Changes in Epidemiology of Acetaminophen Overdoses in an Urban County Hospital After 20 Years

Long, Apple; Magrath, Melissa; Mihalopoulos, Meredith; Rule, Jody; Agrawal, Deepak; Haley, Robert W.; Kleinschmidt, Kurt; Lee, William M.

doi:10.14309/ajg.0000000000001826

Cited by 5 publications

(3 citation statements)

References 10 publications

(9 reference statements)

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“…Our study shows a decline in acetaminophen-opioid supratherapeutic ingestions at our institution after 2014, where the rate of hospitalized APAP-associated acute liver injury or acute liver failure per 100,000 adult admissions is 73.4/100,000. 3 As hydrocodone/acetaminophen supratherapeutic ingestions declined, codeine-acetaminophen, which remained schedule III, may have replaced some hydrocodone-acetaminophen prescriptions. This trend is consistent with findings from a study comparing opioid analgesic exposures reported to Texas Poison Centers during the 6 months before and after the hydrocodone schedule change.…”

Section: Discussionmentioning

confidence: 99%

Declining rates of opioid/acetaminophen combination product overdose: 2011–2020

Harris

Harms

Cao

et al. 2023

Hepatology Communications

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Background: During the opioid epidemic, misuse of acetaminophen-opioid products resulted in supratherapeutic acetaminophen ingestions and cases of hepatotoxicity. In 2014, the US Food and Drug Administration (FDA) limited the amount of acetaminophen in combination products to 325 mg, and the US Drug Enforcement Administration (DEA) changed hydrocodone/acetaminophen from schedule III to schedule II. This study assessed whether these federal mandates were associated with changes in acetaminophen-opioid supratherapeutic ingestions. Methods: We identified emergency department encounters at our institution of patients with a detectable acetaminophen concentration and manually reviewed these charts. Results: We found a decline in acetaminophen-opioid supratherapeutic ingestions after 2014. A downtrend in hydrocodone/acetaminophen ingestions accompanied a relative increase in codeine/acetaminophen ingestions from 2015 onwards. Conclusion: This experience at one large safety net hospital suggests a beneficial impact of the FDA ruling in reducing likely unintentional acetaminophen supratherapeutic ingestions, carrying a risk of hepatotoxicity, in the setting of intentional opioid ingestions.

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Section: Discussionmentioning

confidence: 99%

Declining rates of opioid/acetaminophen combination product overdose: 2011–2020

Harris

Harms

Cao

et al. 2023

Hepatology Communications

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“…Better education regarding the risks associated with APAP toxicity may be making some impact in the U.S. in terms of severity if not overall number of cases. 23 Outcomes have continued to improve in the past two decades with a decline in listing and liver transplantation accompanied by an increase in transplant-free survival. 3 These trends have occurred without a diminution of the severity of liver injury on presentation.…”

Section: Section I: Etiologies and Diagnosismentioning

confidence: 99%

Management of Acute Liver Failure: Update 2022

2022

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Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF) differs depending upon the etiology of the primary liver injury. In turn, the severity of the liver injury and resulting synthetic failure is often the primary determinant of whether a patient is referred for emergency liver transplantation. Injuries by viral etiologies trigger the innate immune system via pathogen-associated molecular patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome further depends upon the relative intensity and composition of cytokine release, resulting in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory response phenotype (CARS). The outcomes of overwhelming immune activation are the systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema, acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood of death.Acute liver failure (ALF) continues to carry a high risk of mortality or the need for transplantation despite recent improvements in overall outcomes over the past two decades. Optimal management begins with identifying that liver failure is indeed present and its etiology, since outcomes and the need for transplantation vary widely across the different etiologies. Most causes of ALF can be divided into hyperacute (ischemia and acetaminophen) and subacute types (other etiologies), based on time of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines and hepatocellular contents into the circulation with multiorgan effects/consequences.Management involves optimizing fluid balance and cardiovascular support, including the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation. Early evaluation for liver transplantation is advised particularly for acetaminophen toxicity, which evolves so rapidly that delay is likely to lead to death.Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute) etiologies heighten the need for urgent listing for liver transplantation. Prognostic scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver Failure Group prognostic index take these features into account and provide reasonable but imperfect predictive accuracy. Future treatments may include liver support devices and/or agents that improve hepatocyte regeneration.

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“…Acetaminophen (APAP) is a safe and effective drug at therapeutic doses, but an overdose can cause severe liver injury resulting in acute liver failure in animals and man 1 . APAP overdose is the most frequent cause of acute liver failure of any etiology in the US and many western countries 1 , 2 , 3 . The mouse model is clinically highly relevant to APAP-induced liver injury (AILI) 4 , therefore the understanding of the pathophysiology of AILI in the mouse can have direct clinical impact on identifying novel therapeutic targets and intervention strategies 4 .…”

Section: Introductionmentioning

confidence: 99%

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Chao,

Niu,

Wang

et al. 2024

Acta Pharmaceutica Sinica B

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Changes in Epidemiology of Acetaminophen Overdoses in an Urban County Hospital After 20 Years

Cited by 5 publications

References 10 publications

Declining rates of opioid/acetaminophen combination product overdose: 2011–2020

Declining rates of opioid/acetaminophen combination product overdose: 2011–2020

Management of Acute Liver Failure: Update 2022

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

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