GGC Medicines


Adult Therapeutics Handbook

Treatment of Paracetamol Overdose

Treatment of Paracetamol Overdose

This guideline reflects the guidance on management of oral paracetamol overdose issued from the Medicines and Healthcare Products Regulatory Agency (MHRA) in September 2012.

Further information can be found on www.toxbase.org (password required) (or contact the National Poisons Information Service (NPIS, 0344 892 0111)), including guidance for other situations and patient groups (e.g. pregnant patients, unintentional therapeutic excess overdoses, IV paracetamol overdose and management of patients in whom IV treatment therapy is not appropriate).

Introduction

In overdose the potential risk of a patient having significant liver damage is directly proportional to the amount of paracetamol ingested. The patient's risk of paracetamol-induced hepatotoxicity should not be stratified according to the presence of risk factors like glutathione deficiency or liver inducing enzymes as these factors are considered to be poorly evidenced. Instead, patient management has been simplified to a single treatment line on the paracetamol treatment nomogram below and the administration of acetylcysteine IV in three sets of infusions with infusion 1 given over 1 hour.

Management options

Acetylcysteine (N-acetylcysteine, Parvolex®, NAC) IV is still the treatment of choice. It can prevent paracetamol-induced hepatotoxicity if given within the first 8 hours since overdose. It may also be effective up to and possibly beyond 24 hours. Hypersensitivity and anaphylaxis reactions are not contraindications to using acetylcysteine (more guidance below). Follow the initial management options outlined below, with further guidance on www.toxbase.org (password required), and use the NHSGGC Adult Acetylcysteine Prescribing and Administration Chart (available in A&E departments and acute receiving units). When checking paracetamol plasma level also check patient's U&Es, Cr, bicarbonate, LFTs, INR and FBC.


<8 hours after oral paracetamol ingestion

  • Consider activated charcoal administration if >150mg/kg paracetamol has been taken within a 1 hour period.
  • For obese patients (>110kg) the toxic dose in mg/kg should be calculated using 110kg, rather than their actual weight.
  • Wait until 4 hours from ingestion then measure plasma level and send for urgent analysis. Await result before deciding whether treatment is required (provided result can be obtained and acted upon within 8 hours of ingestion). Paracetamol plasma levels <4 hours after ingestion cannot be interpreted.
  • If biochemical results suggest acute liver injury then double-check history of paracetamol ingestion, especially the timing. Consider treatment with acetylcysteine infusion - see below.
  • Once paracetamol plasma level is known then use the revised treatment nomogram (below) to assess the risk of severe liver damage. If the paracetamol level is above the treatment line then treat with acetylcysteine infusion - see dosing table below.

8-24 hours after ingestion

  • Send for urgent paracetamol plasma level. If the dose ingested is suspected to be >150mg/kg within 1 hour do not wait for result - commence treatment with acetylcysteine (dosing table below) immediately. The efficacy of acetylcysteine rapidly declines during this period so do not delay treatment.
  • For obese patients (>110kg) the toxic dose in mg/kg should be calculated using 110kg, rather than patient's actual weight.
  • Monitor blood results (details on previous page) and if results suggest acute liver injury then double check history of paracetamol ingestion, especially the timing. Consider treatment with acetylcysteine infusion - dosing table below.
  • Acetylcysteine can be discontinued if plasma paracetamol concentration is later reported to be below the treatment line on the graph below, provided the patient is asymptomatic and LFTs, serum creatinine and INR are normal.

>24 hours after ingestion

  • A plasma concentration measured at this time is likely to be below the limit of detection, even after a substantial overdose. Treat with acetylcysteine if >24 hours after a suspected paracetamol ingestion the:
    • measured concentration >5mg/L at >24 hours ingestion (indicative of a very large overdose) or
    • INR is normal (is <1.3) but ALT >2 times the upper limit of normal or
    • INR is >1.3 (in the absence of any obvious cause) but ALT is normal (<2 times the upper limit of normal) or
    • the patient has jaundice or hepatic tenderness
  • For obese patients (>110kg) the toxic dose in mg/kg should be calculated using 110kg, rather than patient's actual weight.
  • Monitor blood tests (details above) as well as venous or arterial blood gases. If INR or LFTs deranged then repeat bloods at 8-16 hours and consider other causes. Stop acetylcysteine if INR is <1.3 and ALT has not increased further, otherwise continue and recheck bloods at 8-16 hour intervals.
  • For further management guidance refer to TOXBASE www.toxbase.org (password required) or contact National Poisons Information Service (NPIS, 0344 892 0111).

