Acquired methaemoglobinaemia in infancy associated with acute diarrhoea: A case series.

Acute diarrhoeal illness remains a common medical problem in children with nearly 1.7 billion cases globally every year. We report five infants who, following severe diarrhoea, developed methaemoglobinemia. This is an altered state of haemoglobin presenting with cyanosis and can pose a diagnostic dilemma. It should be suspected in young infants without cyanotic heart disease presenting with severe diarrhoea, sepsis and cyanosis disproportionate to their clinical status. Its outcome depends on prompt treatment, the severity of underlying sepsis and co-morbidity.

The first reported use of red blood cell exchange to treat hemoglobin Evans with secondary methemoglobinemia.

This manuscript describes a novel approach for treating patients with long-term sequelae from hemoglobin Evans (Hb Evans). After instituting conservative therapies for approximately 2 years, our patient's symptoms continually worsened. Therefore, we performed red blood cell exchange (RBCx) to reduce his Hb Evans percentage and his co-existing elevation of methemoglobin. Our assumptions of clinical benefit were based on our collective experience performing RBCx for patients with sickle cell disease. After the first exchange, pre- and post-laboratory results supported our approach and the patient experienced marked improvement in his clinical signs and symptoms. This report provides preliminary proof of principle for the use of RBCx to treat Hb Evans and other non-Hb S hemoglobinopathies.

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem.

INTRODUCTION: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. METHODS: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. RESULTS: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. CONCLUSION: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.

Methaemalbumin: a diagnostic surrogate for methaemoglobinaemia and treatment with red cell exchange in a patient with thalassaemia.

A man in his 30s with alpha thalassaemia (four-alpha globin gene deletion) presented with 1 week of shortness of breath and 1 month of general malaise. Pulse oximetry monitoring revealed low peripheral oxygen saturation of approximately 80% despite maximal high-flow nasal cannula oxygen (fractional inspired oxygen 1.0-60 L/min flow). Arterial blood gas samples were chocolate brown in colour, with a low arterial partial pressure of oxygen of 197 mm Hg. This large oxygen saturation gap raised suspicion for methaemoglobinaemia. However, the patient's co-oximetry results were suppressed by the blood gas analyser and delayed a definitive diagnosis. A methaemalbumin screen was sent instead, which was positive at 65 mg/L (reference interval: <3 mg/L). Treatment with methylene blue was initiated but did not result in complete resolution of cyanosis. This patient had been red cell exchange dependent since childhood for thalassaemia. Therefore, an urgent red cell exchange was initiated overnight, leading to an improvement in symptoms and interpretability of co-oximetry results. This resulted in rapid improvement without residual sequelae or complications. We conclude that a methaemalbumin screen can be used as a surrogate test for prompt confirmation of diagnosis in lieu of co-oximetry in cases of severe methaemoglobinaemia or in cases with underlying haemoglobinopathy. Red cell exchange can allow prompt methaemoglobinaemia reversal, especially if methylene blue is only partially effective.

Acute Kidney Injury Following Naphthalene (Mothball) Poisoning.

Naphthalene is a widely available moth repellant in the Asian subcontinent. Toxicity can occur either accidentally or intentionally as a suicide attempt. An overdose can lead to a variety of clinical symptoms, including intravascular hemolysis, and can sometimes lead to life-threatening clinical situations. A young male was admitted to our center with an alleged history of ingesting an unknown quantity of naphthalene balls (mothballs). He developed methemoglobinemia, intra-vascular hemolysis, anuria, and acute kidney injury (AKI), followed by cardiorespiratory arrest. He was treated successfully with intravenous methylene blue and dialysis. Naphthalene toxicity can lead to methemoglobinemia and intravascular hemolysis. This can result in AKI caused by pigment nephropathy.

METHEMOGLOBINEMIA - A CASE REPORT AND LITERATURE REVIEW.

