paracetamol overdose

introduction:

this paper is a brief summary of the MJA 2019 consensus guidelines on Mx of paracetamol overdose to assist in efficient care.
the far majority of paracetamol overdoses do not have any long term sequelae, however, some patients are at risk of developing potentially lethal hepatotoxicity over the succeeding few days due to a toxic metabolite which fortunately can be almost totally prevented if given IV N-acetylcysteine (NAC) within 8-12 hours of ingestion.
The N-acetyle cysteine (Parvolex) infusion is usually for 20 hours and thus if adult patients deemed safe from a security risk viewpoint, then consider admission to an ED Short Stay Observation Unit (SSU).

determine timing and dose of overdose.
should the patient be offered activated charcoal?
does the patient need N-acetyle cysteine (Parvolex) and should it be started NOW instead of waiting on blood levels?
could the patient have taken other dangerous medications in overdose concomitantly?
is the patient safe for discharge from a medical viewpoint?
is the patient safe for discharge from a mental health viewpoint (ie. what is the risk of suicide, etc)?

all self-poisonings where paracetamol may have been accessed
unintentional overdosages which may be at hepatotoxic levels (see below)
the patient shows clinical signs suggestive of paracetamol hepatotoxicity (nausea, vomiting, right upper quadrant pain or tenderness) and paracetamol toxicity may be possible
this should be done at least 4hrs post-ingestion
add INR if > 24hrs since ingestion
add U&E, LFTs, INR and VBG if referred in with an elevated ALT to assess pH and lactate
at Western Health, as a minimum, order FBE, U&E, LFTs, glucose, serum paracetamol +/- HCG and others as indicated

cooperative adult patients who have potentially ingested:
- immediate release paracetamol ≥ 10g or 200 mg/kg (whichever is less) within 2 hours, or,
- immediate release paracetamol ≥ 30 g within 4 hours post ingestion, or,
- modified-release paracetamol ≥ 10 g or ≥ 200 mg/kg (whichever is less) within 4 hours
  - Note in larger overdoses activated charcoal may be indicated up to 24 hours post-ingestion.
dose: adults 50g
NB. activated charcoal is NOT indicated in children under 6 years of age, even if they might have ingested a toxic dose of paracetamol as significant hepatic injury is extremely rare in this group.

Treatment with acetylcysteine ensures survival if administered within 8 hours of paracetamol ingestion
Beyond 8–10 hours after ingestion, efficacy decreases with increasing delay to treatment
all those who ingest ≥ 10 g or 200 mg/kg (whichever is less) should immediately commence acetylcysteine and receive a full 20 hour course of acetylcysteine regardless of their serum paracetamol concentration(s).

acute immediate release ingestions where serum levels will not be available within 8hrs of ingestion (or time unknown or more than 8hrs ago) and EITHER:
- ingestion is likely to be at hepatotoxic levels (see below)
- the patient shows clinical signs suggestive of paracetamol hepatotoxicity (nausea, vomiting, right upper quadrant pain or tenderness)
serum paracetamol above the nomogram line (see below)

Consult the Liver Transplant Unit (or your local gastroenterology unit) if ANY of:
- INR > 3.0 at 48 hours or > 4.5 at any time
- oliguria or creatinine > 200 μmol/L,
- persistent acidosis (pH < 7.3) or arterial lactate > 3 mmol/L
- systolic hypotension with BP < 80mmHg, despite resuscitation
- hypoglycaemia, severe thrombocytopenia or encephalopathy of any degree,
- hepatic encephalopathy or any alteration of consciousness (GCS < 15) not associated with sedative co-ingestions.
DO NOT GIVE clotting factors unless bleeding or after discussion with a Liver Transplant Unit

if full infusion regime indicated, a repeat serum paracetamol and ALT should be done just prior to the 20 hour infusion ending to ascertain whether an ongoing infusion is required

NAC initial infusion regime can be ceased if:
- serum paracetamol > 4hrs post-ingestion under the nomogram AND serum ALT ≤ 50 U/L, OR,
- infusion regime completed and no ongoing infusion indicated (see below)
Indications for ongoing infusion at the rate of the 2nd bag of NAC:
- Paracetamol concentration > 10 mg/L (66 μmol/L), OR
- ALT > 50 U/L and increasing (if baseline ALT > 50 U/L) BUT small fluctuations in ALT (e.g. +/- 20 U/L or +/-10%) are common and do not on their own indicate the need for ongoing acetylcysteine.
Cease the ongoing infusion if ALL of the following apply:
- ALT or AST are decreasing
- INR < 2.0
- Patient clinically well
- for modified-release ingestions and those with an initial paracetamol concentration greater than double the nomogram line, paracetamol concentration has fallen below 10 mg/L (66 μmol/L)

Patients should be advised if they develop abdominal pain, nausea or vomiting further assessment is required.