Strategies for Repair of Congenital Heart Defects in Infants Without the Use of Blood

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1 Strategies for Repair of Congenital Heart Defects in Infants Without the Use of Blood Jacques A. M. van Son, MD, PhD, Hagop Hovaguimian, MD, Ivatury M. Rao, MD, Guo-Wei He, MD, PhD, Gregory A. Meiling, CCP, Douglas H. King, MD, and Albert Starr, MD The Albert Starr Academic Center for Cardiac Surgery, St. Vincent Hospital and Medical Center, and Emanuel Hospital, Portland, Oregon Eleven infants and children with a body weight of less than 10 kg (median weight, 6.8 kg) whose parents were Jehovah's Witnesses underwent repair (n = 10) or palliation (n = 1) of congenital heart defects without the use of blood products and with (n = 9) or without (n = 2) cardiopulmonary bypass (CPB). In 1 neonate (weight, 3.2 kg) with critical aortic stenosis, moderate hypothermia and a 3.5-minute period of inflow occlusion and circulatory arrest allowed an aortic valvotomy; in another patient (weight, 7.0 kg) with tricuspid and pulmonary atresia, transposition of the great arteries, and persistent left superior vena cava, a bilateral bidirectional cavopulmonary shunt procedure was performed without CPB. Use of heparin-bonded tubing allowed reduction of the initial dose of heparin sodium to 1 mg/kg. Tissue perfusion and oxygenation on bypass were adequate, as evidenced by a mean lowest ph of 7.38 ± 0.09 and a mean lowest venous oxygen tension of 65.0 ± 36.2 mm Hg. Although the mean postoperative hematocrit (Hct) was lower than the mean preoperative Hct (p < 0.05, analysis of variance and Scheff6's F test), the Hct within 2 hours after CPB was restored to a value (mean Hct, 27.5% ± 1.0%) between the preoperative Hct (mean value, 42.7% ± 3.5%) and the lowest Hct on CPB (mean value, 18.4% %). The Hct at discharge was 31.8% + 1.1%. The median postoperative blood loss was 9 ml/kg. There was no perioperative mortality. The median stay in the intensive care unit and the hospital was 2 days and 6 days, respectively. We conclude that repair of congenital heart defects with the use of CPB can be safely conducted in select infants with a body weight of 5 kg or more. In symptomatic neonates or infants with a lower body weight, initial palliative procedures circumvent the use of CPB and allow secondary correction of the defect at a later time. (Ann Thorac Surg 199&59:384-8) B oth autologous predonation of blood and perioperative autotransfusion have considerably reduced the need of homologous blood transfusion in cardiac surgery, although neither approach has completely eliminated its use. In infants and small children it is especially difficult to successfully perform bloodless intracardiac procedures because of their smaller blood volume. Our interest in bloodless cardiac operations in infants and children developed as part of a program to provide surgical care to patients of the Jehovah's Witness faith who, based on their interpretation of the Bible (Genesis 9:3-6; Leviticus 17:10; Acts 15:20, 28, 29; 21:25), refuse both homologous and autologous predonated blood transfusions. In this report, we review our operative strategy and experience with infants and children weighing less than 10 kg who underwent corrective cardiac operations for congenital heart defects and whose parents were Jehovah's Witnesses. Accepted for publication Sep 20, Address reprint requests to Dr van Son, Division of Cardiothoracic Surgery, University of California at San Francisco, Room M593, 505 Parnassus Ave, San Francisco, CA Material and Methods Between August 1989 and May 1994, 11 infants and children (9 white and 2 Asian) whose parents were Jehovah's Witnesses and who weighed less than 10 kg underwent repair of congenital heart defects at Emanuel Hospital. The patient data are summarized in Table 1. There were 7 boys and 4 girls. Body weight ranged from 3.2 to 9.6 kg (median weight, 6.8 kg; mean weight, 6.6 kg) and age ranged from 11 days to 32 months (median age, 7 months; mean age, 10.2 months). Seven patients were acyanotic, and 4 were cyanotic; 3 of the