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Year : 2022  |  Volume : 1  |  Issue : 1  |  Page : 33-35

A rare case of congenital methemoglobinemia with severe mitral stenosis: An anesthetic and surgical challenge

Department of Anaesthesiology and Critical Care, Santosh Medical College, Ghaziabad, Uttar Pradesh, India

Date of Submission14-Dec-2021
Date of Decision23-Mar-2022
Date of Acceptance29-Mar-2022
Date of Web Publication20-May-2022

Correspondence Address:
Dr. Ritesh Kumar
Flat No. 904, Tower 4, Orange County, Ghaziabad, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jica.jica_6_21

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Methaemoglobinemia is a condition that occurs when red blood cell contains higher than 1% methaemoglobin (MHb). It can be congenital or acquired. The condition is generally asymptomatic until the serum MHb level reaches as high as 40%. Dyspnea, acidosis, cardiac dysrhythmias, heart failure, seizures, and coma may occur at levels exceeding 45%, and a high mortality rate is seen with levels above 70%. We report a rare association of a case of rheumatic heart disease with severe mitral stenosis with congenital methemoglobinemia diagnosed incidentally during mitral valve replacement procedure under cardiopulmonary bypass.

Keywords: Cardiopulmonary bypass, congenital methemoglobinemia, general anesthesia, mitral stenosis

How to cite this article:
Lakhanpal M, Kumar R, Sarkar D, Tyagi V. A rare case of congenital methemoglobinemia with severe mitral stenosis: An anesthetic and surgical challenge. J Ind Coll Anesth 2022;1:33-5

How to cite this URL:
Lakhanpal M, Kumar R, Sarkar D, Tyagi V. A rare case of congenital methemoglobinemia with severe mitral stenosis: An anesthetic and surgical challenge. J Ind Coll Anesth [serial online] 2022 [cited 2023 Jan 27];1:33-5. Available from: https://www.jicajournal.in//text.asp?2022/1/1/33/345603

  Introduction Top

Methaemoglobinemia (MHB) is a condition that occurs when red blood cell (RBC) contains higher than 1% methaemoglobin (MHb). It results from the presence of iron in the ferric form instead of ferrous form, which leads to a decrease in the release of oxygen to tissues causing functional anemia.[1] It can be congenital or acquired due to the use of drugs, such as nitroglycerine, lidocaine, and sulfonamides.[2],[3],[4],[5] Cyanosis, presence of “chocolate, dark-red, brownish-to-blue”–colored arterial blood, and low SpO2 in the presence of a normal PaO2 on arterial blood gas analysis, gives a clue for MHB. Further assessment of MHb fraction in blood and electrophoresis confirms the diagnosis.

The symptoms are proportional to MHb levels. The condition is generally asymptomatic until the serum MHb level reaches as high as 40%.[6],[7] Dyspnea, acidosis, cardiac dysrhythmias, heart failure, seizures, and coma may occur at levels exceeding 45%, and a high mortality rate is seen with levels above 70%.[8]

  Case Report Top

A 38-year-old male presented to our cardiac emergency unit with acute left lower limb ischemia features. He was a known case of rheumatic heart disease (RHD) with severe mitral stenosis (MS) with thrombus in the left atrium (LA). He was immediately shifted to the intensive care unit for urgent intervention. The clinical examination revealed features consistent with MS but no cyanosis. Other system examinations were grossly normal. Emergency blood investigations showed an hemoglobin (Hb) level of 17.3 g/dl, and other hematological and biochemical parameters were within the normal range. Chest radiograph showed left atrial enlargement with straightening of the heart's left border, i.e., mitralized heart. Electrocardiogram showed features suggestive of left atrial enlargement and atrial fibrillation. Ultrasound Doppler of the left lower limb revealed a thrombus in the left popliteal artery with no flow distally. A review of urgent echocardiography showed features consistent with rheumatic heart disease with severe MS with an LA clot of 2.2 cm × 1.1 cm attached to the interatrial septum, ejection fraction of 60%, and right ventricular systolic pressure of 45 mmHg.

The patient was on various cardiac medications such as oral digoxin, furosemide, aldactone, erythromycin, and warfarin for the past 6 months. There was no history of intake of any other drugs potential for MHB. The family history was insignificant.

The patient was taken up for emergency surgery. Pulse oximeter showed an SpO2 of 97.8% on room air. Invasive lines in the right radial artery and central line through the right internal jugular vein were placed. Standard induction of general anesthesia was performed using fentanyl (200 μg), thiopentone (50 mg), and pancuronium (6 mg) and maintained with intermittent sevoflurane (1%–3%) and midazolam. Baseline arterial blood gas (ABG) was grossly normal with an Hct of 35.7, PaO2 of 261, and SaO2 of 98.7% at FiO2 of 50%; however, the sample blood color was dark.

