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Methemoglobinemia is rare cyanosis cause resulting from oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+), yielding hemoglobin unavailability for oxygen transport with potential life-threatening by hypoxemia. Methemoglobin has a low concentration in red blood cells; methemoglobin is l–2% of total hemoglobin. Acquired methemoglobinemia occurs by methemoglobin formation rate is exceeding the reduction rate, secondary to metabolic chemical components action.
Methemoglobinemia symptoms are not specific. When methemoglobin level increases, typical symptoms increase. Usually, levels above 70% are not compatible with living state.
The goal is presenting two cases without known predisposing factors; they developed methemoglobinemia after ingestion of locally made wine brandy named (MAHIA).
A 36-year-old male without any health history of any type was admitted at emergency department with generalized face and fingertips cyanosis after local wine brandy drink. The patient was chronic smoker of twenty packets/year and occasional alcohol drinker, without family history of remarkable disease. On admission, he was clearly conscious, with body temperature of 37.0°C, heart rate/respiratory rate of 76 beats/min/17 cycles/min, and systolic/diastolic blood pressure of 110 mmHg/70 mmHg. Initial pulse oximetry revealed a hemoglobin oxygenation saturation of 82% without any distress signs with vomiting and fatigue. The chest auscultation showed good air exchange, the heart rate was regular with full and symmetric pulses and the rhythm was without murmurs or gallops; the neurological examination was normal. The patient was oxygenated via nasal canula. Complete blood count (CBC), blood urea nitrogen, electrolytes, creatinine, liver function and acid base equilibrium, prothrombin, partial thromboplastin activation time, and arterial blood gas (ABG) tests were all normal. Methemoglobin fraction was at 31.7%. Methemoglobinemia diagnosis was confirmed, 2 mg/kg of intravenous methylene blue was administered over 10 min. The patient was monitored with serial ABG analysis. However, the patient did not receive blood transfusion since blood was not available. The patient was discharged with methemoglobin of 2% and oxygen saturation of 96–98%.
A 60-year-old male was chronic smoker of forty packets/year and chronic alcoholic drinker without any health history of any type. He was admitted in emergency department with cyanosis lasting 6 h after a high-dose drink of local wine brandy. The patient reported abdominal severe pain episodes with nausea, vomiting, headache, dizziness, fatigue and generalized face and fingertips cyanosis. On admission, he was clearly conscious, with body temperature of 37.0°C, heart rate/respiratory rate of 120 beats/min//28 cycles/min, systolic/diastolic blood pressure of 70 mmHg/40 mmHg. The patient was conscious with the presence of sweat and mottling extremities. Chest investigations including X-ray active lung lesion were negative. To stabilize hemodynamic state and improve oxygenation, crystalloid filling was started. However, the patient did not receive blood transfusion since blood was not available. Electrocardiography revealed sinus tachycardia of 120 beats/min without ischemia. The oximeter showed saturation at 76%. Despite nasal cannula oxygenation, saturation did not improve. ABG was at 98.9%, PaO2 was 100 mmHg, PaCO2 was 36 mmHg, HCO3 was 20.9 mmol/L, pH was 7.44, and BE of −0.7 mmol/L. CBC, blood coagulation parameters, CRP, aminotransferases, CPK/CK-MB, troponin, urea, and creatinine were all normal. Methemoglobin rate was 65%. Considering the time between wine brandy drink to presentation (6 h), gastric decontamination was not done. 2 mg/kg of intravenous methylene blue was administered. Six hours later, the second dose was justified by remaining cyanotic lips. Twelve hours later, blood methemoglobin was 2%. Four days later, the patient was discharged in stable condition.
Methemoglobin is hemoglobin with oxidized iron to the ferric state. Hence, hemoglobin is unable to transport oxygen. Hemoglobin Iron is present in the ferrous form and is slowly but continuously oxidized to methemoglobin. In healthy individuals, hemoglobin is oxidized to methemoglobin and reduced back to hemoglobin on a continuous basis with normal methemoglobin level ranging from 0.5% to 3.0% of available hemoglobin.
