Methemoglobinemia associated with massive acetaminophen ingestion: a case series

Rianprakaisang, Tony; Blumenberg, Adam; Hendrickson, Robert G.

doi:10.1080/15563650.2019.1657883

Cited by 7 publications

(2 citation statements)

References 19 publications

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“…Methemoglobinemia is a well described complication of acetaminophen toxicity in large animal models, including swine and canines [ 30 , 31 ]. However, it is only rarely seen in clinical cases of acetaminophen overdose [ 32 ]. This has made it challenging to find relevant preclinical models, as below a certain dose, animals tend to recover without developing lasting liver injury, while above it, they succumb to the effects of methemoglobinemia.…”

Section: Discussionmentioning

confidence: 99%

Model of Acute Liver Failure in an Isolated Perfused Porcine Liver—Challenges and Lessons Learned

et al. 2022

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Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity and a mortality rate of almost 45%. Medical treatments, apart from supportive care, are limited and liver transplantation may be the only rescue option. Large animal models, which most closely represent human disease, can be logistically and technically cumbersome, expensive and pose ethical challenges. The development of isolated organ perfusion technologies, originally intended for preservation before transplantation, offers a new platform for experimental models of liver disease, such as ALF. In this study, female domestic swine underwent hepatectomy, followed by perfusion of the isolated liver on a normothermic machine perfusion device. Five control livers were perfused for 24 h at 37 °C, while receiving supplemental oxygen and nutrition. Six livers received toxic doses of acetaminophen given over 12 h, titrated to methemoglobin levels. Perfusate was sampled every 4 h for measurement of biochemical markers of injury (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT]). Liver biopsies were taken at the beginning, middle, and end of perfusion for histological assessment. Acetaminophen-treated livers received a median dose of 8.93 g (8.21–9.75 g) of acetaminophen, achieving a peak acetaminophen level of 3780 µmol/L (3189–3913 µmol/L). Peak values of ALT (76 vs. 105 U/L; p = 0.429) and AST (3576 vs. 4712 U/L; p = 0.429) were not significantly different between groups. However, by the end of perfusion, histology scores were significantly worse in the acetaminophen treated group (p = 0.016). All acetaminophen treated livers developed significant methemoglobinemia, with a peak methemoglobin level of 19.3%, compared to 2.0% for control livers (p = 0.004). The development of a model of ALF in the ex vivo setting was confounded by the development of toxic methemoglobinemia. Further attempts using alternative agents or dosing strategies may be warranted to explore this setting as a model of liver disease.

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Section: Discussionmentioning

confidence: 99%

Model of Acute Liver Failure in an Isolated Perfused Porcine Liver—Challenges and Lessons Learned

et al. 2022

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“…Though acetaminophen overdoses are common in the United States, acetaminophen induced methemoglobinemia is rare, though the incidence and risk factors for this are unknown [1] , [2] . The mechanism is thought to be due to oxidative stress from reactive metabolites [2] . However, few prior cases of sulfhemoglobinemia in the setting of acetaminophen overdose have been reported [3] , [4] , [5] .…”

Section: Introductionmentioning

confidence: 99%