Improving the results of ligation of patent ductus arteriosus in small preterm infants

Improving the results of ligation of patent ductus arteriosus in small preterm infants Thirty-two consecutive preterm infants with birth weights under 1,500 grams and with respiratory distress syndrome (RDS) complicated by a patent ductus arteriosus (PDA) underwent ligation of PDA. The indications for operation were massive left-to-right shunting associated with heart failure (cardiomegaly and pulmonary edema) unresponsive to medical treatment. The clinical manifestations of heart failure were related to the severity of RDS. Infants with mild-to-moderate RDS (21) often recovered and later developed typical findings of PDA (bounding pulses, hyperactive precordium, and murmur). They are now operated upon as soon as respiratory support is required. Infants with severe RDS (11) develop cardiomegaly earlier, and retrograde aortography may show massive left-to-right shunting before the presence of a murmur. Ligation is indicated when blood-gas values deteriorate despite medical treatment. Nineteen (59 per cent) of these extremely preterm infants survived to be discharged and 16 (50 per cent) are developing normally. Three have neurologic impairment. None of the survivors has clinical respiratory disease, and their radiologic findings of bronchopulmonary dysplasia are improving.

Ronald J. Nelson, M.D., Donald W. Thibeault, M.D., George C. Emmanouilides, M.D., and Maurice Lippmann, M.D., Torrance and Los Angeles, Calif.

A he incidence of delayed closure of a patent ductus arteriosus (PDA) is increased in the premature infant, particularly in association with the respiratory distress syndrome (RDS). As more effective pulmonary care is given to preterm infants with RDS in neonatal intensive care units (NICU), heart failure caused by left-to-right shunting through a PDA has been observed more frequently. Increasing numbers of infants are undergoing ligation of PDA to control the heart failure. 1-5 However, the indications for the procedure remain controversial,6' 7 and the long-term benefit in patients with severe RDS has been questioned.8 The value of ligation of PDA in a premature infant with RDS requiring prolonged respiratory support was reported from this institution in 1968.9 This communiFrom the Department of Surgery, Division of Perinatal Medicine of the Department of Pediatrics, and the Department of Anesthesiology, Harbor General Hospital, Torrance, Calif. 90509, and the UCLA School of Medicine, Los Angeles, Calif. 90024. Supported in part by Investigative Group Support 470 IG3 and Research Award 496-C1 of the Greater Los Angeles Affiliate of the American Heart Association. Read at the First Annual Meeting of The Samson Thoracic Surgical Society, Santa Barbara, Calif., May 28-30, 1975.

cation will present the development of our approach to the management of PDA associated with RDS in the premature infant and will give the results of operation in 32 consecutive infants with a birth weight under 1,500 grams. Material and methods During a 39 month period from Oct. 1, 1971, to Dec. 31, 1974, 32 consecutive preterm infants with a birth weight under 1,500 grams underwent ligation of PDA. Twenty-four (75 per cent) were transferred to the NICU at Harbor General Hospital at a mean age of 6 hours (range 2 to 72 hours). Eight (25 per cent) were delivered at Harbor General Hospital. The birth weights ranged from 724 to 1,500 grams (mean 1,022 grams) and the gestational ages from 25 to 34 weeks (mean 28.6 weeks). The relationship of birth weight to gestational age is shown in comparison to the Colorado Intrauterine Growth Chart in Fig. 1. The distribution of weight at the time of operation is given in Fig. 2. Eighteen of the infants were male and 14 were female. All infants in the series developed RDS in the first few hours of life. The severity ranged from very mild requiring only a short period of increased ambient 169

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WEEK OF GESTATION

Fig. 1. Scattergram showing birth weight versus week of gestation in comparison to the Colorado Intrautenne Growth Chart.

