Guidelines Clinical focus

Summary statement: new guidelines for

the management of paracetamol
poisoning in Australia and New Zealand

A
large proportion of accidental paediatric expo-
sures and deliberate self-poisoning incidents
involve paracetamol; it is the leading pharma-
ceutical agent responsible for calls to Poisons Informa-
tion Centres in Australia and New Zealand.
Management of paracetamol poisoning has altered since
the previous guidelines were published in 2008 to reflect
current practice by clinical toxicologists. The key
changes from the previous guidelines concern the in-
dications for administration of activated charcoal; the
management of patients taking large or massive over-
doses; modified-release and supratherapeutic in-
gestions; and paediatric liquid paracetamol ingestion.

Main recommendations

The management of patients with paracetamol overdose 4 hours after ingestion. For massive modified-release
is usually straightforward. Acute deliberate self- paracetamol overdoses, absorption may continue until
poisoning, accidental paediatric exposure and inadver- 24 hours after ingestion, and patients may still benefit
tent repeated supratherapeutic ingestions all require from activated charcoal treatment after more than
specific approaches to risk assessment and management. 4 hours.

Each initially involves a risk assessment (Box 1). The key

Modified-release paracetamol
factors to consider in paracetamol poisoning are the
ingested dose and serum paracetamol concentration As per the previous guideline, acetylcysteine treatment
(early), or clinical and laboratory features suggesting liver should be started immediately if more than 200 mg/kg or
Angela L Chiew 10 g (whichever is lower) has been ingested. Two assess-
BSc(Med), MB BS, FACEM1,2 damage (late). Serum paracetamol concentration should
be used to assess the need for acetylcysteine administra- ments of serum paracetamol concentration 4 hours apart
John S Fountain
MB ChB, MEntr3 tion in all patients presenting with deliberate self- are required, the first at least 4 hours after ingestion.

Andis Graudins
poisoning with paracetamol, regardless of the stated The recommendation about when to discontinue ace-
MB BS, PhD, FACEM4,5 dose. The management of acute paracetamol exposure tylcysteine infusion has changed. Serial paracetamol
Geoffrey K Isbister
with known time of ingestion is summarised in a man- concentrations, measured 4 hours apart, must be below
BSc, MD, FACEM6,7 agement flow chart (Box 2) and the management of the nomogram line and decreasing. Furthermore, near the
David Reith
supratherapeutic ingestion is shown in Box 3. completion of acetylcysteine infusion (ie, 2 hours before
FRACP, PhD3 completion of infusion), serum alanine aminotransferase
The paracetamol treatment nomogram has not changed;
Nicholas A Buckley the acetylcysteine regimen remains the same as in the (ALT) and paracetamol concentrations should be
2
BMed, FRACP, MD measured. Acetylcysteine infusion should be continued if
previous guidelines.
the ALT level is increasing (> 50 U/L) or the paracetamol
1 Prince of Wales Hospital,
Sydney, NSW. concentration is greater than 10 mg/L (66 mmol/L).
2 University of Sydney, Changes in management
Sydney, NSW.
Large or massive paracetamol overdoses
3 University of Otago,
Dunedin, Otago,
Gastric decontamination Patients who ingest large or massive doses of paracetamol
New Zealand.
were not discussed in previous versions of the guidelines.
4 Monash University, It was previously recommended that activated charcoal
Melbourne, VIC. Most patients ingest less than 30 g of paracetamol; only a
be administered within 1 hour of paracetamol ingestion.
5 Monash University and small percentage of overdoses involve a paracetamol
Monash Health, Dandenong, The current guideline advises that 50 g of activated
VIC. concentration greater than double the nomogram line.
charcoal should be administered to a cooperative, awake
6 University of Newcastle, Those who ingest greater doses may have decreased
Newcastle, NSW.
adult within 2 hours of ingestion of a toxic dose of
paracetamol clearance and increased risk of hepatotox-
7 Calvary Mater, Newcastle, immediate-release paracetamol, and within 4 hours of
icity despite treatment, and may benefit from modifica-
NSW. modified-release paracetamol ingestion (Box 2).
tion of the standard paracetamol management. Patients
a_chiew@[Link]
For immediate-release paracetamol overdoses of greater considered at high risk of hepatotoxicity are those whose
doi: 10.5694/mja15.00614 than 30 g, activated charcoal should be administered up to initial paracetamol concentration is high.