The objective of this case report is to present a patient with acquired methemoglobinemia due to poisoning of an unknown cause. A 55-year-old man was brought to the Emergency Department, University Hospital Center Zagreb, with an unwell appearance, cyanotic, restless, and presented with a quantitative consciousness disorder. An initial assessment showed decreased oxygen saturation (SpO2 85 [%]), while point-of-care arterial blood gas (ABG) analysis assessed normal partial pressure of oxygen (pO2). Severe lactic acidosis with a compensatory drop in partial pressure of carbon dioxide (pCO2) and high rates of methemoglobin were found. Supportive oxygen therapy and crystalloid solutions were administered, which resulted in rapid clinical recovery within 40 minutes of the initial assessment. Clinical recovery was accompanied by normalized ABG test results taken serially. Typical antidotes, methylene blue and vitamin C, were not administered due to rapid clinical improvement. Methemoglobinemia can be congenital (hereditary) or acquired (toxic). Both conditions are rarely seen in emergency departments, nevertheless, they should be approached properly since methemoglobinemia can be a severe, and fatal, condition. Methemoglobinemia symptoms are the results of inadequate oxygen transport. The diagnosis was confirmed by co-oximetry, while three clinical entities suspected methemoglobinemia: refractory hypoxia, "cyanosis-saturation gap" and dark brown blood. This paper reports our patient's clinical presentation, discusses the causes and mechanisms of possible poisoning, and reviews recent guidelines for methemoglobinemia management.

[An unusual case of central cyanosis]. / Un cas inhabituel de cyanose centrale.

We report the case of a 29-year-old man admitted to the emergency department for dyspnea and changes in mental status during a festivity. Clinically the patient presented a central cyanosis refractory to the administration of high concentration of oxygen. The consumption of poppers is increasingly used by young people for recreational purposes because they are inexpensive and easy to acquire. Methemoglobinemia is a potentially serious and little known complication of popper intoxication. This condition, known as «methemoglobinemia¼, was suspected by the emergency physician and confirmed through non-invasive measurement of methemoglobinemia in arterial blood gases. The early recognition of methemoglobinemia and prompt treatment allowed a favourable evolution of our patient avoiding the development of multi-systemic organ failure or even death.

Nous rapportons le cas d'un homme de 29 ans admis pour dyspnée et altération de l'état de conscience survenue dans le décours d'une soirée festive. Le tableau clinique est marqué par une cyanose centrale réfractaire à l'administration d'oxygène au masque à haute concentration. La consommation de poppers à usage récréatif est de plus en plus fréquente chez les jeunes adultes. C'est une substance peu coûteuse et facile d'accès, consommée, notamment, pour ses propriétés euphorisantes. La méthémoglobinémie est une complication potentiellement grave et peu connue de l'intoxication par poppers. Dans le cas présenté, la méthémoglobinémie, suspectée par le médecin urgentiste, a pu être confirmée rapidement par une mesure non invasive à la gazométrie artérielle. La reconnaissance précoce de la méthémoglobinémie et l'initiation d'un traitement efficace ont permis une évolution rapidement favorable et d'éviter une défaillance multi-systémique pouvant conduire au décès du patient.

Methemoglobinemia and Delayed Encephalopathy After 5-Bromo-2-Nitropyridine Poisoning: A Rare Case Report.

5-bromo-2-nitropyridine, an intermediate in the synthesis of pharmaceutical and pesticide products, is toxic to the human body. However, 5-bromo-2-nitropyridine poisoning has not been previously reported. Here, we report the case of a 40-year-old man who suffered skin and respiratory tract exposure to leaked 5-Bromo-2-nitropyridine at work. After exposure, the patient rapidly developed dizziness, fatigue, nausea, vomiting, chest distress, diffuse cyanosis, and coma. Methemoglobinemia, hemolytic anemia, rhabdomyolysis, and acute renal failure were observed after admission. He improved markedly after treatment, but delayed encephalopathy was confirmed 82 days after the exposure. This case highlights that 5-bromo-2-nitropyridine can be absorbed through the skin and respiratory tract, resulting in methemoglobinemia and delayed encephalopathy.

Rasburicase induced methemoglobinemia: A systematic review of descriptive studies.

PURPOSE: There is an increased number of reports being published on rasburicase-induced methemoglobinemia recently. We aimed to identify and critically evaluate all the descriptive studies that described the rasburicase-induced methemoglobinemia, its treatment approach, and their outcomes. METHODOLOGY: PubMed, Scopus and grey literature databases were searched from inception to January 2022 using search terms "rasburicase" and "methemoglobinemia" without any language and date restriction. A bibliographic search was also done to find additional studies. Only descriptive studies on Rasburicase-induced methemoglobinemia were included for our review. Two contributors worked independently on study selection, data abstraction, and quality assessment, and any disagreements were resolved by consensus or discussion with a third reviewer. RESULT: A total of 24 reports including 27 patients (23 male, 3 female patients, and 1 study did not specify the gender of the patient) aged from 5 to 75 years were included in the review. Immediate withdrawal of the drug and administering methylene blue, ascorbic acid, blood transfusion, and supportive oxygen therapy are the cornerstone in the management of rasburicase-induced methemoglobinemia. CONCLUSION: Rasburicase administration should be followed by careful monitoring of patients for any severe complication and treat it as early as possible appropriately. In a patient who presents with rasburicase-induced haemolysis or methemoglobinemia, it is often important to expect a diagnosis of G6PD deficiency unless otherwise confirmed and to avoid administering methylene blue, even though the patient is from a low-risk ethnicity for G6PDD.

Methemoglobinemia due to Hemolysis Secondary to Infection in a Child: A Case Report.

Methemoglobinemia is a rare condition characterised by hypoxic state manifesting as headache, nausea, fatigue, and confusion. We report a 2-year-old boy presenting with fever and cough for 7 days with an episode of hypoxia as the saturation declined and did not improve on face mask oxygenation. On further evaluation, acute intravascular hemolysis was established following decreased haemoglobin level, increased levels of lactate dehydrogenase, and unconjugated bilirubin in the setting of documented infection. Assessment of arterial blood gas showed a significantly raised saturation gap and detection of methemoglobin confirmed the diagnosis. He was managed conservatively with packed red blood cells transfusion following which hypoxia was corrected. Methemoglobinemia as a result of hemolysis can be a non-cardio-respiratory cause of hypoxia and inciting aetiology needs to be addressed. Keywords: case reports; hemolysis; hypoxia; infection; methemoglobinemia.

Nitrobenzene Induced Methemoglobinemia with Paroxysmal Atrial Fibrillation Treated with Single Volume Exchange Transfusions.

Methemoglobinemia is a potentially fatal condition if left untreated. Conventional treatment of nitrobenzene induced methemoglobinemia dictates the use of methylene blue, which is the antidote of choice. However, its availability in our setting is limited only to the laboratory use. We present a case of a 21-year-old female with intentional ingestion of nitrobenzene. Clinical history and supportive investigations revealed methemoglobinemia and it was successfully managed with single volume exchange transfusions in absence of specific antidote. While exchange transfusions are indicated for severe cases, it may be useful as an alternative treatment in acute life-threatening conditions where methylene blue is not available.

Acquired methemoglobinemia: A systematic review of reported cases.

INTRODUCTION: Acquired methemoglobinemia may cause cyanosis and tissue ischemia unresponsive to oxygen supplementation. METHODS: We performed a literature search to identify cases of acquired methemoglobinemia published between 1980 and 2020. Clinical, diagnostic, and treatment details were extracted from eligible cases. RESULTS: A total of 76 reports involving 87 cases were analyzed. The median age at presentation was 32.5 with male to female ratio of 1.6. Cyanosis and SpO2 <90 % were reported in 82 % and 60 % of cases, respectively. Dapsone or cocaine-based anesthetics were causative in 52 % of cases; most anesthetic-related cases occurred in the peri-procedural setting. Methylene blue (MB) and red cell transfusion were given in 71 % and 10 % of cases, respectively. Compared to MB untreated patients, MB treated patients were more likely to be cyanotic (91.9 % vs 54.2 %), had higher proportions (%) and levels (g/dL) of methemoglobin (MetHb) - 33.2 % vs 15.3 % and 3.1 g/dL vs 1.2 g/dL, respectively. We found that among cyanotic cases, the median MetHb level was 3.0 g/dL (0.4-12.3 g/dL) with 74 % of values ≥ 1.5 g/dL. An SaO2:SpO2 ratio of >1 was not universally present, but always coincided with an [SaO2-SpO2] delta value greater than zero. CONCLUSIONS: Cyanosis and hypoxemia were not universal findings of acquired methemoglobinemia in our series. In addition, not all patients had cyanosis at MetHb ≥ 1.5 g/dL or an SaO2:SpO2 ratio of >1. All those with an SaO2:SpO2 >1 did, however, have a delta value greater than zero - a finding not previously reported which we feel holds diagnostic value.

Recommendations for diagnosis and treatment of methemoglobinemia.

Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indirectly. Inherited forms are due either to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease. Our recommendations are based on a systematic literature search. A series of questions regarding the key signs and symptoms, the methods for diagnosis, the clinical management in neonatal/childhood/adulthood period, and the therapeutic approach of methemoglobinemia were formulated and the relative recommendations were produced. An agreement was obtained using a Delphi-like approach and the experts panel reached a final consensus >75% of agreement for all the questions.

A case report of acquired methemoglobinemia rescued by veno-venous extracorporeal membrane oxygenation.

