History

Fact Explanation
Asymptomatic Patient can be asymptomatic for the 1st 24 hours. [4]
Nausea and or vomiting This is commonly seen within half an hour to 24hours. Commonly accompanied by fatigue and malaise. [4]
Diaphoresis Seen during the initial 24hours period. [4]
Symptoms of dehydration This may occur secondary to severe vomiting. Children often complain of thirst. Young children have reduced urine output and lethargy. [4]
Right upper quadrant abdominal pain [4] Children complain of right upper quadrant abdominal pain after 24 hours of ingestion and it may persist up to about 72 hours. [4]
Bleeding manifestations Coagulopathy occurs between 3 days to 5 days of intoxication. [4]
Confusion and coma Children may develop confusion which might progress to coma within 3 to 5 days of intoxication. [4]
History of accidental ingestion Young children may swallow the tablets if the paracitamol tablets are kept within children’s reach. [1]
Therapeutic misadventure Often parents give their children supra-therapeutic doses of paracitamol expecting a therapeutic benefit. This is commonly seen in infants. [1,4]
History of attempted suicide Older children may use high doses of paracitamol as a method of suicide. [1]
Symptoms of liver failure Paracitamol is hepatotoxic and symptoms of liver failure may develop after about 4 to 6 days of use. Both acute and long term intoxication can cause hepatotoxicity, however the cumulative dose of intoxication is important in predicting the degree of liver damage. [3]
Presence of risk factors of suicide Children with depression, or facing sudden stressful life events are at risk of deliberate self-harm and suicide. [2]
References
  1. SHEEN C.L.. Paracetamol toxicity: epidemiology, prevention and costs to the health-care system. [online] 2002 September, 95(9):609-619 [viewed 13 June 2014] Available from: doi:10.1093/qjmed/95.9.609
  2. HARRINGTON R.. Depression, suicide and deliberate self-harm in adolescence. [online] 2001 March, 57(1):47-60 [viewed 13 June 2014] Available from: doi:10.1093/bmb/57.1.47
  3. DE SILVA GD, GUNATILAKE MD, LAMABADUSURIYA SP. Abuse of paracetamol in childhood fever. Ceylon Med J [online] 1995 Mar, 40(1):46-7 [viewed 14 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7781100
  4. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute
  5. JAMES L. P.. ACETAMINOPHEN-INDUCED HEPATOTOXICITY. Drug Metabolism and Disposition [online] 2003 December, 31(12):1499-1506 [viewed 14 June 2014] Available from: doi:10.1124/dmd.31.12.1499

Examination

Fact Explanation
Signs during the stage 1 From half an hour of ingestion up to 24 hours is considered as the stage 1. During this period children may have insignificant examination findings. Some children may have evidence of dehydration due to recurrent vomiting. [1]
Stage 2 (24 to 72 hours) During the stage 2 of the paracitamol intoxication, children develop tenderness in the right hypochondrium. Hepatomegaly can also be detected. Tachycardia and hypotension are also seen during the second stage. [1]
Stage 3 (3 to 5 days) In the third stage, children develop jaundice, confusion and may progress to coma. Subcutaneous bleeding and mucosal bleeding are seen during the third stage of intoxication. [1]
Stage 4 (5 to 7 days) Children begin to recover during this stage. Often all the abnormal examination findings are returning to normal during this stage. [1]
References
  1. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute

Differential Diagnoses

Fact Explanation
Inborn errors of metabolism [1] Alpha 1-antitrypsin deficiency or fatty acid oxidation abnormalities are common congenital causes of acute hepatic injury.
Reye syndrome [1] This should be considered if a child is given aspirin. Children present with evidence of neurological dysfunction and hepatic failure. [2]
Hepatitis A, B, and C Can cause hepatic failure. [1]
Other infective causes of hepatitis Hepatitis can be caused by cytomegalovirus, Epstein-Barr virus, or varicella. [1] Cytomegalovirus hepatitis is common in immune-compromised children. [3]
Wilson disease Wilson disease presents with features of liver failure and neurological manifestations like chorea and parkinsonism. [4]
References
  1. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute
  2. HALL SM. Reye's syndrome and aspirin: a review. J R Soc Med [online] 1986 Oct, 79(10):596-598 [viewed 14 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1290500
  3. CYBULSKA PAULINA, NI ANDY, JIMENEZ-RIVERA CAROLINA. Viral Hepatitis: Retrospective Review in a Canadian Pediatric Hospital. ISRN Pediatrics [online] 2011 December, 2011:1-4 [viewed 14 June 2014] Available from: doi:10.5402/2011/182964
  4. MANOLAKI NINA, NIKOLOPOULOU GEORGIA, DAIKOS GEORGE L, PANAGIOTAKAKI ELENI, TZETIS MARIA, ROMA ELEFTHERIA, KANAVAKIS EMMANOUEL, SYRIOPOULOU VASSILIKI P. Wilson Disease in Children: Analysis of 57 Cases. Journal of Pediatric Gastroenterology and Nutrition [online] 2009 January, 48(1):72-77 [viewed 14 June 2014] Available from: doi:10.1097/MPG.0b013e31817d80b8

