A Case That Will Take Your Breath Away: Acquired Methemoglobinemia Related to Trimethoprim-Sulfamethoxazole and Phenazopyridine Ingestion for Treatment of Urinary Tract Infection.

Trimethoprim-sulfamethoxazole (TMP-SMX) and phenazopyridine are individually associated with methemoglobinemia through a series of altered reduction-oxidation reactions. We report a case of methemoglobinemia associated with concurrent use of TMP/SMX and phenazopyridine in a 70-year-old woman with recurrent urinary tract infections. She presented to the emergency department for worsening back pain in the setting of recurrent urinary tract infections, concerning for pyelonephritis. During her workup, she became acutely hypoxic. The emergency department provider suspected the presence of abnormal hemoglobin. An arterial blood gas showing elevated levels of methemoglobinemia confirmed the suspicion. The combined use of TMP/SMX and phenazopyridine was thought to be the likely etiology of hypoxia. This case highlights the importance of medication management in the geriatric population, as well as the judicious use of antibiotics for urinary tract infections-a common chief complaint in the primary care setting.

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport.

Inhaled nitric oxide (iNO) is an advanced therapy typically managed by physicians and respiratory therapists in order to increase arterial oxygenation and decrease pulmonary arterial pressure. The Johns Hopkins Lifeline Critical Care Transportation Program (Lifeline) initiated a novel nurse-managed iNO protocol in order to optimize the oxygenation of critically ill patients during interfacility transport. This study was a retrospective chart review of adverse events associated with iNO initiation or continuation by Lifeline on patients transported from March 1, 2020, to August 1, 2022. Basic demographic data and adverse events were recorded. Recorded adverse events included hypotension defined as a mean arterial pressure (MAP) < 65 mm Hg, hypoxemia defined as a decrease of ≥ 10% arterial oxygenation saturation measured by pulse oximetry, new bradycardia or tachyarrhythmia, nitrogen dioxide (NO2) levels greater than 1.0 ppm, methemoglobinemia, and cardiac arrest. Fifteen patients were diagnosed with SARS-CoV-2 infection, of which one also had pulmonary emboli, 2 had bacterial pneumonia, 1 suffered cardiogenic shock from occlusive myocardial infarction and were on VA-ECMO, and 2 had significant thoracic trauma resulting in pulmonary contusions and hemopneumothorax. iNO was continued on 10 patients and initiated on 8 patients, 2 of whom were transitioned from inhaled epoprostenol. Hypotension occurred in 3 (16.7%) patients and one (5.56%) of the hypotensive patients subsequently went on to experience new atrial fibrillation with vasopressor titration. No patients developed worsening hypoxemia, elevated NO2 levels, methemoglobinemia, or suffered cardiac arrest. All 3 patients who experienced hypotension were already on vasopressor support and the hypotension resolved with medication titration. This study shows that iNO administration can be safely managed by appropriately trained nurses.

Methaemoglobinaemia due to alkyl nitrites in a patient with suspected traumatic injuries.

A man in his 60s with no relevant previous medical history presented to an urban, major trauma centre by ambulance after being found with a head injury in a nightclub. The paramedics reported he was hypoxic, hypotensive and tachycardic with altered mental status. At the emergency department, he had oxygen saturations of 85% despite high-flow oxygen and was hypotensive at 88/43mmHg. We were concerned the patient was haemorrhaging given the lack of response to oxygen therapy and their hypotension. However, an arterial blood gas (ABG) established a diagnosis of methemoglobinaemia. Methylthioninium chloride was promptly administered, and the patient's condition improved. He later reported using recreational drugs, including alkyl nitrites ('poppers'). He was monitored until his fraction of methaemoglobin returned to normal baseline levels with serial ABGs. He was discharged 24 hours later. It was suspected that his use of alkyl nitrites was the most likely cause of methaemoglobinaemia.

Emergency treatment with intravenous infusion of methylene blue followed by oral administration in a cat presented with severe recurrent methemoglobinemia.

