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Acetaminophen overdose resident survival guide

Introduction

Overview

Overview

Acetaminophen overdose is the intentional or accidental ingestion of a high dose of acetaminophen. Acute acetaminophen overdose occurs ≤8 hours before presentation, while chronic acetaminophen overdose occurs following the repeated supratherapeutic ingestion of acetaminophen.

Acetaminophen is available in the U.S. market under the following brand names:

  • Tylenol
  • Anacin-3
  • Liquiprin
  • Percocet
  • Tempra
  • Cold and flu medicines
  • Aceta
  • Actimin
  • Apacet
  • Aspirin Free Anacin
  • Atasol
  • Banesin
  • Dapa
  • Datril Extra-Strength
  • Feverall
  • Fibi
  • Genapap
  • Genebs
  • Panadol
Acetaminophen Dosage

Acetaminophen Dosage

Shown below is a table summarizing the commonly used dosages of paracetamol.[1]

Suppository 120 mg, 125 mg, 325 mg, 650 mg
Chewable tablets 80 mg
Regular strength 325 mg
Extra strength 500 mg
Liquid 160 mg/teaspoon
Drops 100 mg / mL, 120 mg / 2.5 mL


Shown below is a table summarizing the recommended maximum doses of paracetamol.[1]

Patients Maximum single dose Minimum dosing intervals (hours) Maximum dose in 24 hours
Adults 1 g 4 4 g
Children 6-12 years 500 mg 4 2 g
Children 1-5 years 240 mg 4 960 mg
Infants 3-12 months 120 mg 4 480 mg
Management

Management

General Approach

Shown below is an algorithm depicting the approach to acetaminophen overdose.[2][3][4]

 
 
 
 
 
 
 
Obtain a focused history:
❑ Time since last ingestion
❑ Number of tablets/other dosing form taken
❑ Frequency of dosage
❑ Other ingested substances
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Characterize the symptoms & examine the patient:
Stage I (first 24 hours): Preclinical toxic effects
❑ Asymptomatic
❑ Nausea & vomiting
❑ Diaphoresis
❑ Coma (with massive doses)

Stage II (24 to 72 hours): Hepatic injury
❑ Right upper quadrant tenderness
❑ Oligouria
❑ Hematuria

Stage III (72 to 96 hours): Hepatic failure
❑ Hepatic tenderness
❑ Jaundice
❑ Impaired consciousness
❑ Asterixis
❑ Foetur hepaticus
❑ Hemorrhage

❑ Death from multiorgan system failure[2]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order labs:
❑ Serum paracetamol concentration (4 hours after acetaminophen ingestion, but not later than 16 hours)
❑ Liver function tests
❑ Prothrombin time (PT) or International normalized ratio (INR)
❑ Renal function tests
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clear information on the timing of acetaminophen ingestion
 
 
 
No clear information on the timing of acetaminophen ingestion
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Order acetaminophen level
❑ Initiate N-acetylcysteine therapy without waiting for acetaminophen levels
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
< 2 hours
 
2-4 hours
 
4-8 hours
 
> 8 hours
 
Recurrent supratherapeutic ingestions
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Administer activated charcoal 1g/kg (max 50 kg)
❑ Wait until 4 hours has passed and measure acetaminophen level
 
❑ Wait until 4 hours has passed and measure acetaminophen level
 
❑ Measure acetaminophen level
 
❑ Order acetaminophen level
❑ Initiate N-acetylcysteine therapy without waiting for acetaminophen levels
 
Initiate N-acetlycysteine therapy if, one or more true:
❑ ALT is elevated, AND
❑ Ingestion of >4 g of acetaminophen per day
OR
❑ Established hepatic failure
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Plot acetaminophen level on the Rumack-Matthew nomogram
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acetaminophen level below the nomogram line
❑ Discharge home
 
Acetaminophen level above the nomogram line
❑ Initiate N-acetylcysteine therapy
 
 
 
 
 
 
 
 
 

Acetylcysteine Therapy

Shown below is an algorithm depicting the oral and IV regimen of N-acetylcysteine.[2][3]

 
 
N-Acetylcysteine treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider oral regimen in case of:
❑ Preclinical toxicity
❑ Hepatic injury
 
Consider IV regimen in case of:
❑ Malnourishment/eating disorders
❑ Failure to thrive in children
❑ AIDS
❑ Alcoholism
❑ Associated febrile illness
❑ Using drugs that induce CYP2E1 p450 system

♦ Carbamazepine, or phenytoin, or phenobarbital
♦ Rifampicin, or rifabutin
♦ Efavirenz, or nevirapine

❑ Hepatic failure
❑ Vomiting and intolerance to oral regimen
❑ Altered mental status
 
 
 
 
 
 
 
 
 
 
 
 
Outpatient
 
Critical care unit
 
 
 
 
 
 
 
 
 
 
 
 
Oral regimen:
❑ Administer a loading dose of 140 mg/kg
❑ Administer a maintenance dose of 70 mg/kg every 4 hours for 17 doses
 
