Literature DB >> 33884558

Evaluation of Dosing Strategies of N-acetylcysteine for Acetaminophen Toxicity in Patients Greater than 100 Kilograms: Should the Dosage Cap Be Used?

Regan A Baum1, Jordan A Woolum2, Abby M Bailey2, Molly M Howell3, Kyle A Weant4, LeeAnn Geraghty5, Sanjay Mohan6,7, Ashley N Webb8, Mark K Su6,7, Peter Akpunonu8,9.   

Abstract

INTRODUCTION: Acetaminophen is a commonly used analgesic and antipyretic, with the potential to cause significant injury when ingested in toxic amounts. Although the antidote n-acetylcysteine (NAC) is available, evidence supporting dose recommendations for patients weighing over 100 kg are lacking. We performed a retrospective, multi-center analysis to determine if a capped NAC dosing scheme is similar to a non-capped dosing scheme in patients weighing over 100 kg.
METHODS: Between January 2009 and January 2016, we identified patients presenting to 12 different centers who were evaluated for acetaminophen poisoning treatment. Patients must have weighed greater than 100 kg and were evaluated and identified as needing treatment for acetaminophen-related poisoning with NAC. The primary outcome was occurrence of hepatic injury, defined as an AST or ALT ≥ 100 IU/L. Secondary endpoints included number of drug-related adverse events, occurrence of hepatotoxicity, cumulative NAC dose, regimen cost, length of hospital and intensive care unit stays, and in-hospital mortality.
RESULTS: There were 83 patients identified as meeting the pre-specified inclusion and exclusion criteria. A capped NAC dosing scheme resulted in no difference in hepatic injury when compared to a non-capped regimen (49.4% vs 50%, p = 1.000). The capped dosage regimen was associated with a lower cumulative dose (285.2 mg/kg vs 304.6 mg/kg, p < 0.001) and cost. No other statistically significant differences were identified among the secondary endpoints.
CONCLUSION: A capped NAC dosing scheme was not associated with higher rates of hepatic injury or hepatotoxicity in obese patients in the setting of acetaminophen poisoning when compared to a non-capped regimen. Further research is needed to verify these results.

Entities:  

Keywords:  Acetaminophen; N-acetylcysteine; Obesity; Overdose; Toxicity

Mesh:

Substances:

Year:  2021        PMID: 33884558      PMCID: PMC8206426          DOI: 10.1007/s13181-021-00822-x

Source DB:  PubMed          Journal:  J Med Toxicol        ISSN: 1556-9039


  16 in total

1.  Acetylcysteine for Acetaminophen Overdose in Patients Who Weigh >100 kg.

Authors:  Bourke W Tillmann; Mai Takematsu; Daniel M Lugassy
Journal:  Am J Ther       Date:  2016 Jan-Feb       Impact factor: 2.688

Review 2.  Drug-induced liver injury in obesity.

Authors:  Bernard Fromenty
Journal:  J Hepatol       Date:  2013-01-05       Impact factor: 25.083

3.  Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose.

Authors:  Summon Chomchai; Chulathida Chomchai
Journal:  Pharmacoepidemiol Drug Saf       Date:  2017-11-17       Impact factor: 2.890

4.  Acetylcysteine for acetaminophen overdose in patients who weigh >100 kg.

Authors:  Shawn M Varney; Jennie A Buchanan; Jamie Kokko; Kennon Heard
Journal:  Am J Ther       Date:  2014 May-Jun       Impact factor: 2.688

5.  Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

Authors:  M J Smilkstein; G L Knapp; K W Kulig; B H Rumack
Journal:  N Engl J Med       Date:  1988-12-15       Impact factor: 91.245

6.  2013 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 31st Annual Report.

Authors:  James B Mowry; Daniel A Spyker; Louis R Cantilena; Naya McMillan; Marsha Ford
Journal:  Clin Toxicol (Phila)       Date:  2014-12       Impact factor: 4.467

Review 7.  Acetaminophen and acetylcysteine dose and duration: past, present and future.

Authors:  Barry H Rumack; D Nicholas Bateman
Journal:  Clin Toxicol (Phila)       Date:  2012-02       Impact factor: 4.467

8.  Obesity as a risk factor in drug-induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat.

Authors:  G B Corcoran; B K Wong
Journal:  J Pharmacol Exp Ther       Date:  1987-06       Impact factor: 4.030

9.  The effect of obesity on acetaminophen pharmacokinetics in man.

Authors:  W H Lee; W G Kramer; G E Granville
Journal:  J Clin Pharmacol       Date:  1981-07       Impact factor: 3.126

Review 10.  Effect of obesity on the pharmacokinetics of drugs in humans.

Authors:  Michael J Hanley; Darrell R Abernethy; David J Greenblatt
Journal:  Clin Pharmacokinet       Date:  2010       Impact factor: 6.447

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  3 in total

1.  Should the Dosage Cap Be Used in Patients Greater than 100 kg Receiving N-acetylcysteine for Acetaminophen Toxicity?

Authors:  Noah Gordon Berland; James Leonard; Diane P Calello
Journal:  J Med Toxicol       Date:  2022-01-10

2.  It's Been a Long Journey: Do We Know Where We Are Going?

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Review 3.  Drug dosing in children with obesity: a narrative updated review.

Authors:  Francesca Gaeta; Valeria Conti; Angela Pepe; Pietro Vajro; Amelia Filippelli; Claudia Mandato
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