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Background: Acute liver failure (ALF) is a devastating condition with high mortality. Currently, liver transplantation is the only life-saving treatment, but the decision to transplant is difficult due to the rapid progression of ALF and persistent shortage of donor organs. Biomarkers that predict death better than current prognostics could help. To our surprise, proteomics recently revealed that lactate dehydrogenase (LDH) is prognostic in ALF by itself and in a novel form of the model for end-stage liver disease (MELD) score called the MELD-LDH. The purpose of this study was to confirm our proteomics results in a larger population. Methods: We reviewed laboratory data from 238 patients admitted to the University of Arkansas for Medical Sciences Medical Center with a diagnosis of ALF and biochemical evidence of acute liver failure over a 12-year period, as well as subset of 170 patients with encephalopathy. Results: LDH was strikingly elevated in the nonsurvivors at the time of peak injury. Receiver operating characteristic (ROC) curve analyses revealed that LDH by itself could discriminate between survivors and nonsurvivors on the first day of hospitalization, although not as well as the MELD and MELD-LDH scores that performed alike. Importantly, however, LDH by itself performed similarly to the MELD at the time of peak injury and the MELD-LDH score moderately outperformed both. The MELD-LDH score also had greater sensitivity and negative predictive value than the MELD and the King's College Criteria. Conclusions: The results support our prior finding that LDH and the MELD-LDH score predict death and therefore transplant need in ALF patients. [ABSTRACT FROM AUTHOR]

Growing clinical and basic science data support the use of fomepizole as an adjunct to N‐acetylcysteine in paracetamol poisoning. This safe antidote may be helpful in severely poisoned patients. [ABSTRACT FROM AUTHOR]

Fomepizole inhibits formation of toxic acetaminophen (APAP) metabolites and may prevent or reverse mitochondrial toxicity. Given these mechanisms, it may be beneficial in patients with severe APAP toxicity. Current patterns of use for this indication are not well-studied. This is a secondary analysis of patients enrolled in the Toxicology Investigators Consortium (ToxIC) database from January 2015 to July 2020. We queried cases in which APAP was listed as an ingested agent and fomepizole was also administered. We excluded cases in which APAP was not the primary agent, N-acetylcysteine (NAC) was not administered, or fomepizole was explicitly administered for another indication. Additionally, we sent a survey to each ToxIC site that administered fomepizole for APAP toxicity to better understand when, why, and how they were using it for this indication. Twenty-five cases of fomepizole administration following an APAP ingestion met our inclusion criteria. There were one to four cases per year between 2015 and 2019 and eight cases in 2020. Seventeen of 25 (68%) cases were for a known acute ingestion. Eighteen of 25 (72%) patients developed hepatotoxicity (AST or ALT > 1000 IU/L) and 10 of 25 (40%) developed coagulopathy (PT > 15s). This was an ill patient population, with 18 of 25 (72%) developing metabolic acidosis (pH <7.20), 12 of 25 (48%) were intubated, 9 of 25 (36%) receiving vasopressors, and 6 of 25 (24%) receiving continuous renal replacement therapy. Overall, mortality was 24%. The use of fomepizole is increasing in frequency in a small subset of critically ill and acutely APAP-poisoned patients. [ABSTRACT FROM AUTHOR]

We read with interest the recent commentary by Isbister and Chiew1 reviewing recent developments in the use of I N i -acetylcysteine (NAC) for the treatment of acetaminophen (APAP) toxicity. This regimen delivers slightly more NAC than the standard three-bag approach (assuming 21 hours of therapy, a total dose of 400 mg/kg as opposed to 300 mg/kg). Unlike the standard FDA-approved three-bag regimen and some of the alternative regimens discussed in the editorial, our regimen uses a single standardized concentration of NAC for all patients (30 g of NAC in 1 L of 5% dextrose in water). [Extracted from the article]