oxygen concentration to severe disease requiring 100 per cent inspired oxygen and intermittent positivepressure ventilation (IPPV)* with high inspiratory pressures (greater than 30 cm. H 2 0). Twenty-three infants (72 per cent) required mechanical ventilation during the first 48 hours. The hypoxemia of RDS was managed by elevated ambient oxygen concentrations and respiratory failure initially by means of continuous positive airway pressure (CPAP) administered by nasal prongs or endotracheal tube and later IPPV with or without positive end-expiratory pressure (PEEP) according to the severity of the blood-gas derangement. CPAP did not exceed 10 cm. H 2 0 and PEEP did not exceed 5 cm. H 2 0. Sodium bicarbonate was given for metabolic acidosis. Umbilical artery catheters were placed in most infants for parenteral fluid administration, arterial blood sampling, and the performance of retrograde aortography. The tip was positioned above the level of the diaphragm and below the PDA (between the sixth and ninth thoracic vertebrae). The status of the PDA was studied by single-film retrograde aortography in most patients. The retrograde aortograms were taken in the NICU with a portable x-ray machine without disturbing the infant. A single anteroposterior chest roentgenogram was taken at the time of rapid manual injection of 1 ml. of meglumine

diatrizoate and sodium diatrizoate, 60 per cent,* per kilogram of body weight through the umbilical artery catheter by one of the authors (D. W. T.). This technique has been more completely described and evaluated in a previous publication.10 The clinical manifestations of heart failure due to left-to-right shunting through a PDA were influenced by the course of the RDS.10 The RDS has been arbitrarily classified into two groups to clarify this relationship. The first group (severe RDS) comprised 11 infants who required IPPV with 20 cm. H 2 0 inspiratory pressure or greater to maintain a Pao2 of 50 to 70 mm. Hg while breathing 100 per cent oxygen. The remaining 21 infants composed the second group (mild-to-moderate RDS); their requirement for respiratory assistance varied from none to IPPV with inspiratory pressures under 20 cm. H 2 0. Heart failure due to left-to-right shunting through a PDA was diagnosed earlier in the infants with severe RDS, and a large left-to-right shunt was frequently demonstrated by aortography before the presence of a systolic murmur. The left-to-right shunting was clinically evidenced by bounding pulses and a hyperactive precordium. The criteria for the diagnosis of heart failure were cardiomegaly and pulmonary edema replacing the changes of hyaline membrane disease on chest roentgenogram in most cases.

*Bird Mark VIII respirator with an infant Q circle.

*Renograffin 60, E. R. Squibb & Sons, Inc., New York, N. Y.

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Infants in the mild-to-moderate RDS group often recovered from their RDS within a few days of birth and later developed the typical clinical findings of PDA and heart failure including the presence of a murmur. All infants received intensive medical management of their congestive heart failure including digitalization and the cautious use of diuretics. Pulmonary edema was managed with ventilatory assistance as determined by respiratory failure. Surgical ligation of the PDA was performed only if the infant's status deteriorated under intensive medical treatment. The condition of the infants was stabilized on a portable transport respirator* with endotracheal tube in place prior to transfer to the operating room. Satisfactory arterial blood gases (Pao_ 50 to 70 mm. Hg, PaC0; 30 to 45 mm. Hg, and pH 7.30 to 7.40) were verified in most cases before transfer. The infants were attended by a neonatologist-cardiologist, anesthesiologist, and respiratory therapist during the transfer. Use of the transport respirator to ventilate the infants was continued during the operative procedure. An increase in pressure was usually necessary while the chest was open. Vigorous attempts to expand atelectatic lung were avoided to minimize the risk of pneumomediastinum and subpleural pneumothorax. Electrocardiogram, heart rate, and rectal temperature were routinely monitored and temperature carefully controlled. The only anesthetic agent used was an occasional muscle relaxant. The ductus was usually approached transpleurally through a posterolateral thoracotomy incision. The PDA was ligated with a heavy suture (No. 2 silk) to avoid cutting through friable ductal tissue. Fluids were administered by infusion pump and blood loss was replaced with 2 to 5 c.c. increments of fresh whole blood. A chest tube was inserted during closure of the thoracotomy but was generally removed at the time of skin closure. Results Nineteen infants (59 per cent) survived to be discharged from the hospital after an average stay of 98 days (range 53 to 206 days). None has died after hospital discharge with a follow-up from 5 to 32 months (mean 17.6 months). One infant was lost to follow-up at 8 months when the family moved to another area of the country. The relationship of birth weight to survival is given in Fig. 3 and the relationship of gestational age to survival in Fig. 4. Survival following operation was *Modified Bird Mark VIII respirator with infant Q circle (more completely described in another report submitted for publication).

