Guideline summary

Updated guidelines for the management of

paracetamol poisoning in Australia and New Zealand
Angela L Chiew 1,2 , David Reith3, Adam Pomerleau3, Anselm Wong4,5, Katherine Z Isoardi6,7, Jessamine Soderstrom8,9,
Nicholas A Buckley2,10

P
aracetamol poisoning is the commonest cause of severe Abstract
acute liver injury in Western countries.1,2 It is also the most
Introduction: Paracetamol is a common agent taken in deliberate
common reason for calls to Poisons Information Centres
self-­poisoning and in accidental overdose in adults and children.
in Australia and New Zealand.3 Not only is it one of the com- Paracetamol poisoning is the commonest cause of severe acute
monest medications involved in deliberate self-­poisoning, it is liver injury. Since the publication of the previous guidelines in 2015,
also involved in a large proportion of accidental paediatric ex- several studies have changed practice. A working group of experts
posures and in overdoses with therapeutic intent when taken for in the area, with representation from all Poisons Information
symptoms such as pain or fever (repeated supratherapeutic in- Centres of Australia and New Zealand, were brought together to
gestions). Since the publication of the previous guidelines in the produce an updated evidence-­based guidance.
Medical Journal of Australia in 2015, further research has emerged, Main recommendations (unchanged from previous guidelines):
particularly regarding acetylcysteine regimens, massive parac- • The optimal management of most patients with paracetamol
etamol ingestions, and modified release paracetamol ingestion. overdose is usually straightforward. Patients who present early
should be given activated charcoal. Patients at risk of hepatotox-
These have led to a change in management of paracetamol poi-
icity should receive intravenous acetylcysteine.
soning, and the 2015 guidelines do not reflect the current prac-
tice recommended by clinical toxicologists. The key changes
• The paracetamol nomogram is used to assess the need for treat-
ment in acute immediate release paracetamol ingestions with a
from the previous guidelines are acetylcysteine regimen (two-­ known time of ingestion.
bag regimen) and dosage, management of patients taking large • Cases that require different management include modified re-
or massive overdoses, staggered ingestions, modified release lease paracetamol overdoses, large or massive overdoses, acci-
paracetamol ingestions and repeated supratherapeutic inges- dental liquid ingestion in children, and repeated supratherapeutic
tion. The full guidelines are available online in the Supporting ingestions.
Information. Major changes in management in the guidelines:
• The new guidelines recommend a two-bag acetylcysteine infu-
sion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h). This
Methods has similar efficacy but significantly reduced adverse reactions
compared with the previous three-bag regimen.
The Treatment of Paracetamol Poisoning Writing Group was • Massive paracetamol overdoses that result in high paracetamol
comprised of clinical toxicologists and pharmacologists from concentrations more than double the nomogram line should be
Australia and New Zealand. All members completed a detailed managed with an increased dose of acetylcysteine.
literature review and critically appraised existing evidence, in- • All potentially toxic modified release paracetamol ingestions
cluding reviewing the relevant chapters from the newly updated (≥  10  g or ≥  200  mg/kg, whichever is less) should receive a full
Australian Therapeutic Guidelines — Toxicology and toxinology.4 course of acetylcysteine. Patients ingesting ≥ 30 g or ≥ 500 mg/kg
Drafts of evidence-­based recommendations, practice points and should receive increased doses of acetylcysteine.
a background manuscript were developed. We conducted a
face-­to-­face meeting in May 2019 to draft the guideline. Further
revisions were made via email and teleconference. The sum- should be used to assess the need for acetylcysteine adminis-
mary recommendations follow the National Health and Medical tration in all patients presenting with deliberate self-­poisoning
Research Council levels of evidence (https​://www.mja.com.au/ with paracetamol, regardless of the stated dose. The parac-
sites/​defau​lt/files/​NHMRC.levels.of.evide​nce.2008-09.pdf) and etamol treatment nomogram (Box 2) can only be used in acute
the Grading of Recommendations Assessment, Development immediate release paracetamol ingestions with a known time
and Evaluation (GRADE) system (www.grade​worki​nggro​ of ingestion.
up.org) to determine the strength of the recommendations. We have summarised with flow charts the management of acute
immediate release paracetamol ingestion (Box 3), acute modified
Recommendations release paracetamol ingestion (Box 4), repeated supratherapeutic
ingestion (Box 5), and a management flow chart for rural and
Acute deliberate self-­poisoning, accidental paediatric exposure remote centres with limited pathology facilities (Box 6).
and inadvertent repeated supratherapeutic ingestions all require
specific approaches to risk assessment and management.
Acetylcysteine infusions
The initial approach focuses on risk assessment (Box 1). Key fac-
tors to consider for paracetamol poisoning are the formulation Acetylcysteine should be administered as a two-­bag regimen
and dose ingested, time since ingestion, and serum paracetamol (Box 7) — this has changed from previous guidelines. The
concentration (early), or clinical and laboratory features suggest- standard three-­bag intravenous weight-­based dosage regimen
MJA 2019