OBJECTIVE: To describe the use of IV infusion followed by oral administration of methylene blue (MB) to successfully treat recurrent methemoglobinemia (MetHb) in a young cat. CASE SUMMARY: A 6-month-old male Ragdoll cat presented with recurrent episodes of severe MetHb and was successfully managed with IV infusion of MB followed by a course of oral MB. Although the definitive cause of the patient's MetHb remains unknown, the cat made a full recovery following treatment without developing any significant side effects secondary to therapy and at the time of writing not had any further recurrences. Follow-up at 6 months found the patient in good health and without any long-term consequences. NEW INFORMATION PROVIDED: To the authors' knowledge, this is the first report of a cat presented with severe MetHb quantitatively assessed via co-oximetry and successfully treated with both IV and oral administration of MB.

Methemoglobinemia, Increased Deformability and Reduced Membrane Stability of Red Blood Cells in a Cat with a CYB5R3 Splice Defect.

Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman's assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range < 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 ± 6% of normal. Genetic analyses revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis.

Inflammatory phenotype, clinicopathologic variables, and effects of long-term methylene blue in dogs with hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency.

OBJECTIVE: To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry results, and describe changes in methemoglobin (MetHb) levels and serum C-reactive protein (CRP) concentrations after long-term per os (PO) methylene blue (MB) therapy. ANIMALS: 21 client-owned dogs (CYB5R deficient, n = 10; healthy controls, 11). PROCEDURES: In this prospective, case-control study, methemoglobin levels were measured using a blood gas analyzer with co-oximetry. Plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were measured using a canine-specific multiplex bead-based assay. Serum CRP concentrations were measured with a canine-specific commercial ELISA kit. Serum CRP concentration and MetHb levels were measured in 6 dogs with CYB5R deficiency after ≥ 60 days of PO MB therapy. RESULTS: As expected, MetHb levels were higher in dogs with CYB5R deficiency compared to controls (P < .001). Plasma TNF-α, IL-6, IL-10, and serum CRP concentrations were no different between CYB5R-deficient and control dogs. Dogs with CYB5R deficiency had lower absolute lymphocyte (P = .005) and eosinophil counts (P = .04) and higher alanine transaminase (P = .04) and alkaline phosphatase activity (P = .02) than controls, but these changes were not clinically relevant. Methemoglobin levels decreased after PO MB therapy (P = .03). CLINICAL RELEVANCE: These results suggest that otherwise healthy dogs with CYB5R deficiency do not have a constitutive proinflammatory phenotype and clinically relevant abnormalities in hematologic and serum chemistry panels are not expected. Dogs with decreased quality of life attributed to methemoglobinemia from CYB5R deficiency might benefit from PO MB therapy.

Acute dapsone poisoning with methemoglobinemia: a case report.

Methemoglobinemia is a common complication of dapsone poisoning. Its´ treatment usually relies on methylene blue infusion. The aim of this study was to report a case of an acute dapsone poisoning with methemoglobinemia treated only with ascorbic acid and activated charcoal. A 16-year-old female voluntary ingested 3 grams of dapsone in an attempt of suicide and presented with desaturation and tachypnea. Lab findings were compatible with methemoglobinemia. After two days of treatment with ascorbic acid and activated charcoal, we observed the disappearance of desaturation and tachypnea. Methemoglobinemia can be treated with ascorbic acid and activated charcoal in limited resource settings.

Toxic Encephalopathy and Methemoglobinemia after 5-Amino-2-(trifluoromethyl)pyridine Poisoning.

The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of this compound is sparse and no related poisoning events have been reported. Here, we report the case of a 35-year-old man who inhaled 5-amino-2-(trifluoromethyl)pyridine at work. After inhalation, the patient rapidly developed symptoms such as dizziness, fatigue, nausea, vomiting, chest tightness, and loss of consciousness. After admission, methemoglobinemia, hemolytic anemia, acute renal failure, and toxic encephalopathy occurred. Symptoms improved significantly after intravenous treatment with a low dose of methylene blue. This revealed that 5-amino-2-(trifluoromethyl)pyridine is toxic to the human body and can be absorbed through the respiratory tract, resulting in methemoglobinemia and toxic encephalopathy; thus, caution should be taken in industrial production.

Dapsone-induced methemoglobinemia and hemolysis in a woman without G6PD deficiency presenting with idiopathic urticaria.

