Year : 2008 | Volume
: 52 | Issue : 2 | Page : 208-
Dapsone Induced Methaemoglobinemia: Early Intraoperative Detection by Pulse Oximeter Desaturation
Mahmood Rafiq, Abdul Qayoom Dar, Shagufta Qazi
Department of Anesthesiology and Critical care, Sheri-Kashmir Institute of medical sciences, Soura, Srinagar, J&K, India
Department of Anesthesiology and Critical care, Sheri-Kashmir Institute of medical sciences, Soura, Srinagar, J&K
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.
|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;52:208-208
|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 Jan 23 ];52:208-208
Available from: https://www.ijaweb.org/text.asp?2008/52/2/208/60625
Methaemoglobinemia is a clinical condition caused by many drugs used in medical practice . the condition can give rise to hypoxemia and oxygen desaturation perioperatively ,, .Dapsone is one such drug which is being often used in the treatment of immune thrombocytopenic purpura ,,, 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  .
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.
Immune thrombocytopenic purpura (ITP) is characterized by the destruction of platelets in the reticuloendothelial system due to platelet-specific autoantibodies ,. 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  . 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  . This effect was later seen in several patients with HIV infection  . Since then the efficacy of dapsone in the treatment of adult ITP has been demonstrated in several studies and a few studies in children ,,,,, 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 ,,,,.
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 ,, . Aniline derivatives, such as lidocaine, prilocaine, and nitrites are the most common methaemoglobin-inducing drugs  . 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  . 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 ,,,
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.
|1||Clary B, Skaryak L, Tedder M, et al. Methemoglobinemia complicating topical anesthesia during bronchoscopic procedures. J Thorac Cardiovasc Surg 1997; 114:293-5.|
|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.|
|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.|
|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|
|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.|
|6||Godeau B, Oksenhendler E, Bierling P. Dapsone for autoimmune thrombocytopenic purpura. Am J Hematol 1993; 44:70-2.|
|7||Linares M, Cervero A, Pastor E, et al. Dapsone for idiopathic thrombocytopenic purpura [letter]. Am J Hematol 1994; 46:371?|
|8||Leonard R H. MD;, Mark P; Bruce D, John A R., Methemoglobinemia: Early Intraoperative Detection by Clinical Observation. Laryngoscope 2004:114:2025-2026.|
|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.|
|10||Blanchette V, Freedman J, Garvey B. Management of chronic thrombocytopenic purpura in children and adults. Semin Hematol 1998; 35:36-51.|
|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.|
|12||Moss C, Hamilton PJ. Thrombocytopenia in systemic lupus erythematosus responsive to dapsone [letter]. Br Med J 1988; 297:266.|
|13||Hernandez F, Linares M, Colomina P, et al. Dapsone for refractory chronic idiopathic thrombocytopenic purpura. Br J Haemotol 1995; 90:473-5.|
|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.|
|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.|
|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.|
|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.|
|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.|
|19||Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med 1999; 34:646-656.|
|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.|
|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.|
|22||Donnelly GB, Randlett D. Methemoglobinemia. N Engl J Med 2000; 343:337|
|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.|