Investigations - for Diagnosis

Fact Explanation
Serum paracitamol levels This is helpful in diagnosing acute intoxication and should be done within 4 to 6 hours of ingestion. [1,2]
References
  1. RAMANAYAKE RP, JAYASINGHE LR, DE SILVA AH, WIJESINGHE WA, KANAGANAYAGAM N. Knowledge and Practices of Paracetamol Administration Among Caregivers of Pediatric Age Group Patients J Family Med Prim Care [online] 2012, 1(1):30-33 [viewed 14 June 2014] Available from: doi:10.4103/2249-4863.94448
  2. WALLACE C I. Paracetamol overdose: an evidence based flowchart to guide management. [online] 2002 May, 19(3):202-205 [viewed 14 June 2014] Available from: doi:10.1136/emj.19.3.202

Investigations - Fitness for Management

Fact Explanation
Hepatic transaminases [2] Hepatic transaminases are slightly elevated during the first 12hours, which becomes marked thereafter. Transaminases begin to normalize after about 5 days of intoxication. [1]
Prothrombin time [2] Elevated after first 24 hours. [1]
Serum bilirubin [2] Elevated after first 24 hours. Direct bilirubin levels are elevated commonly. [1]
Blood urea and nitrogen Elevated after first 24 hours. [1]
Serum electrolytes Assesses the renal function. [1]
Serum creatinine Elevated after first 24 hours. This may be due to either direct renal damage or may be secondary to hepato-renal syndrome. [1]
Random blood sugar Hypoglycemia can occur with liver failure and usually present within 3 to 5 days of intoxication. [1]
Serum ammonia Becomes elevated within 3 to 5 days of intoxication. [1]
References
  1. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute
  2. WALLACE C I. Paracetamol overdose: an evidence based flowchart to guide management. [online] 2002 May, 19(3):202-205 [viewed 14 June 2014] Available from: doi:10.1136/emj.19.3.202

Investigations - Followup

Fact Explanation
Liver function tests During the stage 4 children begin to recover. Hepatic transaminases gradually decrease. Serum bilirubin, and coagulation profile also normalize during this stage. [1]
Renal function test Renal functions should be monitored till it normalizes. [1]
References
  1. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute

Management - General Measures

Fact Explanation
Health education Parents should be educated about the importance of adherence to recommended doses. The maximum dose of paracitamol is 10 to 15 mg/kg every 4 to 6 hours. [2] If it is used as an over-the-counter medication, instructions written on the product information leaflet should be read carefully. Parents should be advised to use a pediatric preparation rather adult preparation of paracitamol. [1]
Basic life support Assessment of the airway, breathing and circulation should be done first. Patency of the airway should be maintained and oxygen should be delivered if necessary. A nasogastric tube will help to prevent aspiration if vomiting is present. Circulatory support is provided with adequate fluid resuscitation. [2]
Anti-emetics Anti-emetics prevent vomiting, secondary to paracitamol intoxication. NAC causes vomiting as a side effect. Anti-emetics are helpful in preventing this as well. [3]
References
  1. RAMANAYAKE RP, JAYASINGHE LR, DE SILVA AH, WIJESINGHE WA, KANAGANAYAGAM N. Knowledge and Practices of Paracetamol Administration Among Caregivers of Pediatric Age Group Patients J Family Med Prim Care [online] 2012, 1(1):30-33 [viewed 14 June 2014] Available from: doi:10.4103/2249-4863.94448
  2. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute
  3. THANACOODY HK, GRAY A, DEAR JW, COYLE J, SANDILANDS EA, WEBB DJ, LEWIS S, EDDLESTON M, THOMAS SH, BATEMAN DN. Scottish and Newcastle Antiemetic Pre-treatment for paracetamol poisoning study (SNAP) BMC Pharmacol Toxicol [online] :20 [viewed 15 June 2014] Available from: doi:10.1186/2050-6511-14-20

Management - Specific Treatments

Fact Explanation
Activated charcoal Administration of activated charcoal (1g/kg body weight) orally, will reduce the absorption of paracitamol. This is effective within 2 to 4 hours of ingestion. [3,4]
N-acetyl cysteine (NAC) NAC should be administered in all patients with history of staggered paracitamol overdose irrespective of serum paracitamol levels. According to the Rumack-Matthew nomogram plasma acetaminophen levels greater than 150 µg/mL after 4 hours of ingestion indicate possible toxicity and need of NAC. NAC is effective only up to 24hours of ingestion. [3,4] A loading dose of 140 mg/kg is administered first. Thereafter 70 mg/kg NAC is administered 17 times, in 4 hours intervals. If the child vomits within 4 hours of administration of oral NAC, the dose should be re-administered. [2,3]
Liver transplantation This is helpful in children with significant liver damage. [1]
References
  1. MAHADEVAN SB, MCKIERNAN PJ, DAVIES P, KELLY DA. Paracetamol induced hepatotoxicity Arch Dis Child [online] 2006 Jul, 91(7):598-603 [viewed 13 June 2014] Available from: doi:10.1136/adc.2005.076836
  2. CRAIG DG, BATES CM, DAVIDSON JS, MARTIN KG, HAYES PC, SIMPSON KJ. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity Br J Clin Pharmacol [online] 2012 Feb, 73(2):285-294 [viewed 14 June 2014] Available from: doi:10.1111/j.1365-2125.2011.04067.x
  3. GERMAINE L. DEFENDI. Consultant For Pediatricians. [online] 2013;12(7):299-306. [viewed 14 June 2014] Available from: http://www.pediatricsconsultant360.com/article/acetaminophen-toxicity-children-diagnosis-clinical-assessment-and-treatment-acute
  4. WALLACE C I. Paracetamol overdose: an evidence based flowchart to guide management. [online] 2002 May, 19(3):202-205 [viewed 14 June 2014] Available from: doi:10.1136/emj.19.3.202