Repair of Total Anomalous Pulmonary Venous Connection in Infancy: Experience From a Developing Country
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1 Repair of Total Anomalous Pulmonary Venous Connection in Infancy: Experience From a Developing Country Shiv Kumar Choudhary, MCh, Anil Bhan, MCh, Rajesh Sharma, MCh, Alok Mathur, MS, Balram Airan, MCh, Anita Saxena, DM, Shyam Sunder Kothari, DM, Rajnish Juneja, DM, and Panangipalli Venugopal, MCh Departments of Cardiothoracic and Vascular Surgery, and Cardiology, Cardiothoracic Center, All India Institute of Medical Sciences, New Delhi, India Background. Corrective surgery for total anomalous pulmonary venous connection in infancy still carries high morbidity and mortality rates in developing countries. The present study evaluates the factors responsible for it. Methods. Seventy-three infants were operated on for total anomalous pulmonary venous connection from January 1987 through October Age ranged from 5 days to 12 months (mean, months), with 10 (13.7%) patients younger than 1 month old. Patient weight varied from 2.0 to 5.2 kg (mean, kg). Most (90.5%) patients were small for their ages (< 50th percentile). Anomalous connection was supracardiac in 42 (57.5%), cardiac in 18 (24.7%), infracardiac in 4 (5.5%), and mixed in 9 (12.3%) patients. Thirty-five patients had obstructed drainage. Preoperatively, 30 patients received antibiotic therapy for respiratory tract infection, 3 patients had balloon atrial septostomy, and 4 patients required mechanical ventilation. Fifteen patients (20.5%) were operated on as an emergency procedure. For supracardiac and infracardiac connections, a posterior approach was used for anastomosis. In cardiac type, coronary sinus was unroofed and the resultant defect along with atrial septal defect was closed with a single patch. Results. The operative mortality rate was 23.3% (17 of 73). Pulmonary hypertensive crisis was the cause of death in 10 patients. Emergency operation and weight less than the 25th percentile were the important risk factors for operative mortality. Young age (< 1 month) and type of drainage did not affect the mortality. Follow-up ranged from 1 to 108 months (mean, months). There were two late deaths. The actuarial survival (Kaplan Meier) at 9 years was 72.87% 5.39%. Conclusion. Failure of early recognition, and thus delayed referral, accounted for onset of cardiac cachexia, respiratory tract infection, and severe pulmonary hypertension, which had a major effect on unfavorable outcome. (Ann Thorac Surg 1999;68:155 9) 1999 by The Society of Thoracic Surgeons Corrective operation for total anomalous pulmonary venous connection (TAPVC) has become more and more successful in recent years [1 5]. This success might be attributed to early referral, substantial improvements in surgical technique, anesthetic management, myocardial preservation techniques, and better intraoperative and postoperative care of neonates and infants. However, in third-world countries, infant TAPVC still carries high morbidity and mortality rates. To identify the factors that could account for this relatively higher morbidity and mortality, we analyzed our data on TAPVC repair in infants. Accepted for publication Jan 12, Address reprint requests to Dr Bhan, Cardiothoracic Center, All India Institute of Medical Sciences, Ansari Nagar, New Delhi , India. Patients and Methods Patient Population From January 1987 through October 1997, 73 infants who had repair for isolated TAPVC at All India Institute of Medical Sciences, New Delhi, formed the basis of this study. There were 48 boys and 25 girls. The age ranged from 5 days to 12 months (mean, months) (Fig 1). Patient weight at operation varied from 2.0 to 5.2 kg (mean, kg) (Fig 2). Most patients were small for age; about 90% weighed less than the 50th percentile of predicted weight for Indian neonates and infants (Table 1). Preoperative diagnosis was established by cardiac catheterization and angiocardiography in 24 patients. In the earlier part of experience all the patients were catheterized. Recently, however, only two-dimensional and Doppler echocardiography have been used for diagnostic evaluation. Only 1 patient in the later 50 patients was catheterized because of doubtful diagnosis. Of these 73 patients, 42 (57.5%) had supracardiac connection, 18 (24.7%) had cardiac connection, 4 (5.5%) had infracardiac 1999 by The Society of Thoracic Surgeons /99/$20.00 Published by Elsevier Science Inc PII S (99)
