Paracetamol ingestion – Emergency management in children

Purpose

This document provides clinical guidance for all staff involved in the care and management of a child presenting to an Emergency Department (ED) in Queensland following a paracetamol ingestion.

This guideline has been developed by senior ED clinicians and Paediatricians across Queensland, with input from Queensland Poisons Information Centre, Clinical Toxicology; Princess Alexandra Hospital and Pharmacy, Gastroenterology and PICU; Queensland Children’s Hospital, Brisbane. It has been endorsed for use statewide by the Queensland Emergency Care of Children Working Group in partnership with the Queensland Emergency Department Strategic Advisory Panel and the Healthcare Improvement Unit, Clinical Excellence Queensland.

Introduction

Paracetamol is a widely used analgesic that is readily available in many different preparations. Accidental or deliberate overdose can cause hepatic failure and death. This can be prevented by the early administration of acetylcysteine.¹

This guideline is based on the recommendations made in 2020 by a group of Australasian Clinical Toxicologists consulting to the Poisons Information Centre.¹

While there are certain groups who are at higher risk of hepatotoxicity (such as those with malnutrition, eating disorders, cystic fibrosis or acute viral infections) the recommended management is conservative and so remains unchanged.

Pharmacokinetics

Paracetamol is rapidly absorbed in the small intestine and reaches peak concentrations within 30 minutes for liquid preparations and one to two hours for standard tablet preparations. Distribution then occurs within two hours for liquid preparations and four hours for standard tablet preparations.² Hepatic biotransformation results in 90% of paracetamol being metabolised to inactive sulphate and glucuronide conjugates which are then excreted by the kidneys. The remaining 10% requires cytochrome P450 to make an intermediary compound of N-acetyl-p-benzoquinone imine (NAPQI) which then in turn binds to intracellular glutathione for renal excretion. Depletion of glutathione occurs with higher production of NAPQI which subsequently binds to other proteins and thus damages hepatocytes. Clinical or biochemical evidence of this damage may take up to 24 hours post overdose to become apparent.³

Acetylcysteine is an effective antidote to paracetamol toxicity by increasing the synthesis and availability of glutathione and directly binding to NAPQI. Appropriate treatment commencing within eight hours of the overdose will prevent almost all serious hepatic injury. ⁴

Assessment

The aim of the initial assessment is to determine the risk of hepatic injury following paracetamol ingestion.

History

History-taking should include information on:

• number, quantity, concentration* and timing of ingestions
• preparation – immediate or modified release, liquid
• intentional or accidental
• symptoms of hepatic injury (such as abdominal pain, nausea or vomiting, anorexia)

* at least 4 different concentrations of liquid paracetamol in Australia

Examination

Full examination focussing on eliciting any toxidromes to suggest co-ingestion, neurological status for co-ingestion risk and hepatic encephalopathy, and serial abdominal examinations which can elicit right upper quadrant tenderness.

Calculation of ingested dose

Use the available information to calculate the dose(mg) per kilogram of paracetamol ingested. When in doubt of the quantity, use the maximum possible ingested dose to determine the potential for hepatic injury.

*Use the ideal body weight for body weight calculations in obese children.

Investigations

Serum paracetamol concentration testing is used to determine the need for acetylcysteine (by plotting on the treatment nomogram provided below). Testing is recommended for patients with a history of:

• ingesting a toxic dose (refer to table in Assessment section)
• deliberate self‐poisoning regardless of the stated ingested dose
• accidental exposures if uncertain of ingested dose

Rumack-Mathew paracetamol treatment nomogram

Reproduced from Daly FF 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 (5): 296-301 with permission from John Wiley and Sons. Link to article. © 2008 AMPCo Pty Ltd. All rights reserved.

Management

Refer to flowchart  [PDF 997.58 KB] for a summary of the emergency management for a child following a paracetamol ingestion:

Contact a Clinical Toxicologist via Queensland Poisons information Centre (QPIC) (ph: 131 126) or local toxicology service urgently for:

• overdoses of 50 g or 1 g/kg (always use lower threshold)
• measured paracetamol concentration is double the nomogram line
• IV paracetamol errors or overdoses
• evidence of hepatotoxicity (ALT greater than 1,000 U/L)

Higher concentrations of acetylcysteine may be required. Contact paediatric critical care specialist (onsite or via Retrieval Services Queensland (RSQ)) as advised by Poisons/QPIC/Clinical Toxicologist.

Refer patients with a deliberate overdose for a psychiatric assessment as per local practices.

Decontamination - Activated charcoal

Activated charcoal may prevent or reduce the need for treatment with acetylcysteine if used appropriately.

Activated charcoal (1g/kg) is only routinely recommended for cooperative patients aged greater than six years if able to be administered up to 2 hours post-ingestion for potentially toxic overdoses of immediate release paracetamol. It may be given up to 4 hours post-ingestion for modified release paracetamol preparations, or for very large overdoses of immediate release paracetamol (≥ 500 mg/kg or ≥ 30g). Multiple doses of activated charcoal may be given for very large overdoses of modified release paracetamol on advice from Poisons Information Centre/Clinical Toxicologist. Activated Charcoal is not recommended in liquid preparation overdose due to the fast absorption time.

Acetylcysteine

Acetylcysteine following single toxic immediate release paracetamol ingestion

The need for acetylcysteine is guided by serum paracetamol concentration plotted on the paracetamol treatment nomogram (see Assessment section).