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Fig. 2. Illustration showing distribution of weight at birth (mean 1,022 grams) and at patent ductus arteriosus (PDA) ligation (mean 916 grams). Closed circles represent hospital deaths. noted with a birth weight as low as 765 grams and with a gestational age as early as 25 weeks. The age at operation is given for the severe RDS group, the mild-to-moderate RDS group, and for the total group in Fig. 5. The mean age at operation of the severe RDS group (7.5 days) is significantly different from the mean age at operation of the mild-to-moderate RDS group (14.8 days) at the 0.01 level according to Student's t test. The survival rate of the severe group was 55 per cent while that for the mild-to- moderate group was 63 per cent. Five of 7 (71 per cent) in the mild-to-moderate RDS group who required only increased ambient oxygen by hood during the first few days of RDS were survivors. Ligation of PDA was performed as early as 2 days of age with survival in the severe RDS group. The value of a properly timed operation is illustrated by a set of identifical twins with severe RDS whose courses are summarized in Fig. 6 by plotting peak inspiratory pressure, inspired oxygen concentration, and cardiac size versus postnatal days. Both twins had a large left-to-right shunt demonstrated by retrograde aortography on Day 3 (Fig. 7) in the absence of a murmur. Because the value of ductal ligation in this early period is controversial, the twin considered to be

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Fig. 5. Histogram showing distribution of postnatal age at PDA ligation for the severe RDS and mild-moderate RDS groups separately and for the total series. RDS, Respiratory distress syndrome.

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Table I. Postoperative

complications No. of cases

Complication Pneumothorax Pneumomediastinum Interstitial emphysema Left phrenic nerve paralysis Left chylothorax Right pleural effusion and collapse of right lung

Table II. Hospital

TWIN A PRESSURE cmH 2 0

5 4 1 1 1 1

Fi0 2

deaths

Time of death re operation

173

Cause of death

In OR 8 hours 12 hours 3 days 3 days 4 days 20 days 35 days

Cardiac arrest PI Cerebellar hemorrhage PI, septicemia DIC Septicemia Adrenal hemorrhage, PI Necrotizing enterocolitis, septicemia, DIC, PI Necrotizing enterocolitis, PI General inanition and PI Laryngeal stenosis with PI Left phrenic nerve paralysis with PI Left chylothorax with PI

36 days 37 days 48 days 95 days 98 days

Legend: OR. Operating room. PI. Pulmonary insufficiency. Disseminated intravascular coagulation.

PRESSURE cmH20

DIC.

Table III. Survivors Status Developing in keeping with gestational; Neurologic abnormality Mild retrolental fibroplasia

No. of cases 16 3 3

in the worst condition (Twin B) underwent operation on the fourth postnatal day while the other twin (Twin A) was continued on vigorous medical management. Twin B steadily improved following ligation of a large ductus (4.5 mm. in diameter), whereas Twin A progressively deteriorated to what was considered an irreversible status and died on the nineteenth postnatal day. The clearing of the heart failure and pulmonary edema on chest roentgenogram of Twin B subsequent to ductal ligation is shown in Fig. 8. Twin B is well and developing normally at this time. The postoperative complications of PDA ligation are listed in Table I. Pneumothorax and pneumomediastinum were the most common complications, and all