RATIONALE: Severe methemoglobinemia (Met-Hb) is rare. The delayed diagnosis and treatment often cause further damage. The management of cellular hypoxemia is challenging and the use of extra-corporeal membrane oxygenation (ECMO) has never been reported. PATIENT CONCERNS: The young patient, healthy with unremarkable past medical history, was sent to emergency room with out-of-hospital circulatory arrest (OHCA) and severe generalized cyanosis. His family reported he ingested sodium nitrite accidentally. DIAGNOSES: After successful resuscitation and return of spontaneous circulation (ROSC), the paradoxically normal arterial blood gas (ABG) with the unusual brownish blood led to the suspicion of Met-Hb. The lab test confirmed it and showed a very high level of 80%. INTERVENTIONS: Because of recovered and normal cardiac function, we placed veno-venous extracorporeal membrane oxygenation (VV-ECMO) for tissue hypoxemia in addition to exchange transfusion, vitamin C, and methylene blue. OUTCOMES: Met-Hb blood level dropped rapidly. After vigorous rehabilitation for weeks, the patient was able to be discharged home without major neurological sequela. LESSONS: VV-ECMO can hyper-oxygenate the hypoxemic tissue regardless the etiology and minimize hypoxemia-reperfusion injury while awaiting the definite diagnosis and therapy.

Metahemoglobinemia secundaria a aplicación de un anestésico tópico (EMLA) / Methemoglobinemia secondary to application of a topical anesthetic (EMLA)

La metahemoglobinemia es un síndrome clínico que se produce por la oxidación del hierro de la hemoglobina impidiendo su adecuada unión al oxígeno, de forma que existe dificultad por parte de los glóbulos rojos tanto para captar el oxígeno, como para cederlo a los tejidos ocasionando hipoxia tisular. Describimos el caso de una paciente que presentó síntomas neurológicos y metahemoglobinemia como reacción adversa por contacto con crema de anestésico tópico (EMLA)

Methemoglobinemia is a clinical syndrome secondary to the oxidation of iron in hemoglobin, preventing its adequate binding to oxygen. Subsequently, red blood cells are unable to appropriately capture oxygen and deliver it to the tissues, causing hypoxia. We describe a case of a patient who presented neurological symptoms in the context of methemoglobinemia as an adverse reaction to the administration of EMLA

Fatal Sodium Nitrite Poisoning: Key Considerations for Prehospital Providers.

Sodium nitrite is a powerful oxidizing agent that causes hypotension and limits oxygen transport and delivery in the body through the formation of methemoglobin. Clinical manifestations can include cyanosis, hypoxia, altered consciousness, dysrhythmias, and death. The majority of reports on sodium nitrite poisonings have been the result of unintentional exposures. We report a case of an intentional fatal overdose of sodium nitrite. A 17-year-old female reportedly drank approximately one tablespoon of sodium nitrite in a self-harm attempt. The patient was hypotensive and cyanotic upon EMS arrival. The patient decompensated rapidly into a bradycardic arrest during transport despite intubation, push-dose epinephrine, and intravenous fluid resuscitation. In the Emergency Department (ED), she received methylene blue and packed red cells but could not be resuscitated despite a prolonged effort. EMS professionals should consider sodium nitrite toxicity in patients with a suspected overdose who present with a cyanotic appearance, pulse oximetry that remains around 85% despite oxygen, and dark brown blood seen on venipuncture. Early prehospital contact with the Poison Control Center and ED prenotification in poisoned patients is encouraged.

Siblings with pediatric sodium chlorite toxicity causing methemoglobinemia, renal failure and hemolytic anemia.

INTRODUCTION: Over the past decade, Miracle Mineral Solution (sodium chlorite) has been promoted as a cure-all for many conditions. CASE REPORT: A 9-year-old boy presented with his brother after they accidentally ingested a small amount of undiluted 22.4% sodium chlorite. Symptoms included nausea, vomiting, diarrhea, and dyspnea. Oxygen saturation remained 71% despite supplemental oxygen (15L/min). The patient was noted to have dark chocolate-appearing blood, minimal urine output, diffuse pallor and cyanosis. He developed methemoglobinemia, renal failure requiring renal replacement therapy and hemolysis requiring blood transfusion. DISCUSSION: These are the 7th and 8th reported cases of sodium chlorite toxicity by ingestion and the second and third in children. Takeaway for Physicians: Miracle Mineral Solution is a commonly purchased potentially lethal compound that can cause methemoglobinemia with respiratory failure, hemolytic anemia requiring transfusion and renal failure requiring dialysis.