ing acute liver injury (late). Serum paracetamol concentration (150 mg/kg body weight over 15–60 min, then 50 mg/kg over

1
Prince of Wales Hospital and Community Health Services, Sydney, NSW. 2 NSW Poisons Information Centre, Children’s Hospital at Westmead, Sydney, NSW. 3 University of Otago, Dunedin,
New Zealand. 4 Victorian Poisons Information Centre, Austin Hospital, Melbourne, VIC. 5 Monash Health, Monash University, Melbourne, VIC. 6 Princess Alexandra Hospital, Brisbane, QLD. 7
Queensland Poisons Information Centre, Queensland Children’s Hospital, Brisbane, QLD. 8 Royal Perth Hospital, Perth, WA. 9 Western Australia Poisons Information Centre, Sir Charles 1
Gairdner Hospital, Perth, WA. 10 University of Sydney, Sydney, NSW. angela.chiew@health.nsw.gov.au ▪ doi: 10.5694/mja2.50428
 Guideline summary
be administered to a cooperative, awake adult if they present
1  Paracetamol dosing that may be associated with acute liver within 2 hours of ingestion of a toxic dose (Box 1) of immedi-
injury ate release paracetamol, or within 4 hours of immediate release
Acute single ingestion* Repeated supratherapeutic ingestion† paracetamol overdoses greater than 30  g.13–15 GRADE: Strong;
Evidence: Low.
≥ 10g or ≥ 200 mg/kg ≥ 10 g or ≥ 200 mg/kg (whichever is less) over
(whichever is less) a single 24-­hour period The paracetamol treatment nomogram has been validated as an
Or excellent predictor of risk but only for acute ingestions of imme-
diate release paracetamol with a known time of ingestion. The
≥ 12 g or ≥ 300 mg/kg (whichever is less) over
current nomogram used in Australia and New Zealand has not
a single 48-­hour period
changed (Box 3),7 except the units on the left and right axis have
Or now been swapped. It is important to check the units used, with
≥ a daily therapeutic dose ‡ per day for more many laboratories recently changing from μmol/L (right axis) to
than 48 hours in patients who also have mg/L (left axis). GRADE: Strong; Evidence: Strong.
abdominal pain or nausea or vomiting
Patients with a high initial paracetamol concentration (greater
* Acute ingestion is defined as any intentional or deliberate paracetamol overdose, in- than double the nomogram line) are at increased risk of acute
cluding staggered or multiple paracetamol ingestions over more than 2 hours. † Repeated
supratherapeutic ingestion refers to any patient who ingests paracetamol for therapeutic
liver injury if given standard acetylcysteine regimens.13,16,17 Only
intent. These doses are a guide for asymptomatic patients at risk for acute liver injury. All a small percentage of paracetamol overdoses will have a parac-
symptomatic patients should be assessed with a paracetamol concentration and alanine etamol concentration greater than double the nomogram line
aminotransferase (ALT). ‡ Therapeutic daily dose of paracetamol in adults is a total dose
of 60 mg/kg over 24 hours and up to a maximum dose of 4 g/day. For paediatric dosage,
and they typically have ingested 30 g or more of paracetamol.
please refer to local guidelines.◆ Those with an initial paracetamol concentration greater than
double the nomogram line may benefit from an increased dose
4 h and 100 mg/kg over 16 h; 300 mg/kg total) developed in the of acetylcysteine.5,13 The second bag in the two-­bag acetylcys-
1970s was empirically derived and not subject to dose ranging teine regimen should be doubled to 200  mg/kg intravenous
studies.5 This regimen has proven to be highly efficacious when acetylcysteine over 16 hours (instead of 100  mg/kg over 16  h).
compared with no treatment, but it causes frequent adverse re- Patients with even higher concentrations (eg, ≥ triple the nomo-
actions and the dosing regimen is complex and prone to error.6,7 gram line) may benefit from even higher acetylcysteine doses.5,18
A two-­bag acetylcysteine regimen slows the initial loading dose These patients should be discussed with a clinical toxicologist
and simplifies the protocol (ie, 200 mg/kg over 4 h followed by or a Poisons Information Centre. GRADE: Strong; Evidence: Low.
100  mg/kg over 16  h). This is widely used in toxicology units Near the completion of acetylcysteine (ie, 2 h before completion
around Australia and has been shown to significantly reduce the of the infusion), alanine aminotransferase (ALT) should be re-
rates of adverse reactions.8–12 GRADE: Strong; Evidence: Low. peated in all patients. For patients with an initial paracetamol
level greater than double the nomogram line, a paracetamol
Immediate release paracetamol ingestion concentration should also be repeated. Acetylcysteine should
be continued if the paracetamol concentration is greater than
The management of acute immediate release paracetamol inges- 10 mg/L (66 μmol/L) or ALT is elevated (> 50 U/L) and increas-
tion — defined as any intentional or deliberate self-­poisoning ing (if baseline ALT > 50 U/L). The normal reference range for
— is summarised in Box 3. ALT varies between pathology laboratories and with patient
age; an elevated ALT greater than 50  U/L is considered sig-
Recommendations on gastric decontamination have not
nificant. Small fluctuations in ALT (eg, ± 20 U/L or ± 10%) are
changed since 2015. Fifty grams of activated charcoal should
common and do not on their own indicate the need for ongoing
acetylcysteine. ALT should be repeated in all cases as
2  Paracetamol treatment nomogram (Rumack–Matthew nomogram) there is a small (<  1%) risk of developing acute liver
injury despite treatment with acetylcysteine within 8
hours.5,17,19,20 GRADE: Strong; Evidence: Low.

