This case report describes a female in her late 80s who presented with progressive dyspnoea and marked hypoxia. Notably, the hypoxia was refractory to high-flow supplemental oxygen. Her medical history included myeloperoxidase (MPO) positive vasculitis, vitamin B12 deficiency with a baseline haemoglobin of 88g/dL and well-controlled hypertension. A venous blood gas showed a MetHb of 10.2% [< 2%], which was initially overlooked. She was admitted to the ward and remained refractory to supplementary oxygen. A subsequent arterial blood gas (ABG) revealed an oxygen saturation (SaO2) of 95% and a methaemoglobin (MetHb) level of 10.7%. On review of her drug history, it was noted that she was taking 100 mg of dapsone once daily for Pneumocystis jirovecii pneumonia (PCP) prophylaxis. Dapsone was discontinued; her symptoms and hypoxia rapidly improved, and she was discharged 48 hours later.

Methemoglobinemia is a rare but potentially serious complication of lidocaine (LDC) use for local anesthesia in infants and young children, yet its prevalence during continuous systemic infusion for neonatal seizures remains unclear. Given the increasing use of LDC as add-on therapy for neonatal seizures, this retrospective cohort study evaluated methemoglobin (MetHb) levels in 51 neonates with (serial) measurements within 96 h before and after LDC infusion. Methemoglobinemia was defined as MetHb > 2% in arterial or capillary blood gas samples. Prevalence increased from 6% (3/51) before LDC to 47% (24/51) after administration (p < 0.001). Most neonates had mildly elevated MetHb levels (< 5%); three had a MetHb level > 5%, with a highest peak of 9.5%. In one neonate LDC was discontinued due to hypoxemia, the others were asymptomatic. In neonates who developed methemoglobinemia after LDC, the mean time to peak MetHb was 29.1 h (95% CI 11.1-73.3), and mean time to recover to < 2% after the peak was 27.5 h (95% CI 8.4-75.5). Over half of neonates receiving regimen III (> 36 weeks without therapeutic hypothermia [TH]) developed methemoglobinemia, compared to none on regimen IV (with TH). This suggests an association with a higher cumulative dose and longer infusion duration.Conclusion: In conclusion, methemoglobinemia occurred in nearly half of neonates receiving continuous LDC for seizures and was associated with the dosing regimen. It is important to be aware of this complication, especially in infants who develop respiratory deterioration and oxygenation problems following continuous LDC administration.

Methemoglobinemia is a rare but potentially life-threatening condition caused by oxidation of hemoglobin iron from the ferrous to ferric state, impairing oxygen delivery to tissues; early recognition is crucial as clinical manifestations may be disproportionate to pulse oximetry readings. We describe a case of a three-year-old female child who presented with acute onset cyanosis and hypoxia unresponsive to supplemental oxygen, despite a normal cardiopulmonary examination and persistently low oxygen saturation on pulse oximetry. Blood gas analysis revealed a discrepancy between low oxygen saturation and oxygen levels, raising suspicion of methemoglobinemia, which was subsequently confirmed by elevated methemoglobin levels. The child was managed with prompt supportive care, including high-flow oxygen therapy, followed by intravenous methylene blue, due to significant symptoms and elevated methemoglobin levels, which resulted in rapid clinical and biochemical improvement. She made a complete recovery without residual complications. This case underscores the importance of considering methemoglobinemia in young children presenting with unexplained hypoxia refractory to oxygen therapy, as timely diagnosis and appropriate treatment can be life-saving.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is among the most common enzyme disorders affecting red blood cells. It often remains unnoticed until the individual is exposed to oxidative stress, which can trigger rapid hemolysis. Methemoglobinemia develops when hemoglobin becomes oxidized into a form that cannot efficiently transport oxygen. This leads to impaired oxygen delivery to tissues and cyanosis that does not improve despite supplemental oxygen. Although uncommon, methemoglobinemia can develop as a serious complication during episodes of severe oxidative stress. We describe the case of an 11-month-old boy who developed acute hemolysis together with methemoglobinemia shortly after his first exposure to peanuts.

Background: The article describes a case of methemoglobinemia in a 4-year-old child with nephrotic syndrome with simultaneous use of therapeutic doses of three drugs that cause methemoglobinemia: lidocaine (topically), benzocaine (topically), and co-trimoxazole (systemically). An increase in the level of methemoglobin in the blood to 47.6% led to the development of respiratory failure. To correct the child's condition, high-flow oxygen therapy was performed and ascorbic acid was administered. During the day, there was a positive trend, the level of methemoglobin decreased to 1.5%. Toxicological examination of urine showed the presence of lidocaine, benzocaine, and trimethoprim. Thus, in conditions of polypragmasia in a child with comorbidity, the simultaneous use of three drugs with the potential of methemoglobinemia caused a significant increase in the level of methemoglobin and the development of respiratory failure, which required hospitalization in the intensive care unit. After 2 days, the patient's condition stabilized and he was transferred to a specialized department. As far as we know, this is the first documented case of methemoglobinemia in a child with polypragmasia.

The coexistence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and methemoglobinemia may produce misleading pulse oximetry readings, creating a significant diagnostic challenge during the perioperative assessment of oxygenation. Methemoglobinemia results from the oxidation of hemoglobin iron to the ferric state, impairing oxygen delivery and altering light absorption, often leading to falsely low oxygen saturation values. A 20-year-old man with confirmed G6PD deficiency and suspected chronic methemoglobinemia underwent an elective electrophysiologic study for recurrent supraventricular tachycardia. On arrival in the operating room, pulse oximetry showed a saturation of 45% on room air, despite preserved clinical status. Arterial blood gas analysis revealed a partial pressure of oxygen (PaO₂) exceeding 400 mmHg, confirming adequate arterial oxygenation and establishing a saturation gap. General anesthesia was induced and maintained with propofol and remifentanil without complications. Due to the risk of hemolysis associated with methylene blue in G6PD deficiency, conservative management was adopted, with hyperbaric oxygen therapy available as a contingency strategy. The intraoperative course was uneventful, with stable hemodynamics and no evidence of tissue hypoxia or hemolysis. This case demonstrates that severe pulse oximetry desaturation does not necessarily reflect true hypoxemia. Recognition of a saturation gap is essential when oximetry findings are discordant with clinical presentation, particularly in patients with G6PD deficiency, in whom standard therapies may be contraindicated. Accurate evaluation requires the integration of clinical assessment with arterial blood gas analysis. This report highlights the diagnostic pitfalls and implications for safe perioperative management.

Intensive recirculating aquaculture systems are vulnerable to spikes of nitrite, which oxidizes hemoglobin to methemoglobin and compromises oxygen transport. Methylene blue (MB) is a classical antidote for methemoglobinemia, yet its use in fish has been limited to injections or immersion baths that are impractical for large-scale operations. This study assessed whether MB incorporated into a medicated feed could mitigate acute nitrite intoxication in Nile tilapia. Fish received either a control diet or 0.1% MB diet. After five days on the experimental diets, fish were exposed to nitrite for 48 h. Control fish experienced five deaths, whereas no mortality or behavioral distress was observed in MB-treated fish. Hematology indicated significantly lower circulating methemoglobin concentration in the MB group, while the control fish had higher hemoglobin concentration and erythrocyte counts, consistent with compensatory erythropoiesis. Gill histology revealed preserved lamellae with only mild changes in MB-fed fish, whereas control fish displayed lamellar aneurysm, edema, capillary congestion, fusion and epithelial hyperplasia. Therefore, oral MB administration appears to ameliorate the physiological consequences of acute nitrite exposure, offering a scalable intervention for emergency management of nitrite spikes. Future work should define dose-response relationships, evaluate post-exposure rescue, quantify gill lesions and assess MB residues in food fish.

Methemoglobinemia is a rare, potentially life-threatening disorder caused by oxidation of hemoglobin iron from the ferric (Fe[3+]) to the ferrous (Fe[2+]) state, impairing oxygen delivery to tissues. Although most cases of methemoglobinemia that are documented are reported after procedural use of benzocaine sprays, those occurring from over-the-counter benzocaine gel are uncommon and often underrecognized. We report a case of an elderly woman with multiple comorbidities who developed significant methemoglobinemia after prolonged Benzocaine use for oral discomfort. She presented with refractory hypoxemia unresponsive to escalating supplemental oxygen. Arterial blood gas analysis revealed elevated methemoglobin levels. Timely recognition and administration of methylene blue resulted in rapid resolution of symptoms. This case highlights the importance of considering methemoglobinemia in patients presenting with unexplained refractory hypoxia, especially in patients who report the use of local anesthetics.

Sulfite, nitrite, and arsenic are pervasive environmental and dietary toxicants that pose significant risks to human health due to their high reactivity and ability to disrupt essential metabolic pathways. While these species are widely used in food preservation, agriculture, industry, and medicine, excessive exposure is associated with oxidative stress, methemoglobinemia, carcinogenesis, and neurological and cardiovascular disorders. Living systems rely heavily on metalloenzymes to regulate homeostasis, signaling functions, and detoxification of these compounds. This review examines the biochemical roles of key metalloenzymes involved in the oxidation, reduction, and transformation of sulfite, nitrite, and arsenic, with emphasis on sulfite oxidase, nitrite- and nitric oxide-related metalloproteins, and arsenic-metabolizing enzymes. We discuss their catalytic mechanisms, metal cofactors, and structural features that enable efficient detoxification, as well as the pathological consequences arising from their dysfunction or absence in humans. Collectively, this work highlights metalloenzymes as critical biochemical safeguards against toxic insult and underscores their importance in maintaining environmental and physiological homeostasis.