2 156 CHOUDHARY ET AL Ann Thorac Surg TAPVC REPAIR IN INFANCY 1999;68:155 9 Table 1. Weight Percentile of Patients a Percentile Weight No. % a For comparison data, see Ghai OP, Menon PSN. Physical growth and behavioral development of indian children in Delhi. New Delhi: Sagar Publications, admission) because of uncorrectable acidosis or progressive cardiovascular deterioration. Fig 1. Age at operation for total anomalous pulmonary venous connection. connection, and 9 (12.3%) patients had a mixed variety of drainage. Eighteen patients (61.9%) of the supracardiac variety, 9 (50%) patients of the cardiac type, all the infracardiac cases, and 4 (44%) of the mixed variety had obstructions. In the patients with supracardiac connection, obstruction was located at the vertical veininnominate vein junction in 8 patients, the vertical veinsuperior venacava junction in 2 patients, and at the interatrial communication in 8 patients. In the patients with cardiac and mixed connections, obstruction was found at the level of the coronary sinus opening in all cases. The mean pulmonary artery systolic pressure in patients who had cardiac catheterization was 64 mm Hg (range, 24 to 110 mm Hg) with a mean aortic systolic pressure of 84 mm Hg (range, 68 to 110 mm Hg). Preoperatively, 30 patients required aggressive antibiotic therapy for severe lower respiratory tract infection. Endotracheal intubation and mechanical ventilation were required to support 4 patients. Balloon atrial septostomy was done in 3 patients for restrictive interatrial communication. Four patients had ventricular fibrillation before they could be put on cardiopulmonary bypass. Fifteen patients (20.5%) had to be operated on as an emergency procedure (within 12 to 24 hours of hospital Fig 2. Weight distribution of patients at operation for total anomalous pulmonary venous connection. Surgical Technique In our initial experience, children less than 3 kg in weight (n 14) were operated on using profound hypothermia and circulatory arrest. The remaining 59 patients were operated on using standard cardiopulmonary bypass and moderate hypothermia. Cold, hyperkalemic blood cardioplegia and topical hypothermia were used for myocardial protection in all patients. In the first group of patients, mean cardiopulmonary bypass time was 56 minutes (range, 47 to 92 minutes), and mean circulatory arrest time was 28 minutes (range, 21 to 39 minutes). In the second group of patients, mean cardiopulmonary bypass time was 45 minutes (range, 34 to 73 minutes), and mean aortic cross-clamp time was 34 minutes (range, 26 to 44 minutes). After midsternotomy, minimal manipulation of heart was done until cardiopulmonary bypass was established. Recently, to prevent prebypass ventricular fibrillation, we established cardiopulmonary bypass with an arterial cannula and a venous cannula in the right atrial appendage, followed by relocation of angled venous cannulas into the superior and inferior vena cavas. The ductus was dissected routinely in all patients and was looped and ligated immediately after initiating the bypass. The vertical vein in patients with supracardiac or infracardiac connections was handled only after initiating bypass. It was looped and controlled. In the patients with supracardiac connection, where the vertical vein drains into the innominate vein, we prefer to control the vertical vein extrapericardially between the pericardium and the left pleura after removing the left lobe of thymus. This method avoids narrowing of the left superior pulmonary vein when the vertical vein is ligated later on. The subsequent correction was done depending upon the type of drainage. In the patients with supracardiac connection, the apex of the heart was lifted cephalad and to the right with the right pleural cavity widely open. This allowed an excellent exposure [6]. Long transverse incisions were made on the common pulmonary venous chamber and on the left atrium. A large anastomosis (2.5 to 3 cm) was made between these two chambers from outside, using a running 6/0 polypropylene suture. Atrial septal defect was closed either through a separate right atriotomy or through the same left atrial incision. The vertical vein was ligated in all patients after termination of cardiopulmonary bypass.
