A review of acetaminophen poisoning.

Acetaminophen poisoning remains one of the more common drugs taken in overdose with potentially fatal consequences. Early recognition and prompt treatment with N-acetylcysteine can prevent hepatic injury. With acute overdose, the Rumack-Matthew nomogram is a useful tool to assess risk and guide management. Equally common to acute overdose is the repeated use of excessive amounts of acetaminophen. Simultaneous ingestion of several different acetaminophen-containing products may result in excessive dosage. These patients also benefit from N-acetylcysteine. Standard courses of N-acetylcysteine may need to be extended in patients with persistently elevated plasma concentrations of acetaminophen or with signs of hepatic injury.

[1]  N. Majlesi,et al.  Comment on "Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose". , 2008, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[2]  Bond Gr,et al.  Population-based incidence and outcome of acetaminophen poisoning by type of ingestion. , 1999 .

[3]  R. Bellomo,et al.  Time to review the selection criteria for transplantation in paracetamol‐induced fulminant hepatic failure? , 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[4]  C. Lieber,et al.  Interaction of acute ethanol administration with acetaminophen metabolism and toxicity in rats fed alcohol chronically. , 1984, Alcoholism, clinical and experimental research.

[5]  P. Zhao,et al.  Effects of ethanol dose and ethanol withdrawal on rat liver mitochondrial glutathione: implication of potentiated acetaminophen toxicity in alcoholics. , 2002, Drug metabolism and disposition: the biological fate of chemicals.

[6]  N. Donaldson,et al.  Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study , 2002, The Lancet.

[7]  A. Makin,et al.  Paracetamol hepatotoxicity and alcohol consumption in deliberate and accidental overdose. , 2000, QJM : monthly journal of the Association of Physicians.

[8]  L. Yip,et al.  A 20-hour treatment for acute acetaminophen overdose. , 2003, The New England journal of medicine.

[9]  William M. Lee,et al.  False positive acetaminophen concentrations in patients with liver injury. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[10]  M. Mullins,et al.  Evaluation of a Simplified N-Acetylcysteine Dosing Regimen for the Treatment of Acetaminophen Toxicity , 2011, The Annals of pharmacotherapy.

[11]  I. Whyte,et al.  Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning? , 1999, Journal of toxicology. Clinical toxicology.

[12]  M. Hynninen,et al.  The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm , 2006, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[13]  D. Davidson Association of acetaminophen hepatotoxicity with fasting and ethanol use , 1995 .

[14]  Lewis S. Nelson,et al.  Hepatotoxicity despite early administration of intravenous N-acetylcysteine for acute acetaminophen overdose. , 2009, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[15]  I. Anderson,et al.  Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. , 2000, Annals of emergency medicine.

[16]  H. Jaeschke,et al.  Peroxynitrite Is a Critical Mediator of Acetaminophen Hepatotoxicity in Murine Livers: Protection by Glutathione , 2002, Journal of Pharmacology and Experimental Therapeutics.

[17]  E. Kuffner,et al.  Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial. , 2001, Archives of internal medicine.

[18]  K. Sathiyaraj,et al.  induced liver toxicity in albino rats , 2011 .

[19]  E. VargasCastrillón Drug-induced liver toxicity. , 2001 .

[20]  L. Prescott,et al.  Paracetamol Overdosage , 1983, Drugs.

[21]  A. Forbes,et al.  Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. , 1991, BMJ.

[22]  A. Proudfoot,et al.  TREATMENT OF PARACETAMOL (ACETAMINOPHEN) POISONING WITH N-ACETYLCYSTEINE , 1977, The Lancet.

[23]  K. Heard,et al.  Massive acetylcysteine overdose associated with cerebral edema and seizures , 2011, Clinical toxicology.

[24]  R. Cantor,et al.  Profound metabolic acidosis and oxoprolinuria in an adult , 2007, Journal of Medical Toxicology.

[25]  S. Thorgeirsson,et al.  Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. , 1974, Pharmacology.

[26]  R. Hoffman,et al.  Acetaminophen Overdose with Altered Acetaminophen Pharmacokinetics and Hepatotoxicity Associated with Premature Cessation of Intravenous N-Acetylcysteine Therapy , 2008, The Annals of pharmacotherapy.

