Paracetamol overdose in adults

Consider – activated charcoal

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1st line –

supportive care

Discuss the patient urgently with a senior colleague if any features of hepatic necrosis are present. These include:

Right subcostal pain and tenderness[3]
Nausea and vomiting[3]
Jaundice[3]
Acute kidney injury[3]
Hepatic encephalopathy[3]
International normalised ratio (INR) >1.3[3]
Hypoglycaemia.[28]

Trigger urgent referral to hepatology if there are indications for urgent liver transplantation:[3]

Arterial pH <7.3
Hepatic encephalopathy grade 3 or 4
Serum creatinine >300 micromoles/L
Prothrombin time (PT) >100 seconds
Serum lactate >3.5 mmol/L on admission or >3.0 mmol/L 24 hours post-paracetamol ingestion or after fluid resuscitation.

Escalate to critical care if the following are present:

The serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level; renal replacement therapy may be needed.[3]
Grade 3 or 4 encephalopathy; tracheal intubation to protect the airway is recommended.[28][29]
Grade 2 encephalopathy; these patients are at high risk of decompensation and require more intensive monitoring.[28][29]

Treat acute kidney injury and hypoglycaemia conventionally.[3] See Acute kidney injury and Non-diabetic hypoglycaemia.

Ensure the patient has access to psychological support if paracetamol was taken in the context of self-harm.[31] See Suicide risk mitigation.

MHRA: treatment nomogram for paracetamol overdose Opens in new window

Back

Consider –

acetylcysteine

Additional treatment recommended for SOME patients in selected patient group

Start treatment with acetylcysteine immediately, without waiting for blood test results, if there is going to be a delay beyond 8 hours in obtaining the serum paracetamol concentration and the patient has ingested ≥150 mg/kg body weight paracetamol as an acute overdose (i.e., all doses taken within 1 hour).[3]

If the patient has ingested <150 mg/kg, wait for blood results before considering treatment with acetylcysteine.[3]

Treatment with acetylcysteine must be started within 8 hours of ingestion for maximum protection.[3]

Give acetylcysteine if the serum paracetamol concentration is on or above the treatment line on the nomogram for your region, or there is evidence of liver injury (e.g., alanine aminotransferase [ALT] above the upper limit of normal).[3]

In the UK, use the nomogram produced by the National Poisons Information Service (NPIS).[27] MHRA: treatment nomogram for paracetamol overdose Opens in new window
Plot the measured serum paracetamol concentration against the time since ingestion on the treatment nomogram for your region; check the units carefully and use the correct scale.
If there is any uncertainty whether the patient's serum paracetamol concentration is above or below the treatment line on the nomogram for your region, treat with acetylcysteine.[3]

Consider giving acetylcysteine if blood tests suggest acute liver injury (e.g., ALT or INR above the upper limit of normal) even if the serum paracetamol concentration is below the treatment line on the nomogram for your region.[27] MHRA: treatment nomogram for paracetamol overdose Opens in new window

Consult your local protocol for guidance on choice of regimen and dosing recommendations. Always discuss with a senior colleague.

In the UK, the Royal College of Emergency Medicine (RCEM) and the NPIS endorse a 12-hour acetylcysteine infusion (Scottish and Newcastle Acetylcysteine Protocol [SNAP] regimen) for the treatment of paracetamol toxicity in adults in the emergency department.[3][60] This is at odds with the Medicines and Healthcare products Regulatory Agency (MHRA)-approved 21-hour infusion which has historically been used.[61]
The SNAP regimen should only be used after discussion with a senior clinician, because SNAP is not licensed or endorsed by the MHRA.[3] The RCEM recognises that in some cases, including delayed presentation, and subject to senior clinical evaluation, the 21-hour infusion protocol may be more appropriate in practice.[60]

Only start an acetylcysteine infusion in a closely monitored area (which has capacity to treat an anaphylactoid reaction).[51]

Give acetylcysteine even if the patient has a history of a previous adverse reaction as the benefits outweigh the risks.[51] Consider using a slower initial infusion of acetylcysteine in these patients to reduce the risk of a further reaction, as well as giving prophylactic treatment (e.g., antihistamines).[51]
Monitor all patients closely for acetylcysteine infusion reactions over the first few hours.[51] Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, and bronchospasm are relatively common.[3]

See the section Adverse reactions to acetylcysteine in Management: Recommendations for more information.