3 Ann Thorac Surg CHOUDHARY ET AL 1999;68:155 9 TAPVC REPAIR IN INFANCY 157 In the patients with cardiac connection (n 15), the coronary sinus was unroofed and a wide opening was made between the left atrium and the coronary sinus, as described by Malm [7]. The atrial septal defect and the coronary sinus were closed by a single patch (synthetic or autogenous pericardium) that was kept away from the conduction tissue at the edge of the coronary sinus. In 3 patients, the wall between the coronary sinus and the left atrium was turned over to close the coronary sinus opening, and the atrial septal defect was closed directly. In the patients with infracardiac connection, the heart was lifted up and a wide anastomosis was made between the pulmonary venous chamber and the left atrium by an obliquely directed incision in the left atrial body. The vertical vein was ligated in all cases. In all patients, we attempted to wean them off cardiopulmonary bypass with inotropic support (dopamine, dobutamine, or both). In our earlier experience, 2 patients could not be weaned off cardiopulmonary bypass. In recent experience, 2 patients had to be put on a left-sided centrifugal pump support because they could not be weaned off cardiopulmonary bypass even with maximal inotropic support. Postoperative Treatment Postoperative care included prolonged elective ventilation, preferably on pressure control mode of ventilation, and an attempt was made to maintain partial pressure of carbon dioxide at approximately 25 mm Hg. The mean duration of ventilation was 4.5 days (range, 2 to 24 days). We have routinely monitored the pulmonary artery pressures since 1988, which has been useful in weaning patients off the ventilator. Various vasodilators have been used to maintain the pulmonary artery pressure within the acceptable range. These included phenoxybenzamine, nitroglycerine, sodium nitroprusside, isoprenaline, and prostaglandin E. To avoid pulmonary congestion, diuretics were used liberally. In view of poor nutritional status, these patients were put on total parenteral nutrition if they required ventilation for more than 72 hours. Weaning Protocol We electively ventilate the patients for the first 24 to 36 hours. If hemodynamic status is satisfactory and systolic pulmonary artery pressure is well below ( 50%) the systemic systolic arterial pressure, weaning is started. While the patient is still paralyzed and sedated, we decrease the minute ventilation and allow partial pressure of carbon dioxide to increase to above 30 mm Hg. The response of systolic pulmonary artery pressure to this change is noted. If pulmonary artery pressure increases significantly, the patient is put back on full ventilation and no attempt is made to wean for the next 24 hours. However, if pulmonary artery pressure does not increase in response to higher partial pressure of carbon dioxide and remains less than half of systemic arterial pressure, weaning continues. Survivors were discharged from the hospital after a mean interval of days (range, 8 to 34 days). Patients were followed up in the outpatient clinic by clinical examination and echocardiography. Statistical Analysis Data were entered into a computerized database and analyzed with BMDP statistical software (BMDP Statistical Software Inc, Los Angeles, CA). Mean values were calculated for continuous, interval level variables and were reported as mean standard deviation. Analysis of time-related survival was done using the Kaplan-Meier method and was expressed as cumulative survival standard error of the mean. A multiple logistic regression model was used to identify independent risk factors for early death. Selection of independent variables was a forward stepwise method with a critical probability value of 0.15 for variable inclusion and exclusion. A value of p less than 0.05 was considered significant in the final model. Results The operative mortality rate for isolated TAPVC was 23.3% (17 of 73 patients). In our experience, pulmonary hypertensive crisis has been the major cause of death (n 10). In 6 patients who died of pulmonary hypertensive crisis, systolic pulmonary artery pressure was more than half of systolic systemic arterial pressure at the time of weaning off cardiopulmonary bypass, and it remained high throughout the subsequent course. In 4 other patients, systolic pulmonary artery pressure decreased significantly (less than half systemic) intraoperatively. In those 10 patients, pulmonary artery pressure started rising paroxysmally after initial 24 hours and was associated with low cardiac output and bradycardia. Ultimately, this paroxysmal rise became refractory to any type of therapy, eventually leading to death. In our initial experience, 2 patients could not be weaned off cardiopulmonary bypass. In both patients ventricular fibrillation developed preoperatively. They were resuscitated and required mechanical ventilation preoperatively. In 2 other patients, a centrifugal pump was used to support left sided heart, but both patients developed right sided failure and died. In the remaining 3 patients, cause of death was refractory ventricular arrhythmia, mediastinitis, and septicemia in 1 patient