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      Massive acetaminophen overdose with metabolic acidosis refractory to N-acetylcysteine, fomepizole, and renal replacement therapy

      case-report

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          Highlights

          • Acetaminophen toxicity can be associated with a metabolic acidosis and treated with Renal Replacement Therapy.

          • Metabolic acidosis refractory to renal replacement therapy likely leads to worse outcomes.

          • Cystatin C should be used as a marker of renal function in acetaminophen toxicity.

          Abstract

          Massive Acetaminophen ( N-acetyl-p-aminophenol; APAP) overdose is a common presentation to emergency departments around the world. While N-acetylcysteine (NAC) remains the cornerstone of treatment for APAP overdose, extracorporeal treatment, in the form of renal replacement therapy with intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT) may provide benefit in cases associated with altered mental status and metabolic acidosis. One treatment with IHD is typically sufficient for resolution of acidosis and global improvement clinically. We describe a case of massive APAP overdose presenting with altered mental status and lactic acidosis, refractory to multiple treatments of IHD as well as CRRT and high-dose NAC along with fomepizole. Despite these interventions, fulminant liver failure progressed with cerebral edema, coagulopathy and death. This is the first description of a fatal acetaminophen ingestion refractory to both IHD and prolonged CRRT. This case highlights the need for further investigation in the management of massive APAP overdose, including optimal method and timing of renal replacement therapy.

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          Most cited references18

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          Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review.

          The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, but such measurements are a poor marker of acute deterioration in kidney function. We performed a systematic review of publications that evaluated the accuracy and reliability of serum and urinary biomarkers in human subjects when used for the diagnosis of established AKI or early AKI, or to risk stratify patients with AKI. Two reviewers independently searched the MEDLINE and EMBASE databases (January 2000-March 2007) for studies pertaining to biomarkers for AKI. Studies were assessed for methodologic quality. In total, 31 studies evaluated 21 unique serum and urine biomarkers. Twenty-five of the 31 studies were scored as having 'good' quality. The results of the studies indicated that serum cystatin C, urine interleukin-18 (IL-18), and urine kidney injury molecule-1 (KIM-1) performed best for the differential diagnosis of established AKI. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin, IL-18, glutathione-S-transferase-pi, and gamma-glutathione-S-transferase performed best for early diagnosis of AKI. Urine N-acetyl-beta-D-glucosaminidase, KIM-1, and IL-18 performed the best for mortality risk prediction after AKI. In conclusion, published data from studies of serum and urinary biomarkers suggest that biomarkers may have great potential to advance the fields of nephrology and critical care. These biomarkers need validation in larger studies, and the generalizability of biomarkers to different types of AKI as well as the incremental prognostic value over traditional clinical variables needs to be determined.
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            Acetaminophen and acetylcysteine dose and duration: Past, present and future

            Acetylcysteine has been utilized successfully in the treatment of acetaminophen overdose since the 1970s. Although prospective trials as to efficacy and safety of acetylcysteine were conducted, there were no randomized controlled trials. This commentary addresses the reasons for this, and the background to choice of dose of acetylcysteine utilized in the oral and IV dosing regimens. Nomograms to predict possible hepatotoxicity based upon time of ingestion of acetaminophen were developed from a relatively arbitrary definition of toxicity as an aspartate aminotransferase/alanine aminotransferase (ALT/AST) greater than 1000 IU/L. While these have proved generally useful, patients still continue to develop hepatic damage after acetaminophen overdose, particularly if they present late after ingestion. The optimum management of these patients remains unclear, and one area of uncertainty is the dose and duration of acetylcysteine in various circumstances. This article discusses the issues that need to be elucidated to better target changes in acetylcysteine dose. The potential for measurements of other markers to improve treatment selection is the subject of further research.
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              Detailed analyses of self-poisoning episodes presenting to a large regional teaching hospital in the UK.

              The primary aim of this paper is to provide comprehensive contemporaneous data on the demographics, patterns of presentation and management of all episodes of deliberate self-poisoning presenting to a large regional teaching hospital over a 12 month period. We undertook detailed, retrospective analyses using information from electronic patient records and local patient-tracking, pathology and administrative databases. Statistical analyses were performed using Chi-squared tests, anova and two-tailed t-tests (Graphpad Prism). One thousand five hundred and ninety-eight episodes of deliberate self-poisoning presented over the year. Demographic data and information on the month, day and time of admission are provided. 70.7% presented to the emergency department (ED) within 4 h of ingestion. 76.3% of patients had only one episode in an extended 29 month follow-up period. A mean of 1.72 drugs were taken per episode with just over half of all episodes involving a single drug only. Paracetamol and ibuprofen were the two most commonly ingested drugs involved in 42.5% and 17.3% of all overdoses respectively. 56.3% of patients taking paracetamol reported ingesting over 8 g (one over the counter packet). Detailed mapping of the patients' pathway through the hospital allowed an estimation of the hospital cost of caring for this patient group at pound 1.6 million pounds per year. We present comprehensive and contemporary data on presentations to hospital resulting from deliberate self-poisoning. We include demographic information, presentation patterns, drugs used, a detailed analysis of episodes involving paracetamol and an estimate of the financial burden to hospitals of overdose presentations.
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                Author and article information

                Contributors
                Journal
                Toxicol Rep
                Toxicol Rep
                Toxicology Reports
                Elsevier
                2214-7500
                06 April 2021
                2021
                06 April 2021
                : 8
                : 804-807
                Affiliations
                [a ]Department of Medicine, Western University, London, ON, Canada
                [b ]Division of Nephrology, Department of Medicine, Western University, London, ON, Canada
                [c ]Division of Critical Care, Department of Medicine, Western University, London, ON, Canada
                Author notes
                [* ]Corresponding author at: 339 Windermere Road, London, ON, N6A 5A5, Canada. paul.cameron@ 123456lhsc.on.ca
                Article
                S2214-7500(21)00072-X
                10.1016/j.toxrep.2021.03.031
                8044808
                33868959
                1b2c4240-6449-4180-9953-3aec3cb28a8b
                © 2021 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 4 January 2021
                : 30 March 2021
                : 31 March 2021
                Categories
                Regular Article

                overdose,acetaminophen,apap,renal replacement therapy,intermittent hemodialysis,metabolic acidosis

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