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Year : 2008  |  Volume : 52  |  Issue : 2  |  Page : 208 Table of Contents     

Dapsone Induced Methaemoglobinemia: Early Intraoperative Detection by Pulse Oximeter Desaturation

Department of Anesthesiology and Critical care, Sheri-Kashmir Institute of medical sciences, Soura, Srinagar, J&K, India

Date of Web Publication19-Mar-2010

Correspondence Address:
Mahmood Rafiq
Department of Anesthesiology and Critical care, Sheri-Kashmir Institute of medical sciences, Soura, Srinagar, J&K
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Source of Support: None, Conflict of Interest: None

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Several drugs cause methaemoglobinemia which can lead to pulse oximeter desaturation and hypoxemia.Children with immune thrombocytopenic purpura are being treated with dapsone which is known to cause methaemoglobinemia and many of these can be planned for elective splenectomy. Preoperative knowledge of drug intake and their adverse effects is essential so is the early detection of the cause of intraoperative hypoxemia and the remedial measures taken.
We present a child on dapsone therapy for treatment of immune thrombocytopenic purpura planned for elective splenec­tomy developed intraoperative pulseoximeter desaturation. The cause of desaturation was identified as methaemoglobinemia caused by dapsone therapy.
Case signifies the importance of knowledge of any preoperative drug intake and its anaesthetic implications. Also patients on dapsone therapy especially children should be monitored for methaemoglobin levels. Since children with immune thrombocy­topenic purpura are being treated with dapsone these days and many of these patients would be planned for splenectomy, monitoring of preoperative methaemoglobin levels and methaemoglobinemia as a cause of intraoperative pulse oximeter desaturation should be kept in mind.

Keywords: Methaemoglobinemia; Dapsone; Idiopathic thrombocytopenic purpura

How to cite this article:
Rafiq M, Dar AQ, Qazi S. Dapsone Induced Methaemoglobinemia: Early Intraoperative Detection by Pulse Oximeter Desaturation. Indian J Anaesth 2008;52:208

How to cite this URL:
Rafiq M, Dar AQ, Qazi S. Dapsone Induced Methaemoglobinemia: Early Intraoperative Detection by Pulse Oximeter Desaturation. Indian J Anaesth [serial online] 2008 [cited 2021 Aug 3];52:208. Available from: https://www.ijaweb.org/text.asp?2008/52/2/208/60625

   Introduction Top

Methaemoglobinemia is a clinical condition caused by many drugs used in medical practice . the condition can give rise to hypoxemia and oxygen desaturation perioperatively [1],[2],[3] .Dapsone is one such drug which is being often used in the treatment of immune thrombocy­topenic purpura [4],[5],[6],[7] and can give rise to clinically signifi­cant methaemoglobinemia. This case report signifies the importance of preoperative drug history, identification and management of this clinical condition [8] .

   Case report Top

A 10-year-old girl presented to the hematology de­partment with complaints of easy bruising and epistaxis following an upper respiratory tract infection.

Physical examination revealed ecchymotic patches on the legs and splenomegaly. She had a platelet count of 30x10 9 .l-1 , but other hematological variables were nor­mal.

Antinuclear antibody, polymerase chain reaction, HIV and hepatitis screening were negative. Bone mar­row analysis excluded any hematological malignancy. A diagnosis of immune thrombocytopenic purpura was made and she was started on oral prednisolone and dap­sone 2mg.kg -1 .day -1 orally. She also received intrave­nous immunoglobulin (IVIG).

After six months of dapsone-prednisolone therapy her platelet count was 18x10 9.l-1. Other laboratory vari­ables remained normal. In view of immune thrombocy­topenia refractory to medical management, splenectomy was planned.