[27]  B. Rumack Acetaminophen Hepatotoxicity: The First 35 Years , 2002, Journal of toxicology. Clinical toxicology.

[28]  P. Watkins,et al.  Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults , 2000, Clinical pharmacology and therapeutics.

[29]  L. Yip,et al.  Intravenous administration of oral N-acetylcysteine. , 1998, Critical care medicine.

[30]  P. Stoddart,et al.  Intravenous paracetamol overdose: two case reports and a change to national treatment guidelines , 2010, Archives of Disease in Childhood.

[31]  M. Kirk,et al.  What is the rate of adverse events after oral N-acetylcysteine administered by the intravenous route to patients with suspected acetaminophen poisoning? , 2003, Annals of emergency medicine.

[32]  K. Dalhoff,et al.  Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning. , 2008, British journal of clinical pharmacology.

[33]  G. Alexander,et al.  Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. , 1991, The New England journal of medicine.

[34]  G. O’Malley,et al.  Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. , 2004, Annals of emergency medicine.

[35]  D. Magid Acetaminophen overdose: A 48-hour intravenous N-acetylcysteine treatment protocol , 1992 .

[36]  B. Sproule,et al.  The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol – a randomized study , 2010, Alimentary pharmacology & therapeutics.

[37]  William M. Lee,et al.  Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. , 2006, Gastroenterology.

[38]  William M. Lee,et al.  Acetaminophen‐induced acute liver failure: Results of a United States multicenter, prospective study , 2005, Hepatology.

[39]  E. Kuffner,et al.  Treatment of Pain or Fever with Paracetamol (Acetaminophen) in the Alcoholic Patient: A Systematic Review , 2000, American journal of therapeutics.

[40]  R Williams,et al.  Early indicators of prognosis in fulminant hepatic failure. , 1989, Gastroenterology.

[41]  R. Clark,et al.  A retrospective evaluation of shortened-duration oral N-acetylcysteine for the treatment of acetaminophen poisoning , 2009, Journal of Medical Toxicology.

[42]  L. Prescott Paracetamol overdosage. Pharmacological considerations and clinical management. , 1983, Drugs.

[43]  K. Heard,et al.  Clinical course of repeated supratherapeutic ingestion of acetaminophen , 2011, Clinical toxicology.

[44]  L. Prescott,et al.  Plasma-paracetamol half-life and hepatic necrosis in patients with paracetamol overdosage. , 1971, Lancet.

[45]  W. Waring,et al.  Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose. , 2008, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[46]  L. Prescott Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. , 1981, Archives of internal medicine.

[47]  L. Prescott,et al.  Unusual complications of paracetamol poisoning. , 1997, QJM : monthly journal of the Association of Physicians.

[48]  W. Waring,et al.  Lower incidence of anaphylactoid reactions to N-acetylcysteine in patients with high acetaminophen concentrations after overdose , 2008, Clinical toxicology.

[49]  T. Siu,et al.  Persistently increased acetaminophen concentrations in a patient with acute liver failure. , 2011, Clinical chemistry.

[50]  G. Hall,et al.  MALIGNANT HYPERTHERMIA: A HUMAN AND PORCINE STRESS SYNDROME? , 1975, The Lancet.

[51]  C. Zwingmann,et al.  Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N‐acetylcysteine , 2010, Hepatology.

[52]  William M. Lee,et al.  Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States , 2002, Annals of Internal Medicine.

[53]  J. Clements,et al.  Clinical Pharmacokinetics of Paracetamol , 1982, Clinical pharmacokinetics.

[54]  D. Reith,et al.  Acetaminophen Causes an Increased International Normalized Ratio by Reducing Functional Factor VII , 2000, Therapeutic drug monitoring.

[55]  F. Larsen,et al.  MELD score as a predictor of liver failure and death in patients with acetaminophen‐induced liver injury , 2007, Hepatology.

[56]  A. Y. Lu,et al.  N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[57]  W. Waring,et al.  Delayed onset of acute renal failure after significant paracetamol overdose: A case series , 2010, Human & experimental toxicology.