Multiple or staggered immediate release

paracetamol ingestions

Any multiple or staggered paracetamol ingestions

over more than 2 hours for the purpose of deliberate
self-­harm are distinct from repeated supratherapeutic
ingestions, which are ingestions of excessive paraceta-
mol for therapeutic purposes (Box 5). Staggered inges-
tions should be treated as per acute immediate release
paracetamol ingestion (Box 3) using the earliest time of
ingestion for the paracetamol nomogram. Hence, if it is
more than 8 hours since the first dose of paracetamol
MJA 2019

or the paracetamol concentration cannot be obtained

within 8 hours, then commence treatment with ace-
tylcysteine. If the first paracetamol concentration was
measured within 2 hours of the last ingested paraceta-
mol dose, it should be repeated after 2 hours to ensure
2
there is no ongoing absorption. If either concentration
 Guideline summary

3  Acute immediate release paracetamol ingestion management flow chart

MJA 2019

ALT = alanine aminotransferase. * Cooperative adult patients who have potentially ingested ≥ 10 g or ≥ 200 mg/kg (whichever is less). For paracetamol ingestions ≥ 30 g, activated charcoal
should be offered until 4 hours after ingestion. † Baseline ALT measurement. ‡ If paracetamol concentration will not be available until ≥ 8 hours after ingestion, commence acetylcysteine
while awaiting paracetamol concentration. § For acetylcysteine dosage, see Box 7. ¶ Patients should be advised that if they develop abdominal pain, nausea or vomiting, further assessment 3
◆
is required. For patients in rural or remote regions where pathology services are not available, see Box 6.
 Guideline summary