latter were polycythemic (hematocrit [Hct] > 45%). Six patients had undergone previous palliative cardiac procedures (including aortopulmonary shunt, pulmonary artery banding, balloon atrial septostomy) or ligation of a patent ductus arteriosus, or both. Seven older children with a body weight exceeding 10 kg who underwent operative correction of congenital heart defects using cardiopulmonary bypass (CPB) were excluded from this report. Perioperative Management Perioperative evaluation included full blood count, coagulation and chemistry profiles, chest radiography, electrocardiography, and echocardiography. Cardiac catheterization was performed in only 5 patients. Five patients 1995 by The Society of Thoracic Surgeons /95/$ (94)00841-T

2 Ann Thorac Surg VAN SON ET AL ;59:384-8 CONGENITAL HEART OPERATIONS IN JEHOVAH'S WITNESSES Table 1. Summary of Patient Data Preoperative Patient Weight Age BSA Hematocrit Previous No. (kg) (too) (m 2) Diagnosis (%) Procedures Procedures ,33 CAVC defect, Down's 42 None Repair of CAVC defect, syndrome, PDA ligation of PDA TGA 68 BAS Senning CAVC defect, Down's 38 PAB Repair of CAVC defect, syndrome, PFO closure of PFO, PA debanding VSD, PFO, PDA 33 None Closure of VSD and PFO, ligation of PDA CAVC defect 41 PAB Repair of CAVC defect, PA debanding DORV, VSD, PDA 40 PAB, ligation Repair of DORV, PA of PDA debanding VSD, PFO 32 None Closure of VSD and PFO TGA 56 PAB, left BT Arterial switch, closure shunt, BAS of ASD, closure of BT shunt TAPVC (supracardiac) 38 None Repair of TAPVC 10 a 3,2 11 d 0.22 AS 37 None Aortic valvotomy 11 a TA, TGA, pulmonary 49 Bilateral BT Bilateral BDCPS, atresia, persistent left shunts closure of bilateral BT SVC shunts This patient had operation without the use of cardiopulmonary bypass. AS = aortic stenosis; ASD atrial septal defect; BAS = balloon atrial septostomy; BDCPS ~ bidirectional cavopulmonary shunt; BSA = body surface area; BT Blalock-Taussig; CAVC = complete atrioventricular canal; DORV - double-outlet right ventricle; PA pulmonary artery; PAB = pulmonary artery banding; PDA = patent ductus arteriosus; PFO = patent foramen ovale; SVC - superior vena cava; TA = tricuspid atresia; TAPVC total anomalous pulmonary venous connection; TGA = transposition of great arteries; VSD = ventricular septal defect. with an Hct of 38% or less were treated with synthetic erythropoietin (100 U/kg three times a week), which stimulated the bone marrow, as evidenced by a median 8% increase in the reticulocyte count and a median 6% increase in Hct. In all cases, informed consent relating to the use of albumin as volume replacement was obtained from the patient's parents even though its use has generally been accepted by Jehovah's Witnesses. After induction of anesthesia and insertion of monitoring lines, a median sternotomy was performed. Total correction of congenital heart defects with CPB was performed only if the Hct of the patient on CPB was predicted to be higher than 15%. If the predicted Hct was less than 16%, initial palliative procedures such as aortopulmonary shunt or pulmonary artery banding were performed. Predicted Hct was calculated according to an empiric formula: [EBV (preoperative Hct - 3)]/(EBV + PV) where EBV is the patient's estimated blood volume, and PV is the priming volume. In 9 patients, CPB was instituted in routine fashion with aortic cannulation and dual venous cannulation. In the 6 largest patients, Medtronic Minimax oxygenators (Minneapolis, MN) with heparin-bonded tubing (Carmeda BioActive Surface; Carmeda AB, Stockholm, Sweden) were used to allow reduction of the initial systemic heparin sodium dose to 1 mg/kg. In the other 3 patients, Capiox oxygenators (Terumo Corp, Tokyo, Japan) with nonheparin-bonded tubing (Gish Biomedical, Irving CA) were used because the heparin-bonded circuits require a larger priming volume, and this could have led to an unacceptable decrease in Hct. The initial heparin dose in these 3 patients was 3 mg/kg, and heparin was added to the priming solution. Additional heparin was administered for maintenance of anticoagulation and was