MJA 203 (5) j 7 September 2015

215
Clinical focus Guidelines

Although no randomised control trials have investi-

1 Paracetamol dosing that may be associated with hepatic injury
gated optimum acetylcysteine dosage in these patients,
Adults and children > 6 years Children (aged 0e6 it is the practice of many clinical toxicologists to adjust
of age years)* the dose in large paracetamol overdoses. Who might
Acute single > 200 mg/kg or 10 g (whichever is > 200 mg/kg over a period benefit from an increase in acetylcysteine dose and the
ingestion lower) over a period of <8 hours of < 8 hours optimum dose have not yet been determined. One
Repeated > 200 mg/kg or 10 g (whichever is > 200 mg/kg over a single approach, in patients with a paracetamol concentration
supratherapeutic lower) over a single 24-hour period 24-hour period more than double the nomogram line, is to double the
ingestion concentration of the 16-hour infusion of acetylcysteine
> 150 mg/kg or 6 g (whichever is > 150 mg/kg per 24-hour
lower) per 24-hour period for the period for the preceding
from 100 mg/kg (current standard acetylcysteine third-
preceding 48 hours 48 hours bag infusion) to 200 mg/kg intravenous acetylcysteine.
Serum ALT and paracetamol levels should be checked
> 100 mg/day or 4 g/day > 100 mg/kg per 24-hour near the completion of acetylcysteine infusion. Ace-
(whichever is lower) per 24-hour period for more than
tylcysteine should be continued if the ALT level is
period, for more than 48 hours in 48 hours
those who also have symptoms increasing (> 50 U/L) or the paracetamol concentration
indicating possible liver injury is greater than 10 mg/L (66 mmol/L). The Poisons In-
(eg, abdominal pain, nausea or formation Centre or a clinical toxicologist may be
vomiting) consulted for the most current advice on managing
* For obese children, the body weight used for calculations should be an ideal body weight. u these patients, including the optimal acetylcysteine
regimen.

2 Management flow chart for acute paracetamol exposure with known time of ingestion

ALT ¼ serum alanine aminotransferase. u

216 MJA 203 (5) j 7 September 2015

 Guidelines Clinical focus

3 Management flow chart for repeated supratherapeutic paracetamol ingestion

ALT ¼ serum alanine aminotransferase. u

Liquid paracetamol ingestion by children less 150 mg/L (1000 mmol/L), it should be measured again
than 6 years of age 4 hours after ingestion, and acetylcysteine infusion
No recommendations were made in the previous guide- commenced if the value is still greater than 150 mg/L
line. When ingestion of more than 200 mg/kg of liquid (1000 mmol/L), as per the paracetamol nomogram.
paracetamol by a child under 6 years of age is suspected The 2-hour paracetamol concentration should only be
(in obese children, this should be based on an ideal body used to guide management in a healthy child less than
weight), serum paracetamol concentration should be 6 years of age, after an isolated liquid paracetamol
measured at least 2 hours after ingestion. If the concen- ingestion. In all other cases, such as children who present
tration 2e4 hours after ingestion is less than 150 mg/L later than 4 hours after ingestion, and children who are
(1000 mmol/L), acetylcysteine is not required. If the older than 6 years of age, treatment is the same as that for
2-hour paracetamol concentration is greater than acute paracetamol exposure in adults.

MJA 203 (5) j 7 September 2015

217
Clinical focus Guidelines

Repeated supratherapeutic ingestion  persistent acidosis (pH < 7.3) or arterial lactate
Patients should have serum paracetamol and ALT con- > 3 mmol/L;
centrations measured if they meet the criteria for supra-  systolic hypotension with blood pressure less than
therapeutic ingestion (Box 1). The main changes in the 80 mmHg, despite resuscitation;
guidelines concern the criteria for assessment in those  hypoglycaemia;
who have ingested more than 100 mg/kg per day or
 severe thrombocytopenia;
4 g/day (whichever is lower) per 24-hour period for
longer than 48 hours. Patients only require assessment if  encephalopathy of any degree, or any alteration of
they have symptoms such as abdominal pain or nausea or consciousness (Glasgow coma scale < 15) not associ-
vomiting. Management is outlined in Box 3. ated with co-ingestion of sedatives.

Conclusions
Acetylcysteine dosing recommendation
The guideline essentially remains unchanged, except that This is a summary of the updated guidelines for the
dosing should be based on actual body weight rounded management of paracetamol poisoning in Australia and
up to the nearest 10 kg, with a ceiling weight of 110 kg. New Zealand. The full guidelines are available on
the website of the Medical Journal of Australia ([Link].
[Link]/sites/default/files/issues/203_05/Guidelines_
Hepatotoxicity paracetamol_Aus_NZ_2015.pdf).
This was not discussed in detail in the previous guide-
Where there are any concerns regarding the management
lines. Acetylcysteine should be continued until the patient
of paracetamol ingestion, advice can always be sought
is clinically improving, ALT levels are decreasing, the
from a clinical toxicologist or the Poisons Information
international normalised ratio (INR) is improving and
Centre (telephone: 13 1126 in Australia, 0800 764 766 [0800
less than 2, and the paracetamol concentration is less than
POISON] in New Zealand).
10 mg/L (66 mmol/L). Regular clinical review and
12-hourly (or more frequent) blood tests are recom- Acknowledgements: We thank Clinical Associate Professor Simone Strasser (Royal
Prince Alfred Hospital) and transplant hepatologists from around Australia and the King’s
mended if there is clinical deterioration. College, London, for their input regarding patients requiring discussion with a liver
transplant unit.
A liver transplant unit should be consulted if any of the
Competing interests: No relevant disclosures.
following criteria are met:
Provenance: Commissioned; not externally peer reviewed. n
 INR > 3.0 at 48 hours or > 4.5 at any time;
 oliguria or creatinine > 200 mmol/L; ª 2015 AMPCo Pty Ltd. Produced with Elsevier B.V. All rights reserved.

218 MJA 203 (5) j 7 September 2015