4  Acute ingestion modified release paracetamol management flow chart

MJA 2019

ALT = alanine aminotransferase; MR = modified release. * Patients should be advised that if they develop abdominal pain, nausea or vomiting, further assessment is required. † If parac-
4 ◆
etamol concentration is static or rising, a repeat dose of activated charcoal may be beneficial; please seek further advice. ‡ For acetylcysteine dosage, see Box 7.
 Guideline summary
or more (whichever is less) should be offered ac-
5  Repeated supratherapeutic ingestion management flow chart tivated charcoal up to 4 hours after ingestion. For
massive modified release paracetamol overdoses
(≥ 30 g or ≥ 500 mg/kg), absorption may continue
up to 24 hours after ingestion; patients may ben-
efit from activated charcoal beyond 4 hours.21
The nomogram should not be used to assess the
need for treatment of potentially toxic modified
release paracetamol ingestions. Paracetamol con-
centrations are useful to guide further manage-
ment such as acetylcysteine dosage (eg, the need
for increased or prolonged treatment) and the
need for further decontamination (eg, further
doses of activated charcoal if paracetamol concen-
trations remain unchanged or rise). Importantly,
all patients who ingest 10 g or more or 200 mg/kg
or more (whichever is less) of paracetamol should
immediately commence treatment with acetyl-
cysteine (Box 4) and receive a full 20-­hour course
of acetylcysteine regardless of their serum parac-
etamol concentration.
All patients who ingest 30 g or more or 500 mg/kg
or more of modified release paracetamol or have
a paracetamol concentration greater than double
the nomogram line should receive an increased
dose of acetylcysteine.21 The second bag in the
current standard intravenous acetylcysteine reg-
imen should be doubled to 200  mg/kg intrave-
nous acetylcysteine over 16 hours. This is because
the majority of the preparation is modified re-
lease and initial paracetamol concentrations may
only reflect the immediate release component of
the preparation. Hence, following large modified
release paracetamol ingestions, acetylcysteine
doses may be inadequate due to ongoing parac-
etamol absorption. Patients who report ingesting
less than a toxic dose (< 10 g and < 200 mg/kg)
should have two serum paracetamol concentra-
tions 4 hours apart, starting at least 4 hours after
ALT = alanine aminotransferase. * Therapeutic daily dose of paracetamol in adults is a total dose of 60 mg/kg
over 24 hours and up to a maximum dose of 4 g/day. For paediatric dosage, refer to local guidelines. † Patients
ingestion. If either is above the nomogram line,
with abnormal liver function tests, not felt to relate to paracetamol ingestion, should have further investigation a standard course of acetylcysteine should be
by their local medical provider for other causes. ‡ For acetylcysteine dosage, see Box 7. § If ALT > 1000 U/L, a given.
20-­hour course of acetylcysteine should be completed and a clinical toxicologist or Poisons Information Centre
should be consulted. ¶ Patients with significant acute liver injury secondary to paracetamol will have a very Acetylcysteine is often required for much longer
high and/or rapidly rising ALT. Small fluctuations in ALT (eg, ± 20 U/L or ± 10%) are common and do not on their
◆
own indicate the need for ongoing acetylcysteine. ** For criteria of when to cease acetylcysteine, see Box 8. durations. ALT and a paracetamol concentration
should be checked near the completion of the sec-
ond bag of acetylcysteine. Acetylcysteine should
is above the nomogram line (using time from the earliest inges- be continued if ALT is elevated (>  50  U/L) and increasing (if
tion), start or continue treatment with acetylcysteine. GRADE: baseline ALT > 50 U/L) or if the paracetamol concentration is
Weak; Evidence: Very low. 10  mg/L or over (66  μmol/L). Higher doses of acetylcysteine
may be required in subsequent infusions if the paracetamol
Modified release paracetamol ingestions concentration remains 100  mg/L or over (>  660  μmol/L) and
further advice should be sought. GRADE: Strong; Evidence: Very
Modified release paracetamol contains 69% modified release low.
and 31% immediate release paracetamol in a 665  mg tablet. In
the previous guidelines, management was very similar to that Rural and remote centres
for immediate release paracetamol. However, evidence from
case series from Australia and Europe has shown that this ap- Many rural and remote health care facilities do not have access to
MJA 2019

