Keywords

Methemoglobinemia, nitrobenzene, methylene blue, acute kidney injury

Case Report

A 45-year-old male was brought to the casualty with alleged history of consumption of insecticide with suicidal intent. Patient was immediately intubated as he was cyanosed, not responding to painful stimuli and Glasgow coma scale (GCS) was only 3/15. Post intubation vital examination revealed blood pressure of 120/70 mmHg, pulse rate was 70/min and SpO₂ was 84% with 100% FiO₂. Arterial blood gas (ABG) analysis revealed pH - 7.21, PaO₂ - 523 mmHg, SaO₂ - 100%, PCO₂ - 41.4 mmHg and cHCO₃ - 17 mmol/L. The insecticide compound was identified as 20% nitrobenzene.

A provisional diagnosis of methemoglobinemia was made based on cyanosis and saturation gap¹ in ABG analysis. Initial evaluation revealed, blood sugar of 129 mg/dL, complete hemogram showed hemoglobin of 11.2 g/dL, total count of 8,100 cells/mm³, platelet count was 1.70 lakhs/mm³. Renal function test, electrolytes and liver function tests were normal at the time of admission. Urine analysis was negative for albumin, sugars and ketones, with 2-3 pus cells and 1-2 epithelial cells. Ultrasonogram of abdomen showed normal study. Electrocardiography at admission was sinus rhythm with no dynamic changes and echocardiography showed normal left ventricular (LV) function with an ejection fraction of 60%.

During course of intensive care unit (ICU) stay, he was treated with methylene blue 50 mg IV (1 mg/kg), ascorbic acid 500 mg, antibiotics, IV fluids and 1 unit of fresh blood was transfused. Patient had a transient improvement in pulse oximeter saturation values (from 84% to 94%), which again transiently dropped low after few hours and improved again with further administration of methylene blue.

Patient developed oliguria and hypotension on the second day of admission and hence was started on inotropes. Acute kidney injury was substantiated by progression to anuria and raise in renal parameters (Table 1 and Fig. 1). Urine analysis showed albumin 1+, with erythrocytic casts and granular casts. Renal biopsy was not done. Inspite of optimum treatment with methylene blue and other supportive measures patient developed refractory hypotension. Dialysis was planned but patient deteriorated rapidly and patient could not be revived.

Discussion

When hemoglobin loses an electron and becomes oxidized, the iron atom is converted to the ferric state (Fe³⁺), resulting in the formation of methemoglobin.² The physiological level of methemoglobin in the blood is 0-2%.³ Methemoglobin concentrations of 10-20% are tolerated well, but levels above this are often associated with symptoms. Methemoglobinemia can cause headache, dyspnea, chest pain, tachypnea, tachycardia, confusion, lethargy and metabolic acidosis occurs leading to coma, seizures, bradycardia and arrhythmias. Anemic or glucose-6-phosphate dehydrogenase (G6PD) deficient patients suffer more severe symptoms.⁴  Levels above 70% may cause death. Methemoglobin causes shifting of oxygen dissociation curve to left, implying increase in oxygen affinity. This results in anemic hypoxia, where oxygen carrying capacity is impaired though PaO₂ is normal or elevated.⁵ There is a difference between the SpO₂ that has been measured by means of pulse oximeter and the SO₂ that has been calculated by means of ABG analysis.

Methylene blue is used as first choice of antidote in methemoglobinemia poisoning. At pharmacologic doses it has reducing properties (1-2 mg/kg). Hence, it is used to reduce methemoglobin to hemoglobin. Normally, through the NADH or NADPH-dependent methemoglobin reductase enzymes, methemoglobin is reduced back to hemoglobin. When large amounts of methemoglobin occur secondary to toxins, methemoglobin reductases are overwhelmed. Methylene blue, when injected intravenously as an antidote, is itself first reduced to leucomethylene blue, which then reduces the heme group from methemoglobin to hemoglobin. However at high doses (>7 mg/dL), it acts as an oxidizing agent and induces methemoglobinemia, reversing this pathway.⁶ Methylene blue, as antidote in methemoglobinemia is associated with good clinical outcomes, is well-documented. In our patient, though the saturation improved with methylene blue (Table 2 and Fig. 2), ascorbic acid and blood transfusion, patient’s clinical outcome was hampered by acute kidney injury (AKI), clinically ascertained by oliguria, rising renal parameters, persistent hypotension and metabolic acidosis.

Conclusion

AKI secondary to myoglobinemia and hemoglobinemia is well-known. AKI secondary to methemoglobinemia is known to occur in animals and laboratory settings. Human case presentations are rare, but have been documented as secondary to topical benzocaine use and renal replacement therapy was necessitated.⁷ This case is presented for rarity of methemoglobinemia-induced AKI and to emphasis the need for heightened awareness for occurrence of AKI in methemoglobinemia, as prompt dialysis may significantly improve the outcome.

References

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