Surgery was scheduled with platelet and steroid cover. Following morphine 0.1mg.kg -1 i.v, anaesthesia was induced with thiopentone sodium 5mg.kg -1 and muscle relaxation was achieved with atracurium 0.5mg.kg -1 . Oxygen 100% with halothane 2% was used to ventilate the child. The trachea was intubated and correct placement confirmed by five point auscultation and capnography. Pulse oximeter showed oxygen satu­ration (SpO 2 ) of 94%.

When the gas mixture was changed to 60:40 ni­trous oxide and oxygen respectively the SpO 2 dropped to 88%. FiO 2 was increased from 0.4 to 1.0. Vital signs, physical examination, end tidal carbon dioxide, airway pressures were unremarkable. Conventional arterial blood gas analysis revealed PaO 2 of 300mmHg, pH 7.40 PaCO 2 38mmHg, HCO3 22.3 meq.l -1 and SaO 2 of 99%. A simultaneous co-oximetry blood gas analysis was per­formed revealing methaemoglobin level of 5.9%. No treatment for methaemoglobinemia at this level was re­quired, the failure of pulse oximetry to depict true oxy­gen saturation of haemoglobin was realized and the pa­tient was again ventilated with a FiO 2 of 0.4.

Splenectomy was completed in approximately 60 minutes time during which SpO 2 ranged between 88%and 97%. The girl was transferred to a high dependency unit for monitoring, with oxygen therapy by polymask at 5 l min -1 . Arterial blood gas analysis and co-oximetry done on the first post operative day showed an SaO 2 96%, PaO 2 115mmHg and methaemoglobin of 4.1%.Si­multaneous SpO 2 was 89% breathing room air.

   Discussion Top

Immune thrombocytopenic purpura (ITP) is char­acterized by the destruction of platelets in the reticu­loendothelial system due to platelet-specific autoantibod­ies [9],[10]. The resulting thrombocytopenia rarely can cause life-threatening hemorrhages, but this risk increases in patients with chronic ITP. Immune thrombocytopenic purpura can occur at any age and may occur in other­wise healthy patients or may complicate the course of other diseases such as HIV infection [11] . The course of ITP may be acute or chronic and is unpredictable. First­line therapy in chronic ITP includes corticosteroids and intravenous immunoglobulin, the use of other agents in patients with refractory disease is less well determined.

In 1988 dapsone was discovered serendipitously to boost platelet count in a patient with systemic lupus erythematosus [12] . This effect was later seen in several patients with HIV infection [12] . Since then the efficacy of dapsone in the treatment of adult ITP has been dem­onstrated in several studies and a few studies in chil­dren [4],[5],[6],[7],[13],[14] In contrast to the adult studies, a high pro­portion of clinically significant methaemoglobinemia re­quiring discontinuation of drug developed in children re­ceiving dapsone . The mechanism whereby dapsone in­creases platelet counts is still unknown, although several theories exist [14],[15],[16],[17],[18].

Normal haemoglobin contains iron in its ferrous state (Fe2+), which facilitates oxygen delivery and re­lease to body tissues. Methaemoglobin arises from oxi­dation of the iron component of haemoglobin from its ferrous (Fe2+) to the ferric (Fe3+) form. Ferric iron is unable to bind oxygen, creating a functional anaemia. Stress and the resultant methaemoglobinemia shifts the oxygen hemoglobin dissociation curve to left, thereby, reducing the oxygen carrying capacity of blood and im­pairing tissue oxygenation. The normal methaemoglobin level is less than 1%. Clinical cyanosis begins to appear at values of approximately 10% and is readily detected when levels reach 15% of total haemoglobin. Symptoms of fatigue, weakness, dyspnea, headache, dizziness, and tachycardia typically appear when methaemoglobin lev­els reach 20%. More serious cardiopulmonary and neu­rological complications occur at values approaching 50%, and death often ensues with 60% to 70% methaemoglobin

Four mechanisms in the body maintain the equi­librium between haemoglobin and methaemoglobin. NADH-methaemoglobin reductase accounts for approxi­mately 95% of the methaemoglobin reduction. An auxil­iary enzyme NADPH-methaemoglobin reductase is de­pendent on NADH provided by the hexose monophos­phate shunt pathway and is responsible for approximately 5% of methaemoglobin reduction in vivo. The auxiliary system assumes greater significance when the primary system is overwhelmed during poisoning with an oxida­tive toxin. Methylene blue can act as a cofactor and greatly accelerate the enzymatic reduction of methaemoglobin along the NADH dependent pathway. Two enzymatic mechanisms of methaemoglobin reduc­tion using ascorbic acid and glutathione play only a mi­nor role in maintaining the normal physiologic equilib­rium.

Methaemoglobinemia may be acquired or congeni­tal. In acquired methaemoglobinemia, exposure to cer­tain drugs or chemicals may cause oxidation of haemo­globin to methaemoglobin faster than methaemoglobin can be reduced by NADH metHb reductase. Commonly reported oxidative substances include amyl nitrite, aniline dyes, benzocaine, bismuth subnitrate, cetacaine, dapsone, lidocaine, nitroglycerin, p-aminosalycilic acid, phenytoin, prilocaine, primaquine, pyridine, silver nitrate, and sul­fonamides [1],[2],[3] . Aniline derivatives, such as lidocaine, prilocaine, and nitrites are the most common methaemoglobin-inducing drugs [2] . In our case dapsone therapy for immune thrombocytopenic purpura led to methaemoglobinemia.

The diagnosis of methaemoglobinemia should be suspected in patients with unexplained cyanosis (or hy­poxic symptoms) after exposure to a known oxidative drug or in patients with disparate pulse oximetry and conventional arterial blood gas values. Haemoglobin oxy­gen saturation measurement by conventional arterial blood gas analysis is calculated using the partial pres­sure of oxygen and pH levels and may be falsely reas­suring in cases of methaemoglobinemia, failure to ap­preciate this may prove disastrous. The diagnosis is con­firmed by blood gas analysis using multiple wavelength co-oximeters, which directly measures oxygen satura­tion of haemoglobin and also measures methaemoglobin levels.

Management consists of removing the offending agent and administration of activated charcoal if the route of intoxication was oral. Supplemental oxygen be admin­istered but is not likely to improve oxygenation. Typically, methylene blue (1-2 mg.kg -1 ) administered intravenously over a period of 3 to 5 minutes produces rapid conversion of methaemoglobin to haemoglobin [19] . Its use is recom­mended in all patients with methaemoglobin levels greater than 30% or in patients with methaemoglobin at lower levels who have co- morbidity or symptoms [20],[21],[22],[23]

This case emphasizes the importance of knowl­edge of preoperative drug intake and its anaesthetic im­plications. Children with immune thrombocytopenic pur­pura being treated with dapsone should have methaemoglobin levels monitored and methaemog lobinemia as a cause of intraoperative pulse oximeter desaturation should be considered.

