Poisoning - Paracetamol

Disclaimer

These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline. 

Read the full PCH Emergency Department disclaimer.

Aim 

To guide staff with the assessment and management of paracetamol poisoning in children.

This guideline provides an outline of the general approach to paracetamol poisoning. Specific information about poisoning presentations can be obtained from Poisons Information Service on 13 11 26 or refer to the Toxicology Handbook (L Murray et al).1

Background

Paracetamol overdose can occur as either a single large ingestion, usually as a deliberate self-poisoning, or as an accidental supra-therapeutic ingestion over days.

  • Morbidity and mortality is from hepatic injury. Life-threatening liver failure is rare.
  • An effective and well-tolerated antidote is available (N-Acetyl Cysteine (NAC)), and if given within 8 hours of ingestion, carries a 100% survival rate.

Limitations of this guideline

  • This guideline will cover single overdoses, or staggered ingestions over a period of less than 8 hours of the immediate-release preparation of paracetamol.
  • Supra-therapeutic overdoses of >60mg/kg/day in children (>4g/day in adults), or those involving modified release preparations (Panadol Osteo® , Duatrol SR®) cannot be interpreted using the nomogram, and advice should be sought from the Poisons Information Service 13 11 26 or local toxicology services.

Management - Approach to paracetamol toxicity

Resuscitation

  • Resuscitation is only required in the event of co-ingestion of other agents, or in the rare event of massive acute ingestions causing coma, severe lactic acidosis and hypoglycaemia

Risk assessment

  • The threshold for hepatic injury following an acute ingestion varies, but is generally around 200mg/kg
  • The risk of hepatotoxicity (without treatment with NAC) can be determined by plotting the post-ingestion paracetamol level on the nomogram below
  • Time of ingestion
    • If time of ingestion is unknown, assume that it took place at the earliest possible time, to give the worst-case scenario
    • Patients presenting over 8 hours after ingestion with elevated transaminases are assumed to have early toxicity
    • Patients presenting over 24 hours post ingestion with no elevated transaminases and a negative paracetamol level have a negligible risk of toxicity.

Clinical features

  • Most patients will initially present with no symptoms, or only mild gastrointestinal symptoms
  • Massive overdose is rare, but may cause coma and metabolic acidosis
  • Four chronological phases are described in cases of significant acute overdose:
    • Under 24 hours
      • Asymptomatic
      • Mild nausea and vomiting
    • 1-3 days
      • Right upper quadrant tenderness
      • Hepatotoxicity
    • 3-4 days (severe cases)
      • Fulminant hepatic failure and/or death
      • Acidosis
      • Renal failure
    • Day 4 to 2 weeks
      • Recovery.

Supportive care and monitoring

  • General supportive care, such as IV fluid, antiemetics, thromboembolic prophylaxis should be given as required on a case by case assessment
  • Patients with rising transaminases or INR >2.5 should have four hourly observations and BSL monitoring.

Investigations

  • Screening tests in deliberate paracetamol overdoses should include an ECG and BSL
  • When a patient has taken an overdose of another agent, screening paracetamol levels should be taken anytime after 30 minutes post-ingestion. Four hour levels do not need to be done unless screening indicates a detectable level which may represent a potentially toxic overdose of paracetamol.
  • Specific tests, including paracetamol levels, transaminases, INR, renal function, glucose, blood gases and platelets should be done only according to the time of presentation post-ingestion and / or concerning clinical features

Recommended investigations according to time from paracetamol ingestion1

Test Time after paracetamol ingestion
< 8 hours
8-24 hours > 24 hours
Serum paracetamol At 4 hours post ingestion or as soon after as possible
At presentation At presentation
Transaminases (ALT, AST)
Not indicated 
At presentation and at end of 20 hour NAC infusion At presentation
INR Not indicated
Not indicated
At presentation
Creatinine and urea Not indicated Not indicated At presentation
Blood glucose Not indicated Not indicated
At presentation
Blood gas Not indicated
Not indicated
At presentation

Decontamination

  • Activated charcoal is never indicated in small children with isolated paracetamol overdose.

Enhanced elimination

  • Not clinically useful.

Antidote

N-Acetyl Cysteine (NAC)

  • Intravenous NAC is indicated in all patients who have a risk assessment suggesting the potential for hepatotoxicity or who present with clinical symptoms of hepatic injury
  • Management and use of NAC in patients with a known time of overdose is shown in the flow chart below.

Nomogram for acute single dose paracetamol poisoning

Nomogram for acute single dose paracetamol poisoning

*Ensure that correct units are used (i.e. µmol/L or mg/L)

At PCH, paracetamol levels are measured as mg/L which is read on the right side of graph.