10 15 20 POSTNATAL DAYS

25

30

Fig. 6. Clinical course of a set of identical twins (28 week gestation) with severe RDS complicated by PDA who both developed a massive left-to-right shunt by Day 3 on aortography. Twin A (1,000 grams) developed massive cardiomegaly by Day 4 and, despite intensive medical treatment, required progressively higher inspiratory pressures at 100 per cent Fi«„ until death on Day 19. Twin B (1,060 grams) underwent ligation of PDA on Day 4 after similar medical management to Twin A and subsequently showed steady improvement, with cardiac size returning to normal within 2 days. 0, Normal heart size. /, Moderate cardiomegaly. //, massive cardiomegaly. cases of pneumomediastinum except one were noted early in the series before attempts to expand atelectatic lung during the operation were avoided. The time of death in relation to the operation and the cause of death

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Fig. 7. Retrograde aortograms on Day 3 for (A) Twin A and (B) Twin B showing each to have a massive left-to-right shunt through a widely patent ductus arteriosus with most of the contrast material in the pulmonary arterial tree and very little in the aortic arch. The ductal murmur wasfirstaudible 24 hours after the aortogram in each twin. for the 13 infants who died in the hospital are listed in Table II. Two of the deaths were related to complications of the operative procedure (left phrenic nerve paralysis and chylothorax). The remainder were associated with an advanced stage of disease prior to the procedure or with other complications of extreme prematurity. The survivors have now been followed from 5 to 32 months (mean 17.6 months), and the pertinent data are summarized in Table III. Sixteen (50 per cent of total series) are developing normally in relation to their gestational age. Three children have neurologic abnormalities. One has microcephaly, psychomotor retardation, and mild-to-moderate spastic quadriplegia. Another has microcephaly, psychomotor retardation, and spastic diplegia. A third child was doing well until he was discovered in his crib at home at 6 months of age with a respiratory arrest. Subsequent to this prolonged episode of hypoxia, he has had cortical blindness and cerebral palsy. All survivors have shown varying degrees of the late changes of bronchopulmonary dysplasia (BPD) on chest roentgenogram. Subsequent chest films have shown improvement or clearing of these changes as illustrated in Fig. 9. No child is currently limited by respiratory insufficiency or recurrent pulmonary infections. Discussion The appearance of heart failure because of persistence of a PDA in a premature infant with RDS requires that the infant be kept alive until the pulmonary

vascular resistance falls sufficiently to allow left-toright shunting. The relative contributions of the altered hemodynamics of the left-to-right shunt, the immature heart and lungs, and the surfactant abnormality to the course of these infants have not been well clarified.7 Unfortunately, detailed cardiac catheterization studies are formidable and risky in these tiny infants. The closure of the PDA is one component of the problem that can be therapeutically altered and would appear to be of benefit in some patients. Our current indications for operative closure are based on the demonstration of a PDA with left-to-right shunting associated with heart failure that is progressive despite vigorous medical management. The infants with mild-to-moderate RDS usually recover from their RDS within a few days and then present with classical findings including bounding pulses, hyperactive precordium, systolic murmur, cardiomegaly, and pulmonary edema. We now perform ligation when respirator assistance is needed to control respiratory failure, although preoperative use of mechanical ventilation is kept at a minimum. The early use of retrograde aortography in the group with severe RDS has revealed the unexpected finding that a large left-to-right shunt may occur as early as 36 hours after birth in the absence of the usual systolic murmur. Presumably, the PDA is so large that turbulent flow does not occur. Some constriction of the ductus may be necessary in order to generate a murmur. In the group with severe RDS, our operative indications require clinical evidence of heart failure