If acetylcysteine was started without waiting for blood results, review the patient when the results of blood tests are available and discontinue acetylcysteine if the patient is not at risk of liver toxicity, evidenced by:[3]

Serum paracetamol concentration below the treatment line
INR and ALT are within normal ranges
The patient is asymptomatic.

Primary options

acetylcysteine: consult local protocol for dose guidelines

8-24 hours since ingestion

Back

1st line –

supportive care

Discuss the patient urgently with a senior colleague if any features of hepatic necrosis are present. These include:

Right subcostal pain and tenderness[3]
Nausea and vomiting[3]
Jaundice[3]
Acute kidney injury[3]
Hepatic encephalopathy[3]
International normalised ratio (INR) >1.3[3]
Hypoglycaemia.[28]

Trigger urgent referral to hepatology if there are indications for urgent liver transplantation:[3]

Arterial pH <7.3
Hepatic encephalopathy grade 3 or 4
Serum creatinine >300 micromoles/L
Prothrombin time (PT) >100 seconds
Serum lactate >3.5 mmol/L on admission or >3.0 mmol/L 24 hours post-paracetamol ingestion or after fluid resuscitation.

Escalate to critical care if the following are present:

The serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level; renal replacement therapy may be needed.[3]
Grade 3 or 4 encephalopathy; tracheal intubation to protect the airway is recommended.[28][29]
Grade 2 encephalopathy; these patients are at high risk of decompensation and require more intensive monitoring.[28][29]

Treat acute kidney injury and hypoglycaemia conventionally.[3] See Acute kidney injury and Non-diabetic hypoglycaemia.

Ensure the patient has access to psychological support if paracetamol was taken in the context of self-harm.[31] See Suicide risk mitigation.

Back

Consider –

acetylcysteine

Additional treatment recommended for SOME patients in selected patient group

Start treatment with acetylcysteine without delay, without waiting for blood results if the patient presents with an acute overdose, 8-24 hours after acute ingestion and:

It is thought that ≥150 mg/kg paracetamol has been ingested (or an unknown amount) has been ingested as an acute overdose (i.e., all doses taken within 1 hour) or
There are clinical features of liver injury (e.g., jaundice, hepatic tenderness).

If the patient is asymptomatic and has ingested <150 mg/kg, wait for blood results before considering treatment with acetylcysteine.[3]

Give acetylcysteine if the serum paracetamol concentration is on or above the treatment line on the nomogram for your region or there is suspicion of liver injury (e.g., alanine aminotransferase [ALT] above the upper limit of normal).

In the UK, use the nomogram produced by the National Poisons Information Service (NPIS). MHRA: treatment nomogram for paracetamol overdose Opens in new window[27]
Plot the measured serum paracetamol concentration against the time since ingestion on the treatment nomogram for your region; check the units carefully and use the correct scale.
If there is any uncertainty whether the patient’s serum paracetamol concentration is above or below the treatment line on the nomogram for your region, treat with acetylcysteine.[3]

Consult your local protocol for guidance on choice of regimen and dosing recommendations. Always discuss with a senior colleague.