Staggered overdoses

  • Defined as paracetamol taken over ≥1 hour.
  • Send for paracetamol levels and monitor blood tests (details above). Note: In staggered overdose the treatment nomogram is unreliable.
  • Clinically significant toxicity is unlikely if, following at least 24 hours since the last paracetamol ingestion, the following criteria is met:
    • paracetamol measured concentration is not detectable (<5mg/L)
    • INR <1.3
    • plasma creatinine normal
    • ALT <2 times the upper limit of normal
    • patient asymptomatic
  • If there is any uncertainty, then treat with acetylcysteine (dosing table below). For further management guidance refer to www.toxbase.org (password required) or contact National Poisons Information Service (NPIS, 0344 892 0111).

Unintentional therapeutic excess overdoses

See TOXBASE (www.toxbase.orgpassword required) for information or contact the National Poisons Information Service (NPIS, 0344 892 0111) for advice.

Paracetamol overdose treatment nomogram

  • Determine the need for acetylcysteine by plotting the measured plasma paracetamol level (in mg/L) against the time since ingestion. If plasma level falls above the line then give acetylcysteine as detailed below.
  • If timing of ingestion is unreliable then treat with acetylcysteine regardless of whether the plasma level is above or below the treatment line.
  • If overdose is staggered (taken over longer than 1 hour) then the nomogram is unreliable; see above.

N.B. In NHSGGC paracetamol plasma levels reported in units of mg/L.

Table 1 - Acetylcysteine adult dosing table 

Each ampoule = 200mg/ml acetylcysteine

If viewing Table 1 on a mobile device please view as landscape to view detail of all 3 infusions.

Regimen 1st infusion 2nd infusion 3rd infusion
Infusion fluid 200ml 5% glucose or sodium chloride 0.9% 500ml 5% glucose or sodium chloride 0.9% 1000ml 5% glucose or sodium chloride 0.9%
Preparation Use a 250ml infusion bag and remove 50 ml prior to adding in the required drug volume Add the required volume of the drug to the 500ml infusion bag Add the required volume of the drug to the 1000ml infusion bag
Duration of infusion 1 hour 4 hours 16 hours
Drug dose 150mg/kg acetylcysteine 50mg/kg acetylcysteine 100mg/kg acetylcysteine
Patient weight1(kg) Ampoule volume2 (ml) Infusion rate (ml/hour) Ampoule volume2 (ml) Infusion rate (ml/hour) Ampoule volume2 (ml) Infusion rate (ml/hour)
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
≥100 83 283 28 132 55 66
1 Dose calculations are based on the weight in the middle of each band.
2 Ampoule volume has been rounded up to the nearest whole number.

Important notes

  1. Obese patients (>110kg) - the dose should be calculated using a weight of 110kg rather than the patient's actual weight.
  2. Patients <40kg - access paediatric dosing table through www.toxbase.org (password required).
  3. Hypersensitivity and anaphylaxis reactions with acetylcysteine are not contraindications as the benefit of treatment still outweighs the risk of not treating. True anaphylaxis is rare with acetylcysteine but can be managed by stopping the infusion, managing the reaction as per Management of anaphylaxis and then re-starting at a slower rate (e.g. give infusion 1 over 2 hours and infusion 2 over 8 hours).
  4. Re-check INR, Cr, bicarbonate, LFT at or just before the end of the 21 hour acetylcysteine infusion and manage as per guidance in TOXBASE. There may be circumstances when acetylcysteine may need to be continued beyond 21 hours in which case continue at the dose and rate used in the 3rd infusion bag above. There is no need for a further loading dose unless a second overdose has been taken. See TOXBASE  for further details.