[58]  M. Rela,et al.  Use and outcome of liver transplantation in acetaminophen‐induced acute liver failure , 1998, Hepatology.

[59]  G. Bond,et al.  Acetaminophen ingestion in childhood--cost and relative risk of alternative referral strategies. , 1994, Journal of toxicology. Clinical toxicology.

[60]  P. Dargan,et al.  Fatal anaphylactoid reaction to N-acetylcysteine: caution in patients with asthma , 2002, Emergency medicine journal : EMJ.

[61]  P. Blanc,et al.  Early metabolic acidosis and coma after acetaminophen ingestion. , 1999, Annals of emergency medicine.

[62]  A. Woolf,et al.  Acetaminophen Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management , 2006, Clinical toxicology.

[63]  G. Bond,et al.  Population-based incidence and outcome of acetaminophen poisoning by type of ingestion. , 1999, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[64]  L. Prescott,et al.  Paracetamol, alcohol and the liver. , 2000, British journal of clinical pharmacology.

[65]  B. Bailey,et al.  Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death. , 2004, Annals of Emergency Medicine.

[66]  I. Whyte,et al.  The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine. , 2005, Annals of emergency medicine.

[67]  K. Olson,et al.  Value of rapid screening for acetaminophen in all patients with intentional drug overdose. , 1989, Annals of emergency medicine.

[68]  Edward W Cetarukcol,et al.  Tylenol Extended Relief Overdose , 1997 .

[69]  E. Caravati Unintentional Acetaminophen Ingestion in Children and the Potential For Hepatotoxicity , 2000, Journal of toxicology. Clinical toxicology.

[70]  C. Burke,et al.  Bactrian (“Double Hump”) Acetaminophen Pharmacokinetics: A Case Series and Review of the Literature , 2010, Journal of Medical Toxicology.

[71]  J. Stockman,et al.  Aminotransferase Elevations in Healthy Adults Receiving 4 Grams of Acetaminophen Daily: A Randomized Controlled Trial , 2008 .

[72]  C. Lieber,et al.  Alcohol and the Liver , 1992 .

[73]  L. Sung,et al.  Dilution of intravenous N-acetylcysteine as a cause of hyponatremia. , 1997, Pediatrics.

[74]  J. Lin,et al.  Sulfate depletion after acetaminophen administration and replenishment by infusion of sodium sulfate or N-acetylcysteine in rats. , 1981, Biochemical pharmacology.

[75]  J. Stockman Acute Liver Failure in Children: The First 348 Patients in the Pediatric Acute Liver Failure Study Group , 2008 .

[76]  J. Critchley,et al.  Intravenous N-acetylcysteine: still the treatment of choice for paracetamol poisoning. , 1979, British medical journal.

[77]  J. Mitchell,et al.  Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. , 1983, The Journal of clinical investigation.

[78]  B. Rumack,et al.  Acetaminophen poisoning and toxicity. , 1975, Pediatrics.

[79]  R. Shih,et al.  Tylenol Extended Relief overdose. , 1997, Annals of emergency medicine.

[80]  E. Schwartz,et al.  Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. , 2009, Annals of emergency medicine.

[81]  R. Clark,et al.  A prospective evaluation of shortened course oral N-acetylcysteine for the treatment of acute acetaminophen poisoning. , 2007, Annals of emergency medicine.

[82]  C. Gelotte,et al.  Aminotransferase activities in healthy subjects receiving three-day dosing of 4, 6, or 8 grams per day of acetaminophen , 2007, Clinical toxicology.

[83]  L F Prescott,et al.  Kinetics and metabolism of paracetamol and phenacetin. , 1980, British journal of clinical pharmacology.

[84]  R. Chang,et al.  Earlier identification of patients at risk from acetaminophen-induced acute liver failure. , 1998, Critical care medicine.

[85]  F. Bendtsen,et al.  Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury , 2002, The Lancet.

[86]  R. Dart,et al.  The Safety Profile of Sustained Release Paracetamol During Therapeutic Use and Following Overdose , 2005, Drug safety.

[87]  A. Singer,et al.  The temporal profile of increased transaminase levels in patients with acetaminophen-induced liver dysfunction. , 1995, Annals of emergency medicine.

