Management of acetaminophen (paracetamol) poisoning in children and adolescents
- Kennon Heard, MD
Kennon Heard, MD
- Professor of Emergency Medicine
- University of Colorado School of Medicine
- Richard Dart, MD, PhD
Richard Dart, MD, PhD
- Director of Rocky Mountain Poison & Drug Center
- University of Colorado School of Medicine
- Section Editor
- Michele M Burns, MD, MPH
Michele M Burns, MD, MPH
- Section Editor — Pediatric Toxicology
- Assistant Professor of Pediatrics
- Harvard Medical School
- Deputy Editor
- James F Wiley, II, MD, MPH
James F Wiley, II, MD, MPH
- Senior Deputy Editor — Adult and Pediatric Emergency Medicine
- Senior Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Clinical Professor of Pediatrics and Emergency Medicine/Traumatology
- University of Connecticut School of Medicine
Since its clinical introduction in 1950, acetaminophen (N-acetyl-p-aminophenol; APAP; paracetamol) has become the most widely used analgesic-antipyretic in the United States. The popularity of acetaminophen among pediatricians increased when concerns were raised about an association between aspirin and Reye's syndrome.
Acetaminophen is available in hundreds of over-the-counter and prescription medications. Although it is remarkably safe when used at therapeutic doses, overdose of acetaminophen has been recognized to cause fatal and nonfatal hepatic necrosis since 1966 . In addition, repeated supratherapeutic doses can cause hepatotoxicity in children with certain risk factors, including decreased oral intake [2-4].
The management of acetaminophen intoxication in children and adolescents will be presented here. The clinical manifestations and diagnosis of acetaminophen poisoning in children and the evaluation and management of acetaminophen poisoning in adults is discussed separately. (See "Clinical manifestations and diagnosis of acetaminophen (paracetamol) poisoning in children and adolescents" and "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis" and "Acetaminophen (paracetamol) poisoning in adults: Treatment".)
The initial management of acetaminophen poisoning in children and adolescents depends upon the type of exposure and the patient’s clinical status:
Exploratory ingestions in young children — These exposures usually involve small amounts of acetaminophen in an otherwise asymptomatic child. Hepatotoxicity is rare. Treatment consists of the following (see 'Management of acute poisoning' below):
- Davidson DG, Eastham WN. Acute liver necrosis following overdose of paracetamol. Br Med J 1966; 2:497.
- Sztajnkrycer MJ, Bond GR. Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Pediatr 2001; 13:177.
- Rivera-Penera T, Gugig R, Davis J, et al. Outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatotoxicity. J Pediatr 1997; 130:300.
- Heubi JE, Barbacci MB, Zimmerman HJ. Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J Pediatr 1998; 132:22.
- Wang GS, Monte A, Bagdure D, Heard K. Hepatic failure despite early acetylcysteine following large acetaminophen-diphenhydramine overdose. Pediatrics 2011; 127:e1077.
- Schwartz EA, Hayes BD, Sarmiento KF. Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. Ann Emerg Med 2009; 54:421.
- Woodhead JL, Howell BA, Yang Y, et al. An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury. J Pharmacol Exp Ther 2012; 342:529.
- Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012; 50:91.
- Dart RC, Rumack BH. Intravenous acetaminophen in the United States: iatrogenic dosing errors. Pediatrics 2012; 129:349.
- Gray T, Hoffman RS, Bateman DN. Intravenous paracetamol--an international perspective of toxicity. Clin Toxicol (Phila) 2011; 49:150.
- Beringer RM, Thompson JP, Parry S, Stoddart PA. Intravenous paracetamol overdose: two case reports and a change to national treatment guidelines. Arch Dis Child 2011; 96:307.
- Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev 2006; :CD003328.
- Buckley NA, Whyte IM, O'Connell DL, Dawson AH. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. J Toxicol Clin Toxicol 1999; 37:753.
- Spiller HA, Winter ML, Klein-Schwartz W, Bangh SA. Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. J Emerg Med 2006; 30:1.
- Spiller HA, Krenzelok EP, Grande GA, et al. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med 1994; 23:519.
- Underhill TJ, Greene MK, Dove AF. A comparison of the efficacy of gastric lavage, ipecacuanha and activated charcoal in the emergency management of paracetamol overdose. Arch Emerg Med 1990; 7:148.
- Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319:1557.
- Prescott LF. Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. Arch Intern Med 1981; 141:386.
- Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991; 303:1026.
- Harrison PM, Keays R, Bray GP, et al. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet 1990; 335:1572.
- Harrison PM, Wendon JA, Gimson AE, et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991; 324:1852.
- Daly FF, Fountain JS, Murray L, et al. Guidelines for the management of paracetamol poisoning in Australia and New Zealand--explanation and elaboration. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. Med J Aust 2008; 188:296.