In the UK, the Royal College of Emergency Medicine (RCEM) and the NPIS endorse a 12-hour acetylcysteine infusion (Scottish and Newcastle Acetylcysteine Protocol [SNAP] regimen) for the treatment of paracetamol toxicity in adults in the emergency department.[3][60] This is at odds with the Medicines and Healthcare products Regulatory Agency (MHRA)-approved 21-hour infusion which has historically been used.[61]
The SNAP regimen should only be used after discussion with a senior clinician, because SNAP is not licensed or endorsed by the MHRA.[3] The RCEM recognises that in some cases, including delayed presentation, and subject to senior clinical evaluation, the 21-hour infusion protocol may be more appropriate in practice.[60]

Only start an acetylcysteine infusion in a closely monitored area (which has capacity to treat an anaphylactoid reaction).[51]

Give acetylcysteine even if the patient has a history of a previous adverse reaction as the benefits outweigh the risks.[51] Consider using a slower initial infusion of acetylcysteine in these patients to reduce the risk of a further reaction, as well as giving prophylactic treatment (e.g., antihistamines).[51]
Monitor all patients closely for acetylcysteine infusion reactions over the first few hours.[51] Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, and bronchospasm are relatively common.[3]

See the section Adverse reactions to acetylcysteine in Management: Recommendations for more information.

Serum paracetamol concentration below the treatment line
INR and ALT are within normal ranges
The patient is asymptomatic.

Primary options

acetylcysteine: consult local protocol for dose guidelines

>24 hours since ingestion

Back

1st line –

supportive care

Discuss the patient urgently with a senior colleague if any features of hepatic necrosis are present. These include:

Right subcostal pain and tenderness[3]
Nausea and vomiting[3]
Jaundice[3]
Acute kidney injury[3]
Hepatic encephalopathy[3]
International normalised ratio (INR) >1.3[3]
Hypoglycaemia.[28]

Trigger urgent referral to hepatology if there are indications for urgent liver transplantation:[3]

Arterial pH <7.3
Hepatic encephalopathy grade 3 or 4
Serum creatinine >300 micromoles/L
Prothrombin time (PT) >100 seconds
Serum lactate >3.5 mmol/L on admission or >3.0 mmol/L 24 hours post-paracetamol ingestion or after fluid resuscitation.

Escalate to critical care if the following are present:

The serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level; renal replacement therapy may be needed.[3]
Grade 3 or 4 encephalopathy; tracheal intubation to protect the airway is recommended.[28][29]
Grade 2 encephalopathy; these patients are at high risk of decompensation and require more intensive monitoring.[28][29]

Treat acute kidney injury and hypoglycaemia conventionally.[3] See Acute kidney injury and Non-diabetic hypoglycaemia.

Ensure the patient has access to psychological support if paracetamol was taken in the context of self-harm.[31] See Suicide risk mitigation.

Back

Consider –

acetylcysteine

Additional treatment recommended for SOME patients in selected patient group

Start acetylcysteine without delay, without waiting for blood results if the patient presents >24 hours after acute ingestion and:[3]

It is thought that ≥150 mg/kg paracetamol has been ingested as an acute overdose (i.e., all doses taken within 1 hour) or
There are clinical features of liver injury (e.g., jaundice, hepatic tenderness).

If the patient is asymptomatic and has ingested <150 mg/kg, wait for blood results before considering treatment with acetylcysteine.[3]

Give acetylcysteine if blood tests show:[3]

Alanine aminotransferase (ALT) is above the upper limit of normal OR
INR >1.3 (in the absence of another cause, e.g., warfarin)
Paracetamol level is detectable.

Any patient who is asymptomatic and presents more than 7 days after the last dose of paracetamol was ingested does not normally require further assessment if:[3]

They have had no new symptoms since the time of ingestion and
They have no history of chronic kidney or liver disease and
The timing of ingestion is certain.

Consult your local protocol for guidance on choice of regimen and dosing recommendations. Always discuss with a senior colleague.