Management flowchart for acute paracetamol exposure with known time of ingestion2

    Management flowchart for acute paracetamol exposure with know time of ingestion

  • Patients who present with an unknown time of ingestion must have a NAC commenced on arrival. The NAC may be ceased if and when history or laboratory testing confirms a non-toxic overdose or on advice from toxicology services.
  • Patients presenting over 24 hours post ingestion should only be given NAC in the event that serum paracetamol is detectable, or hepatic transaminases are elevated. Guidance from toxicological services is recommended in these cases.
  • Continuation of the infusion beyond 20 hours may be indicated in patients with delayed presentations, repeated supra-therapeutic ingestions, or those with evidence of hepatotoxicity. The third infusion dose should be repeated until transaminase levels are falling and the patient is clinically improving.
  • NAC is known to cause an anaphylactic reaction in 10-50% of patients, with symptoms including hypotension, flushing, rash and angio-oedema. 
    • Reactions typically occur after the first bag and can be treated using an oral antihistamine such as loratadine or promethazine. 
  • Cessation of the infusion should only occur in severe reactions and should be restarted once the reaction is settling. This reaction does not indicate anaphylaxis.
  • Patients should be cardiac monitored for the first infusion bag, and can be discontinued after this time unless an anaphylactic reaction has occurred.
  • The dosage of NAC in children is the same as in adults, but should be infused in smaller volumes of 5% dextrose (5% dextrose with 0.9% NaCl can be used if hyponatraemia is of concern).

Infusion protocol for N-Acetyl Cysteine in acute paracetamol overdose

Intravenous for paracetamol poisoning4

  • Use actual measured body weight to calculate acetylcysteine dose (use ideal body weight to quantify extend of paracetamol overdose in obese children)3
  • Smaller volume for dilution may be used in younger infants or fluid restricted patients (7mL/kg for the first infusion, 14mL/kg for the second infusion).5,6
  • Glucose 5% as diluent may be substituted with sodium chloride 0.45% or 0.9% if clinically necessary.
  • If ongoing acetylcysteine infusion is required, repeat second infusion.
  • Refer to PCH Medication Monograph Acetylcysteine (internal WA Health only).

Infants or children <20kg


Acetylcysteine dose  Glucose 5% for dilution Infusion duration
First infusion 200mg/kg 100mL 4 hours
Second infusion 100mg/kg 250mL 16 hours

Children 20 - 50kg


Acetylcysteine dose  Glucose 5% for dilution Infusion duration
First infusion 200mg/kg 250mL 4 hours
Second infusion 100mg/kg500 500mL 16 hours

Children or adolescents > 50kg

(Recommended ceiling weight: 110kg)


Acetylcysteine dose  Glucose 5% for dilution Infusion duration
First infusion 200mg/kg 500mL 4 hours
Second infusion 100mg/kg500 1000mL 16 hours

Disposition and follow-up

  • Medical discharge can be given in the following scenarios:
    • Patients with a four-hour paracetamol level below 150mg/L
    • Patients presenting within 8 hours with a level below the treatment threshold.
    • All patients who have received NAC within 8 hours of ingestion (except for those with massive overdoses) at the end of the infusion
    • Patients who have received NAC whose transaminases are improving and who are clinically well
    • All cases of deliberate poisoning should be assessed psychiatrically.

When to seek additional advice

  • Overdose of modified release preparations
  • Repeated supra-therapeutic overdoses
  • Massive overdoses (>500mg/kg)
  • Delayed presentations with elevated transaminases.

Nursing

  • Baseline observations include temperature, heart rate, respiratory rate, oxygen saturation, blood pressure and neurological observations
  • Minimum of hourly observations should be recorded whilst in the emergency department
  • Any significant changes should be reported immediately to the medical team
  • Apply Emla® approximately 1 hour prior to expected time of blood collection.

Patients requiring IV N-acetylcysteine

  • 30 minutely heart rate, respiratory rate, blood pressure, oxygen saturation for first 2 hours then hourly if stable
  • Observe for localised reaction and anaphylactoid reactions as per above medical guidelines.

Bibliography

  1. Murray L, Little M, Pascu O, Hoggett K. Toxicology Handbook 3rd Churchill Livingston 2015.
  2. Management Flowchart for Acute Paracetamol Exposure with Known Time of Ingestion - Guidelines for the management of paracetamol poisoning in Australia and New Zealand - explanation and elaboration. Medical Journal of Australia. 2008; 188 (5); 298.
  3. Chiew AL, Fountain JS, Graudins A, et al. Summary statement. New guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust 2015; 2013: 215-218.doi:10.5694/mja15.00614.
  4. Chiew A, Reith D, Pomerleu A, Wong A, Isosardi KZ, J Soderstrom, Buckley N. Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust 2019; p1-9. doi: 10.5694/mja2.50428
  5. Micromedex® 2.0. Greenwood Village, Colorado, USA: Truven Health Analytics; 2019 [Available from: http://www-micromedexsolutions-com.pklibresources.health.wa.gov.au/].
  6. Chiew AL, Reith D, Pomerleau A, Wong A, Isoardi KZ, Soderstrom J, et al. Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Medical Journal of Australia. 2019

Endorsed by:  Director, Emergency Department  Date:  May 2018


 Review date:   May 2021


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