- Tucker JR. Late-presenting acute acetaminophen toxicity and the role of N-acetylcysteine. Pediatr Emerg Care 1998; 14:424.
- Kanter MZ. Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning. Am J Health Syst Pharm 2006; 63:1821.
- www.acetadote.net (Accessed on June 04, 2009).
- Dawson AH, Henry DA, McEwen J. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust 1989; 150:329.
- Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med 1998; 31:710.
- Yip L, Dart RC. A 20-hour treatment for acute acetaminophen overdose. N Engl J Med 2003; 348:2471.
- Wallace CI, Dargan PI, Jones AL. Paracetamol overdose: an evidence based flowchart to guide management. Emerg Med J 2002; 19:202.
- Whyte IM, Buckley NA, Reith DM, et al. Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII. Ther Drug Monit 2000; 22:742.
- Wu ML, Tsai WJ, Deng JF, Yang CC. Hemodialysis as adjunctive therapy for severe acetaminophen poisoning: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1999; 62:907.
- Marbury TC, Wang LH, Lee CS. Hemodialysis of acetaminophen in uremic patients. Int J Artif Organs 1980; 3:263.
- Mahadevan SB, McKiernan PJ, Davies P, Kelly DA. Paracetamol induced hepatotoxicity. Arch Dis Child 2006; 91:598.
- O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97:439.
- Kozer E, McGuigan M. Approaches toward repeated supratherapeutic doses of paracetamol in children: a survey of medical directors of poison centres in North America and Europe. Drug Saf 2002; 25:613.
- Anker AL, Smilkstein MJ. Acetaminophen. Concepts and controversies. Emerg Med Clin North Am 1994; 12:335.
- Smilkstein MJ. Acetaminophen. In: Goldfrank's Toxicologic Emergencies, Goldfrank LR, Flomenbaum NE, Lewin NA, et al. (Eds), Appleton & Lange, Stamford 1998. p.541.
- Bateman DN, Woodhouse KW, Rawlins MD. Adverse reactions to N-acetylcysteine. Hum Toxicol 1984; 3:393.
- Jones AL. Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol 1998; 36:277.
- Kozer E, Koren G. Management of paracetamol overdose: current controversies. Drug Saf 2001; 24:503.
- Kearns GL, Leeder JS, Wasserman GS. Acetaminophen intoxication during treatment: what you don't know can hurt you. Clin Pediatr (Phila) 2000; 39:133.
- Divoll M, Greenblatt DJ, Ameer B, Abernethy DR. Effect of food on acetaminophen absorption in young and elderly subjects. J Clin Pharmacol 1982; 22:571.
- Heubi JE, Bien JP. Acetaminophen use in children: more is not better. J Pediatr 1997; 130:175.
- Birmingham PK, Tobin MJ, Henthorn TK, et al. Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations. Anesthesiology 1997; 87:244.
- van Lingen RA, Deinum HT, Quak CM, et al. Multiple-dose pharmacokinetics of rectally administered acetaminophen in term infants. Clin Pharmacol Ther 1999; 66:509.
- Cullen S, Kenny D, Ward OC, Sabra K. Paracetamol suppositories: a comparative study. Arch Dis Child 1989; 64:1504.
- Henretig FM, Selbst SM, Forrest C, et al. Repeated acetaminophen overdosing. Causing hepatotoxicity in children. Clinical reports and literature review. Clin Pediatr (Phila) 1989; 28:525.
- Mofenson HC, McFee R, Caraccio T, Greensher J. Combined antipyretic therapy: another potential source of chronic acetaminophen toxicity. J Pediatr 1998; 133:712.
- Mayoral CE, Marino RV, Rosenfeld W, Greensher J. Alternating antipyretics: is this an alternative? Pediatrics 2000; 105:1009.
- Rosefsky JB. Alternating antipyretics: is this an alternative? Pediatrics 2001; 108:1236.
- Walker RJ. Paracetamol, nonsteroidal antiinflammatory drugs and nephrotoxicity. N Z Med J 1991; 104:182.
- Exploratory ingestions in young children
- Intentional ingestions
- Inappropriate therapeutic dosing
- Iatrogenic intravenous overdose
- MANAGEMENT OF ACUTE POISONING
- Gastrointestinal decontamination
- - Indications
- - Administration
- - Adverse reactions
- Anaphylaxis (anaphylactoid reaction)
- - Duration of treatment
- - Monitoring during treatment
- Other therapies
- Extracorporeal removal
- Liver transplantation
- MANAGEMENT OF CHRONIC POISONING
- RESUMING ACETAMINOPHEN THERAPY
- ADDITIONAL RESOURCES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS