Hrev_master Abstract Methemoglobinemia (MET) is a life-threatening condition resulting from the development of methemoglobin (MetHb), which binds oxygen irreversibly, causing refractory hypoxia and so-called “functional anemia”. MET can be caused by hereditary or acquired processes. Acquired forms are the most common. Symptoms correlate with the MetHb level and range from cyanosis and dyspnea to dysrhythmias, metabolic acidosis, coma, and cardiac arrest. MetHb levels above 70% are fatal. Methylene blue (MB) is the specific antidote. In all cases, support- ive treatment, including intravenous hydration, glucose correction, and oxygen supplementation, must be started immediately. Exchange transfusion has been used successfully to treat MET and may be appropriate in patients for whom MB is ineffective. We report the case of a 54-year-old woman who presented to our emer- gency department for the acute and sudden development of chest pain, shortness of breath, and severe cyanosis after drinking a sig- nificant amount of boiled courgette water. Arterial blood gas anal- ysis revealed a MetHb level of 26%. She was treated immediately with MB, oxygen supplementation, and hydration with normaliza- tion of her MetHb in 12 hours. Our recommendation is to always investigate MET in patients with unexplained cyanosis and refrac- tory hypoxia. Case Report A 54-year-old woman presented to our emergency department complaining of sudden severe chest pain and shortness of breath. Her past medical history was unremarkable. She denied any aller- gies or drug assumptions. Physical examination revealed symmet- rical air entry without wheezing or crackles, but severe cyanosis of the lips and extremities, most notably on her fingernails. Cardiovascular and abdominal evaluations were normal. Blood pressure was 110/80 mmHg, heart rate was 85 beats/min, body temperature was 36°C, respiratory rate was 18 breaths/min, and Emergency Care Journal 2024; volume 20:12034 [Emergency Care Journal 2024; 20:12034] [page 15] Eating vegetables is not always a good advice. A case report and literature review of acquired methemoglobinemia Andrea Vercelli,1 Irene Nasone,2,3 Laura Pagani,1 Alessandro Dacrema,1 Alberto Veneziani,1 Antonio Agosti,1 Erika Poggiali1 1Emergency Department, Guglielmo da Saliceto Hospital, Piacenza; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan; 3Emergency Department, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy Correspondence: Andrea Vercelli, Emergency Department, Guglielmo da Saliceto Hospital, via Taverna 49, 29121, Piacenza, Italy. Tel.: +39.0523.303044 E-mail: A.Vercelli@ausl.pc.it Key words: methemoglobinemia, methemoglobin, methylene blue, cyanosis, hypoxia, courgette. Contributions: AV, IN, and EP collected details of the case and draft- ed the manuscript. IN, LP, AD, and AV cared for the patient. AA and EP critically revised the manuscript. All the authors approved the final version. Conflicts of interest: EP is a member of the editorial board of Emergency Care Journal. The authors declare no conflict of interest. Availability of data and materials: All data underlying the findings are fully available upon reasonable request to Andrea Vercelli, A.Vercelli@ausl.pc.it Ethics approval and consent to participate: As this was a descriptive case report and data was collected without patient identifiers, ethics approval was not required under our hospital’s Institutional Review Board guidelines. Received: 27 December 2023. Accepted: 12 January 2024. Early view: 26 January 2024. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2024 Licensee PAGEPress, Italy Emergency Care Journal 2024; 20:12034 doi:10.4081/ecj.2024.12034 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Highlights - Acquired methemoglobinemia (MET) is an acute life-threatening condition that can occur after exposure to hemoglobin-oxidizing agents. - Drugs, nitrates-nitrites present in well water, vegetables, coloring compounds, cleaning solutions, and recreational drugs (poppers, cocaine adulterans) can cause MET. - The diagnosis should be suspected in case of unexplained cyanosis and refractory hypoxia. - Symptoms correlate with the methemoglobin level. - Severe MET can lead to cardiovascular collapse and death. - Methylene blue (MB) is the antidote to MET reserved for patients with significantly elevated methemoglobin levels. Caution should be taken in using MB, especially in case of hemolysis or when a history of G6PD deficiency is obscure. - Exchange transfusion is appropriate and successful in patients for whom MB is ineffective. Non -co mmerc ial us e o nly oxygen saturation was 83% on room air. The electrocardiogram displayed a sinus rhythm with a normal P-R interval, QRS com- plex, and QTc. Lung ultrasound showed a normal A pattern. Echocardiography ruled out cardiac injury and pericardial effu- sion. The patient was immediately placed on 15 Lt/min of oxygen through a non-rebreather reservoir bag oxygen mask, but her oxy- gen saturation did not improve. Arterial blood gas (ABG) analysis with oxygen revealed a significantly elevated methemoglobin (MetHb) level of 26% (normal value 0-1.5) with a pH of 7.39, pCO2 of 46.6 mmHg, pO2 of 80 mmHg, SpO2 95%, and a PaO2/FiO2 ratio of 80 mmHg. A diagnosis of methemoglobinemia (MET) was made, and an intravenous injection of methylene blue (MB) 1% at 1 mg/kg over 5 minutes was initiated. Thirty minutes later, ABG analysis showed a MetHb level of 7.8%. The patient developed bradycardia with a heart rate of 38 beats per minute and was treated with atropine with a rapid increase in her heart rate. ABG analyses were done every 3 hours until a normal level of MetHb was reached (0.3% after 12 hours), with a complete resolu- tion of cyanosis and chest pain. Supplemental oxygen was there- fore discontinued. All the laboratory tests, including high-sensitiv- ity cardiac troponin I, resulted in the normal range. The patient claimed to have drunk a significant amount of water derived from cooked courgettes that she had prepared at home approximately two hours before the onset of her symptoms. A review of the online literature revealed that courgettes are a potential cause of MET having a high nitrate content.1 After a 24- hour observation period in our emergency department observation unit, in the absence of clinical symptoms and with normal ECG monitoring, the patient was discharged home with a full recovery. Discussion MET is an acute life-threatening condition that requires prompt diagnosis and treatment. This rare condition is character- ized by the conversion of functional ferrous iron (Fe2+) in hemoglobin (Hb) to ferric iron (Fe3+), resulting in the formation of MetHb.2,3 MetHb binds oxygen irreversibly and shifts the oxygen dissociation curve of Hb to the left, causing tissue hypoxia and a state of “functional anemia” without a decrease in Hb concentra- tion.4,5 Under physiological conditions, MetHb reduction is accom- plished mainly by red cell NADH-cytochrome b5 reductase (NADH-MetHb reductase) so efficiently that there are insignifi- cant amounts of MetHb in the circulating blood.3 Hereditary and acquired methemoglobinemia MET can result from either congenital or acquired mecha- nisms.6 Inherited forms are due to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease.3,7-9 Based on the sever- ity of the enzyme deficiency, this condition can be classified into two different subtypes: type I, due to missense variants that cause production of an unstable enzyme purely in the red blood cells, associated with MetHb levels above 25%, cyanosis, headache, fatigue, and dyspnea; and type II, associated with high morbidity and mortality because of severe neurologic manifestations caused by variants that lead to low expression or low activity of the enzyme in all the tissues and the lipid metabolism.7 Acquired forms are the most common and can occur after the exposure to hemoglobin-oxidizing agents, such as drugs (e.g., dap- sone,10-12 antimalarials, topical benzocaine,13,14 lidocaine15 nitrates, nitrites, rasburicase, and alanine dyes), and nitrates-nitrites present in well water16,17 