Acute Kidney Injury- A Rarity in Methemoglobinemia


Dr Umarani.R , Dr Baburaj.K, Dr Jino Vincent, Dr Saravanan.M    11 December 2017


Methemoglobinemia, nitrobenzene, methylene blue, acute kidney injury


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 GCS  was only 3/15. Post intubation vital examination revealed blood pressure of 120/70mm of Hg, pulse rate was 70 per minute and SpO2 was 84% with 100% Fio2. 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 11.2gm/dl, total count of 8100 cells/cu.mm, platelet count was 1.70 lakhs/cu.mm. 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. Ultra sonogram of abdomen showed normal study. Electrocardiography at admission was sinus rhythm with no dynamic changes and Echocardiography showed normal LV function with an ejection fraction of 60%.

During course of ICU stay, he was treated with methylene blue 50mg iv (1mg/kg), ascorbic acid 500mg, antibiotics, IV fluids and one 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. 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.



When hemoglobin loses an electron and becomes oxidized, the iron atom is converted to the ferric state (Fe3+), resulting in the formation of methemoglobin.3 The physiological level of methemoglobin in the blood is 0% to 2%.4 Methemoglobin concentrations of 10% to 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 occur leading to coma, seizures, bradycardia and arhythmias. Anemic or G6PD-deficient patients suffer more severe symptoms.5  Levels above 70% may cause death. Methemoglobin causes shifting of oxygen dissociation curve to left, implying increase in oxygen affinity. Thus resulting in anemic hypoxia, where oxygen carrying capacity is impaired though PaO2 is normal or elevated.6 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 arterial blood-gas analysis.

Methylene blue is used as first choice of anti-dote in methemoglobinemia poisoning. At pharmacologic doses it has reducing properties (1-2mg/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 (>7mg/dl), it acts as an oxidizing agent and induces methemoglobinemia, reversing this pathway.7

Methylene blue as anti-dote in methemoglobinemia is associated with good clinical outcomes is well documented. In our patient, though the saturation improved with methylene blue, ascorbic acid and blood transfusion, patient’s clinical outcome was hampered by AKI, clinically ascertained by oliguria, rising renal parameters, persistant hypotension and metabolic acidosis.


AKI secondary to myoglobinemia and hemoglobinemia is well known. AKI secondary to methemglobinemia 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.8 This case is presented for rarity of METHEMOGLOBINEMIA INDUCED ACUTE KIDNEY INJURY and to emphasis the need for heightened awareness for occurrence of AKI in methemoglobinemia, as prompt dialysis may significantly improve the outcome.



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