paracetamol toxicity

Survival from a paracetamol overdose is generally considered to be 100% in cases receiving NAC within 8 hours of exposure.

Most overdoses presenting to ED are straightforward.
History Risk factors for toxicity:
- alcohol use
- phenytoin, carbamazepine, rifampicin, phenobarbitol
- depleted glutathione: starvation/eating disorders, HIV, cystic fibrosis

Ingestions >75mg/kg/24h are significant
Clinical presentation toxicity risk peaks 48-96h
Pathogenesis - most paracetamol metabolised by glucuronidation, a small portion by CYP2E1 → produces NAPQI
- with adequate glutathione, NAPQI is detoxified to conjugation
- when glutathione depleted, e.g. in massive overdose, NAPQI binds to numerous proteins = toxicity
→ leading to uncoupling of oxidative phosphorylation = failure of ATP synthesis, release of Ca from mitochondrial stores, lactic acidosis
Diagnostic investigations U+E
LFT and coag screen - liver function
As with the sick liver patient
Management - N-acetylcisteine - converted to glutathione → conventionaly SNAP protocol (finishes within 12h)
- NAC is well known for Anaphylactoid reaction - stop, chlorphenamine, resume at half rate
- Toxic dose = 150mg/kg

important guidelines

Toxbase - SNAP protocol

nomogram limitations

  • assumes immediate release paracetamol

continuing after initial infusion (Toxbase)

For SNAP regime: take bloods just before end of 2nd treatment bag. Check if:

  • ALT is above the upper limit of normal, OR
  • ALT doubled or more from admission, even if within normal range, OR
  • paracetamol concentration >10mg/L
    If true, continue infusion at rate and dose of 2nd bag (10h bag)

After 22h NAC (2nd 10h bag), check if

  • the ALT is more than two times the upper limit of normal, OR
  • the ALT is above the upper limit of normal and increased from the previous value AND doubled or more since the admission measurement, OR
  • the INR is greater than 1.3 and increased from previous value (in the absence of another cause e.g. warfarin) AND the ALT is above the upper limit of normal.
    If true, NAC should be continued at rate and dose of 3rd bag

Re-check INR, U+E, ALT every 10h

side notes about critically unwell patients

  • compensation for metab acidosis → ventilate with higher MV

King's college criteria

pH < 7.3, or

In a 24h period, all 3 of:

  • INR > 6 (PT > 100s) +
  • Cr > 300mmol/L +
  • grade III or IV encephalopathy

#incomplete #toxicology

https://litfl.com/paracetamol-toxicity/
https://derangedphysiology.com/main/required-reading/environmental-injuries-and-toxicology/Chapter-511/paracetamol-toxicity
https://www.toxbase.org/information/miscellaneous/paracetamol/paracetamol---guidance-on-when-to-take-bloods-and-interpretation-of-these-results-at-the-end-of-the-modified-12-hour-acetylcysteine-infusion-regimen-snap/