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Table of Contents
CASE REPORT  
Year : 2012  |  Volume : 15  |  Issue : 1  |  Page : 50-53
Perioperative challenges in a patient of severe G6PD deficiency undergoing open heart surgery


Department of Cardiac Anaesthesiology and Critical care, CARE Hospital, Bhubaneswar, Orissa, India

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Date of Submission05-May-2011
Date of Acceptance25-Jul-2011
Date of Web Publication5-Jan-2012
 

   Abstract 

We describe a successful perioperative management of a case of 38-year-old male, presented with chronic jaundice with severe mitral stenosis and moderate tricuspid regurgitation; upon evaluation, he was found to have severe glucose-6-phosphate dehydrogenase (G6PD) deficiency. Usually, patients deficient in G6PD exhibit increased hemolysis andtherefore increased need for blood transfusion after cardiac surgery as well as impaired oxygenation in the postoperative period leading to prolonged ventilation. On reperfusion after a period of ischemia, the antioxidant system recruits all of its components in an attempt to neutralize the overwhelming oxidative stress of free radicals, as the free radical scavenging system is deficient in these patients, the chances of free-radical-induced injury is more. Our patient underwent mitral valve replacement and tricuspid annuloplasty under cardiopulmonary bypass with necessary precautions to reduce the formation of free radicals. Treatment was targeted toward theprevention of free radical injuryin the G6PD-deficient patient. He had an uneventful intraoperative and postoperative course.

Keywords: Cardiopulmonary bypass, free radical injury, G6PD deficiency, mitral valve replacement

How to cite this article:
Chowdhry V, Bisoyi S, Mishra B. Perioperative challenges in a patient of severe G6PD deficiency undergoing open heart surgery. Ann Card Anaesth 2012;15:50-3

How to cite this URL:
Chowdhry V, Bisoyi S, Mishra B. Perioperative challenges in a patient of severe G6PD deficiency undergoing open heart surgery. Ann Card Anaesth [serial online] 2012 [cited 2019 Sep 15];15:50-3. Available from: http://www.annals.in/text.asp?2012/15/1/50/91483



   Introduction Top


Glucose-6-phosphate dehydrogenase deficiency (G6PD), an-X-linked disorder, although rare but is the most common enzyme disorder affecting an estimated 400 million people worldwide. [1] Cardiac surgery and cardiopulmonary bypass (CPB) involve perioperative ischemia and reperfusion, contact of blood with circuit surfaces,hypothermia,hypoperfusion,hyperperfusion, acidosis, and drug interactions in which cell damage is likely to occur. [2],[3],[4],[5],[6] It has been postulated that deficiency of G6PD potentiates the harmful effect of free radicals in such patients undergoing cardiac surgery. [3],[4],[7] . The literature on patients with G6PD deficiency undergoing cardiac surgery is rare; therefore the authors wish to share their experience and strategy in managing a series of such patients.


   Case Report Top


A 38-year-old male was admitted to our hospital with chronic rheumatic heart disease having severe mitral stenosis in atrial fibrillation with a history of jaundice for past 6 years.

Routine blood tests were normal, while evaluating for the cause of jaundice we noticed high bilirubin level (total bilirubin=7 mg/dl, direct bilirubin=0.72 mg/dl, and indirect bilirubin=6.28 mg/dl), and normal liver function tests. Ultrasonography of abdomen revealed hepatosplenomegaly with liver parenchymal disease and acalculous cholecystitis.