IV regimen:
❑ Administer 150 mg/kg in 200 mL glucose 5% solution infused over 15 minutes
❑ Administer 50 mg/kg in 500 mL glucose 5% solution infused over the next 4 hours
❑ Administer 100 mg/kg in 1000 mL glucose 5% solution over the following 16 hours
 
 
 
 
 
 
 
 
 
 
 
 
❑ Monitor the patient for vomiting after the loading dose
❑ Discharge the patient with three maintenance doses to be taken at home
 
❑ Monitor
♦ Blood pressure
♦ Oxygen saturation
♦ Hypoglycemia
❑ Monitor the liver and renal function every 12 hours
 
 
 
 
 
 
 
 
 
 
 
 
Reevaluate the patient in 12 hours
❑ Measure ALT level
❑ Measure acetaminophen level
 
Continue the treatment until:
❑ Resolution of encephalopathy
❑ Improvement of ALT, creatinine and INR
❑ The patient receives a liver transplant (if applicable)
 
Rumack-Matthew Nomogram

Rumack-Matthew Nomogram

Criteria for Liver Transplantation

Criteria for Liver Transplantation

  • Arterial pH < 7.3
  • Hepatic encephalopathy grade III/IV
  • Serum creatinine concentration > 300 μmol/L
  • Prothrombin time > 100 seconds
  • Arterial lactate concentration > 3.5 mmol/L on admission or > 3.0 mmol/L 24 hours after paracetamol ingestion[2]
Do’s

Do’s

  • Measure serum acetaminophen concentrations between 4 and 16 hours post-ingestion. Values taken before 4 hours are not useful as it takes about 4 hours for maximal drug absorption. Likewise values taken after 16 hours are less useful as liver failure may have already occurred.
  • Look for ketones on urinalysis and low blood urea concentration as a sign for malnourishment or starvation.
  • In case of acetaminophen ingestion prior to 2 hours of the presentation, administer activated charcoal as it was found to be superior to gastric lavage and substance induced emesis, although both of them are potentially useful.[5][6]
  • N-acetylcysteine can be administered 8 hours following the ingestion of acetaminophen; however, it is most beneficial within the first 8 hours of ingestion.
  • Provide a supportive treatment when needed: fluid replacement, symptomatic treatment for nausea and vomiting, intensive supportive treatment in case of acute liver failure.
  • If a patient vomits following oral N-acetylcysteine, administer a trial of anti emetic; however, in such cases IV N-acetylcysteine is preferred.
  • Stop the infusion if IV N-acetylcysteine precipitates an anaphylactoid reaction, treat with H1-antihistaminics and resume IV N-acetylcysteine at a slower infusion rate.
  • If acetaminophen level can not be obtained, assume that that patient has overdose of acetaminophen and treat with N-acetylcysteine.
Dont’s

Dont’s

  • Do not overlook acetaminophen in those who have signs suggestive of overdose with other agents.
  • Do not use activated charcoal after 4 hours of acetaminophen ingestion.[7]
  • Do not delay treatment with antidote more than 8 hours following the ingestion of acetaminophen.
  • Do not use the Rumack-Matthew nomogram to stratify patients who ingested acetaminophen more than 8 hours ago or whose history of ingestion is unclear.[2][3][4]
References

References

  1. ↑ 1.0 1.1 Ferner, RE.; Dear, JW.; Bateman, DN. (2011). “Management of paracetamol poisoning”. BMJ. 342: d2218. PMID 21508044.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Ferner RE, Dear JW, Bateman DN (2011). “Management of paracetamol poisoning”. BMJ. 342: d2218. doi:10.1136/bmj.d2218. PMID 21508044.
  3. ↑ 3.0 3.1 3.2 3.3 Heard KJ (2008). “Acetylcysteine for acetaminophen poisoning”. N Engl J Med. 359 (3): 285–92. doi:10.1056/NEJMct0708278. PMC 2637612. PMID 18635433.
  4. ↑ 4.0 4.1 4.2 Wallace CI, Dargan PI, Jones AL (2002). “Paracetamol overdose: an evidence based flowchart to guide management”. Emerg Med J. 19 (3): 202–5. PMC 1725876. PMID 11971827.
  5. ↑ Buckley, NA.; Whyte, IM.; O’Connell, DL.; Dawson, AH. (1999). “Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose”. J Toxicol Clin Toxicol. 37 (6): 753–7. PMID 10584587.
  6. ↑ Underhill, TJ.; Greene, MK.; Dove, AF. (1990). “A comparison of the efficacy of gastric lavage, ipecacuanha and activated charcoal in the emergency management of paracetamol overdose”. Arch Emerg Med. 7 (3): 148–54. PMID 1983801. Unknown parameter |month= ignored (help)
  7. ↑ Spiller, HA.; Winter, ML.; Klein-Schwartz, W.; Bangh, SA. (2006). “Efficacy of activated charcoal administered more than four hours after acetaminophen overdose”. J Emerg Med. 30 (1): 1–5. doi:10.1016/j.jemermed.2005.02.019. PMID 16434328. Unknown parameter |month= ignored (help)


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2], Rim Halaby, M.D. [3]