neutralized with protamine sulfate after CPB to restore the preoperative activated clotting time. To minimize the CPB circuit volume, the length and the diameter of the CPB tubing were reduced, and arterial filters were not used. The priming solution comprised the following: Plasmalyte, ml; 25% albumin, 103 ± 26 ml; 10% mannitol, ml; and NaHCO3, 16 ± 5 meq. All procedures were performed with moderate hypothermia (20 to 28 C). The flow on CPB was expressed as a percentage of predicted full flow, which was 150 ml kg-1. min 1. The degree of hemodilution on CPB was calculated as 100 (preoperative Hct lowest measured Hct/preoperative Hct). In all nine procedures, myocardial protection was achieved by the administration of blood cardioplegia through the aortic root. Cardioplegic solution was allowed to return to the CPB circuit if the Hct and potassium level were in acceptable ranges. Topical heart

3 386 VAN SON ET AL Ann Thorac Surg CONGENITAL HEART OPERATIONS IN JEHOVAH'S WITNESSES 1995;59:384-8 cooling was achieved with slushed ice. Blood samples were taken before CPB and every 20 minutes thereafter to check arterial and venous blood gases, Hct, and electrolyte levels. Arterial and venous pressures and urinary output were continuously monitored. At the end of CPB, 1 mg/kg of furosemide was administered if urinary output was inadequate. Intotropic support and sodium nitroprusside were used when indicated. Cardiopulmonary bypass was not employed in 2 patients. An 11-day-old neonate (patient 10, Table 1) with critical aortic stenosis underwent aortic valvotomy using moderate hypothermia (28 C). Both venae cavae were snared with tapes after placement of a single cannula in the ascending aorta and placement of a purse-string suture in the right atrium. The heart continued to beat and empty itself. After induced ventricular fibrillation, the aorta was cross-clamped. During a period of 3.5 minutes of circulatory arrest, a commissurotomy was performed on the rudimentary commissures between the right and left aortic valve leaflets and between the right and noncoronary leaflets. After closure of the aortotomy, the caval tapes were released, air was evacuated from the heart, and the aortic clamp was removed with spontaneous recovery of heart action and resulting excellent hemodynamics. The other patient, a 12-month-old-boy (patient 11), underwent a bidirectional cavopulmonary shunt procedure for tricuspid and pulmonary atresia and transposition of the great arteries. This patient also had a persistent left superior vena cava. The right and left superior venae cavae were anastomosed to the corresponding pulmonary arteries in a sequential fashion without the use of a temporary superior vena cava-right atrial shunt. Subsequently bilateral Blalock-Taussig shunts were clipped. Postoperatively, the patients were continuously monitored in the intensive care unit (ICU). Blood tests were done on specific clinical indications to save blood. Patients received crystalloid solution at one fourth to one half the usual maintenance rates. Mechanical ventilation was continued until adequate spontaneous ventilation resumed. Patients were then extubated if in hemodynamically stable condition. Loss of red blood cells was calculated as the product of chest drainage and the lowest Hct after operation and was corrected for body weight. Patients who had an uncomplicated postoperative course were generally transferred to their room on the second postoperative day. Oral iron supplementation was begun before discharge if indicated. Statistical Analysis Analysis of variance and Scheff6's F test were used to determine associations between the preoperative and intraoperative Hct levels. A p value equal to or less than 0.05 was considered significant. Results All 11 patients underwent successful repair (n = 10) or palliation (n = 1, patient 11) of their congenital heart defects with CPB and without the use of blood products Table 2. Cardiopulmonary Bypass Data Variable Mean arterial pressure (rnm Hg) Bypass flow (% full flow) Hemodilution (%) Bypass time (rain) Aortic cross-clamp time (min) Lowest nasopharyngeal temperature ( C) Lowest ph Lowest PaO 2 (ram Hg) Lowest PvO 2 (mm Hg) Urinary output (ml/kg) Value ± ± ± ± ± 6.3 a Data are shown as the mean -+ the standard error of the mean. PaO 2 arterial oxygen tension; PvO 2 - venous oxygen tension. (n = 9) or without CPB (n = 2) and without postoperative blood transfusions. The data on the 9 patients who underwent CPB are summarized in Table 2. Hematocrit was lowest on initiation of CPB and increased during CPB. The 3 polycythemic patients had greater hemodilution than the 6 patients without polycythemia (59.6% % versus 50.3% %, respectively). None of the patients showed evidence of progressive metabolic acidosis during CPB, a finding suggesting adequate oxygenation: the mean lowest ph was 7.38 (range, 7.34 to 7.42) and the mean lowest venous oxygen tension, mm Hg. There was no difficulty in terminating CPB in any of the 9 patients, nor were electrocardiographic changes seen that could indicate myocardial ischemia. Cardiopulmonary bypass was discontinued at a nasopharyngeal temperature of 37 C or greater and a rectal temperature of 35 C or greater. Intraoperative hemodilution resulted in significant declines in Hct values, frequently exceeding 50%. All intraoperative and postoperative Hct levels were significantly lower than the preoperative levels (p ~ 0.05). However, the first Hct obtained in the ICU (within 2 hours after discontinuation of CPB) was restored to a value (mean, 27.5% %) between the preoperative Hct (mean, 42.7% _+ 3.5%) and the lowest Hct on CPB (mean, 18.4% %) (Fig 1). The Hct rose to 31.8% % at discharge (p > 0.05 compared with the first Hct in the ICU). The median postoperative blood loss in the 9 patients who underwent CPB was 9 ml/kg; it was greater in the polycythemic patients (median loss, 12 ml/kg) than in the nonpolycytemic patients (median loss, 7 ml/kg). The mean volume of crystalloid solution required during operation (including priming solution) and in the ICU was 185 _+ 53 ml/kg. The postoperative blood loss in the 2 patients in whom CPB was not employed was 9 ml/kg and 4 ml/kg. There were no perioperative or late deaths. The mean stay in the ICU was 3.5 days (median stay, 2 days; range, 1 to 22 days). The mean hospital stay was 7.9 days (median stay, 6 days; range, 3 to 27 days). Postoperatively, 2 patients had complications that were not related to the CPB technique. One patient (patient 2) had sinus node

4 Ann Thorac Surg VAN SON ET AL ;59:384-8 CONGENITAL HEART OPERATIONS IN JEHOVAH'S WITNESSES Hct T 1 Preop CPB ICU Disch Time Fig 1. Perioperative hematocrit (Hct) levels in the 9 patients who underwent cardiopulmonary bypass (CPB). (Disch = discharge; ICU = intensive care unil) dysfunction after a Senning repair of transposition of the great arteries. The other patient, who had critical aortic stenosis and had been in poor clinical condition preoperatively (patient 10), had a prolonged stay in the ICU (22 days) because of pulmonary edema, ascites, and periods of apnea and bradycardia. Comment Our experience with 11 infants and children who had a body weight of less than 10 kg and whose parents were Jehovah's Witnesses confirms the experience of others [1-4] that in select patients, it is possible to safely employ CPB and perform cardiac operations without the use of blood or blood components. We have used a number of perioperative measures to minimize blood loss and maintain an adequate Hct: (1) pretreatment with synthetic erythropoietin when the Hct is 38% or lower to increase the Hct [5]; (2) avoidance of cardiac catheterization when possible; (3) use of low-energy electrocautery in chest wall, pericardial, and great vessel dissections; (4) minimal prebypass fluid administration; (5) reduction of priming volume by minimizing the CPB circuit volume; (6) use of moderate CPB flow rates and gentle cardiotomy suction to minimize blood cell destruction; (7) employment of ultrafiltration to remove excess water without loss of plasma, thereby retaining the latter's oncotic and buffering capacities; (8) whenever feasible, avoidance of deep levels