or vegetables (e.g., courgette, spinach, beets, and green beans),1,18,19 or coloring compounds,20 and cleaning solu- tions.21 A well-studied exposure to a chemical that can cause MET in infants is nitrate (above 10 mg/L) in well water. Infants have a higher risk of developing MET, since they drink more water per body weight compared to children and adults, have lower NADH cyb5r reductase activity that converts MetHb to hemoglobin, and have a higher percentage of fetal hemoglobin, which is easier to convert to methemoglobin.22 Acquired MET should be also sus- pected in infants presenting with acute severe diarrhea, sepsis, and cyanosis disproportionate to their clinical status.23 Some recreational drugs are also associated with acquired MET with very high levels of MetHb (>90%) and fatalities, includ- ing amyl nitrate (poppers),24-26 nitrous oxide (laughing gas), and adulterants used in cocaine (local anesthetics, phenacetin).27,28 Sepsis-induced MET must be taken into consideration in patients with septic shock and unexplained acute hemolysis, since it may be the only early sign of Clostridium perfringens sep- ticemia, and it should be promptly treated with antibiotics, control of the source of infection, oxygen supplementation, and massive blood transfusion.29 In addition but more rare, severe ascorbic deficiency can cause MET in patients with different hemoglobinopathies, including HbE β thalassemia,30 and sickle-cell anemia, particularly when splenic function is defective. Diagnosis and clinical features of acquired methemoglobinemia MET is a clinical diagnosis that should be suspected when an adult or child presents with unexplained cyanosis or hypoxia that does not resolve with supplemental oxygen and the likely presence of chocolate-colored blood. “Refractory hypoxia” is a diagnostic clue for MET. ABG is used to confirm the diagnosis by speciating hemoglobin and calculating the proportion and concentration of MetHb. Venous blood gas and pulse oximetry are not helpful,31 and there is often a discrepancy between the oxygen saturation deter- mined by ABG and the oxygen saturation measured by pulse oximetry.5 After exposure to an oxidizing substance that induces MetHb formation, the onset of symptoms is typically abrupt. The symptoms correlate with the MetHb level4,32 and range from cyanosis (MetHb < 10%), dyspnea, headache, fatigue, anxiety, and irritability (MetHb 20%), to dysrhythmias, metabolic acidosis, and coma (MetHb > 30%), which can be fatal if left untreated (33-36). Death occurs when MetHb levels rise above 70%. Treatment of acquired methemoglobinemia When possible, the agent causing MetHb should be stopped or removed, and supportive treatment, including intravenous hydra- tion, glucose correction, and oxygen supplementation, should be started immediately. High-flow oxygen delivered by non- rebreather masks increases oxygen delivery to tissues and enhances the natural degradation of MetHb.5 If necessary, car- diopulmonary support with mechanical ventilation and pressure support are indicated. No studies have examined the treatment of MET in the context of cardiac arrest.37 Methylene blue The specific antidote of MET is methylene blue (MB), which is a serotonergic drug that is converted into leucomethylene blue and allows for the reduction of the heme group from MetHb to Hb via the NADPH-dependent HMP shunt.32,38 There are no random- ized trials evaluating methylene blue for the treatment of MET, but Mini Review [page 16] [Emergency Care Journal 2024; 20:12034] Non -co mmerc ial us e o nly observational data consistently demonstrate resolution or improve- ment after MB administration.37 MB usually works rapidly and effectively. In cases of acquired MET, treatment with MB should occur when MetHb exceeds 20-30%, or at lower levels, if the patient is symptomatic. Treatment decisions should be made on clinical presentation and not withheld for confirmational laborato- ry values.5 The usual starting dose is 1-2 mg/kg (0.2 mL/kg of a 1% solution) infused intravenously over 5 min.32 The dose can be repeated at 1 mg/kg if MetHb does not significantly decrease with- in 30–60 min or the patient remains symptomatic. MB should reduce MetHb levels significantly in less than an hour. Benign side effects include green or blue discoloration of urine. Patients with continued production of MetHb from long-acting oxidant stress such as after dapsone ingestion may require repeat dosing every 6-8 hr for up to 2-3 days, or MB may be given as a continuous IV infusion of 0.10-0.25 mg/kg/hr.6 Caution should be used in patients receiving selective sero- tonin reuptake inhibitors and other serotonergic antidepressants since MB, acting as a potent monoamine oxidase inhibitor (MAO- A), may precipitate serotonin syndrome.39 MB should be used cau- tiously in pregnant women because of potential teratogenicity and intestinal atresia, and in patients with renal failure or in anes- thetized patients since it may inhibit guanylate cyclase, decreasing nitric oxide-mediated vasodilatation, and leading to systemic and pulmonary hypertension.6 In pregnant patients, the benefit-risk ratio must be always considered; despite potential (not evidenced) risks, MB should be evaluated with MetHb > 30% or high MetHb levels associated with lactic acidosis or hemodynamic disorders. Since the reduction of the heme group from MetHb to Hb depends on NADPH, which in turn is generated by glucose-6- phosphate dehydrogenase (G6PD), MB is ineffective in individu- als deficient in G6PD (favism) and can precipitate hemolysis.40,41 In these cases, exchange transfusion and hyperbaric oxygen may be useful.37 Ascorbic acid If MB is not available or in patients with G6PD deficiency, high-dose ascorbic acid (vitamin C), up to 10 g/dose intravenously, has been used to treat MET.42,43 However, most published case reports demonstrate its use in conjunction with other treatment modalities. The effect is slow and often requires multiple doses over several hours to have any significant effect.43,45 Dosing is not standardized, ranging in adults from 0.5 g every 12 hr x 16 doses, 1 g every 12 hr x 14 doses, 1.5-2 g IV x 3-4 infusions, 5 g every 6 hr x 6 doses, or even 10 g x one dose, while doses in children have ranged from 0.5 g every 12 hr x 16 doses and 1 g every 4 hr x 8 doses.6 High-dose ascorbic acid administration is associated with increased urinary excretion of oxalate. In the presence of renal insufficiency, high-dose ascorbic acid may be predisposed to renal failure due to hyperoxaluria.46 Ascorbic acid is not likely to be effective in resuscitation situations.37 N-acetylcysteine N-acetylcysteine has been suggested for the treatment of MET in patients with G6PD deficiency and acetaminophen-induced MET, even if its mechanism of action is still unclear. N-acetylcys- teine acts as a cofactor to enhance reduction and increase intracel- lular glutathione in vitro, however in a double-blind crossover human volunteer study, it was ineffective.47 Other If MB administration is ineffective after the second dose, G6PD and NADPH-MetHb reductase deficiency should be considered as reasons for refractoriness to treatment. Refractory MET can be treated with blood transfusions, red blood cell exchange, hemodial- ysis, and hyperbaric oxygen.6,37 Recently, Williams et al. reported a rare case of secondary MET in a patient with hemoglobin Evans who was successfully treated with red blood cell exchange.48 Hyperbaric oxygen therapy can be used as monotherapy and in con- junction with other therapies. Since the reduction of MetHb concen- trations can be delayed up to several hours,49-51 its use is impractical in the setting of cardiopulmonary collapse or cardiac arrest. Conclusions Our case highlights the importance for emergency clinicians to maintain a high degree of suspicion of MET in all patients, both adults and children, who present with unexplained cyanosis and hypoxia that does not resolve with supplemental oxygenation. Suspicion of MET must be confirmed by ABG analysis. If prompt- ly recognized and treated, MET rapidly resolves with no signifi- cant acute sequelae, as in our patient. For this reason, a complete medical history that includes medications, drugs, and foods, espe- cially homemade vegetable soups, is crucial in identifying and removing the trigger to restore normal tissue oxygenation and metabolism, avoid long-term consequences, and reduce the risk of subsequent episodes. Further research is needed to fully under- stand the underlying mechanisms of acquired MET and to develop guidelines for safe nitrate-rich food consumption. References 1. Savino F, Maccario S, Guidi C, et al. Methemoglobinemia caused by the ingestion of courgette soup given in order to resolve con- stipation in two formula-fed infants. Ann Nutr Metab 2006;50:368-71. 2. Prchal J. Chapter 51: Methemoglobinemia and Other Dyshemoglobinemias. 10th ed. McGraw Hill; 2021. 3. Mansouri A, Lurie AA. Concise review: methemoglobinemia. Am J Hematol 1993;42:7-12. 4. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: eti- ology, pharmacology, and clinical management. Ann Emerg Med 1999;34:646-56. 5. Ludlow JT, Wilkerson RG, Nappe TM. Methemoglobinemia. StatPearls Publishing; 2021. 6. Iolascon A, Bianchi P, Andolfo I, et al. SWG of red cell and iron of EHA and EuroBloodNet. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol 2021;96:1666- 78. 7. Percy MJ, Lappin TR. Recessive congenital methaemoglobi- naemia: cytochrome b(5) reductase deficiency. Br J Haematol 2008;141:298-308. 8. Dekker J, Eppink MH, van Zwieten R, et al. Seven new mutations in the nicotinamide adenine dinucleotide reduced-cytochrome b(5) reductase gene leading to methemoglobinemia type I. Blood 2001;97:1106-14. 9. Nicolas-Jilwan M. Recessive congenital methemoglobinemia type II: Hypoplastic basal ganglia in two siblings with a novel mutation of the cytochrome b5 reductase gene. Neuroradiol J 2019;32:143-7. 10. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobine- mia: a retrospective series of 138 cases at 2 teaching hospitals. Mini Review [Emergency Care Journal 2024; 20:12034] [page 17] Non -co mmerc ial us e o nly Medicine (Baltimore) 2004;83:265-73. 11. Ward KE, McCarthy MW. Dapsone-induced methemoglobine- mia. Ann Pharmacother 1998;32:549-53. 12. Guay J. Methemoglobinemia related to local anesthetics: a sum- mary of 242 episodes. Anesth Analg 2009;108:837-45. 13. McGuigan MA. Benzocaine-induced methemoglobinemia. Can Med Assoc J 1981;125:816. 14. Kane GC, Hoehn SM, Behrenbeck TR, Mulvagh SL. Benzocaine- induced methemoglobinemia based on the Mayo Clinic experi- ence from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. Arch Intern Med 2007;167:1977-82. 15. O'Donohue WJ Jr, Moss LM, Angelillo VA. Acute methe- moglobinemia induced by topical benzocaine and lidocaine. Arch Intern Med 1980;140:1508-9. 16. Avery AA. Infantile methemoglobinemia: reexamining the role of drinking water nitrates. Environ Health Perspect 1999;107:583-6. 17. Johnson CJ, Kross BC. Continuing importance of nitrate contam- ination of groundwater and wells in rural areas. Am J Ind Med 1990;18:449-56. 18. Sanchez-Echaniz J, Benito-Fernández J, Mintegui-Raso S. Methemoglobinemia and consumption of vegetables in infants. Pediatrics 2001;107:1024-8. 19. Cannata G, Abate L, Scarabello C, et al. The Dose Makes the Poison: A Case Report of Acquired Methemoglobinemia. Int J Environ Res Public Health 2020;17:1845. 20. Chow CK, Hong CB. Dietary vitamin E and selenium and toxicity of nitrite and nitrate. Toxicology 2002;180:195-207. 21. Freeman L, Wolford RW. Methemoglobinemia secondary to cleaning solution ingestion. J Emerg Med 1996;14:599-601. 22. Fossen Johnson S. Methemoglobinemia: Infants at risk. Curr Probl Pediatr Adolesc Health Care 2019;49:57-67. 23. Jajoo V, Masavkar S, Ahmed Zaki S, Pawar P. Acquired methaemoglobinaemia in infancy associated with acute diarrhoea: A case series. Trop Doct 2023. doi: 10.1177/00494 755231205632. Epub ahead of print. 24. Wilkerson RG. Getting the blues at a rock concert: a case of severe methaemoglobinaemia. Emerg Med Australas 2010;22:466-9. 