After midline sternotomy, a standard aorto-bicaval cardiopulmonary bypass (CPB) was initiated, which again revealed dark-colored blood in the aortic line, almost the same as that of the venous line blood during CPB [Figure 1]. However, during CPB, ABG analysis revealed an Hct 28.2, PaO2 of 463 mmHg, and SaO2 of 99.4%. Mitral valve replacement with a metallic prosthesis (size 31/33) along with LA clot removal was performed. Total perfusion time was 65 min, ischemia time was 30 min. The patient came off smoothly from CPB, and a left popliteal embolectomy was done through the transfemoral route. The patient had an uneventful recovery postoperatively. Inotropic supports in the form of epinephrine (0.025–0.05 μg/kg/min) and dobutamine (5 μg/kg/min) were used for 2 days and then tapered off.
Figure 1: Chocolate-brown arterial and venous lines of the cardiopulmonary bypass machine

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[Figure 1] shows chocolate-brown arterial and venous lines of the CPB machine; note that both lines have the same dark color though PaO2 was 463 mmHg and arterial oxygen saturation was 99.4% at a fraction of inspired oxygen of 1.0.

Postoperatively, the patient was investigated for any abnormal Hb, which revealed increased serum MHb levels of 23.8% (normal <1%) with a normal Hb typing by high-performance liquid chromatography. The patient's mother and brother's arterial blood samples showed a similar dark color and a normal ABG.

The patient was discharged on the 7th postoperative day to avoid drugs that precipitate an increase in methemoglobin levels.

  Discussion Top

MHb is formed when the ferrous (Fe2) iron moiety of Hb is oxidized to the ferric (Fe3) state. Methemoglobinemia is a potentially severe Hb disorder in which methemoglobin accumulates in erythrocytes in large amounts (>1%) and leads to the incapability of carrying oxygen, which interferes with oxygen delivery to the tissues causing tissue hypoxia.[2],[3] Methemoglobinemia may be congenital or acquired which is due to exposure to certain oxidizing substances such as aniline dyes, nitrates, or nitrites, and notably many medications such as local anesthetics (lidocaine, prilocaine, and benzocaine), dapsone, nitric oxide, Pyridium, nitrous oxide, and naphthalene that may lead to the conversion of Hb to methemoglobin.[2],[3],[4],[5] In the normal physiological state, small amounts of methemoglobin are formed by the reaction between oxygen and Hb. However, these amounts are usually limited to <0.02 of the total amount of Hb. However, any amount more significant than this is rapidly converted back to Hb by reducing enzymes, i.e., cytochrome-b5 reductase and nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase. Cytochrome-b5 reductase has more than 95% of the reducing capacity of erythrocytes, and NADPH methemoglobin reductase has <5% of normal erythrocyte reducing capacity.

The symptoms are proportional to MHb levels. Usually, such patients remain asymptomatic except for discoloration of skin and blood till the MHb level is <15%. When levels are > 15%, cardiac and neurological symptoms develop due to hypoxia such as weakness, headache, dyspnea, tachycardia, dizziness, lethargic, stuporous, and confused comatose at a concentration of 55%–60%. At 70%, circulatory collapse occurs, and it becomes fatal.[3] If cyanosis occurs peroperatively, we usually focus on the airway, pulmonary, and cardiovascular systems to rule out the cause. However, if the condition is not readily diagnosed and corrected, then comes the role of Hb in oxygen transport. In such a scenario, MHB should also be considered in the differential diagnosis, mainly when pulse oximetry displays the low saturation and cyanosis fails to respond to supplemental oxygen. Early recognition during the intraoperative period may be the first step in the diagnosis and treatment of MHB.

In our case, the arterial blood was dark-colored, simulating venous blood without the feature of cyanosis in the patient and with normal arterial blood gas values. Polycythemia in our patient indicated an abnormal Hb with altered O2 affinities such as methemoglobinemia or sulfhemoglobinemia. Acquired causes of methemoglobinemia were ruled out, as there was no history of intake of any drug or substance which precipitates methemoglobinemia. The patient's mother and brother also had the same dark-colored arterial blood, suggesting it to be an inherited condition in this patient, i.e., congenital MHB.

Congenital MHB is a rare recessively inherited disorder. In cases that have been previously reported, a condition usually diagnosed in childhood as a child generally develops discoloration of skin even with MHb levels <15%. However, our case is a rare one due to the following reasons:

  • A rare association of RHD with severe MS and methemoglobinemia, and it was an incidental diagnosis
  • Even though serum MHb level was 23.8% and the patient was asymptomatic with no neurological symptoms, the cardiac symptoms can be attributed to the existing severe MS.