of hypothermia to reduce the obligatory duration of CPB rewarming; (9) delay of heparin reversal after bypass until we are confident all active bleeding sites have been secured, thereby permitting continued use of cardiotomy suction to maximize perfusate return to the patient who still is in continuity with the CPB system; (10) gradual return of the entire volume of residual perfusate from all components of the CPB system; and (11) postoperative oral iron supplementation in patients with depleted red cell mass to increase the Hct. An additional technique to reduce perioperative blood loss (which we did not use) is intraoperative administration of aprotinin [6]. We set a tentative limit for body weight of 5 kg for infants of Jehovah's Witnesses to undergo repair of congenital heart defects with CPB without the use of blood. In symptomatic patients with a lower body weight, initial palliative procedures circumvent the use of CPB and allow secondary correction of the defect at a later time; this was done in 6 patients in this series. Balloon valvuloplasty is a valuable treatment option for the neonate or infant with congenital aortic or pulmonary valve stenosis; alternatively, as was done in 1 neonate in this series with critical aortic stenosis, use of venous inflow occlusion with a short period of circulatory arrest allows performance of an aortic valvotomy. Use of CPB can also be avoided in infants and children with univentricular physiology who need a bidirectional cavopulmonary shunt by temporary insertion of a superior vena cava-right atrial shunt. Use of such a shunt may not be necessary in the occasional patient with bilateral superior venae cavae and a bridging vein in whom bilateral bidirectional cavopulmonary shunts are created in a sequential fashion. Concern that hemodilution may lead to inadequate oxygenation in the infant on CPB and in the early postoperative period [7] prompted us to use moderate hypothermia and set a tentative limit of no less than 16% for the Hct on CPB in infants or children of Jehovah's Witnesses, although in older children and adolescents (body weight, 9.1 to 63 kg), others [3] have reported an Hct of 10.5 % during CPB without untoward postoperative effects. Moderate hypothermia should decrease oxygen consumption to approximately 25% of normal I2]. Hypothermia, on the other hang increases viscosity of blood, peripheral vascular resistance, and arteriovenous shunting, thereby impairing peripheral perfusion and oxygenation. However, hemodilution counteracts and offsets these effects of hypothermia [8, 9]. There was no evidence of impaired tissue perfusion or inadequate oxygen delivery in the patients in our study, as reflected by an adequate ph, arterial oxygen tension, venous oxygen tension, and urinary output. We did not experience any difficulty in weaning from CPB in terms of prolonged CPB or inotropic support. We were concerned that crystalloid hemodilution might cause cardiac, cerebral, and pulmonary edema with its resulting untoward effects on the physiology of these organs [8]. Addition of plasma proteins may be effective in decreasing extravascular water [10]; therefore we added 25% albumin to the priming solution. None of the 9 patients who underwent CPB had development of cardiac edema to such an extent that it precluded chest closure. Also, crystalloid hemodilution did not grossly interfere with cerebral or pulmonary function, as manifested by absence of detrimental neurologic sequelae in all patients and early extubation (mean time, hours) in 8 of the 9 patients who underwent CPB, respectively. Hemodilution also facilitated postoperative

