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).
Alert
Additional management is required for modified release paracetamol ingestions. Refer to section below. Treat mixed immediate and modified release ingestions as modified and contact Queensland Poisons information Centre (QPIC) (Ph: 131 126) or local toxicology service.
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 staggered toxic ingestion of immediate release paracetamol with intent of self harm
Treatment is as per acute immediate release ingestion, using the time of first ingestion.
If a dose was ingested within 2 hours of initial bloods, repeat paracetamol concentration 2 hours later to capture ongoing absorption and commence acetylcysteine if either level above nomogram treatment line (see Investigations).
Acetylcysteine following toxic modified release paracetamol ingestions
Modified 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 acetylcysteine administration if an unknown quantity or a potentially toxic quantity has been ingested.
| Acetylcysteine administration following modified release paracetamol ingestions |
|---|
|
Modified release ingestion ≤ 200 mg/kg or ≤ 10g
| - Commence acetylcysteine if paracetamol concentration taken at least 4 hours post ingestion is above the nomogram treatment line
- Repeat paracetamol concentration and ALT 4 hours after initial bloods to capture ongoing absorption. Commence acetylcysteine if above nomogram treatment line.
|
|
Modified release ingestion ≥ 200 mg/kg or ≥ 10g or unknown
| - Commence acetylcysteine immediately after taking bloods (see Investigations).
- Patients will require a full 20 hour course regardless of serum paracetamol concentration.
- Repeat paracetamol concentration and ALT 4 hours after initial bloods to capture ongoing absorption.
If either of the paracetamol levels are double the nomogram treatment line, administer double dose second bag of acetylcysteine (see “Acetylcysteine administration”). Recommend discussion with Poisons Information Centre (Ph: 131 126) or local toxicology service. |
|
Modified release massive ingestion ≥ 500 mg/kg or ≥ 30 g
| Administer a double dose second bag of acetylcysteine (see “Acetylcysteine administration”). Recommend discussion with Poisons Information Centre (Ph: 131 126) or local toxicology service. |
Acetylcysteine following repeated supratherapeutic ingestions
Acetylcysteine administration following repeated supratherapeutic ingestions*
Commence acetylcysteine if serum paracetamol concentration taken on presentation is greater than 20 mg/L or ALT greater than 50 U/L.
If acetylcysteine is indicated, repeat levels at 8 hours after initial testing. Discontinue acetylcysteine if ALT is less than 50 U/L or static, AND paracetamol concentration is less than 10 mg/L. Otherwise continue acetylcysteine, recheck ALT every twelve hours and seek advice from Queensland Poisons information Centre (QPIC) (Ph: 131 126) or local toxicology service.
*Refer to Assessment section for definition
Acetylcysteine administration
Alert
Careful attention is required when ordering fluids. Fluid adjustment orders are required for smaller children due to risk of hyponatremia if using the total adult fluid volume (1500mls). Secondary seizures have resulted when using 5% glucose. 4,5,6
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.
Indications for referral to a liver transplant unit
- INR greater than 3.0 at 48 hours or greater than 4.5 at any time
- oliguria or creatinine greater than 200 µmol/L
- persistent acidosis pH less than 7.3 or lactate >3 mmol/L
- systolic hypotension despite resuscitation
- hypoglycaemia
- severe thrombocytopenia
- encephalopathy not otherwise explained 1