It was thought that jaundice was as a result of hemolysis; while investigating this,severe deficiency of G6PD was detected. The blood level of G6PD activity was 0.13 U/gHb (normal value=4.6-13.5U/gHb), i.e. <10% of normal activity [[Table 1]; class-II or severe G6PD deficiency as per World Health Organization (WHO) classification]. [8],[9],[10],[11] Normal reticulocyte counts and normal red cell osmotic fragility indicated the absence of active hemolysis. Blood tests for the presence of cold agglutinins were negative. Preoperative 2D-echocardiographic examination showed severe Mitral stenosis (MS), moderate Mitral regurgitation (MR), and moderate tricuspid regurgitation with moderate pulmonary arterial hypertension; and Right ventricle (RV) dysfunction but with good Left ventricle (LV) function (ejection fraction=60%). Upper Gastrointestinal (GI) endoscopy showed grade-1 esophagealvarices. The portal Doppler study did not correlate with overt portal hypertension.
Table 1: Classes of G6PD enzyme variants

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In the preoperative period, good urinary flow was ensured with the help of intravenous mannitol 0.5 g/kg once daily and furosemide 10 mg thrice daily in order to prevent any renal tubular injury due to free hemoglobin. In the premedication, allopurinol (600 mg) was given orally in the night before the surgery and in the morning 2 h before the surgery. General anesthesia was induced with midazolam, fentanyl, and pancuronium, and the depth of anesthesia was maintained with isoflurane. A median sternotomy was done. After heparinization, CPB was instituted with aortobicavalcannulation. Intermittent antegrade warm blood cardioplegia was administered every 15 min to providemyocardial protection. Through a right atrial transseptal approach, a mitral valve was replaced with a 31 mm mechanical valve and tricuspid ring annuloplasty was performed. Normothermia (36°C) was maintained throughout the procedure, and mean arterial blood pressure during CPB was maintained around 70 mm Hg. During the bypass period, the urine output was maintained with the use of Mannitol 100 ml and furosemide 20 mg in the reservoir. Just prior to aortic clamp removal amiodarone (150 mg) was added to the reservoir to prevent postoperative atrial fibrillation, as per our institutional policy. The patient came off CPB uneventfully. Duration of CPB was 124 min and aortic cross-clamp time was 68 mins.

Immediately after coming off CPB, two units of fresh frozen plasma and two units of platelets were transfused. The urine was normal in color; we presumed lack of hemolysis because of this. The patient was transferred to ICU, mechanically ventilated overnight. The total volume of blood in the chest drainage system was 400 ml in 24 hrs. One unit of packed cell transfusion was used to restore the haemoglobin level to 8.5.

The laboratory investigation carried out to assess hemolysis are shown in [Table 2].
Table 2: Pre and postoperative hematological and biochemical parameters

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Postoperative analgesia was maintained with infusion of fentanyl at a rate of 1-2 mm/kg/h started immediately after shifting the patient to the ICU and was continued for first 24 h and then reduced to 0.5 mm/kg/h for next 48 h. No hemolysis was noted in the postoperative period, and the patient was discharged on the sixth postoperative day.


   Discussion Top


Deficiency of a nicotinamide adenine dinucleotide phosphate (NADP) dependent enzyme, G6PD, is responsible for a myriad of pathologic mechanisms in the human body. The enzyme plays an important role in the hexose monophosphate/pentosephosphate shunt, and its deficiency is the most important defect in this pathway. The usual clinical expression of this disorder includes anemia, jaundice, hepatosplenomegaly, and reticulocytosis, all consequences of hemolysis. [12] Hemolysis usually occurs after exposure to drugs or to other substances that produce peroxides (e.g. H 2 O 2 ), resulting in oxidation of Hb and red blood cell membranes. [2],[3],[4],[13] In clinical practice, fever, infections, and diabetic ketosisare also the other common precipitating events. [3]

The diagnosis of G6PD deficiency is made by a quantitative spectrophotometric analysis or, more commonly, by a rapid Beutler fluorescent spot test detecting the generation of Reduced nicotinamide adenine dinucleotide phosphate (NADPH) from NADP. [13] The test is positive if the blood spot fails to fluoresce under ultraviolet light. WHO classifies G6PD genetic variants into five classes [8],[9],[10],[11] [Table 1]; of which the first three are deficiency states.

