Acetaminophen overdose

Back

1st line –

acetylcysteine

Physicians are advised to consult the poison control center and/or medical toxicologist for guidance. Consider the need to assess and treat for co-ingestion of other drugs, particularly in cases of intentional overdose.

For a single acute ingestion of acetaminophen, patients should be transferred to the emergency department for evaluation and consideration of acetylcysteine.

If the estimated ingestion is unknown, >10 g, or ≥200 mg/kg (whichever is less), 2023 US and Canadian consensus guidelines recommend acetylcysteine should be started immediately, if waiting for testing will result in treatment starting more than 8 hours after ingestion.[1] Other indications for administering acetylcysteine before the acetaminophen concentration is available include: if the patient is unconscious (and there is reasonable suspicion of acetaminophen toxicity), estimated ingestion is ≥30 g (high-risk ingestion), or if the patient presents with hepatotoxicity possibly from acetaminophen.

In practice, the initial dose is typically administered as soon as the need for treatment becomes evident.[1]

The serum acetaminophen level should be checked 4 hours after ingestion.[1] If a patient presents within 4 hours of ingestion, the level is drawn when 4 hours have elapsed since the possible overdose. Patients presenting between 4 and 8 hours after ingestion should have acetaminophen levels measured as soon as possible.

Once the acetaminophen level is obtained, it should be plotted against the time since ingestion on the revised Rumack-Matthew nomogram. [Figure caption and citation for the preceding image starts]: Revised Rumack-Matthew nomogram for the acute ingestion of acetaminophenDart RC et al. JAMA Netw Open. 2023;6(8):e2327739; used with permission [Citation ends].

If the plot falls on or above the treatment line, the patient should be treated with acetylcysteine. It can be given either orally or intravenously.[76][89]

If the plotted acetaminophen level falls below the treatment line on the Rumack-Matthew nomogram, then toxicity is exceedingly rare. Further evaluation and acetylcysteine is not required, or it can be discontinued.

Acetylcysteine is indicated beyond standard duration of therapy (21 hours for intravenous administration; 72 hours for oral administration) in patients with continued evidence of liver injury/dysfunction, abnormalities in predictors of poor prognosis, or persisting presence of serum acetaminophen detected by laboratory testing.[94] Consult the poison control center for guidance on a suitable dose for these patients. End points for treatment with acetylcysteine in such cases are a clinically well-appearing patient with undetectable acetaminophen level <10 micrograms/mL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal for the patient (or if elevated, have decreased from 25% to 50% from peak), and international normalized ratio (INR) <2.0.

Acetylcysteine dose regimens vary widely. If using an alternative regimen, it is recommended to use an approved or published intravenous or oral protocol that delivers a minimum of 300 mg/kg over 20-24 hours.[1] Abbreviated courses of oral acetylcysteine should be used with caution only in early-presenting, well-appearing patients with favorable laboratory studies.

Rarely, hemodialysis is recommended in addition to treatment with acetylcysteine in a patient with a very large ingestion of acetaminophen (e.g., concentration of 900 micrograms/mL or greater with acidosis or altered consciousness due to acetaminophen toxic effects); consult with a poison center or toxicologist.[1] The acetylcysteine infusion dose may need to be adjusted in patients on hemodialysis; consult your local drug information source for more information.

Primary options

acetylcysteine: children and adults: 150 mg/kg intravenous infusion over 1 hour, followed by 50 mg/kg infusion over 4 hours, then 100 mg/kg infusion over 16 hours; OR 140 mg/kg orally as a loading dose, followed by 70 mg/kg every 4 hours for 72 hours

Consider – activated charcoal

Back

Consider –

activated charcoal

Treatment recommended for SOME patients in selected patient group

Activated charcoal may be considered in a cooperative patient presenting within 4 hours of acute single acetaminophen ingestion; charcoal may decrease the need for acetylcysteine when given within 4 hours of ingestion.

Evidence (very low quality) suggests that activated charcoal is the best choice to reduce absorption of acetaminophen.[76] Patients receiving activated charcoal at a median 2 hours post-ingestion of a large dose of acetaminophen (≥40 g) had significantly lower acetaminophen concentrations (measured ≥1 hour after charcoal) than those who did not.[78]

Primary options

charcoal, activated: children: 0.5 to 1 g/kg orally/nasogastrically as a single dose, usual dose 10-50 g/dose (depending on age); adults: 25-100 g orally/nasogastrically as a single dose

8-24 hours since ingestion

Back

1st line –

acetylcysteine

Acetylcysteine should be started immediately if the patient presents >8 hours after ingestion. It can be given either intravenously or orally.[89] Obtain an acetaminophen level as soon as possible, as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and international normalized ratio (INR).

For patients with acetaminophen levels that plot on or above the treatment line on the revised Rumack-Matthew nomogram, the patient should have acetylcysteine continued.

If the plotted acetaminophen level falls below the treatment line on the Rumack-Matthew nomogram, the patient is asymptomatic, and there is no evidence of renal injury or liver damage/dysfunction (normal laboratory tests), acetylcysteine may be discontinued.