In the UK, the Royal College of Emergency Medicine (RCEM) and the National Poisons Information Service (NPIS) endorse a 12-hour acetylcysteine infusion (Scottish and Newcastle Acetylcysteine Protocol [SNAP] regimen) for the treatment of paracetamol toxicity in adults in the emergency department.[3][60] This is at odds with the Medicines and Healthcare products Regulatory Agency (MHRA)-approved 21-hour infusion which has historically been used.[61]
The SNAP regimen should only be used after discussion with a senior clinician, because SNAP is not licensed or endorsed by the MHRA.[3] The RCEM recognises that in some cases, including delayed presentation, and subject to senior clinical evaluation, the 21-hour infusion protocol may be more appropriate in practice.[60]

Only start an acetylcysteine infusion in a closely monitored area (which has capacity to treat an anaphylactoid reaction).[51]

Give acetylcysteine even if the patient has a history of a previous adverse reaction as the benefits outweigh the risks.[51] Consider using a slower initial infusion of acetylcysteine in these patients to reduce the risk of a further reaction, as well as giving prophylactic treatment (e.g., antihistamines).[51]
Monitor all patients closely for acetylcysteine infusion reactions over the first few hours.[51] Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, and bronchospasm are relatively common.[3]

See the section Adverse reactions to acetylcysteine in Management: Recommendations for more information.

Primary options

acetylcysteine: consult local protocol for dose guidelines

time of ingestion uncertain

Back

1st line –

supportive care

Discuss the patient urgently with a senior colleague if any features of hepatic necrosis are present. These include:

Right subcostal pain and tenderness[3]
Nausea and vomiting[3]
Jaundice[3]
Acute kidney injury[3]
Hepatic encephalopathy[3]
International normalised ratio (INR) >1.3[3]
Hypoglycaemia.[28]

Trigger urgent referral to hepatology if there are indications for urgent liver transplantation:[3]

Arterial pH <7.3
Hepatic encephalopathy grade 3 or 4
Serum creatinine >300 micromoles/L
Prothrombin time (PT) >100 seconds
Serum lactate >3.5 mmol/L on admission or >3.0 mmol/L 24 hours post-paracetamol ingestion or after fluid resuscitation.

Escalate to critical care if the following are present:

The serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level; renal replacement therapy may be needed.[3]
Grade 3 or 4 encephalopathy; tracheal intubation to protect the airway is recommended.[28][29]
Grade 2 encephalopathy; these patients are at high risk of decompensation and require more intensive monitoring.[28][29]

Treat acute kidney injury and hypoglycaemia conventionally.[3] See Acute kidney injury and Non-diabetic hypoglycaemia.

Ensure the patient has access to psychological support if paracetamol was taken in the context of self-harm.[31] See Suicide risk mitigation.

Plus – acetylcysteine

Back

Plus –

acetylcysteine

Treatment recommended for ALL patients in selected patient group

Start treatment with acetylcysteine without delay if the time of ingestion of an acute overdose is unknown and all doses were taken within 1 hour.[3]

Consult your local protocol for guidance on choice of regimen and dosing recommendations. Always discuss with a senior colleague.

In the UK, the Royal College of Emergency Medicine (RCEM) and the National Poisons Information Service (NPIS) endorse a 12-hour acetylcysteine infusion (Scottish and Newcastle Acetylcysteine Protocol [SNAP] regimen) for the treatment of paracetamol toxicity in adults in the emergency department.[3][60] This is at odds with the Medicines and Healthcare products Regulatory Agency (MHRA)-approved 21-hour infusion which has historically been used.[61]
The SNAP regimen should only be used after discussion with a senior clinician, because SNAP is not licensed or endorsed by the MHRA.[3] The RCEM recognises that in some cases, including delayed presentation, and subject to senior clinical evaluation, the 21-hour infusion protocol may be more appropriate in practice.[60]

Only start an acetylcysteine infusion in a closely monitored area (which has capacity to treat an anaphylactoid reaction).[51] Treatment must be started within 8 hours of paracetamol ingestion to give maximum protection against liver damage.[3]

Give acetylcysteine even if the patient has a history of a previous adverse reaction as the benefits outweigh the risks.[51] Consider using a slower initial infusion of acetylcysteine in these patients to reduce the risk of a further reaction, as well as giving prophylactic treatment (e.g., antihistamines).[51]
Monitor all patients closely for acetylcysteine infusion reactions over the first few hours.[51] Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, and bronchospasm are relatively common.[3]

See the section Adverse reactions to acetylcysteine in Management: Recommendations for more information.

