INTRODUCTION: Acquired methemoglobinemia is a rare and potentially lethal complication of various oxidative chemicals, including aniline dyes, nitrites, antibiotics (dapsone) and topical anesthetics such as benzocaine. In most patients symptoms are mild and resolve without specific therapy, however, intravenous methylene blue may be required with more severe involvement. In cases of continued exposure to an oxidizing agent or enzyme deficiency, standard treatment may be ineffective and rarely, hyperbaric oxygen treatment or red-cell exchange transfusion can be efficacious. We present the case of an adult who was successfully treated with a red cell exchange transfusion.
CASE PRESENTATION: A 53-year-old female of Irish decent with diffuse infiltrates on chest radiograph developed hypoxemia requiring endotracheal intubation. In preparation for intubation the patient was given 20%-benzocaine as a topical anesthetic, as well as viscous lidocaine to the posterior pharynx. Shortly after intubation the patient developed cyanosis. Oxygen saturation by pulse-oximetry (Sp02) was 86% despite ventilation with 100% oxygen. An arterial blood gas was drawn and sent for multiple-wavelength co-oximetry. The results showed an arterial oxygen saturation of 40.8% despite a partial pressure of oxygen (PaO2) of 352. The methemoglobin level was 51.8%.The patient was given two doses of intravenous methylene blue without improvement. The patient became hypotensive and was transfused with type-specific packed red blood cells. Hyperbaric oxygen therapy was considered, however the patient was too unstable for transfer to a facility with this capability. She remained hypotensive with methemoglobin levels above 45%. Ascorbic acid (1000mg) was given and emergent red-cell exchange transfusion was initiated, with 93% of the circulating red-cell volume exchanged over four hours resulting in resolution of methemoglobinemia. The patient was successfully liberated from mechanical ventilation and subsequently had a full recovery. Glucose-6-phosphate dehydrogenase (G6PD) and cytochrome b5 reductase levels will be assessed 3 months after discharge.
DISCUSSIONS: Methemoglobin is an altered state of hemoglobin in which the ferrous irons of the heme molecule are oxidized to the ferric state rendering it unavailable for oxygen binding resulting in a functional anemia. Once formed, methemoglobin can be reduced enzymatically via either an adenine dinucleotide (NADH)-dependent reaction catalyzed by cytochrome b5 reductase or an alternative pathway utilizing the nicotine adenine dinucleotide phosphate (NADPH)-dependent methemoglobin reductase system. The former is the primary physiologic pathway. Additionally, cellular antioxidants such as ascorbic acid and glutathione can directly reduce methemoglobin non-enzymatically. Acquired methemoglobinemia is most commonly secondary to drugs or exposure to exogenous agents, which can accelerate the formation of methemoglobin. Pulse oximetry is inaccurate in monitoring oxygen saturation in the presence of methemoglobin and multiple-wavelength co-oximetry is imperative in establishing the diagnosis. Intravenous methylene blue is the treatment of choice for symptomatic patients. Response is usually immediate and the dose may be repeated within an hour, however this is usually unnecessary. For patients failing to respond to standard treatment, hyperbaric oxygen, blood or exchange transfusion is indicated. Exchange transfusion is more widely and rapidly available compared to hyperbaric oxygen. Exchange transfusion involves replacement of the patient's red cells with donor cells and has been used in the treatment of various hemoglobinopathies. Case reports on its use in methemoglobinemia are few and indications are based on anecdotal reports.
CONCLUSION: This case highlights several important issues in the diagnosis and treatment of methemoglobinemia. Recognition of a discrepancy between PaO2 and SpO2 followed by prompt diagnosis by the use of co-oximetry is essential. Furthermore, if a patient fails to respond to standard therapy, the use of exchange transfusion should be strongly considered.
DISCLOSURE: Michael Pritchett, None.