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 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.
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 N-acetyl cysteine (NAC).1
This guideline is based on the recommendations made in 2015 by a group of Australasian Clinical Toxicologists consulting to the Poisons Information Centre.1,2
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.
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.1 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.1,3
NAC 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.
The aim of the initial assessment is to determine the risk of hepatic injury following paracetamol ingestion.
History-taking should include information on:
- number, quantity and timing of ingestions
- symptoms of hepatic injury (such as abdominal pain, nausea or vomiting, anorexia)
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 per kilogram of paracetamol ingested. When in doubt of the quantity, use the maximum possible ingested dose to determine the potential for hepatic injury.
||Acute single ingestion
||Repeated supratherapeutic ingestion
|0 – 6 years
||Greater than 200 mg/kg over a period of 8 hours
||Any of the following:
- greater than 200 mg/kg over a single 24-hour period
- greater than 150 mg/kg per 24-hour period for the preceding 48 hours
- greater than 100 mg/kg per 24-hour period for greater than 48 hours (may have abdominal pain, nausea or vomiting)
|Over 6 years
||Greater than 200 mg/kg or 10g (whichever is lower) over a period of 8 hours
||Any of the following:
- greater than 200 mg/kg or 10g (whichever is lower) over a single 24-hour period
- greater than 150 mg/kg or 6g (whichever is lower) per 24-hour period for the preceding 48 hours
- greater than 100 mg/kg or 4g (whichever is lower) per 24-hour period for greater than 48 hours AND symptoms indicating possible liver injury (such as abdominal pain, nausea or vomiting)
*Use the ideal body weight for body weight calculations in obese children
ALERT – Administer NAC immediately if paracetamol concentration levels are not likely to be available within eight hours of a potentially toxic ingestion (due to delay in presentation to ED or time for testing or uncertain time of ingestion) or patient has symptoms of hepatic injury (abdominal pain, nausea and anorexia). Do not delay for paracetamol concentration levels.
Serum paracetamol concentration testing is used to determine the need for NAC (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
|Children aged less than 6 years post-ingestion of liquid paracetamol
- Serum paracetamol concentration at 2 hours post-ingestion. Concentrations less than 150mg/L require no further treatment. Repeat at 4 hours post-ingestion if 2-hour level is greater than or equal to 150mg/L.
|Patients with single potentially toxic paracetamol ingestion
||Time of presentation
|Within 8 hours of ingestion
||Serum paracetamol concentration at 4-8 hours post-ingestion.
If initial paracetamol concentration is more than double the nomogram line, at end of NAC infusion repeat level and measure ALT.
|8-24 hours post-ingestion
||Serum paracetamol concentration and ALT on presentation and commence NAC while awaiting level
If initial paracetamol concentration is above the nomogram treatment line measure ALT at end of NAC infusion.
|Greater than 24 hours post-ingestion
||Serum paracetamol concentration, transaminases (ALT/AST), INR/PT, creatinine, urea, glucose and arterial or venous blood gas on presentation.
Follow up as clinically indicated.
||Serum paracetamol concentration and ALT on presentation.
Seek toxicologist advice for further testing.
|Patients post-ingestion of sustained release paracetamol (e.g. Panadol Osteo®, Osteomol®)
- Serum paracetamol concentration minimum of 4 hours post-ingestion.
- ALT and repeat serum paracetamol concentration 4 hours after initial testing to capture the delayed release. Repeat paracetamol levels and ALT again 2 hours prior to cessation of the infusion.
|Patients with potentially toxic repeated supratherapeutic ingestions
- Serum paracetamol concentration and ALT on presentation.
- Repeat at 8 hours after initial measurement if either serum paracetamol concentration greater than 20mg/L or ALT greater than 50U/L.
- Check ALT at 12-hourly-intervals if ALT greater than 50U/L or paracetamol concentration is greater than 10mg/L.
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.
Refer to flowchart for a summary of the emergency management for a child following a paracetamol ingestion.
Activated charcoal is not a life-saving treatment but may prevent or reduce the need for treatment with NAC if used appropriately.
Activated charcoal is only routinely recommended for cooperative patients aged greater than six years if able to be administered one to two hours post-ingestion. It may be given up to four hours post-ingestion for very large overdoses, or beyond this time frame for large overdoses of sustained release paracetamol preparations on advice from Poisons Information Centre/Clinical Toxicologist. It is not recommended in liquid preparation overdose due to the fast absorption time.
N-Acetyl Cysteine (NAC)
NAC following single toxic paracetamol ingestion
The need for NAC is guided by serum paracetamol concentration levels using a treatment nomogram (see Assessment section).
|Time from ingestion
||Indications for NAC
||NAC will not be required for children aged less than 6 years with serum paracetamol concentration less than 150mg/L at 2 hours post-ingestion of liquid paracetamol.
