Paracetamol poison

Last Updated on by FRCEM Intermediate

Mechanism

  • Once the reserves of glutathione are depleted, the toxic metabolite NAPQI builds up and causes hepatic necrosis

Clinical features:

  • Often asymptomatic
  • Nausea and vomiting (settles with 24 hrs)
  • Right subcostal pain (suggests development of hepatic necrosis)
  • AKI
  • Hepatic necrosis

Management

Calculate ingested dose in mg/kg

  • Disregard any additional kilos in excess of 110 kg
  • If pregnant, enter pre-pregnancy, not actual weight
  • All paracetamol ingestions > 75 mg/kg are significant
  • Check paracetamol level at 4 hours

If ingestion < 1 h ago AND dose > 150 mg/kg:

  • Give single dose activated charcoal 50 g PO with IV antiemetic
  • Delay blood sampling until 4 h post-ingestion
  • Admit to observation ward while sampling awaited

If single ingestion > 1 h but < 4 h ago:

  • Delay blood sampling until 4 h post-ingestion
  • Admit to observation ward while sampling awaited
  • After 4 h, obtain venous gas, INR, U&E, LFT, FBC and paracetamol level and await results

 

If single ingestion ≥ 4 h but < 8 h ago…

And dose < 150 mg/kg OR dose > 150 mg/kg and it will be possible to act on blood results within 8 h of ingestion:

  • Obtain venous gas, INR, U&E, LFT, FBC and paracetamol level and await results

And dose > 150 mg/kg and it will not be possible to act on blood results within 8 h of ingestion:

  • Start NAC within 1 h of arrival and obtain venous gas, INR, U&E, LFT, FBC and paracetamol level

 

If single ingestion 8 – 24 h ago…

And dose is < 150 mg/kg

  • Obtain venous gas, INR, U&E, LFT, FBC and paracetamol level and await results

And dose is > 150 mg/kg

  • Start NAC within 1 h of arrival and obtain venous gas, INR, U&E, LFT, FBC and paracetamol level

 

If single ingestion > 24 h ago:

  • If jaundice or liver tenderness, start NAC immediately and admit to AMU (check if referral to liver unit is required) Otherwise, obtain venous gas, INR, U&E, LFT, FBC and paracetamol level and await results

If ingestion is staggered (ingestion over longer than 1 h) or timingunclear:

  • Start NAC within 1 h of arrival and obtain venous gas, INR, U&E, LFT, FBC and paracetamol level (if necessary, delay blood sampling to ensure that 4 h have passed since last tablets were taken)

 

NAC Treatment Required

Start or continue NAC if any of the following are true (if possible, within 8h of ingestion):

  • 4 – 15 h after single ingestion, paracetamol level is on or above treatment line
  • >15 h after single ingestion, paracetamol is still detectable
  • >4 h after last tablets of a staggered ingestion, paracetamol is detectable
  • >4 h after ingestion of uncertain timing, paracetamol is detectable
  • INR > 1.3
  • ALT > 53 IU/L

If INR, ALT or creatinine are raised, admit to AMU. If blood results are normal, manage on ED observation ward.

 

NAC is not required or can be discontinued if:

  • Paracetamol level is below the treatment line at 4 – 15 h post-ingestion

OR

  • Paracetamol is undetectable > 15 h after single ingestion

OR

  • Paracetamol is undetectable > 4 h after last tablets of staggered ingestion or ingestion of uncertain timing
  • AND: ALT is within normal range, INR < 1.3 ,Patient has no symptoms suggesting liver damage

If creatinine is raised, admit to AMU. If creatinine is normal, manage self-harm. Discuss with ED senior if other blood results are abnormal or if patient complains of nausea or abdominal pain.

N-acetylcysteine regime

  • 150mg/kg in 200mIs of 5% dextrose over 1 hour
  • 50mg/kg in 500mIs of 5% dextrose over 4 hours
  • 100mg/kg in IL of 5% dextrose over 16 hours

Post NAC management

  • Repeat INR and biochemistry
  • Give further NAC if:
    • Transaminase activity:
    • >2 x admission level
    • 3 x normal maximum
    • If INR > 1.3

High risk patients

Patients with induced liver enzymes

  • Medications — anti-epileptics (carbamazepine, phenobarbitone, phenytoin), St. John’s wort, rifampicin
  • Alcohol

Patients with reduced glutathione

  • Anorexia
  • Pre-existing liver disease, HIV

Indications for liver transplant:

  • pH < 7.30
  • INR > 6.5 AND serum creatinine > 300 micromol/L AND grade 3 or 4 encephalopathy (within a 24 h period)
  • Arterial lactate > 3.5 mmol/L after 4 h of early fluid resuscitation
  • Arterial lactate > 3.0 mmol/L after 12 h off fluid resuscitation

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