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Cyclophosphamide-induced methemoglobinemia

Bone Marrow Transplantation volume 32, pages 1109–1110 (2003)Cite this article

Acute methemoglobinemia is a life-threatening disorder caused by chemicals and drugs, but rarely by chemotherapeutic agents. A high index of suspicion should be employed in patients with cyanosis out of proportion to their cardiopulmonary status. Prompt diagnosis, removal of toxic drugs, and treatment can quickly reverse methemoglobin (MetHb) formation. We report a case of methemoglobinemia in which cyclophosphamide is the likely etiologic toxic agent.

A 42-year-old Caucasian woman with metastatic carcinoma of the breast was admitted to the hospital for high-dose chemotherapy followed by autologous stem cell support using the previously published STAMP-I protocol1 consisting of cyclophosphamide 1.875 mg/m2/day i.v. and cisplatin 55 mg/m2/day i.v. day –6 to day −4. Her concomitant medications included ondansetron, diphenhydramine, fluticasone inhaler, lorazepam as needed, magnesium sulfate and continuous metoclopramide infusion through the admission course as per protocol. There was no significant past medical history of diabetes or cardiopulmonary disease. Before receiving BCNU on day −3, the patient complained of fatigue, headache, and lightheadedness. On examination, the following were observed: BP 124/64 mmHg, a pulse of 105, temperature of 98.7, mild cyanosis in the face and the lips, and mild basilar crackles in the lungs. She was hypoxic by pulse oximetry and required oxygen supplementation. The patient had 5 kg weight gain, and diuresis was begun with furosemide. She had a transient improvement, but her oxygen requirement continued to increase subsequently and was becoming hypoxic on 100% non-rebreather mask with pulse oximetry around 85–90%. An arterial blood gas evaluation on 100% FiO2 revealed pH of 7.37, PaO2 of 201 mmHg, PaCO2 of 28.4 mmHg, HCO3 of 17 mmol/l, oxygen saturation of 87%, and serum bicarbonate of 18 mmol/l. CO-oximetry on arterial blood showed carboxyhemoglobin (COHb) and MetHb concentrations of 0.2 and 10.7%, respectively. Her hemoglobin count was 11.3 gm/dl. Methylene blue was administered as 90 mg (1 mg/kg) i.v. infusion over 5 min. At 1 h following the administration of methylene blue, the MetHb level decreased to 3.2%. Repeat arterial blood gases confirmed the improvement in the oxygen saturation. On the same day, the patient received carmustine (BCNU) 600 mg/m2 as per protocol without any further complications, and was discharged as per protocol 3 days later, uneventfully. The MetHb level 24 h after the methylene blue injection was 1.7%. Hemoglobin electrophoresis showed no hemoglobin M. Cytochrome b5 reductase (NADH diaphorase) of red cells was 10.3 IU/g HB (normal 10–19.4).

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University Detroit, Childrens Hospital of Michigan, 3901 Beaubien BLVD, Detroit, 48201, MI, USA

    N Shehadeh, R Dansey & S Seen

  2. Department of Pediatrics, Barbara Ann Karmanos Cancer Institute, Wayne State University, Childrens Hospital of Michigan, 3901 Beaubien BLVD, Detroit, 48201, MI, USA

    E Abella

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  1. N Shehadeh
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  2. R Dansey
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Shehadeh, N., Dansey, R., Seen, S. et al. Cyclophosphamide-induced methemoglobinemia. Bone Marrow Transplant 32, 1109–1110 (2003). https://doi.org/10.1038/sj.bmt.1704278

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