acetaminophen overdose | gutsandgrowth

A recent study (TM Leventhal et al. Clin Gastroenterol Hepatol 2019; 17: 2110-6) provides more data indicating that acetaminophen levels are frequently undetectable even in patients suspected of developing acute liver failure (ALF) due to acetaminophen overdose.

The authors performed a retrospective study with 434 subjects from the ALF study group who met criteria for either ALF (coagulopathy and hepatic encephalopathy w/in 26 weeks of first symptoms) or Acute Liver Injury (ALI) (severe liver injury with coagulopathy but no encephalopathy). In this group, all of the patients had liver disease attributed to acetaminophen (APAP) toxicity.

Key findings:

227 patients (52%) had undetectable acetaminophen levels
Transplant-free survival rate was 79.5% (including both ALF and ALI patients)
APAP-protein adduct data was available for 37 patients in cohort; all patients with this assay had evidence of APAP toxicity regardless of whether APAP level was detected

Discussion Points:

Symptoms from APAP toxicity frequently emerge >24 hours after ingestion. APAP, though, has a short half-life, approximately 2-2.5 hours. Thus, most patients will have APAP clearance from plasma in 18 hours
Unintentional overdose, often with multiple doses over therapeutic limit of 4 g/day (in adults), more frequently is associated with an undetectable APAP level than a single large intentional overdose which results in a higher peak level

My take: This study shows that APAP levels are unreliable in determining APAP ingestions and not predictive of ALF. The use of N-acetylcysteine should not be determined by APAP levels in patients with suspected overdose.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

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A recent open-label “NACSTOP trial” (A Wong et al. Hepatology 2019; 69: 774-84) examined a 12-hour regimen of acetylcysteine in patients at lower risk for severe hepatotoxicity from acetaminophen overdose.

Background/Methods: Intravenous acetylcysteine is generally delivered as 300 mg/kg over 20 hours in “nearly every patient deemed at any risk for hepatotoxicity following acetaminophen overdose.” Administration within 8 hours of an acute single acetaminophen overdose prevents hepatotoxicity in nearly all patients.

In this study, patients with normal serum alanine transaminase (ALT) and normal creatinine at presentation and at 12 hours along with acetaminophen level of <20 mg/L at 12 hours were assigned to either a 12 hour (250 mg/kg) or 20 hour (300 mg/kg) acetylcysteine (IV) infusion.

1411 Acetaminophen overdoses were identified; of these, 449 met criteria for study participation. 100 patients out of these 449 eligible were enrolled.

Key findings:

There was no difference in ALT or INR at 20 hours between the two groups.
No hepatotoxicity was evident in either group. 96 of 96 were well at 14-day telephone followup.

Discussion: “A normal ALT on presentation has a high negative predictive values (100%) of individuals developing any serious liver injury (ALT >1000 IU/L) in those receiving acetylcysteine.” [Al-Hourani et al. QJM 2013; 1065: 541-6)

My take: This study shows that a shortened acetylcysteine infusion is likely safe in selected patients at low risk for hepatotoxicity.

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