CPB is known to be a potent activator of systemic inflammation through the production of oxygen free radicals like superoxideanions(O2 - ), hydroxyl radical (OH - ), hypochloride (Ocl - ), etc. [2],[3],[4],[14],[15],[16],[17] G6PD deficient patients are known to be very sensitive to oxidative stress manifesting as rapid hemolysis when exposed to infections, certain drugs, and extracorporeal circulation. [3],[18] During CPB, the oxidative stress along withmechanical trauma from roller pumps and cardiotomy suction can result in red cell lysis, endothelial injury, and capillary leak during the postbypass period. [4,19] Thus all vital organs, but more commonly kidneys and lungs are at greater risk of injury. [19],[16],[20] In cardiac surgical settings, these risks are compounded by commonly used drugs known to decrease the G6PD level (e.g. paracetamol, aspirin, other NSAID, sulfonamides, nitrates). [13],[15],[20]

The free radical scavenging mechanisms try to limit such deleterious effects. [7],[14],[18] The free radical generation can be minimized by the use of free radical scavengers such asmannitol and allopurinol. [7],[14],[18],[17],[21],[22] Reduced NADP(NADPH)is an important free radical deactivator. G6PD is responsible for maintaining adequate levels of NADPH inside the cell. NADPH is important to keep glutathione, a tri-peptide, in its reduced form. Reduced glutathione(G-SH) acts as a scavenger for the deleterious oxidative metabolites in the cells. [2],[3] One of the prototype reactions is:

2G-SH+H 2 O 2→G-S-S-G+2H 2 O

[Figure 1] depicts the pentose phosphate pathway, and the importance of G6PD in the production of NADPH and reduced glutathione (G-SH). Therefore, G6PD deficiency leads to the accumulation of free radicals and consequent cell membrane damage. In the red blood cells, NADPH is the key metabolite preventing oxidative injury by free radicals; consequently they are the most vulnerable to undergolysis due to theoxidative stress. [3] CPB-induced systemic inflammatory response and production of free radicals in the presence of deficient free radical deactivating system can lead to endothelial injury and capillary leak [19] in the lungs, it increases the risk of impaired oxygenation and prolonged ventilation. Excessive hemolysis with the release of free hemoglobin can exhaust haptoglobin and causesblockage of renal tubules leading to renal failure. A few studies have shown a correlation between hypothermia, rewarming, and generation of free radicals. [4],[23] Therefore, avoiding hypothermia during CPB may help such a patient subset.
Figure 1: Pentose phosphate pathway. G6PD catalyzes NADP+ to its reduced form, NADPH, in the pentose phosphate pathway. (G6PD=Glucose-6-phosphate dehydrogenase; ATP=Adenosine triphosphate; ADP=Adenosine diphosphate; NADP+=Nicotinamide adenine dinucleotide phosphate [oxidized form]; NADPH=Reduced NADP; GSSG=Oxidized glutathione; GSH=Reduced glutathione.)

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In the postoperative period, measurement of bloodcounts (RBC, Hb, hematocrit), haptoglobin, reticulocyte count, and indirect bilirubin showedthe degree of hemolysis. Renal function (blood urea, serumcreatinine) tests in the first few postoperative days assess renal dysfunction which could be due tohemolysis.

In summary, careful workup in the preoperative period and strategies to minimize hemolysis by avoiding oxidizing drugs and hypothermia, limiting the aortic cross clamp time, total CPB time, and maintaining good urine output is central to the successful management of such type of cases.

 
   References Top

1.Beutler E. G6PD: Population genetics and clinical manifestations. Blood Rev 1996;10:45-52.  Back to cited text no. 1
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2.Gerrah R, Shargal Y, Elami A. Impaired oxygenation and increased hemolysis after cardiopulmonary bypass in patients with glucose-6-phosphate dehydrogenase deficiency. Ann Thorac Surg 2003;76:523-7.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Das DK, Engelman RM, Liu X, Maity S, Rousou JA, Flack J, et al. Oxygen-derived free radicals, and hemolysis during open heart surgery. Mol Cell Biochem 1992;111:77-86.  Back to cited text no. 3
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4.Prasad K, Kalra J, Bharadwaj B, Chaudhary AK. Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. Am Heart J 1992;123:37-45.  Back to cited text no. 4
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5.Goldhaber JI, Weiss JN. Oxygen free radicals and cardiac reperfusion abnormalities. Hypertension 1992;20:118-27.  Back to cited text no. 5
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6.Ferrari R, Ceconi C, Curello S, Cargnoni A, Pasini E, De Giuli F, et al. Role of oxygen free radicals in ischemic and reperfused myocardium. Am J Clin Nutr 1991;53:215S-222S.  Back to cited text no. 6
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7.Vaage J, Valen G. Could treatment with scavengers of oxygen free radicals minimize complications in cardiac surgery?. Klin Wochenschr 1991;69:1066-72.  Back to cited text no. 7
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8.Mazza, Joseph. Manual of Clinical Hematology. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 101-2.  Back to cited text no. 8
    