5 388 VAN SON ET AL Ann Thorac Surg CONGENITAL HEART OPERATIONS IN JEHOVAH'S WITNESSES 1995;59:384-8 diuresis and reduced the requirement of diuretic medication to maintain urinary output. Clotting abnormalities after cardiac operations are most critical in the presence of polycythemia. In our patients, as in two other reports [2, 3], measured postoperative blood loss was greater in polycythemic than nonpolycythemic patients; this may have been caused mainly by the greater dilution by pump priming solution in the former group. None of the patients required reexploration for surgical bleeding. Early return of clotting factors and their rapid concentration with diuresis were probably the most important measures for preserving clotting capacity. The moral and ethical concerns about repair of congenital heart defects in children of Jehovah's Witnesses are monumental because the child is undergoing the risk of an open heart operation without blood because of the parents' consciences and cognitive choices. Without ignoring this concern, we show great respect for the parents' religious belief and make a strong effort to avoid the use of blood products in their children. As a result of this intent not to use blood products, they have, in fact, not been required in this experience. This intent and the careful selection of patients in terms of body weight, some of whom require treatment with erythropoietin, have made it possible to test the limits of hemodilution without introducing additional mortality and morbidity. We have expanded our policy to try to avoid the use of blood products in cardiac operations on infants and children with a body weight of 5 kg or more who need repair of congenital heart defects with CPB and whose parents are not of the Jehovah's Witness faith. In these patients, we use only blood to prime the CPB circuit when the predicted Hct on CPB is less than 20%. When the use of blood cannot be avoided, we strive for use of donor-directed blood. Employment of the techniques outlined and additional use of cell-saving techniques generally result in minimal homologous blood transfusion requirements in these patients. In summary, it is gratifying that perfection of surgical techniques and continual improvements in perfusion and cell-saving technology have steadily lowered the risk of CPB and cardiac operations in infants and children. Although the patients in this series represent a select group, currently available technology generally allows correction of congenital heart defects with CPB and without the use of blood in patients with a body weight of 5 kg or more. In symptomatic neonates and infants with a lower body weight, initial palliative procedures circumvent the use of CPB and allow secondary correction of the defect at a later time. References 1. Henling CE, Carrnichael MJ, Keats AS, Cooley DA. Cardiac operation for congenital heart disease in children of Jehovah's Witnesses. J Thorac Cardiovasc Surg 1985;89: Kawaguchi A, Bergsland J, Subramanian S. Total bloodless open heart surgery in the pediatric age group. Circulation 1984;70(Suppl 1): Stein JI, Gombotz H, Rigler B, Metzler H, Suppan C, Beitzke A. Open heart surgery in children of Jehovah's Witnesses: extreme hemodilution on cardiopulmonary bypass, Pediatr Cardiol 1991;12: Garcia Rinaldi R, Pagan JL, Melendez FJ, Porro R, Barcelo J, Rivera M. Cardiac surgery on Jehovah's Witnesses at Instituto Cardiovascular-Hospital Pavia. Bol Asoc Med P R 1992; 84: Vanelli P, Castelli P, Conderni AM, Santoli C. Blood saving in Jehovah's Witnesses [Letter]. Ann Thorac Surg 1991;52: Royston D, Taylor KM, Bidstrup BP, Sapsford RN. Effect of aprotinin on need for blood transfusion after repeat openheart surgery. Lancet 1987;2: Kawarnura M, Minamikawa O, Yokochi H, Maki S, Yasuda T, Mizukawa Y. Safe limit of hemodilution in cardiopulmonary bypass. Comparative analysis between cyanotic and acyanotic congenital heart disease. Jpn J Surg 1980;10: Utley JR, Wachtel C, Cain RB, Spaw EA, Collins JC, Stephens DB. Effects of hypothermia, hemodilution, and pump oxygenation on organ water content, blood flow and oxygen delivery, and renal function. Ann Thorac Surg 1981;31: Laks H, Pilon RN, Klovekorn WP, Anderson W, MacCallum JR, O'Connor NE. Acute hemodilution: its effect on hemodynamics and oxygen transport in anesthetized man. Ann Surg 1974;180: Laks H, Standeven J, Blair O, Hahn J, Jellinek M, Willman VL. The effects of cardiopulrnonary bypass with crystalloid and colloid hemodilution on myocardial extravascular water. J Thorac Cardiovasc Surg 1977;73: