Paracetamol overdose Adults



These guidelines relate to adult patients only. For paediatric patients please use "Paracetamol XS Paediatrics" and discuss with your EM senior.


Background

  • Hepatocellular necrosis is the major toxic effect.
  • Biochemical evidence of maximal damage may not be attained until 72 - 96 hours after ingestion.
  • At risk dose is more than 75mg paracetamol/kg body weight.
  • Severe liver damage is defined as a peak plasma ALT exceeding 1000 u/L.
  • Those who present > 12 hours post ingestion tend to be more severely poisoned and at greater risk.
  • Acute renal tubular damage and necrosis may also occur.
  • If there is doubt about the timing or the need for treatment - treat.
  • Methionine is ineffective in patients who have been given oral activated charcoal.
  • NAC is the treatment of choice when patients are vomiting or present more than 8 hours after ingestion..

High risk patients

  • Regular alcohol ingestion
  • Other enzyme (liver microsomal oxidases) inducers (e.g. carbamazepine, phenytoin, phenobarbitone, primidone and rifampicin)
  • Glutathione depletion (e.g. malnutrition and HIV)

Do NOT take plasma levels within 4 hours of ingestion as they are unreliable.

But patients may give inaccurate histories. If in doubt, treat with NAC.


Staggered overdose

Treat with NAC and admit to the CDU.


Treatment nomogram

Antidote doses ADULT

NAC Adult Dosing
Adult NAC prescription
Each ampoule = 200mg/mL acetylcysteine
Please circle appropriate weight and volume
Regimen 1st infusion 2nd infusion 3rd infusion
Fluid 200 mLs 5% DW or NaCl 0.9% 500mLs 5%DW or NaCl 0.9% 1000 mLs 5%DW or NaCl 0.9%
Duration of infusion 1 hour 4 hours 16 hours
Drug dosage 150 mg/kg NAC 50 mg/kg NAC 100 mg/kg NAC
Patient Wt1
(kg)
Ampoule vol2
(ml)
Infusion rate
(ml/h)
Ampoule voll 2
(ml)
Infusion rate
(ml/h)
Ampoule vol 2
(ml)
Infusion rate
(ml/h)
40-49 34 234 12 128 23 64
50-59 42 242 14 129 28 64
60-69 49 249 17 129 33 65
70-79 57 257 19 130 38 65
80-89 64 264 22 131 43 65
90-99 72 272 24 131 48 66
100-109 79 279 27 132 53 66
>110 83 283 28 132 55 66

1 Dose calculations are based on the weight in the middle of each band. If the patient weighs less than 40kg use the paediatric dosage table.

2 Ampoule volume has been rounded up to the nearest whole number

Please Note: The Summary of Product Characteristics should be referred to for full prescribing information.  This version is provided by the MHRA and is subject to further user-testing.


Management of Adult patients who present within 8 hours of ingestion

  • Consider charcoal if more than 150 mg/kg body weight taken and presentation within 1 hour of ingestion.
  • Take blood for plasma paracetamol concentration at 4 hours post ingestion.
  • Assess whether at high risk of severe liver damage (see above).
  • Confirm timings of ingestion.
  • If presenting with in 4 hours of ingestion, do not start NAC immediately. Wait until 4 hours post ingestion and take P&S levels. Start NAC if level taken at 4 hours is in the appropriate treatment range.
  • If the paracetamol concentration result is not available within 8 hours of ingestion ( > 150 mg/kg or > 12 g in total) start NAC immediately. It can be stopped later if subsequent level well below treatment line.

Mx of all patients who present 8-15 hours after ingestion.

  • Urgent action is required ( antidote efficacy drops sharply).
  • Give NAC immediately without waiting for the result of the plasma paracetamol concentration measurement if it is thought that more than 150 mg/kg body weight or a total of 12 g or more has been ingested.
  • Take P&S levels, INR, creatinine and ALT.
  • If the paracetamol concentration result is not available within 8 hours of ingestion ( > 150 mg/kg or > 12 g in total) start NAC immediately.
  • In patients already receiving NAC, only discontinue NAC if the plasma paracetamol concentration is below the treatment line on the graph and there is no abnormality of the INR, plasma creatinine or ALT and the patient is asymptomatic. Continue the infusion if there is any doubt as to the timing of the overdose.
  • At the end of NAC infusion check INR and plasma creatinine concentration.
  • Patients who are symptomatic or in whom the INR and/or plasma creatinine are abnormal require further monitoring.
  • Vitamin K should be given if the INR is increased.
  • FFP / clotting factors are only indicated for active bleeding.

Mx of patients who present 15-24 hours after ingestion:

  • Start all patients on an infusion of NAC.
  • Measure the plasma paracetamol concentration on admission.

The infusion may be stopped and the patient discharged from medical care if each of the following criteria is met:

  • The patient is asymptomatic.
  • The INR and plasma creatinine are normal.
  • The plasma paracetamol concentration is less than 10 mg/L (0.07 mmol/L) 24 hours after ingestion.
  • Patients in whom the INR and/or plasma creatinine are abnormal or whose plasma paracetamol concentrations exceed 10 mg/L at 24 hours after ingestion require further monitoring and contact with a hepatologist.

Mx of patients who present longer than 24 hours after ingestion:

  • All should have their INR, plasma creatinine concentration, ALT and venous pH (or hydrogen ion / bicarb concentration) determined.
  • We recommend that they all be discussed with a poisons information centre or a specialist liver or poisons unit.

Specialist advice on those with liver disease.

Patients who develop severe liver damage may merit discussion with a specialist liver unit (not necessarily a liver transplant unit). Such discussions are likely to be of greater benefit if they are held early. Patients in this category include those who have an INR greater than 3.0, an elevated plasma creatinine, evidence of acidosis or encephalopathy, hypotension (mean arterial pressure less than 60 mmHg) or pre-existing liver disease.


Adverse reactions to NAC

  • N-acetylcysteine adverse effects may be localised to infusion site or be more generalised.
  • Usually occur during the first 30 minutes of administration (large dose given rapidly).
  • Include nausea, flushing, itching, erythematous rashes, urticaria, angioedema, bronchospasm and, rarely, ↑BP or ↓BP.
  • Infusion of NAC should be stopped and an antihistamine given.
  • Once adverse effects settled, resume infusion at the lowest infusion rate (100 mg/kg over 16 hours).


Content by Dr Íomhar O' Sullivan 23/06/2000.   Reviewed by Dr ÍOS 10/07/2004 and 14/02/2007. Based upon 2007 guidelines published by the Paracetamol Information Centre and TOXBASE. Last review dateDr ÍOS 7/11/18