proach appears inadequate.21–23 Patients developed acute liver 24-­hour pathology or have very limited pathology services (eg,
injury despite standard treatment such as early acetylcysteine point of care testing only). These facilities can still manage cer-
and decontamination. Therefore, the recommended manage- tain acute paracetamol poisoning cases, provided acetylcysteine
ment has changed considerably (Box 4). All modified release is available and the patient is not at high risk of developing acute
paracetamol overdoses (including mixed ingestion of immediate liver injury. Box 6 outlines the management of acute immediate
and modified release paracetamol) of 10 g or more or 200 mg/kg release paracetamol ingestion for rural and remote facilities and
5
 Guideline summary

6  Acute immediate release paracetamol ingestion management flow chart for rural and remote facilities* (no pathology availability)

* This flow chart applies to facilities that do not have the capacity to measure a paracetamol concentration and/or alanine aminotransferase (ALT) but are able to administer intravenous
acetylcysteine. All other facilities should follow the immediate release paracetamol ingestion management flow chart (Box 3). Patients who have ingested modified release overdoses ≥ 10 g
or ≥ 200 mg/kg (whichever is less) should have activated charcoal and acetylcysteine started and transfer arranged. † For acetylcysteine regimen, see Box 7. ‡ These patients are at increased
◆
risk of acute liver injury and so require further assessment at a hospital that has pathology services.

the criteria for determining when transfer is required. GRADE: the adult acute paracetamol exposure guideline. GRADE: Strong;
Weak; Evidence: Very low. Evidence: Very low.

Paediatric liquid paracetamol ingestion

Repeated supratherapeutic ingestion
These recommendations are unchanged from the 2015 guide-
Patients who ingest excessive paracetamol for a therapeutic pur-
lines. In children under 6 years of age where ingestion of more
pose (eg, pain, viral illness) or ingest therapeutic doses of par-
than 200 mg/kg of liquid paracetamol is suspected, a serum par-
acetamol and have symptoms of acute liver injury (eg, abdominal
acetamol concentration should be measured at least 2 hours after
pain, nausea and vomiting) are managed as per repeated suprath-
ingestion.24 If the 2–4-­hour concentration is below 150  mg/L
erapeutic ingestion (Box 5). If the ingestion is deliberate or inten-
(1000 μmol/L), acetylcysteine is not required. If the 2-­hour par-
tional, they should be managed as per acute intentional ingestion.
acetamol concentration is greater than 150 mg/L (1000 μmol/L),
There is little evidence to guide risk assessment for repeated
this should be repeated 4 hours after ingestion and acetyl-
ingestion of high doses of paracetamol. The margin of safety
MJA 2019

cysteine commenced if this is 150 mg/L or more (1000 μmol/L).

has for many years been assumed to be high.25 Minor subclini-
A 2-­hour concentration should only be used in a well child cal elevations of serum ALT are quite common with prolonged
under 6 years of age with isolated liquid paracetamol ingestion. therapy.26 Hepatotoxicity has been reported at doses within the
In all other cases, a 4-­hour concentration should be performed. therapeutic range of paracetamol (in some cases at doses less than
6 Further, for children who present later than 4 hours after inges- the recommended 4 g/day). The reasons why certain individuals
tion or in children older than 6 years of age, treatment is as per are at greater risk of toxicity are unclear,27 but toxicity could be
 Guideline summary