Although our patient was an asymptomatic and accidental finding and did not require any treatment for methemoglobinemia, in a known case, the following therapy can be employed; Preoperative treatment with Vitamin C helps in nonenzymatic reduction of methemoglobin, and methylene blue is the antidote (1–2 mg/kg IV over 3–5 min) and acts by increasing the level of NADH methemoglobin reductase, which helps in conversion of ferric ion to ferrous ion. Exchange transfusion and hemodialysis can also be used in severe cases. In acquired, methemoglobinemia offending drug should be withdrawn, and care should be taken to avoid further exposure to the offending agent.

Several issues are to be kept in mind when anesthetizing patients with methemoglobinemia, including the potential for decreased O2 carrying and delivery to the tissues, which may be exacerbated by intraoperative blood loss and low hematocrit due to hemodilution during CPB, interference with regular intraoperative monitoring devices, and the potential for medications to cause or exacerbate methemoglobinemia.[2],[3] Anderson et al. have reported two cases of methemoglobinemia in patients undergoing aortic reconstruction. The first patient developed methemoglobinemia while on a nitroglycerin infusion, and the second after receiving benzocaine spray before intubation. Both patients were treated with methylene blue and ascorbic acid, with the resolution of their hypoxia and cyanosis. They have suggested that methemoglobinemia, although rare, must be considered in surgical patients presenting with acute respiratory distress and cyanosis.[9],[10] CPB can aggravate the MHB by impairing its reduction in RBC after CPB, either due to a lack of energy substrates for the different MHb-reducing enzymes or reduced activity of the enzymes themselves or due to sublethal damage of the erythrocytes as a result of CPB, possibly as a consequence of inflammatory response of the extracorporeal circulation.[11] Besides, patients with significant cardiac, pulmonary diseases, or anemic may be more likely to suffer from the consequences of methemoglobinemia.

  Conclusion Top

Congenital MHB in a patient with a cardiac illness, although does not pose any added surgical challenge, and open-heart procedures can be safely performed in such a patient. However, one needs to be cautious regarding certain offending drugs during the anesthetic and postoperative management. Moreover, the dark-colored arterial blood posed a minor confusion while placing invasive arterial lines confusing it with venous access. It created a transient confusion in the surgeon and perfusionist during CPB regarding inadequate oxygenation by the CPB machine. The severity of MHB may be aggravated under CPB, and the availability of methylene blue for symptomatic patients is a critical factor in managing a case of methemoglobinemia. A high index of suspicion for methemoglobinemia will help overcome such minor hurdles to achieve a better outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Mohorovic L, Materljan E, Brumini G. Consequences of methemoglobinemia in pregnancy in newborns, children, and adults: Issues raised by new findings on methemoglobin catabolism. J Matern Fetal Neonatal Med 2010;23:956-9.  Back to cited text no. 1
Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: Etiology, pharmacology, and clinical management. Ann Emerg Med 1999;34:646-56.  Back to cited text no. 2
Hall DL, Moses MK, Weaver JM, Yanich JP, Voyles JW, Reed DN. Dental anesthesia management of methemoglobinemia-susceptible patients: A case report and review of literature. Anesth Prog 2004;51:24-7.  Back to cited text no. 3
Kumar U, Aggarwal P, Handa R, Saxena R, Wali JP. Central cyanosis in a young man. Postgrad Med J 1999;75:693-6.  Back to cited text no. 4
Prachal JT, Gregg XT. Red cell enzymopathies. In: Hoffman R, Banz EJ, Shattil SJ, editors. Hematology Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000. p. 561-75.  Back to cited text no. 5
Khan NA, Kruse JA. Methemoglobinemia induced by topical anesthesia: A case report and review. Am J Med Sci 1999;318:415-8.  Back to cited text no. 6
Hamirani YS, Franklin W, Grifka RG, Stainback RF. Methemoglobinemia in a young man. Tex Heart Inst J 2008;35:76-7.  Back to cited text no. 7
Curry S. Methemoglobinemia. Ann Emerg Med 1982;11:214-21.  Back to cited text no. 8
Anderson CM, Woodside KJ, Spencer TA, Hunter GC. Methemoglobinemia: An unusual cause of postoperative cyanosis. J Vasc Surg 2004;39:686-90.  Back to cited text no. 9
Wolak E, Byerly FL, Mason T, Cairns BA. Methemoglobinemia in critically ill burned patients. Am J Crit Care 2005;14:104-8.  Back to cited text no. 10
Young B. Methemoglobinemia: An unusual cause of postoperative cyanosis. AANA J 2008;76:99-102.  Back to cited text no. 11


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