Review the patient when the results of blood tests are available and discontinue acetylcysteine if:

The serum paracetamol concentration is is below the treatment line
INR and ALT are within normal ranges
The patient is asymptomatic.

Primary options

acetylcysteine: consult local protocol for dose guidelines

staggered overdose

Back

1st line –

supportive care

Discuss the patient urgently with a senior colleague if any features of hepatic necrosis are present. These include:

Right subcostal pain and tenderness[3]
Nausea and vomiting[3]
Jaundice[3]
Acute kidney injury[3]
Hepatic encephalopathy[3]
International normalised ratio (INR) >1.3[3]
Hypoglycaemia.[28]

Trigger urgent referral to hepatology if there are indications for urgent liver transplantation:[3]

Arterial pH <7.3
Hepatic encephalopathy grade 3 or 4
Serum creatinine >300 micromoles/L
Prothrombin time (PT) >100 seconds
Serum lactate >3.5 mmol/L on admission or >3.0 mmol/L 24 hours post-paracetamol ingestion or after fluid resuscitation.

Escalate to critical care if the following are present:

The serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level; renal replacement therapy may be needed.[3]
Grade 3 or 4 encephalopathy; tracheal intubation to protect the airway is recommended.[28][29]
Grade 2 encephalopathy; these patients are at high risk of decompensation and require more intensive monitoring.[28][29]

Treat acute kidney injury and hypoglycaemia conventionally.[3] See Acute kidney injury and Non-diabetic hypoglycaemia.

Ensure the patient has access to psychological support if paracetamol was taken in the context of self-harm.[31] See Suicide risk mitigation.

Plus – acetylcysteine

Back

Plus –

acetylcysteine

Treatment recommended for ALL patients in selected patient group

Start treatment with acetylcysteine without delay, without waiting for blood test results in all patients who have ingested a staggered overdose (all tablets taken over a period of more than 1 hour but less than 24 hours).[3]

Consult your local protocol for guidance on choice of regimen and dosing recommendations. Always discuss with a senior colleague.

In the UK, the Royal College of Emergency Medicine (RCEM) and the National Poisons Information Service (NPIS) endorse a 12-hour acetylcysteine infusion (Scottish and Newcastle Acetylcysteine Protocol [SNAP] regimen) for the treatment of paracetamol toxicity in adults in the emergency department.[3][60] This is at odds with the Medicines and Healthcare products Regulatory Agency (MHRA)-approved 21-hour infusion which has historically been used.[61]
The SNAP regimen should only be used after discussion with a senior clinician, because SNAP is not licensed or endorsed by the MHRA.[3] The RCEM recognises that in some cases, including delayed presentation, and subject to senior clinical evaluation, the 21-hour infusion protocol may be more appropriate in practice.[60]

Give acetylcysteine even if the patient has a history of a previous adverse reaction as the benefits outweigh the risks.[51] Consider using a slower initial infusion of acetylcysteine in these patients to reduce the risk of a further reaction, as well as giving prophylactic treatment (e.g., antihistamines).[51]
Monitor all patients closely for acetylcysteine infusion reactions over the first few hours.[51] Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, and bronchospasm are relatively common.[3]

See the section Adverse reactions to acetylcysteine in Management: Recommendations for more information.

Review the patient when the results of blood tests are available.

Discontinue acetylcysteine if the patient is not at risk of liver toxicity. This would be if:

The serum paracetamol concentration is not detectable (<10 mg/L)
ALT is within normal range
INR ≤1.3
The patient has no symptoms suggesting liver damage.

