Critical Cases - Acetaminophen Induced Methemoglobinemia!




  • 32  year old male p/w possible medication overdose
  • Pt reports  3-4 days taking 6g of acetaminophen daily for dental pain
  • Pt c/o some abdominal cramping with nausea/vomiting


  • hypertension

Physical Exam

T: 100.6  HR 80 BP 140/90 Pox 86% on RA and 86% on 4L nasal canula

  • General: appears comfortable in no distress




  • Lactate 2.2
  • ALT 9332 AST 9330 Tbili 9.2
  • PT 17.5 INR 1.5
  • Hepatitis panel negative
  •  COVID Ag/PCR neg
  • ABG: pH 7.5 PCO2 24 PO2 186 HCO3 22.5
  • Methemoglobin 9.1 (ref range 0.0-1.5%)
  •  Ammonia 101
  • Acetaminophen <5



 Case Discussion

  • Our patient has a negative tylenol level, but elevated LFTs and last tylenol use was 24 hours ago
  • Another indication for NAC is any evidence of liver injury (rise in ALT/AST)
  • What about the elevated methemoglobin level?? 


 Proposed mechanisms for methemoglobinemia in acetaminophen overdose:

  • NAPQI-induced oxidation
  • Depletion of glutathione stores
  • Production of oxidant-metabolites including paraaminophenol
  • G6PD deficiency results in inability to reduce NADP to NADPH




    Patient was found to be G6PD deficient at 3 U/gHb (Ref 9.9-16.6)

  • G6PD is necessary to reduce methemoglobin
  • Giving methylene blue in this case would worsen the oxidative stress as it accumulates without G6PD
  • NAC was started given liver injury

    Patient was evaluated for transplant but liver enzymes began to downtrend and patient labs improved along with clinical status

  • Patient ultimately discharged in good condition from the hospital


Key Points

  • Acetaminophen is a rare cause of methemoglobinemia
  • Remember methemoglobinemia as a potential complication of acetaminophen overdose in patients with G6PD deficiency





 Rianprakaisang T, Blumenberg A, Hendrickson RG. Acetaminophen-associated methemoglobinemia. Clin Toxicol (Phila). 2020;58(7):785-786. doi:10.1080/15563650.2019.1682153


Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55(6):871-876.