each. Echocardiographic evaluation done in early postoperative period showed no evidence of anastomotic obstruction. However, 2 patients in whom pulmonary veins were found small and hypoplastic intraoperatively died of pulmonary hypertensive crisis. Operative mortality in different age groups and morphologic groups is shown in Tables 2 and 3. Risk factors for early death were analyzed by univariate and multiple logistic regression analysis (Table 4). By univariate analysis, age less than 1 month, obstructed drainage, weight less than 25th percentile, preoperative requirement for ventilation, and emergency surgery were significant risk factors for operative mortality. However, by multiple logistic regression, only emergency repair ( p 0.002) and weight less than 25th percentile ( p 0.045) were significant risk factors for operative death. All operating room survivors required inotropic support postoperatively for 3 to 16 days. The mean duration of ventilation was 4.5 days (range, 2 to 24 days). Thirty-
4 158 CHOUDHARY ET AL Ann Thorac Surg TAPVC REPAIR IN INFANCY 1999;68:155 9 Table 2. Age and Operative Mortality Rate Age at Repair (mo) No. Deaths % Total one patients received total parenteral nutrition, commencing after 72 hours of ventilation. Five patients had serious postoperative infection (mediastinitis in 3 and septicemia in 2). Two of those patients died. Besides this, 6 other patients had wound-related problems but recovered with conservative therapy. The follow-up ranged from 1 to 108 months (mean, months) and was 96.4% complete. There has been one late death after 12 months due to meningitis. Another patient died unexpectedly after 16 months. The actuarial survival (Kaplan-Meier) at 9 years was 72.87% 5.39% (Fig 3). The surviving patients are in excellent clinical condition and have normal growth. Follow-up echocardiography did not show any obstruction at the site of anastomosis or pulmonary vein stenosis. Comment Total anomalous pulmonary venous connection is a rare congenital malformation with unfavorable natural prognosis. Only 20% of patients survive the first year of life [8]. Although initially associated with high mortality rates, results of correction of TAPVC in infancy have improved markedly in recent years. Operative mortality of 5% or less has been reported at some institutions [1, 3, 9, 10]. This improvement could be attributed partly to improved accuracy of diagnosis by echocardiography [11]. In our experience, echocardiography alone was sufficient to provide complete diagnosis in 49 of the later 50 patients. Greater attention to preoperative stabilization, substantial improvement in surgical technique and myocardial preservation, and better intraoperative and Table 4. Risk Factors for Operative Death (Univariate Analysis by Logistic Regression) Variables Age 1 month versus 1 month Obstructed versus nonobstructed drainage Weight (percentile) 25th versus 25th Preoperative ventilation required versus not required Emergency versus elective repair Preoperative ventricular fibrillation Infradiaphragmatic connection versus other Odds Ratio 95% Confidence Interval p Value Not available a Not available a a Risk could not be estimated due to few number of cases. postoperative care of neonates and infants have also contributed to improved surgical results [1 4, 9, 10, 12]. Previously, various risk factors, including younger age at operation, anatomic type of connection, pulmonary arte- Table 3. Anatomic Type and Operative Mortality Rate Anatomic Type No. Deaths % Supracardiac Obstructed Unobstructed Cardiac Obstructed Unobstructed Infracardiac Obstructed Mixed Obstructed Unobstructed Total Fig 3. Actuarial survival (Kaplan-Meier) after repair of total anomalous pulmonary venous connection.
5 Ann Thorac Surg CHOUDHARY ET AL 1999;68:155 9 TAPVC REPAIR IN INFANCY 159 rial hypertension, presence or absence of obstruction, preoperative metabolic acidosis and need for ventilatory support, and urgency of operative repair [12 16], were considered to influence the operative mortality rate. However, with present surgical methods, these factors have become less and less important [1, 2, 4, 9, 17]. In our experience, urgency for operative repair was the most important single factor associated with death ( p 0.002). Another important predictor was weight less than the 25th percentile ( p 0.045). Obstructed pulmonary venous drainage and need for preoperative mechanical ventilation, though significant risk factors in univariate analysis, were eliminated in the final model. When combined, the patients with these risk factors represent a group of very sick infants who required surgical repair on an emergency basis, most often. However, as reported by other investigators [1, 2, 12, 18], younger age ( 1 month) and type of drainage were not significant risk factors for early death in our experience. We treated these patients aggressively and an operation was planned as soon as possible, rather than attempting to stabilize them metabolically and hemodynamically. This approach is favored by some [2] and criticized by others [13]. We had a relatively high operative mortality rate (23.3%). The two important factors that might have contributed