Primary options

acetylcysteine: consult local protocol for dose guidelines

therapeutic excess

Back

1st line –

supportive care

Discuss the patient urgently with a senior colleague if any features of hepatic necrosis are present. These include:

Right subcostal pain and tenderness[3]
Nausea and vomiting[3]
Jaundice[3]
Acute kidney injury[3]
Hepatic encephalopathy[3]
International normalised ratio (INR) >1.3[3]
Hypoglycaemia.[28]

Trigger urgent referral to hepatology if there are indications for urgent liver transplantation:[3]

Arterial pH <7.3
Hepatic encephalopathy grade 3 or 4
Serum creatinine >300 micromoles/L
Prothrombin time (PT) >100 seconds
Serum lactate >3.5 mmol/L on admission or >3.0 mmol/L 24 hours post-paracetamol ingestion or after fluid resuscitation.

Escalate to critical care if the following are present:

The serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level; renal replacement therapy may be needed.[3]
Grade 3 or 4 encephalopathy; tracheal intubation to protect the airway is recommended.[28][29]
Grade 2 encephalopathy; these patients are at high risk of decompensation and require more intensive monitoring.[28][29]

Treat acute kidney injury and hypoglycaemia conventionally.[3] See Acute kidney injury and Non-diabetic hypoglycaemia.

Ensure the patient has access to psychological support if paracetamol was taken in the context of self-harm.[31] See Suicide risk mitigation.

Back

Consider –

acetylcysteine

Additional treatment recommended for SOME patients in selected patient group

Start treatment with acetylcysteine without delay, without waiting for blood results if the patient presented with a therapeutic excess (excessive doses of paracetamol taken with intent to treat pain or fever and without self-harm intent) and there are clinical features of liver injury (e.g., jaundice, hepatic tenderness).[3]

In asymptomatic patients, start acetylcysteine if the patient has ingested excessive paracetamol, with intent to treat pain or fever and without self-harm intent (usually taken over >24 hours), if blood tests indicate a risk of hepatotoxicity:[3]

Alanine aminotransferase (ALT) is above the upper limit of normal or
International normalised ratio (INR) >1.3 (in the absence of another cause, e.g., warfarin) or
Paracetamol concentration is >10 mg/L.

Consult your local protocol for guidance on choice of regimen and dosing recommendations. Always discuss with a senior colleague.

In the UK, the Royal College of Emergency Medicine (RCEM) and the National Poisons Information Service (NPIS) endorse a 12-hour acetylcysteine infusion (Scottish and Newcastle Acetylcysteine Protocol [SNAP] regimen) for the treatment of paracetamol toxicity in adults in the emergency department.[3][60] This is at odds with the Medicines and Healthcare products Regulatory Agency (MHRA)-approved 21-hour infusion which has historically been used.[61]
The SNAP regimen should only be used after discussion with a senior clinician, because SNAP is not licensed or endorsed by the MHRA.[3] The RCEM recognises that in some cases, including delayed presentation, and subject to senior clinical evaluation, the 21-hour infusion protocol may be more appropriate in practice.[60]

Give acetylcysteine even if the patient has a history of a previous adverse reaction as the benefits outweigh the risks.[51] Consider using a slower initial infusion of acetylcysteine in these patients to reduce the risk of a further reaction, as well as giving prophylactic treatment (e.g., antihistamines).[51]
Monitor all patients closely for acetylcysteine infusion reactions over the first few hours.[51] Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, and bronchospasm are relatively common.[3]

See the section Adverse reactions to acetylcysteine in Management: Recommendations for more information.

If acetylcysteine was started without waiting for blood results, review the patient when the results of blood tests are available.

Discontinue acetylcysteine if the patient is not at risk of liver toxicity. This would be if:

The serum paracetamol concentration is not detectable (<10 mg/L) and
ALT is within normal range and
INR ≤1.3 and
The patient has no symptoms suggesting liver damage.

Primary options

acetylcysteine: consult local protocol for dose guidelines