9.WHO working group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989;67:601-11.  Back to cited text no. 9
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10.Ruwende C, Hill A. Glucose-6-phosphate dehydrogenase deficiency and malaria. J Mol Med 1998;76:581-8.  Back to cited text no. 10
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11.Gregg XT, Prchal JT. Red cell enzymopathies. In: Hoffman R, editor. Hematology: Basic principles and practice. 4 th ed. Philadelphia: Churchill Livingstone; 2000. p. 657-60.  Back to cited text no. 11
    
12.Tas S, Donmez AA, Kirali K, Alp MH, Yakut C. Aortic valve replacement in patient with glucose-6-phosphate dehydrogenase deficiency and autoimmune haemolytic anemia. J card surg 2005;20:380-1.  Back to cited text no. 12
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13.Beutler E. Glucose-6-Phosphate Dehydrogenase Deficiency. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA, editor. Hematology. New York: McGraw-Hill;1990. p. 591-606.  Back to cited text no. 13
    
14.Utley JR. Pathophysiology of cardiopulmonary bypass: Current issues. J Card Surg 1990;5:177-89.  Back to cited text no. 14
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15.Younster I, Arcavi L, Schechmaster R, Akayzen Y, Poplisky H, Shimonov J. Medications and glucose-6-phosphate dehydrogenase deficiency: An evidence based review. Drug Saf 2010;33:713-26.  Back to cited text no. 15
    
16.Dogra N, Puri GD, Rana SS. Glucose-6-phosphate dehydrogenase deficiency and cardiac surgery. Perfusion 2010;25:417-21.  Back to cited text no. 16
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17.Kevin LG, Novalija E, Stowe DF. Reactive oxygen species as mediators of cardiac injury and protection: The relevance to anesthesia practice. Anesth Analg 2005;101:1275-87.  Back to cited text no. 17
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18.Niki E, Komuro E, Takahashi M, Urano S, Ito E, Terao K. Oxidative hemolysis of erythrocytes and its inhibition by free radical scavengers. J Biol Chem 1988;263:19809-14.  Back to cited text no. 18
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19.Boyle EM Jr, Pohlman TH, Johnson MC, Verrier ED. Endothelial cell injury in cardiovascular surgery: The systemic inflammatory response. Ann Thorac Surg 1997;63:277-84.  Back to cited text no. 19
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20.Elyassy AR, Rowshan HH. Perioperative management of Glucose-6-Phosphate Dehydrogenase deficient patient: A review of literature. AnesthProg 2009;56:86-91.  Back to cited text no. 20
    
21.England MD, Cavorocchi NC, O'Brian JF, Solice E, Pluth JR, Orszulak TA, et al. Influence of antioxidants (Mannitol and Allopurinol) on oxygen free radical generation during and after cardiopulmonary bypass. Circulation 1986;74:134-7.  Back to cited text no. 21
    
22.Sies H. Strategies of antioxidant defense. Eur J Biochem 1993;215:213-9.  Back to cited text no. 22
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23.Iyengar J, George A, Rissell JC, Das DK. Generation of Free Radicals During Cold Injury and Rewarming. Vasc Endovascular Surg 1990;24:467-74.  Back to cited text no. 23
    

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Correspondence Address:
Vivek Chowdhry
Aditya CARE Hospital, Bhubaneswar 751 014, Orissa
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.91483

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