25. Reisinger A, Vogt S, Essl A, et al. Lessons of the month 3: Intravenous poppers abuse: case report, management and possible complications. Clin Med (Lond) 2020;20:221-23. 26. Barrangou-Poueys-Darlas M, Gerardin M, Deheul S, et al. Poppers Use and High Methaemoglobinaemia: 'Dangerous Liaisons'. Pharmaceuticals (Basel) 2021;14:1061. 27. Hunter L, Gordge L, Dargan PI, Wood DM. Methaemo-globi- naemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review. Br J Clin Pharmacol 2011;72:18-26. 28. Houghton L, Jones Q, Wathen C. An unusual complication of cocaine toxicity. Acute Med 2013;12:96-7. 29. Koubaissi SA, Al Assaad RG, Itani Z, Bouakl I. Black Urine and Methemoglobinemia in the Setting of Sepsis Due to Clostridium Perfringens. Clin Med Insights Case Rep 2020;13:117 9547620981894. 30. Allen A, Fisher C, Premawardhena A, et al. Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabol- ic and clinical implications. Blood 2012;120:2939-44. 31. Haymond S, Cariappa R, Eby CS, Scott MG. Laboratory assess- ment of oxygenation in methemoglobinemia. Clin Chem 2005;51:434-44. 32. Skold A, Cosco DL, Klein R. Methemoglobinemia: pathogenesis, diagnosis, and management. South Med J 2011;104:757-61. 33. Gupta A, Jain N, Agrawal A, et al. A fatal case of severe methaemoglobinemia due to nitrobenzene poisoning. BMJ Case Rep 2011;2011:bcr0720114431. 34. Harvey M, Cave G, Chanwai G. Fatal methaemoglobinaemia induced by self-poisoning with sodium nitrite. Emerg Med Australas 2010;22:463–5. 35. Kreutz RW, Kinni ME. Life-threatening toxic methemoglobine- mia induced by prilocaine. Oral Surg Oral Med Oral Pathol 1983;56:480–2. 36. Margulies DR, Manookian CM. Methemoglobinemia as a cause of respiratory failure. J Trauma 2002;52:796–7. 37. Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2023;148:e149-84. 38. Pushparajah Mak RS, Liebelt EL. Methylene Blue: An Antidote for Methemoglobinemia and Beyond. Pediatr Emerg Care 2021;37:474-7. 39. Zuschlag ZD, Warren MW, K Schultz S. Serotonin Toxicity and Urinary Analgesics: A Case Report and Systematic Literature Review of Methylene Blue-Induced Serotonin Syndrome. Psychosomatics 2018;59:539-46. 40. Liao YP, Hung DZ, Yang DY. Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. Vet Hum Toxicol 2002;44:19-21. 41. Rosen PJ, Johnson C, McGehee WG, Beutler E. Failure of methy- lene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med 1971;75:83-6. 42. Rehman A, Shehadeh M, Khirfan D, Jones A. Severe acute haemolytic anaemia associated with severe methaemoglobi- naemia in a G6PD deficient man. BMJ Case Rep 2018;2018:bcr2017223369. 43. Rino PB, Scolnik D, Fustiñana A, Mitelpunkt A, Glatstein M. Ascorbic acid for the treatment of methemoglobinemia: the expe- rience of a large tertiary care pediatric hospital. Am J Ther 2014;21:240-3. 44. Park EJ, Lee M, Min YG. Successful treatment of NO-induced methemoglobinemia with low-dose vitamin C. Clin Toxicol (Phila) 2017;55:686. 45. Park SY, Lee KW, Kang TS. High-dose vitamin C management in dapsone-induced methemoglobinemia. Am J Emerg Med 2014;32:684.e1–684.e3. 46. Lee KW, Park SY. High-dose vitamin C as treatment of methe- moglobinemia. Am J Emerg Med 2014;32:936. 47. Tanen DA, LoVecchio F, Curry SC. Failure of intravenous N- acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: a randomized controlled trial. Ann Emerg Med 2000;35:369–373. 48. Williams LA 3rd, Adamski J, Kinard TN, et al. The first reported use of red blood cell exchange to treat hemoglobin Evans with secondary methemoglobinemia. J Clin Apher 2023;38: 755-9. 49. Lindenmann J, Matzi V, Kaufmann P, et al. Hyperbaric oxygena- tion in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia: a case report. Inhal Toxicol 2006;18:1047– 9. 50. Cho Y, Park SW, Han SK, et al. A case of methemoglobinemia successfully treated with hyperbaric oxygenation monotherapy. J Emerg Med 2017;53:685–7. 51. Altintop I, Sanri E, Tatli M, et al. Methemoglobinemia treated with hyperbaric oxygen therapy: a case report. Turk J Emerg Med 2018;18:176-8. Mini Review [page 18] [Emergency Care Journal 2024; 20:12034] Non -co mmerc ial us e o nly