If greater than or equal to 150mg/L do not commence NAC but repeat level at 4 hours.
||Commence NAC if:
- serum paracetamol concentration levels taken at 4 hours post-ingestion are greater than or equal to 150mg/L or
- serum paracetamol concentration levels taken 4-8 hours post-ingestion are above the nomogram treatment line.
Await serum levels if results are expected within 8 hours of ingestion. If results are not expected within 8 hours, commence NAC and review serum levels when available. Continue NAC if levels taken within 4-8 hours of ingestion are above the nomogram treatment line. Otherwise cease infusion.
|Greater than 8 hours
||Commence NAC immediately if present 8 -24 hours post-ingestion.
If present greater than 24 hours post-ingestion, collect bloods for further testing prior to commencing NAC (refer to Investigations).
Continue NAC if serum paracetamol concentration levels above the nomogram treatment line or ALT greater than 50U/L.
||Commence NAC immediately. Continue NAC if paracetamol concentration is greater than 10mg/L or ALT is greater than 50U/L.
NAC following sustained release paracetamol ingestions
Sustained release paracetamol preparations (such as Panadol Osteo and Osteomol both with 665mg paracetamol/tablet) result in potentially delayed peak concentrations above the nomogram treatment line. A single measurement of paracetamol level is not adequate to make decisions around NAC administration if an unknown quantity or a potentially toxic quantity has been ingested.
|In addition to the management previously described for single toxic ingestions, repeat serum level four hours after initial testing and commence NAC if level is above the treatment line.
For all patients requiring NAC:
- measure paracetamol concentration levels and ALT two hours before completion of the NAC infusion.
- continue the NAC infusion and seek toxicology advice if ALT is greater than 50U/L or paracetamol concentration is greater than 10mg/L
NAC following repeated supratherapeutic ingestions*
|Commence NAC if either serum paracetamol concentration greater than 20mg/L or ALT greater than 50U/L.
Repeat levels at 8 hours after initial testing. Discontinue NAC if ALT less than 50U/L or static AND paracetamol concentration is less than 10mg/L. Otherwise continue NAC and recheck ALT every 12 hours.
*Refer to Assessment section for definition
ALERT – Careful attention is required when ordering fluids. Fluid adjustment orders are required for smaller children due to risk of hyponatremia using the total adult fluid volume (1700mls). Secondary seizures have resulted when using 5% glucose. 4,5,6
Refer to the NAC guideline and use the appropriate order form (based on child’s weight) or the electronic ordering system.
The total NAC dosing is 300mg/kg administered over 20 hours in two sequential IV infusions and is compatible with any glucose and/or sodium-based fluids. Dosing is calculated on actual body weight up to 110kg (with dosing based on 110kg weight for children over 110kg). NAC is packaged in 10mL ampoules each containing 2000mg (20%). Doses are written in mg. While the recommended regime uses two bags, some smart pumps are yet to be updated to accommodate this and, at present ieMR has both two and three-bag options. The two-bag regime can be run using the mL/hour functionality on the pumps as per the NAC forms.
Prescribe the entire treatment course at the time of the initial presentation to avoid administration delays.
Adverse drug reactions
Anaphylactoid reactions including rash, pruritus, angioedema, bronchospasm and rarely hypotension may occur following NAC 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
For patients with ongoing liver impairment, continue NAC and 12-hourly-blood-testing until clinically improving, ALT is reducing, INR is improving and less than 2 and the paracetamol level is less than 10mg/L.
Indications for referral to a liver transplant unit
- INR greater than 2.0 at any time
- oliguria or creatinine greater than 200 mmol/L
- persistent acidosis pH less than 7.3
- systolic hypotension despite resuscitation
- severe thrombocytopenia
- encephalopathy not otherwise explained 2
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.
|Toxicology advice is required for the following:
- overdoses of more than total of 50 g or 1 g/kg (always use lower threshold)
- tested paracetamol concentration is double the nomogram line
- IV overdoses
- evidence of hepatotoxicity (ALT greater than 1,000 IU/L)
|Reason for contact
||Who to contact
(including management, disposition or follow-up of all children requiring a NAC infusion)
|Follow local practices. Options:
- Poisons Information Centre 13 11 26 (24-hour service)
- onsite/local paediatric service
- Queensland Children’s Hospital experts via Children’s Advice and Transport Coordination Hub (CATCH) on 13 CATCH (13 22 82)
- local and regional paediatric videoconference support via Telehealth Emergency Management Support Unit TEMSU (access via QH intranet) on 1800 11 44 14 (24-hour service)
||First point of call is the onsite/local paediatric service
When to consider discharge from ED
Consider discharge for the following patients:
- NAC infusion not required (based on assessment of serum paracetamol concentration levels or clear history of quantity of accidental ingestion)
- if ingestion deliberate, a psychiatric assessment has been conducted as appropriate.
On discharge, educate the family regarding safe paracetamol administration and storage.
Not routinely required.
When to consider admission
Admission to an inpatient service or SSU is recommended for patients requiring ongoing NAC infusion once serum paracetamol concentration levels are available.