[88]  J. Neuberger,et al.  Early indicators of prognosis in fulminant hepatic failure: an assessment of the King's criteria. , 1997, Journal of hepatology.

[89]  J T Slattery,et al.  Dose‐dependent pharmacokinetics of acetaminophen: Evidence of glutathione depletion in humans , 1987, Clinical pharmacology and therapeutics.

[90]  H. Spiller,et al.  Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. , 2006, The Journal of emergency medicine.

[91]  A. Woolf,et al.  Effect of metoclopramide dose on preventing emesis after oral administration of N-acetylcysteine for acetaminophen overdose. , 1999, Journal of toxicology. Clinical toxicology.

[92]  R. Hoffman,et al.  Intravenous paracetamol – an international perspective of toxicity , 2011, Clinical toxicology.

[93]  J. Coulson,et al.  Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine , 2010, Clinical toxicology.

[94]  Dean P. Jones,et al.  Mechanisms of pathogenesis in drug hepatotoxicity putting the stress on mitochondria. , 2010, Molecular interventions.

[95]  R. Clark,et al.  Prospective evaluation of mild to moderate pediatric acetaminophen exposures. , 2000, Annals of emergency medicine.

[96]  D. Spyker,et al.  2009 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual Report , 2010, Clinical toxicology.

[97]  Trends in Outpatient Prescription Drug Use and Related Costs in the US , 2012, PharmacoEconomics.

[98]  B. Bailey,et al.  Management of anaphylactoid reactions to intravenous N-acetylcysteine. , 1998, Annals of emergency medicine.

[99]  K. Olson,et al.  Massive acetaminophen ingestion with early metabolic acidosis and coma: treatment with IV NAC and continuous venovenous hemodiafiltration , 2010, Clinical toxicology.

[100]  D. Amre,et al.  Fulminant hepatic failure secondary to acetaminophen poisoning: A systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation , 2003, Critical care medicine.

[101]  K. Dalhoff,et al.  Serum phosphate is an early predictor of outcome in severe acetaminophen‐induced hepatotoxicity , 2002, Hepatology.

[102]  J. Schweinle,et al.  Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6-12 months) safety of acetaminophen in adult patients with osteoarthritis. , 2006, Clinical therapeutics.

[103]  J. Diamond,et al.  A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. , 1994, Annals of emergency medicine.

[104]  L. Hoegberg,et al.  Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication. , 2002, British journal of clinical pharmacology.

[105]  William M. Lee,et al.  Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. , 2009, Gastroenterology.

[106]  P. Bétrémieux,et al.  Intravenous propacetamol overdose in a term newborn , 2003, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[107]  L. Prescott Oral or intravenous N-acetylcysteine for acetaminophen poisoning? , 2005, Annals of emergency medicine.

[108]  R. Dart,et al.  Does Therapeutic Use of Acetaminophen Cause Acute Liver Failure? , 2007, Pharmacotherapy.

[109]  N. Kaplowitz,et al.  How to protect against acetaminophen: don't ask for JUNK. , 2008, Gastroenterology.

[110]  P. Zhao,et al.  Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver , 2002, Hepatology.

[111]  G. Knapp,et al.  Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985) , 1988, The New England journal of medicine.

[112]  B B Brodie,et al.  Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. , 1973, The Journal of pharmacology and experimental therapeutics.

[113]  S. Aks,et al.  Late increase in acetaminophen concentration after overdose of Tylenol Extended Relief. , 1996, Annals of emergency medicine.

[114]  J. Wendon,et al.  More on serum phosphate and prognosis of acute liver failure , 2003, Hepatology.

[115]  P. Dargan,et al.  Measuring plasma paracetamol concentrations in all patients with drug overdose or altered consciousness: Does it change outcome? , 2001, Emergency medicine journal : EMJ.

[116]  J. Neuberger,et al.  Blood lactate but not serum phosphate levels can predict patient outcome in fulminant hepatic failure , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[117]  Roger Williams,et al.  A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987-1993). , 1995, Gastroenterology.

[118]  G. Alexander,et al.  Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine , 1990, The Lancet.