Paracetamol Toxicity

Last Updated on by frcemuser

Overview

  • glutathione depletion leads to the builds up of toxic metabolite NAPQI and causes hepatic necrosis

Initial assessment

Calculate ingested dose in mg/kg to work out if significant ingestion:

  • Disregard any additional kilos in excess of 110 kg
  • If pregnant, enter pre-pregnancy, not actual weight
  • All paracetamol ingestions ≥ 75 mg/kg/24hrs are significant
  1. 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
    • After 4 h, obtain venous gas, INR, U&E, LFT, FBC and paracetamol level and await results
  2. 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
  3. 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
  4. 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
  5. 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
  6. If ingestion is staggered (ingestion over longer than 1 h) or time of ingestion is unknown:
    • 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 – 24 h after single ingestion, paracetamol level is on or above treatment line
  • >24 h after single ingestion, paracetamol is still detectable
  • >4 h after last tablets of staggered ingestion, paracetamol is detectable
  • >4 h after ingestion of uncertain timing, paracetamol is detectable
  • INR > 1.3
  • ALT > 53 IU/L

(N.B. The level of detection of paracetamol is 10 mg/L.)

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

NAC treatment not required

NAC is not required or can be discontinued if:

  • Paracetamol level is below the treatment line at 4 – 24 h post-ingestion
  • OR
  • Paracetamol level is undetectable > 24 h after single ingestion
  • OR
  • Paracetamol level 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.

21-hour NAC regime

Infusion NAC dose Infusion fluid Duration
1 150 mg/kg 200 mL 1 h
2 50 mg/kg 500 mL 4 h
3 100 mg/kg 1000 mL 16 h

 

Re-check the INR, plasma creatinine and ALT at, or just before, the end of the 21 hours of infusion. Paracetamol concentration should only be re-checked at the end of the 21 hour infusion if a large overdose was ingested. If re-checked continue NAC therapy if the paracetamol concentration is above the therapeutic range i.e. 20 mg/L or more. In patients with severe liver toxicity, also check lactate, venous pH or plasma bicarbonate.

Acetylcysteine treatment may be stopped if the blood results meet the following criteria:

  • INR is 1.3 or less, AND
  • ALT is within the normal range
  • If the ALT is above the normal range (with an INR of 1.3 or less), acetylcysteine may still be stopped if:
    • ALT is less than two times the upper limit of normal AND
    • The increase in ALT value is not more than a doubling of the admission value

Acetylcysteine should be continued if blood results are abnormal and meet ANY of the following criteria:

  • the ALT is more than two times the upper limit of normal OR
  • the ALT has doubled or more since the admission measurement AND is above the upper limit of normal OR
  • the INR is greater than 1.3 (in the absence of another cause e.g. warfarin) AND the ALT is above the upper limit of normal OR
  • the INR has risen by 0.5 or more from the admission measurement

If acetylcysteine is to be continued, continue at the dose and infusion rate used in the 3rd treatment bag. It is not necessary to give a further loading dose unless a second overdose has been taken. Repeat all blood tests in a further 8-16 hours.

NAC adverse reactions

  • anaphylactoid reactions is NOT a contraindication to intravenous acetylcysteine in patients with paracetamol overdose when antidote treatment is clinically indicated.
  • Reactions can often be controlled by simply stopping the infusion temporarily.
  • Consider giving chlorphenamine 10 mg IV and nebulised salbutamol 5 mg if bronchospasm is present.
  • Once reaction has settled, restart the first bag at half the rate, then give the 2nd and 3rd bag at the normal rate.

Referral for liver transplant

  • Arterial pH < 7.30
  • INR > 6.5 (PT > 100 sec)
  • Creatinine 3.4 mg/dL (300 µmol/L)
  • Grade III or IV hepatic encephalopathy

+/-

  • Lactate > 3.5 mmol/L after fluid resuscitation (<4 hrs) OR lactate > 3 mmol/L after full fluid resuscitation (12 hours)
  • Phosphate > 3.75 mg/dL (1.2 mmol/L) at 48-96 hours

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