BACKGROUND: The appearance of bite cells associated with methemoglobinemia can be caused by oxidizing drugs such as dapsone in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or high drug serum levels. Bite cells are often pathognomonic for oxidant injury in patients with G6PD deficiency and suggest active hemolysis. CASE PRESENTATION: We report a case of a woman with no prior history of G6PD deficiency who presented with anemia, methemoglobinemia and bite cells on peripheral blood smear after dapsone therapy for new onset idiopathic urticaria. Laboratory tests for G6PD, blood count and liver function were within normal limits prior to initiation of therapy. During the patient's hospital course, moderate methemoglobinemia and anemia were identified despite mildly increased serum G6PD level. These pathologies were reversed upon stopping dapsone therapy. CONCLUSION: This case highlights the potential for therapeutic levels of dapsone to induce side effects in patients without G6PD deficiency and highlights the importance of routine blood monitoring for anemia and hemolysis during the course of drug therapy.

Intentional dapsone overdose: a rare cause of acquired methaemoglobinaemia in the emergency department.

A woman in her 30s presented to our emergency department with vomiting and lethargy after an intentional ingestion of unknown antimicrobial pills which was later found to be dapsone. The patient developed cyanosis, hypoxia and tachycardia due to acute methaemoglobinaemia (level of 30.9% on venous blood gas analysis). As dapsone is notorious for prolonged and rebound methaemoglobinaemia, she was managed with repeated doses of intravenous methylene blue and oral multidose activated charcoal which warranted elective intubation and intensive care unit admission. Subsequent drug-induced hepatitis and delayed dapsone-induced haemolysis were managed conservatively. She was discharged in a stable condition with outpatient follow-ups. Physician familiarity with the nuances of this rare condition and its complications contributes to better patient care.

Dapsone for Refractory Gastrointestinal Symptoms in Children With Immunoglobulin A Vasculitis.

Immunoglobulin A vasculitis (IgAV) is a systemic small-vessel vasculitis. Although corticosteroids (CS) are the primary treatment for gastrointestinal manifestations associated with IgAV, some patients develop refractory or recurrent symptoms such as vomiting and abdominal pain despite CS treatment. Dapsone, a synthetic sulfone antimicrobial, has been used to treat cutaneous purpura in IgAV, but few authors have reported its use for refractory gastrointestinal symptoms. In this retrospective observational study, we describe results in 7 children with IgAV who were treated with dapsone for abdominal pain resistant to CS. Dapsone rapidly relieved abdominal pain in all 7 patients, who then were tapered off CS without relapse. Side effects of mild methemoglobinemia and hemolysis appeared to be manageable with planned monitoring and dose adjustment; a single patient who discontinued dapsone had fatigue and hypoxia associated with methemoglobinemia. No side effects were life-threatening. Dapsone may be considered as a therapeutic option for gastrointestinal symptoms refractory to CS in children with IgAV.

Skin ulcers as a complication of short-term use of phenazopyridine in an old man: A case report.

INTRODUCTION: Phenazopyridine is an azo dye, which exerts local anesthetic or analgesic action on urinary tract mucosa through an unknown mechanism. Besides its common complications including orange discoloration of the urine and gastrointestinal problems, it may have rare side effects like hemolytic anaemia, methemoglobinemia, renal failure, and skin changes. We reported a paraplegic man with skin ulcers on scretom and right foot after about 3 days of phenazopyridine use CASE REPORT: A 62-year-old man presented with flesh shaped deep ulcers in lower parts of the body. He declared that at first a bluish discoloration was developed in the lower extremities and scrotum skin after use of eight phenazopyridine tablets (200 mg) and then these lesions turned to blisters and ulcers and they were prurient. The patient underwent sonography and CT-angiography; however, no pathologic findings were found. He just received losartan for many years as past drug history. According to the history, a delayed drug hypersensitivity reaction was suspected and the patient wounds healed after using special type of dressings and antibiotic therapy regarding positive wound cultures. CONCLUSION: Phenazopyridine severe skin changes are hardly reported. We described a case who experienced severe skin reactions and ulcers following phenazopyridine use not related to other complications including renal dysfunction, methemoglobinemia, and hemolytic anemia.