   References Top

1.Clary B, Skaryak L, Tedder M, et al. Methemoglobinemia com­plicating topical anesthesia during bronchoscopic procedures. J Thorac Cardiovasc Surg 1997; 114:293-5.  Back to cited text no. 1      
2.Prachal JT, Gregg XT. Red cell enzymopathies. In: Hoffman R, Banz EJ, Shattil SJ, eds. Hematology basic principles and prac­tice. 3rd ed. New York: Churchill Livingstone, 2000:561-75.  Back to cited text no. 2      
3.Linden CH, Burns MJ. Poisoning and drug overdosage. In: Braunwald E, et al., eds. Harrison's Principles of Internal Medi­cine, 15th ed. New York: McGraw-Hill; 2001:2612.  Back to cited text no. 3      
4.Durand JM, Lefevre P, Hovette P, et al. Dapsone for thromb­ocytopenic purpura related to human immunodeficiency virus infection. Am J Med 1991; 90:675-7  Back to cited text no. 4      
5.Durand JM, Lefevre P, Hovette P, et al. Dapsone for idiopathic autoimmune thrombocytopenic purpura in elderly patients. Br J Haematol 1991; 78:459-63.  Back to cited text no. 5      
6.Godeau B, Oksenhendler E, Bierling P. Dapsone for autoimmune thrombocytopenic purpura. Am J Hematol 1993; 44:70-2.  Back to cited text no. 6      
7.Linares M, Cervero A, Pastor E, et al. Dapsone for idiopathic thrombocytopenic purpura [letter]. Am J Hematol 1994; 46:371?  Back to cited text no. 7      
8.Leonard R H. MD;, Mark P; Bruce D, John A R., Methemo­globinemia: Early Intraoperative Detection by Clinical Obser­vation. Laryngoscope 2004:114:2025-2026.  Back to cited text no. 8      
9.Meeker, Nathan D B S. Goldsby, Robert ; Terrill, Kelly R. Pharm.D.; Dapsone Therapy for Children with Immune Throm­bocytopenic Purpura. Journal of Pediatric Hematology/Oncol­ogy 2003; 25:173-175.  Back to cited text no. 9      
10.Blanchette V, Freedman J, Garvey B. Management of chronic thrombocytopenic purpura in children and adults. Semin Hematol 1998; 35:36-51.  Back to cited text no. 10      
11.Oksenhendler E, Bierling P, Farcet JP, et al. Response to therapy in 37 patients with HIV-related thrombocytopenic purpura. Br J Haematol 1987; 66:491-5.  Back to cited text no. 11      
12.Moss C, Hamilton PJ. Thrombocytopenia in systemic lupus erythematosus responsive to dapsone [letter]. Br Med J 1988; 297:266.  Back to cited text no. 12      
13.Hernandez F, Linares M, Colomina P, et al. Dapsone for refrac­tory chronic idiopathic thrombocytopenic purpura. Br J Haemotol 1995; 90:473-5.  Back to cited text no. 13      
14.Godeau B, Durand JM, Roudot-Thoraval F, et al. Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases. Br J Haemotol 1997; 97:336-9.  Back to cited text no. 14      
15.Radaelli F, Calori R, Goldaniga M, et al. Adult refractory chronic idiopathic thrombocytopenic purpura: can dapsone be pro­posed as second-line therapy [letter]. Br J Haemotol 1999; 104:641-2.  Back to cited text no. 15      
16.Dutta TK, Goel A, Ghotekar LH, et al. Dapsone in treatment of chronic idiopathic thrombocytopenic purpura in adults. J Assoc Physicians India 2001; 49:421-5.  Back to cited text no. 16      
17.Lush R, Iland H, Peat B, et al. Successful use of dapsone in refractory pregnancy-associated idiopathic thrombocytopenic purpura. Aust NZ J Med 2000; 30:105-7.  Back to cited text no. 17      
18.Tsuji K, Ogino T, Seki N, et al. Synthesis and effects of novel thiazole derivatives against thrombocytopenia. Bioorg Med Chem Lett 1998; 8:2473-8.  Back to cited text no. 18      
19.Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med 1999; 34:646-656.  Back to cited text no. 19      
20.Linden CH, Burns MJ. Poisoning and drug overdosage. In: Braunwald E, et al., eds. Harrison's Principles of Internal Medi­cine, 15th ed. New York: McGraw-Hill; 2001:2612.  Back to cited text no. 20      
21.Benz EJ. Hemoglobinopathies. In: Braunwald E, et al., eds. Harrison's Principles of Internal Medicine, 15th ed. New York: McGraw-Hill; 2001:671-672.  Back to cited text no. 21      
22.Donnelly GB, Randlett D. Methemoglobinemia. N Engl J Med 2000; 343:337  Back to cited text no. 22      
23.Hoskin R W, and Granger R. Intraoperative decrease in pulse oximeter readings following injection of isosulfan blue. Cana­dian Journal of Anaesthesia 2001;48:38-40.  Back to cited text no. 23      


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