Intracellular mechanisms are maintaining methemoglobin level <1%. These protective mechanisms are reducing oxidant potential to inactive substances. Major red blood cell reduction of methemoglobin pathway depends on the presence of reduced nicotine adenine dinucleotide (NADH) dependent methemoglobin reductase, and to lesser extent, NADH phosphate (NADPH) dependent methemoglobin reductase. Clinically, methemoglobinemia is present in two categories: Acquired and hereditary. Congenital methemoglobinemia is due to structural abnormalities in hemoglobin molecule (hemoglobin-M), or to metabolic problems such as erythrocyte methemoglobin reductase, pyruvate kinase or glucose-6- phosphate- dehydrogenase (G6PD)- deficiency.[1,2,3] Patients with G6PDdeficiency show increased the risk of developing methemoglobinemiaby exposure to oxidizing agent, due low-NADPH-level. Commonly, methemoglobinemia is acquired secondary to oxidizing effects of exogenous-substances. Methemoglobinemia symptoms are unclear and nonspecific but typically increasing with increased methemoglobin levels.
Cyanosis is occurring when methemoglobin is ≥10%, whereas 20–50% will cause respiratory distress, dizziness, headache, and fatigue. Lethargy and stupor develop around 50%, and death might occur around 70%. Seizures, cardiovascular failure and coma are revealed with higher methemoglobin fractions. Our cases showed cyanotic lips and nails with dizziness, headache, and fatigue; they ingested locally made wine brandy (MAHIA) simultaneously in identical circumstances and presented concurrently identical clinical symptomatology of methemoglobinemia. However, “relationship between MAHIA drink and methemoglobinemia” was not reported in the literature.
Acquired methemoglobinemia is frequent and caused by a wide variety of drugs, chemicals, and toxins including nitrates and nitrites.[1,2,3,4] In addition, dapsone, prilocaine, phenazopyridine, sulfonamide, naphthalene, antimalarial, and smoke inhalation are potential causes of acquired methemoglobinemia. Methemoglobinemia was caused in our cases by wine brandy prepared from dates’ extracts with alcohol [Figure 1].
Methemoglobinemia should be considered in cyanosis patient without cardiopulmonary deficiency unresponsive to oxygen therapy. Methemoglobined blood has degrees of chocolate brown color depending on concentration, which yields cyanotic appearance.
Definitive diagnosis is based on ABG analysis with cooximetry. Our both cases diagnosis of methemoglobinemia was evidenced by cyanosis with the absence of cardiopulmonary disease.
Methemoglobinemia should be considered in patients with a normal arterial PO2, and low oxyhemoglobin saturation. Arterial PO2 is unchanged since measuring dissolved oxygen in plasma. Similarly, oxygen saturation should be normal since derived from PO2.[4,5,6]
Initial treatment of suspected methemoglobinemia is supportive and includes removing inciting agents from clothes, skin, gastrointestinal tracts, and oxygen administration.
With sever symptoms (stupor, coma, angina) and methemoglobin level ≥30%, treatments includes 2 mg/kg of intravenous methylene blue solution at 1% over 5–10 min.
The transfusion or hyperbaric oxygen should be used.[1,2,3,4,5,6] Therefore, large doses of methylene blue might result in higher levels of methylene blue than leucomethylene blue, which will result in hemolysis and paradoxically, methemoglobinemia in patients with G6PD deficiency. Although ascorbic acid allows reducing methemoglobin and is used to treat hereditary methemoglobinemia, it is not used in acquired methemoglobinemia. Indeed, the pharmacological action mechanism of methylene blue is known to activate a normally dormant reductase enzyme system which reduces the methylene blue to leucomethylene blue, which in turns can reduce methemoglobin to hemoglobin.
Methylene blue is absorbed from the gastrointestinal tract and should be reduced in tissues to leuco form which is slowly excreted in urine together with an unchanged drug with imparting blue color to urine and feces. Methylene blue large dose produces methemoglobinemia.
Patients received methylene blue considering their methemoglobinemia clinical symptoms, and did not require transfusion exchange or use hyperbaric chamber since reserved for second line treatment when patients are not improved, or methylene blue cannot be used.
Methemoglobinemia is medical emergency that demonstrated acute hypoxia with life-threatening potential. High dose wine brandy is concomitant with methemoglobinemia with high risk of fatal outcome whenever under diagnosed and untreated.
There are no conflicts of interest.