver Morgan, Azeem Majeed
It is suggested that the 1998 regulations may have been associated with reduced admissions to liver units and liver transplants, reduced hospital attendance due to paracetamol poisoning and reduced sales of paracetAMol.
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52 Citations2002Laura P. James, Elayna Wells +2 more
All patients with an acute acetaminophen overdose should be observed and treated for at least 48 hours postingestion, and the best predictor of a low risk of toxicity was the presence of normal values for the PT, AST, or ALT within 48 hours of ingestion.
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45 Citations1996Daniel R. Douglas, James B. Sholal +1 more
The data suggest that, in most cases, the diagnostic approach to an overdose of ER APAP need not deviate from that used for an IR APAP overdose, and the need for an alternate poisoning screening strategy is not suggested.
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45 Citations1997Edward W Cetarukcol, Richard C. Dart +3 more
It is concluded that the elimination half-life of TER acetaminophen is similar to that reported in overdose of immediate-releaseacetaminophen overdose, and the use of a single 4-hour acetamophen determination may lead to failure to recognize patients with potentially toxic TER ingestion.
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38 Citations2006Eran Kozer, Revital Greenberg +2 more
This paper reviews the literature on chronic supratherapeutic paracetamol exposure in children and the different dosing guidelines and suggests the following approach: liver injury secondary to repeated dosing of par acetamol should be considered when a child has received more than 75 mg/kg/d for at least 2 d.
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28 Citations1999Robert O. Wright, Robert O. Wright +5 more
This study supports the efficacy of high-dose metoclopramide to prevent emesis after the oral loading dose of N-acetylcysteine.
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Although the formulations appear to have equal bioavailability, their half-lives and peak concentrations were significantly different and further study is required to determine whether these differences affect the assessment and management of poisoned patients.
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A convincing hepatoprotective effect of early i.v. cysteamine and oral methionine has been demonstrated in patients at risk of hepatic, renal, pancreatic or myocardial injury as a consequence of severe paracetamol overdosage.
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A case of fatal paracetamol (acetaminophen) poisoning in a 26-year-old woman who developed liver necrosis is described and the importance of continuing N-acetylcysteine treatment in spite of "safe" serum concentrations in the above cases is stressed.