ACETYLCYSTEINE following single toxic immediate release paracetamol ingestion

Time from ingestion		Indications for acetylcysteine
	2 hours	Acetylcysteine will not be required for well children aged less than 6 years with serum paracetamol concentration less than 150 mg/L at 2 hours post-ingestion of liquid paracetamol. If greater than or equal to 150 mg/L do not commence acetylcysteine but repeat level at 4 hours and manage as below.
	4-8 hours	Commence acetylcysteine if: serum paracetamol concentration taken at 4 hours post-ingestion is greater than or equal to 150 mg/L or serum paracetamol concentration taken 4-8 hours post-ingestion is above the nomogram treatment line. If initial serum paracetamol concentration is greater than double the nomogram line, patients will require a double dose second bag of acetylcysteine (see “Acetylcysteine administration” below). Recommend discussion with Poisons Information Centre (Ph: 131 126). Await serum levels if results are expected within 8 hours of ingestion. If results are not expected within 8 hours, commence acetylcysteine and review serum levels when available. Continue acetylcysteine if levels taken within 4-8 hours of ingestion are above the nomogram treatment line. Otherwise cease infusion.
	8-24 hours	Commence acetylcysteine immediately after taking bloods (see Investigations). Continue acetylcysteine if serum paracetamol concentration above the nomogram treatment line or ALT greater than 50 U/L. If initial serum paracetamol concentration is greater than double the nomogram line, patients will require a double dose second bag of acetylcysteine (see “Acetylcysteine administration” below). Recommend discussion with Poisons Information Centre (Ph: 131 126).
	≥ 24 hours or unknown	Commence acetylcysteine immediately after taking bloods (see Investigations). Continue acetylcysteine if paracetamol concentration is greater than 10 mg/L or ALT greater than 50 U/L. If serum paracetamol concentration is higher than 100 mg/L, seek advice from Poisons Information Centre clinical toxicologist (Ph: 131 126) or local toxicology service.

Acetylcysteine following repeated supratherapeutic ingestions

Acetylcysteine administration

Refer to the Acetylcysteine guideline and use the appropriate order form (based on child’s weight) or the electronic ordering system.

The total acetylcysteine dosing is 300 mg/kg administered over 20 hours in two sequential IV infusions in crystalloid solution (200 mg/kg over 4h, then 100 mg/kg over 16h). Double the dose of the second bag of acetylcysteine (to 200mg/kg over 16h) for those patients with doses resulting in high paracetamol concentrations more than double the nomogram line, or those who ingest ≥ 30 g or ≥ 500 mg/kg of modified release paracetamol. Dosing is calculated on actual body weight up to 110 kg (with dosing based on 110 kg weight for children over 110 kg). Acetylcysteine is packaged in 10 mL ampoules each containing 2,000 mg (20%).  Doses are written in mg.

Where a two bag regime is available on smart pumps, use these profiles. If not available, confirm if the general acetylcysteine profile will allow the infusion to run. If not, revert to the mL/hour functionality (if programmed). Due to differences in doses and durations, it is not suitable to use the superseded three bag regime profile to run the two bag regime.

Prescribe the entire treatment course at the time of the initial presentation to avoid administration delays.

Ceasing acetylcysteine infusion for single ingestions of immediate or modified release paracetamol

• Measure paracetamol concentration and ALT two hours before the end of the second bag of acetylcysteine infusion.
• If paracetamol concentration is less than 10 mg/L and ALT less than 50 U/L, no further treatment required after infusion is complete.
• If paracetamol concentration is greater than 10 mg/L, or ALT is greater than 50 U/L, continue the acetylcysteine infusion and seek advice from Poisons Information Centre (Ph: 131 126).

Ceasing acetylcysteine infusion for repeated supratherapeutic paracetamol ingestion

• Repeat paracetamol concentration 8 hours after initial blood tests
• If paracetamol concentration is less than 10 mg/L and ALT less than 50 U/L, cease acetylcysteine
• If paracetamol concentration is greater than 10 mg/L, or ALT is greater than 50 U/L, continue the acetylcysteine infusion and seek advice from Poisons Information Centre (Ph: 131 126).

Adverse drug reactions

Anaphylactoid reactions including rash, pruritus, angioedema, bronchospasm and rarely hypotension may occur following acetylcysteine administration with females and asthmatics at higher risk. Progression to a more clinically significant reaction is rare.

If drug reactions occur, slow the infusion or temporarily cease the infusion, treat with antihistamines or bronchodilators and restart once the reaction settles.

Ongoing liver impairment

Seek specialist advice (Toxicology/Gastroenterology/Critical Care) for patients with ongoing evidence of liver impairment.

For patients with ongoing liver impairment, continue acetylcysteine and 12-hourly-blood-testing until clinically improving, ALT is reducing, INR is improving and less than 2.0 and the paracetamol level is less than 10mg/L.

Escalation and advice outside of ED

Clinicians can contact the services below if escalation of care outside of senior clinicians within the ED is needed, as per local practices. Transfer is recommended if the child requires a higher level of care.

Critical care is unlikely to be required following a paracetamol overdose in isolation but may be required if co-ingestions have occurred. Seek critical care advice (onsite or via RSQ) if advised by toxicologist or child is critically unwell.

Inter-hospital transfers

Disposition

When to consider discharge from ED

Consider discharge for the following patients:

• Acetylcysteine infusion not required (based on assessment of serum paracetamol concentration levels or clear history of quantity of accidental ingestion)

AND

• if ingestion deliberate, a psychiatric assessment has been conducted as appropriate.

On discharge, educate the family regarding safe paracetamol administration and storage.

Follow-up

Not routinely required.

When to consider admission

Admission to an inpatient service or SSU is recommended for patients requiring ongoing acetylcysteine infusion once serum paracetamol concentration and ALT levels are available.

Related documents

Guidelines

• Paediatric Medication Guideline Acetylcysteine (Intravenous)

Forms

• N-Acetylcysteine order form - Child (less than 20kg)
• N-Acetylcysteine order form - Child (20-50kg)
• N-Acetylcysteine order form - Child (greater than 50kg)