7  Standard acetylcysteine regimen 8  Criteria for the cessation of ongoing treatment with
Standard two-­bag regimen* † acetylcysteine
Cessation of acetylcysteine
• Initial infusion
‣ acetylcysteine 200 mg/kg (maximum 22 g) in glucose 5% 500 mL • In patients who require acetylcysteine beyond 20 hours, acetylcysteine
(child, 7 mL/kg up to 500 mL) or sodium chloride 0.9% 500 mL (child, can be ceased if all the following criteria have been met:
7 mL/kg up to 500 mL) intravenously, over 4 hours ‣ ALT or AST are decreasing;
• Second acetylcysteine infusion ‣ INR < 2.0; and
‣ acetylcysteine 100 mg/kg (maximum 11 g) in glucose 5% 1000 mL ‣ patient is clinically well
(child, 14 mL/kg up to 1000 mL) or sodium chloride 0.9% 1000 mL
And
(child, 14 mL/kg up to 1000 mL) intravenously, over 16 hours†‡
• For modified release ingestions and patients with an initial paracetamol
• If ongoing acetylcysteine is required, continue at the rate of the second concentration greater than double the nomogram line, paracetamol
infusion (eg, 100 mg/kg over 16 h). Higher ongoing infusion rates (eg, concentration < 10 mg/L (66 μmol/L)
200 mg/kg over 16 h) may be required for massive paracetamol
ingestions and a clinical toxicologist should be consulted ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = international
normalised ratio.◆
* Acetylcysteine is also compatible with 0.45% saline + 5% dextrose. † For adults (aged
≥ 14 years), dosing should be based on actual body weight rounded up to the nearest 10 kg,
with a ceiling weight of 110 kg. For children (aged < 14 years), use actual body weight. ‡ If
the initial paracetamol concentration was more than double the nomogram line following (AST) decline. Acetylcysteine is generally continued at the rate
an acute ingestion, increase acetylcysteine dose to 200 mg/kg (maximum 22 g) in glucose of the second infusion (eg, 100 mg/kg over 16 h) (Box 7). Higher
5% 1000  mL (child, 14  mL/kg up to 1000  mL) or sodium chloride 0.9% 1000  mL (child,
14 mL/kg up to 1000 mL) intravenously, over 16 hours. Monitoring with pulse oximetry for
infusion rates may be warranted for massive paracetamol inges-
the first 2 hours of the infusion is recommended. ◆ tions, especially if the paracetamol concentration is 100 mg/L or
more (660 μmol/L) at the completion of the initial acetylcysteine
infusion — a clinical toxicologist should be consulted in such
influenced by age, comorbidities, alcohol use, nutritional status cases. Regular clinical review and blood tests at least every 12
(eg, prolonged fasting), concurrent medicine use, and genetics. hours are recommended for patients requiring prolonged treat-
Some patients are likely to be at increased risk for acute liver in- ment. GRADE: Strong; Evidence: Low.
jury after repeated supratherapeutic ingestion due to glutathione
depletion or cytochrome P450 (CYP450) induction. Clinical flags Hepatotoxicity and subsequent liver failure
would include pregnancy, prolonged fasting, chronic alcohol-
ism, febrile illness and chronic use of CYP450-­inducing drugs, Only a small proportion of patients develop hepatotoxicity (ALT
such as carbamazepine.28 Hence, the threshold for a potentially > 1000 U/L). Early symptoms include nausea, vomiting, abdomi-
toxic dose has been made deliberately and conservatively low in nal pain, and right upper quadrant tenderness. Of these, only a
these and previous guidelines. Patients who meet the criteria for minority will develop fulminant hepatic failure, and most pa-
supratherapeutic ingestion (Box 1) should have the paracetamol tients recover fully with standard treatments.33,34 Typically, in
concentration and ALT measured. There is evidence that the com- patients with paracetamol-­induced acute liver injury, ALT and
bination of a low paracetamol concentration and normal ALT at AST will rise for 3–4 days before recovering.35 Acetylcysteine is
any time indicates there is minimal risk of subsequent hepatotox- continued until the criteria in Box 8 are met. Investigations that
icity.29–31 If the paracetamol concentration is greater than 20 mg/L monitor liver function and guide prognosis should be performed
(132 μmol/L) or ALT is greater than 50 U/L, then acetylcysteine is regularly in all patients with hepatotoxicity, including electro-
commenced, and pathology repeated 8 hours after the initial sam- lytes, urea, creatinine, liver function tests, INR, blood sugar, phos-
pling. Acetylcysteine can be ceased at this stage if the paracetamol phate, and venous blood gas (looking at the pH and lactate levels).
concentration is less than 10 mg/L and ALT is less than 50 U/L
or static. Patients with significant acute liver injury secondary to A liver transplant unit should be consulted if any of the follow-
paracetamol will have a very high and/or rapidly rising ALT.30,32 ing criteria are met:
Small fluctuations in ALT (eg, ± 20 U/L or ± 10%) are common and
do not on their own indicate the need for ongoing acetylcysteine. • INR greater than 3.0 at 48 hours or greater than 4.5 at any time;
All patients with an initial ALT greater than 1000 U/L should re- • oliguria or creatinine greater than 200 μmol/L;
ceive at least a full 20-­hour course of intravenous acetylcysteine. • persistent acidosis (pH <  7.3) or arterial lactate greater than
GRADE: Strong; Evidence: Very low. 3 mmol/L;
• systolic hypotension with blood pressure below 80  mmHg,
Cessation of acetylcysteine despite resuscitation;
Some patients will require ongoing treatment with acetyl- • hypoglycaemia, severe thrombocytopenia, or encephalopathy
cysteine if they have a persistently high paracetamol concen- of any degree; or
tration greater than 10  mg/L (66  μmol/L) or ALT greater than • any alteration of consciousness (Glasgow Coma Score <  15)
50 U/L and increasing (if baseline ALT > 50 U/L) — small fluc- not associated with sedative co-ingestions.
tuations in ALT (eg, ± 20 U/L or ± 10%) are common and do not
on their own indicate the need for ongoing acetylcysteine. There Do not give clotting factors unless the patient is bleeding or after
is very little evidence to guide when is the optimum time to cease discussion with a liver transplant unit. GRADE: Strong; Evidence:
MJA 2019

