Methemoglobinemia: What the anaesthetist must know

Abstract

Sir, Methemoglobinemia is an uncommon but potentially serious haemoglobin disorder in which oxygenation product of haemoglobin, i.e., methemoglobin accumulates in erythrocytes in large amounts. It is not capable of carrying oxygen and thus interferes with oxygen delivery to the tissues.[12] A 1½-year-old child was posted for cystoscopy and dilatation for urethral stricture. He was referred to our centre with complaints of difficulty in micturition and bluish discoloration of nails and lips. Cardiorespiratory examination revealed no abnormality. Saturation measured 83% on room air. Further cardiopulmonary work-up, including echocardiography, pulmonary angiography were normal. Haemoglobin electrophoresis revealed absence of abnormal form of haemoglobin and glucose-6-phosphate dehydrogenase (G6PD) level was normal. Methemoglobin level in the blood was 5% (normal value being < 1%). Arterial blood gas (ABG) analysis on room air showed pH: 7.3, pCO2: 25, pO2: 56, HCO3: 14, BE: −8.3 and SaO2: 87.8%. Perioperatively ascorbic acid 60 mg tds was started. Child was premedicated with glycopyrrolate 30 mcg intravenous (IV), midazolam 0.3 mg IV and ketamine 4 mg IV. Methylene blue ampoule was kept ready in operation theatre. Anaesthesia was induced with fentanyl 15 mcg, propofol 15 mg and atracurium 4 mg. No 1.5 proseal laryngeal mask airway was inserted after lubricating with liquid paraffin. Liquid paraffin was also used for lubrication of surgical instruments and cystoscope. Anaesthesia was maintained with 100% oxygen, isoflurane and controlled ventilation. Standard non-invasive monitors were used. Co-oximetry was not available. The procedure was uneventful. Intraoperative oximetry reading varied between 82% and 86%. Congenital methemoglobinemia occurs due to deficiency of enzymes nicotinamide adenine dinucleotide (NADH) b5 reductase and nicotinamide adenine dinucleotide phosphate flavin reductase.[123] Individuals with G6PD deficiency are more susceptible as this enzyme helps in inhibition of oxidation of haemoglobin and reduction of methemoglobin.[2] Haemoglobin M disease is another congenital cause, in which substitution of amino acid in heme moiety occurs, which results in oxidised haemoglobin. Acquired methemoglobinemia is more common and occurs on exposure to oxidising agents such as aniline dyes, nitrobenzene, nitrate, nitrite, benzocaine, prilocaine, dapsone, pyridium, nitric oxide, nitrous oxide and naphthalene due to overwhelming of capacity of reducing enzymes.[2] Children are more susceptible due to the presence of foetal haemoglobin, which oxidises more easily, low levels of NADH reductase, higher gastric pH, which promotes growth of nitrate reducing organisms causing conversion of dietary nitrates to nitrite.[234] Clinically, this disorder is differentiated from cardiopulmonary diseases by lack of significant pulmonary and cardiac finding on history, examination and investigations and cyanosis, which fails to respond to supplemental oxygen. ABG reveals the classical ‘saturation gap’, with normal paO2 despite cyanosis.[2] Regardless of aetiology, symptoms appear depending on methemoglobin level in blood. Chocolate colour cyanosis presents at levels of 5-15% and appears early in anaemic patients. Nevertheless, at least 5 g of reduced haemoglobin must be present for cyanosis to be appreciated. At 30-40%, weakness, headache, dyspnoea, tachycardia and dizziness occurs. Patient will be lethargic, stuporous, confused and comatose at concentration of 55-60%. At 70% circulatory collapse occurs.[12] Intraoperative monitoring should ideally include co-oximetry, which detects the presence as well as quantifies methemoglobin level.[5] Pre-operative treatment with vitamin C helps in non-enzymatic reduction of methemoglobin. Injection methylene blue is the antidote and the dose is 1-2 mg/kg IV over 3-5 min.[23] It acts by increasing the level of NADH methemoglobin reductase, which helps in conversion of ferric ion to ferrous ion. Exchange transfusion and haemodialysis is indicated in severe cases. In acquired methemoglobinemia offending drug should be withdrawn and care should be taken to avoid further exposure to offending agent. Anaesthetic drugs, which induce methemoglobinemia are local anaesthetics, the “caines” (prilocaine, benzocaine, lidocaine, eutectic mixture of local anaesthetics cream), nitrous oxide, metoclopramide, nitroglycerine, sodium nitroprusside and should be avoided.[12] Predisposing factors for methemoglobinemia include age (infants under 6 months), the status of the area being sprayed or injected (inflamed areas and broken skin absorb more of the drug), concomitant use of other drugs which also have been implicated in causing methemoglobinemia and the genetic make-up of the patient (due to altered haemoglobin, G6PD deficiency or methemoglobin reductase enzyme deficiency). Use of local anaesthetic agents in lower doses may be an approach to be followed in this group of patients.[6] Heightened awareness of proper dosing and the risk of methemoglobinemia is particularly important for clinicians involved in endoscopy, intubation, bronchoscopy or similar invasive procedures using topical anaesthetic-containing sprays. Knowledge of the condition, appropriate monitoring and avoidance of the precipitating factors and availability of antidote are key factors in managing a case of methemoglobinemia.