Acetylcysteine is indicated beyond standard duration of therapy (21 hours for intravenous administration; 72 hours for oral administration) in patients with continued evidence of liver injury/dysfunction, abnormalities in predictors of poor prognosis, or persisting presence of serum acetaminophen detected by laboratory testing.[94] Consult the poison control center for guidance on a suitable dose for these patients. End points for treatment with acetylcysteine in such cases are a well-appearing patient, acetaminophen level <10 micrograms/mL, serum AST or ALT (normal for the patient or, if elevated, have decreased from peak by 25% to 50%), and INR <2.0.

Rarely, hemodialysis is recommended in addition to treatment with acetylcysteine for patients with a very large ingestion of acetaminophen (e.g., concentration of 900 micrograms/mL or greater with acidosis or altered consciousness due to acetaminophen toxic effects); consult with a poison center or toxicologist.[1] The acetylcysteine infusion dose may need to be adjusted in patients on hemodialysis; consult your local drug information source for more information.

Primary options

Consider – evaluation for liver transplant

Back

Consider –

evaluation for liver transplant

Treatment recommended for SOME patients in selected patient group

Laboratory criteria are helpful when evaluating patients for liver transplantation due to acetaminophen hepatotoxicity. However, patients with significant hepatotoxicity should be referred to a liver transplant facility as early as possible, ideally before metabolic acidosis, coagulopathy, and encephalopathy occur.

Referral for liver transplant is indicated if arterial pH <7.3 AND lactate >3.0 mmol/L after fluid resuscitation, OR prothrombin time (PT)/international normalized ratio (INR) >100 seconds/6.0 seconds AND encephalopathy grade 3 or more AND creatinine >3.3 mg/dL (292 micromol/L) within 24 hours AND a normal arterial pH.[58][99]

Other predictors of poor prognosis without transplant include arterial lactate concentration >3.5 mmol/L after fluid resuscitation (<4 hours) OR lactate >3 mmol/L after full fluid resuscitation OR phosphate >3.75 mg/dL (>1.2 mmol/L) at 48-96 hours.[58][99]

>24 hours since ingestion or time unknown

Back

1st line –

acetylcysteine

Acetylcysteine should be started immediately if the patient presents >24 hours after ingestion. It can be given either intravenously or orally.[89] Obtain an acetaminophen level as soon as possible, as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and international normalized ratio (INR).

For patients with acetaminophen >10 micrograms/mL or abnormal AST/ALT (unless baseline for patient), acetylcysteine is continued. If acetaminophen is <10 micrograms/mL and AST/ALT normal (or baseline for patient), and the patient is clinically well-appearing, acetylcysteine may be discontinued.

Acetylcysteine is indicated beyond standard duration of therapy (21 hours for intravenous administration; 72 hours for oral administration) in patients with continued evidence of liver injury/dysfunction, abnormalities in predictors of poor prognosis, or persisting presence of serum acetaminophen detected by laboratory testing.[94] Consult the poison control center for guidance on a suitable dose for these patients. End points for treatment with acetylcysteine in such cases are a clinically well-appearing patient with undetectable acetaminophen level <10 micrograms/mL, AST and ALT normal for the patient (or if elevated, have decreased from 25% to 50% from peak), and INR <2.

Primary options

Consider – evaluation for liver transplant

Back

Consider –

evaluation for liver transplant

Treatment recommended for SOME patients in selected patient group

repeated supratherapeutic acetaminophen ingestion

Back

1st line –

acetylcysteine

Physicians are advised to consult the poison control center and/or medical toxicologist for guidance.

Repeated supratherapeutic ingestion is defined as multiple episodes of acetaminophen ingestion over a period greater than 24 hours that results any of the following: findings consistent with acetaminophen toxicity (repeated vomiting, right upper quadrant abdominal tenderness, or mental status changes); >6 g/day or >150 mg/kg/day (whichever is less) over period of 24-48 hours; >4 g/day or >100 mg/kg/day (whichever is less) over >48 hours.[1] Discussion with a medical toxicologist or poison control center is strongly advised.

Acetaminophen levels should be measured as soon as possible.

For patients with signs or symptoms of hepatotoxicity, acetylcysteine should be started immediately, while awaiting laboratory results and any other necessary evaluation to exclude other differential diagnoses. It can be given either intravenously or orally.[89]

For all other patients, acetylcysteine should be started if acetaminophen level is ≥20 micrograms/mL, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level is abnormal (unless abnormal aminotransferase level is baseline for the patient).[1] It can be given either orally or intravenously.[89]

For patients with detectable acetaminophen levels, or any indication of acute kidney injury or liver injury/dysfunction, acetylcysteine is continued. If there is no detectable acetaminophen, and no evidence of renal injury or liver damage/dysfunction (normal laboratory tests), and the patient is asymptomatic, acetylcysteine may be discontinued.

Acetylcysteine is indicated beyond standard duration of therapy (21 hours for intravenous administration; 72 hours for oral administration) in patients with continued evidence of liver injury/dysfunction, abnormalities in predictors of poor prognosis, or persisting presence of serum acetaminophen detected by laboratory testing.[94] Consult the poison control center for guidance on a suitable dose for these patients. End points for treatment with acetylcysteine in such cases are asymptomatic clinical status, undetectable acetaminophen level, serum AST or ALT (normal for the patient or, if elevated, have decreased from peak by 25% to 50%), and international normalized ratio (INR) <2.0.

Primary options