acetylcysteine, with no published data on what is an acceptable Strong.

rate of decline in transaminases. In patients requiring ongoing
acetylcysteine, treatment should be continued until the patient Seeking advice from a Poisons Information Centre
has met all the criteria outlined in Box 8, with international nor-
malised ratio (INR) below 2 and the patient being clinically well It is recommended to seek advice from a Poisons Information 7
likely more important than the ALT/aspartate aminotransferase Centre in the following situations:
 Guideline summary

• very large overdoses — immediate release or modified release for more detailed information please access the full guidelines,
paracetamol overdoses of 50 g or over or 1 g/kg (whichever is available in the online Supporting Information.
less); If there are any concerns regarding the management of parac-
• high paracetamol concentration, more than triple the nomo- etamol ingestion, advice can always be sought from a clinical
gram line; toxicologist or a Poisons Information Centre (dialling 131126, in
• intravenous paracetamol errors or overdoses, as the treatment Australia, or 0800 764766, in New Zealand).
threshold is lower; Acknowledgements: Angela Chiew receives funding from a National Health and
• patients with hepatotoxicity (ie, ALT > 1000 IU/L); and Medical Research Council Early Career Fellowship (ID 1159907).

• neonatal paracetamol poisonings. Competing interests: Angela Chiew, Katherine Isoardi, Jessamine Soderstrom and
Nicholas Buckley were involved in the 2019 Australian Therapeutic Guidelines —
Toxicology and Toxinology Guidelines Writing Group and received travel and meeting
These are situations where the risk of hepatotoxicity and com- expenses. Jessamine Soderstrom receives royalties from the Toxicology handbook from
Elselvier. David Reith chairs the Medicines Adverse Reactions Committee for Medsafe.
plications is greater, where the optimum advice is potentially
changing, and where it may be most useful to seek advice. Provenance: Not commissioned; externally peer reviewed. ■
Conclusion This article is a summary of the full guidelines, available online in the Supporting
Information.

This is a summary of the updated guidelines for the manage-

ment of paracetamol poisoning in Australia and New Zealand, © 2019 AMPCo Pty Ltd

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