Hepatic Failure Despite Early Acetylcysteine Following Large Acetaminophen-Diphenhydramine Overdose

Abstract

We describe the case of a patient with massive acetaminophen-diphenhydramine overdose and a 4-hour serum acetaminophen concentration of 653 μg/mL. The patient was treated with acetylcysteine 5 hours after ingestion. Because of a persistently elevated serum acetaminophen level of 413 μg/mL 45 hours after ingestion, a medical toxicologist recommended that the patient be treated with a second bolus of acetylcysteine (150 mg/kg followed by 12.5 mg/kg per hour for 4 hours, then 6.25 mg/kg per hour). On hospital day 3, she developed hepatic failure despite early treatment. Her transaminase levels and hepatic synthetic function began to improve on hospital day 6, and acetylcysteine was discontinued on hospital day 10. In cases of massive acetaminophen overdose, standard acetylcysteine dosing may not be adequate. We suggest that elevated serum acetaminophen concentrations at the end of a standard 20-hour acetylcysteine infusion should be discussed with the local poison center.

Outcomes from massive paracetamol overdose: a retrospective observational study

“…It is known that NAPQI generation rises with increasing paracetamol dose, and also that hepatic injury prolongs paracetamol half‐life. Furthermore, there are several case reports, and one observational study, of patients developing hepatotoxicity despite receiving acetylcysteine within 8 h of reported overdose .…”

“…In particular, it is not clear whether the modelling assumptions underlying the initial acetylcysteine dose calculations hold true with very large overdoses, and whether therapy could be better tailored to individual cases in these situations . Several case reports, and one recent observational study, highlight adverse outcomes in patients with massive paracetamol overdoses despite early acetylcysteine treatment . Such patients have higher cysteine and mercapturate to glucuronide conjugate ratios, implying increased proportions of paracetamol undergoing conversion to NAPQI and consistent with the need for supplemental acetylcysteine beyond that suggested by the original models .…”

Risk Factors, Clinical Presentation, and Outcomes in Overdose With Acetaminophen Alone or With Combination Products

“…14 Although the biological mechanism of liver injury is well described, a few case reports have suggested that delayed hepatoxicity and persistently elevated serum APAP levels may be associated with overdoses due to APAP combination compounds. 15,16 Although the mechanism for this is not entirely clear, according to case reports and small case series, the delayed toxicity may be related to delayed gastrointestinal motility and increased absorption when APAP is combined with either diphenhydramine or opioids. 15,17–19 To date, no large-scale studies have examined differences in clinical presentation or clinical outcomes of APAP combination compounds.…”

“…15,16 Although the mechanism for this is not entirely clear, according to case reports and small case series, the delayed toxicity may be related to delayed gastrointestinal motility and increased absorption when APAP is combined with either diphenhydramine or opioids. 15,17–19 To date, no large-scale studies have examined differences in clinical presentation or clinical outcomes of APAP combination compounds. 15,16,20 …”

“…15,17–19 To date, no large-scale studies have examined differences in clinical presentation or clinical outcomes of APAP combination compounds. 15,16,20 …”