to such a high mortality rate are late referral and underdeveloped infants. Only 10 patients (13.7%) presented before the age of 1 month. This is in contrast to western experience where most patients ( 50%) were referred for an operation before 1 month of age [3, 4]. We believe that this delay, caused by limited diagnostic facilities at peripheral centers, contributed to development of severe pulmonary arterial hypertension, which was the major cause of operative death. This situation is similar to development of pulmonary arterial hypertension in other congenital heart diseases with high pulmonary blood flow. Bando and colleagues [19] also found that older age at operation was a contributing factor to pulmonary arterial hypertensive crisis and subsequent death. Late referral is also responsible for a prolonged period of malnutrition and ultimately cardiac cachexia. Second, most of our patients (90%) had less than the 50th percentile of predicted body weight for age and sex; of these, more than 50% were below the 25th percentile. This finding reflects the severity of disease and the degree of malnutrition leading to severe underdevelopment. These underdeveloped infants are high-risk candidates and react unfavorably to stresses such as cardiopulmonary bypass and postoperative events. These malnourished infants are also predisposed to a variety of chest infections. In the present series, 30 (42%) patients required preoperative antibiotic therapy for significant respiratory tract infections. We also noticed a higher incidence of postoperative pulmonary arterial hypertension in underdeveloped infants. Similarly, we found postoperative intrabronchial hemorrhage a frequent occurrence in grossly malnourished and underdeveloped infants. Postoperative sepsis was also more common in these patients, partly from malnutrition and partly because they required prolonged mechanical ventilation and invasive monitoring. We thank Mr Rajvir Singh, MSc (Stat), for statistical analysis. References 1. Lupinetti FM, Kulik TJ, Beekman RH, Crowley DC, Bove EL. Correction of total anomalous pulmonary venous connection in infancy. J Thorac Cardiovasc Surg 1993;106: Cobanoglu A, Menashe VD. Total anomalous pulmonary venous connection in neonates and young infants: repair in current era. Ann Thorac Surg 1993;55: Sono S, Brawn WJ, Mee RBB. Total anomalous pulmonary venous drainage. J Thorac Cardiovasc Surg 1989;97: Serraf A, Bruniaux J, Lacour-Gayet F, et al. Obstructed total anomalous pulmonary venous return. Towards neutralization of a major risk factor. J Thorac Cardiovasc Surg 1991;101: Kirklin JW, Barratt-Boyes BG, eds. Cardiac surgery. 2nd ed. New York: Churchill Livingstone, 1993: Bhan A, Sharma R, Iyer KS, Venugopal P. Improved exposure of TAPVC repair by posterior approach [Letter]. Ann Thorac Surg 1996;62: Malm JR. Secundum atrial septal defects and associated anomalous pulmonary venous drainage. In: Cooper P, ed. The craft of surgery. 1st ed. Boston, Massachusetts: Little Brown, 1964: Van Praagh R, Harken AH, Delisle G, Gross RE. Total anomalous pulmonary venous drainage to the coronary sinus: a revised procedure for its correction. J Thorac Cardiovasc Surg 1972;64: Phillips SJ, Kongtahworn C, Zeff RH, Skinner JR, Chandramouli B, Gay JH. Correction of total anomalous pulmonary venous connection below the diaphragm. Ann Thorac Surg 1990;49: Raisher BD, Grant JW, Martin TC, Strauss AW, Spray TL. Complete repair of total anomalous pulmonary venous connection in infancy. J Thorac Cardiovasc Surg 1992;104: Van der Velde ME, Parness IA, Colan SD, et al. Twodimensional echocardiography in the pre- and post operative management of totally anomalous pulmonary venous connection. J Am Coll Cardiol 1991;18: Bove EL, de Leval MR, Taylor JFN, Macartney FJ, Szarnicki RJ, Stark J. Infradiaphragmatic total anomalous pulmonary venous drainage: surgical treatment and long term results. Ann Thorac Surg 1981;31: Bando K, Turrentine MW, Ensing GJ, et al. Surgical management of total anomalous pulmonary venous connection: thirty-year trends. Circulation 1996;94(Suppl II):II Hammon JW Jr, Bender HW Jr, Graham TP Jr, et al. Total anomalous pulmonary venous connection in infancy. Ten years experience including studies of post-operative ventricular function. J Thorac Cardiovasc Surg 1980;80: Turley K, Tucker WY, Ullyot DJ, Ebert PA. Total anomalous pulmonary venous connection in infancy: influence of age and type of lesion. Am J Cardiol 1980;45: Lincoln CR, Rigby ML, Mercanti C, et al. Surgical risk factors in total anomalous pulmonary vensous connection. Am J Cardiol 1988;61: Wilson WR Jr, Ilbawi MN, DeLeon SY, et al. Technical modifications for improved results in total anomalous pulmonary venous drainage. J Thorac Cardiovasc Surg 1992;103: Yee ES, Turley K, Hsich WR, Ebert PA. Infant toal anomalous pulmonary venous connection: factors influencing timing of presentation and operative outcome. Circulation 1987; 76(Suppl):III Bando K, Turrentine MW, Sharp TG, et al. Pulmonary hypertension after operation for congenital heart disease: analysis of risk factors and management. J Thorac Cardiovasc Surg 1996;112:
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