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19-27-74Fig. 8. Serial chest roentgenograms of Twin B showing (A) severe hyaline membrane disease on the day of birth, (B) clearing of the hyaline membrane disease and the appearance of massive cardiomegaly, increased pulmonary flow, and pulmonary edema immediately preoperatively on Day 4, and (C) return of the heart to near-normal size and clearing of the pulmonary changes within 48 hours postoperatively. (cardiomegaly and pulmonary edema) that is unresponsive to vigorous medical management together with demonstration of a large left-to-right shunt. Delay is avoided once these conditions are met. Retrograde aortography is particularly helpful in this group where clinical evidence of a left-to-right shunt (bounding pulses and hyperactive precordium) may exist without a murmur. If an infant with severe RDS and cardiomegaly has deteriorating blood-gas values, a retrograde

aortogram is performed even though a murmur is not present. The long-term value of PDA ligation in premature infants with RDS has been questioned in the series from the University of California at San Francisco.8 Six (40 per cent) of 15 infants with RDS and ligation of PDA were discharged from the hospital. One of these died with a respiratory infection in a fibrotic lung 7 weeks later, 2 had hydrocephalus with severe retarda-

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Fig. 9. Chest roentgenograms of an infant born after 28 weeks' gestation who weighed 1,250 grams at birth. The infant had severe RDS and underwent PDA ligation at 7 days of age. A, At 3 months of age there is moderate linear streaking of both lung fields consistent with the late changes of bronchopulmonary dysplasia. B, At nearly 10 months of age there is marked radiographic improvement of the bronchopulmonary dysplasia.

tion (one is blind from retrolental fibroplasia), and 2 showed significant slowing of psychomotor development. In our series, 6 (54 per cent) of 11 patients with severe RDS requiring inspiratory pressures greater than 20 cm. H 2 0 were discharged from the hospital. Five of these survivors are developing normally in relation to their gestational age and are not limited by sequelae of their prematurity. Thirteen (62 per cent) of 21 patients with mild-to-moderate RDS were discharged from the hospital, and 11 of these are doing well. Gay and co-authors2 included 20 premature infants with birth weights under 1,500 grams in their group of infants with severe RDS (defined as requiring mechanical ventilation). Ten (50 per cent) of these survived. Three were well and 3 had mild bronchopulmonary dysplasia. One had severe bronchopulmonary dysplasia and was respirator dependent, one had neurologic impairment, one had neonatal meningitis, and one had the explosive onset of heart failure. We conclude that (1) the procedure of ductal ligation in the premature infant weighing less than 1,500 grams can be safely performed; (2) ligation of the PDA controls heart failure due to the large left-to-right shunt; (3) a significant number (50 per cent) of infants, even with severe RDS, survive and appear to be doing well; (4) the management of infants requiring intubation and respirator support for bronchopulmonary dysplasia remains an unsolved problem; and (5) other problems of prematurity such as poor nutrition, necrotizing

enterocolitis, sepsis, disseminated intravascular coagulation, and neurologic abnormalities continue to be a significant cause of death and disability. The value of PDA ligation in the premature infant with RDS will be further clarified by improved physiological understanding and progress in the management of other problems of prematurity. We currently feel that PDA ligation has an adjunctive role in the management of patients with the triad of PDA, RDS, and prematurity. It is indicated when intensive medical management fails to control congestive heart failure associated with a large left-to-right shunt. The procedure should be done early to minimize the time on mechanical ventilation. REFERENCES 1 Kitterman, J. A., Edmunds, L. H., Jr., Gregory, G. A., Heymann, M. A., Tooley, W. H., and Rudolph, A. M.: Patent Ductus Arteriosus in Premature Infants, N. Engl. J. Med. 287: 473, 1972. 2 Gay, J. H., Daily, W. J. R., Meyer, B. H. P., Trump, D. S., Cloud, D. T., and Molthan, M. E.: Ligation of the Patent Ductus Arteriosus in Premature Infants: Report of 45 Cases, J. Pediatr. Surg. 8: 677, 1973. 3 Gupta, J. M., van Vliet, P. K. J., Fisk, G. C , and Wright, J. S.: Ductus Ligation in Respiratory Distress Syndrome, J. THORAC. CARDIOVASC. SURG. 63:

643,

1972. 4 Horsley, B. L., Lerberg, D. B., Allen, A. C , Zuberbuhler, J. R., and Bahnson, H. T.: Respiratory Distress From Patent Ductus Arteriosus in the Premature Newborn, Ann. Surg. 177: 806, 1973.

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5 Murphy, D. A., Outerbridge, E., Stern, L., Karn, G. M., Jegier, W., and Rosales, J.: Management of Premature Infants With Patent Ductus Arteriosus, J. THORAC. CARDIOVASC. SURG. 67: 221,

1974.

6 Neal, W. A., Bessinger, F. B., Jr., Hunt, C. E., Lucas, R. V., Jr.: Patent Ductus Arteriosus Complicating Respiratory Distress Syndrome, J. Pediatr. 86: 127, 1975. 7 Lees, M. H.: Commentary: Patient Ductus Arteriosus in Premature Infants—A Diagnostic and Therapeutic Dilemma, J. Pediatr. 86: 132, 1975. 8 Edmunds, L. H., Jr., Gregory, G. A., Heymann, M. A., Kitterman, J. A., Rudolph, A. M., and Tooley, W. H.: Surgical Closure of the Ductus Arteriosus in Premature Infants, Circulation 48: 856, 1973. 9 Siassi, B., Emmanouilides, G. C , Cleveland, R. J., and Hirose, F.: Patent Ductus Arteriosus Complicating Prolonged Assisted Ventilation in Respiratory Distress Syndrome, J. Pediatr. 74: 11, 1969. 10 Thibeault, D. W., Emmanouilides, G. C , Nelson, R. J., Lachman, R. S., Rosengart, R. M., and Oh, W.: Patent Ductus Arteriosus Complicating the Respiratory Distress Syndrome in Preterm Infants, J. Pediatr. 86: 120, 1975.

Discussion D R . B E R T R A N D W. M E Y E R Los Angeles. Calif.

We agree completely with the authors that the indications for surgery and the time for carrying out this surgery can be very difficult to determine. Like the authors, we monitor the blood gases very closely. If there is deterioration in the Po2 below 60 or the Pco2 below 40, when there is adequate ventilation, cardiac support, use of diuretics, and so forth, then we consider carrying out diagnostic procedures to establish the presence of a left-toright shunt and perform surgery. Our cardiologists prefer a technique which was not mentioned by the authors, namely that of echocardiography. I know nothing about the technique of echocardiography. However, our cardiologists throw the beam through the aortic wall and through the left auricle, at the aortic valve level. In this way they measure the size of the aorta and left auricle. I am told this ratio must be 1:1. If the left auricle size is greater than the aortic size by a ratio of over 1.3, and if there are other indications of the left-to-right shunt (namely, a hyperdynamic heart, bounding pulses, and so forth), then the cardiologists feel that the presence of a large left-to-right shunt is indicated. They have not been wrong in any of our series. I would like to mention a surgical technique that we have found. We feel that it should be done with dispatch. The operation should be carried out within 20 to 30 minutes skin to skin. Little or no anesthesia is used. We have very carefully watched the temperature of these babies because they tend to be hypothermic. They have no regulatory mechanism. Therefore, we operate under fairly hot lamps and use other devices to keep the temperature near normal.

1 77

Another word of caution. Simple ligation is fine, but these ductus are very, very tender and friable and will tend to fracture if not handled carefully. We have now operated upon 16 premature infants and have had two deaths. One of the deaths was caused by pulmonary atresia and a hypoplastic right ventricle. The other patient had a far-advanced respiratory distress syndrome with bronchopulmonary dysplasia. I am told that the other babies have all left the hospital and are now doing well. I would like to ask the author one question. In the autopsies done on the babies that died, were there any other associated intracardiac abnormalities? DR. E D W I N C. Salt Lake City. Utah

McGOUGH

We, too, have been very interested in this problem. We also have difficulty in identifying the optimal candidate for this procedure. We are concerned about the real value of medical treatment of a large left-to-right shunt even with cardiac compensation because of the increased pulmonary blood flow, as we are not yet able to determine how this increased pulmonary blood flow affects the underlying pulmonary disease. Because of this, we have adopted the policy of ligation of the ductus when a significant shunt is present in the premature infant with respiratory distress syndrome. In the first 6 infants, the ductus was ligated in the operating room. From these six procedures, several problems became apparent: (1) management of intubation; (2) ventilatory support while in transit; (3) monitoring while in transit; and (4) maintenance of body temperature. From an analysis of these problems, the following protocol was developed for the ligation of the patent ductus in the Newborn Intensive Care Unit (NICU) without moving the child. 1. The infant is placed on an Ohio warmer with electrocardiographic and skin temperature monitoring. 2. Prior to the operation the neonatologist intubates the infant and establishes ventilatory support. Base-line bloodgas values are obtained. 3. The room is closed to traffic, and essential personnel wear a mask and gown. 4. The infant is paralyzed with curare, and the operative procedure is accomplished with local anesthesia. 5. The chest tube is removed at the completion of the procedure. Following this protocol, we were able to eliminate the difficulties encountered with the initial 6 infants, which we believe could influence the early mortality rate. [SLIDE] This slide summarizes our experiences with 15 consecutive premature infants with RDS operated upon in the NICU. Pertinent are the 30 day mortality rate of 13 per cent, a zero infection rate, and an average operative time of 17 minutes. The two deaths occurred at 8 and 15 days postoperatively, one caused by acute tubular necrosis and the second by an intracerebral hemorrhage.

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In three recently reported series, the average 30 day mortality rate was 39 per cent. In this unique situation where intubation, ventilation, monitoring, and transportation present a greater threat to the infant than the operative procedure itself, we believe it is better to bring the operating room to the infant than to take the infant to the operating room. DR. C A R T E R A. P R I N T U P , J R . Pasadena, Calif.

In Pasadena, we had the same problem. We did not know when to operate or which of these babies to operate upon. We group our patients somewhat differently than Dr. Nelson did. We considered various parameters, obvious ones to begin with — prematurity, small size, and then respiratory difficulty, the large heart, and pulmonary vascular engorgement. Respiratory difficulty was gauged by increasing Flo2's, by increasing pressures, and by the obvious complications of respirators such as pneumothoraces and pneumomediastinum. Our first group comprised patients who primarily had congestive heart failure related to the ductus with little or no hyaline membrane disease. Group III is just the (mirror) image of this. Almost complete hyaline membrane disease with very little or no effect from the ductus. Group II was, of course, a combination. In the first group there were 6 infants, 5 of whom survived. The sixth died of necrotizing enterocolitis. All 5 of the survivors are well. In Group II 9 infants died of various problems in the first 30 days. There were no intraoperative deaths. Only 2 of the survivors in Group III are well, less than 50 per cent. Thus when the main problem is hyaline membrane disease (Group III), the children are disabled by either continuing bronchopulmonary dysplasia and/or cerebral problems which they are all prone to have. Therefore, we concluded that with our grouping, surgery is most likely beneficial, certainly not directly harmful, in Groups I and II. However, in our Group III, surgery is probably not beneficial and probably not indicated. I will mention two other things. In the diagnosis of PDA, the angiograms are, of course, very obvious. We found that we can use a bidirectional Doppler placed over the femoral artery. If there is a very significant backflow, then the presence of a PDA is almost assured.

The Journal of Thoracic and Cardiovascular Surgery

We found also as Dr. Meyer said that occasionally these ductus will tear at surgery and that exposure is difficult when infants weigh about 700 grams. We use a hemoclip to ligate each end of the patent ductus. I will stress each end because one of the infants who died died from a thrombosis of the left pulmonary artery which originated in the cul-de-sac of a single-ligated ductus early in the series. D R . NELSON (Closing) I would like to thank each of the discussers for their significant contributions to the discussion of this potentially very important problem. I think that the grouping of infants as given by Dr. Printup emphasizes that we are talking about a group of infants that is not at all homogenous. There are many contributing factors and degrees of severity, and the relative contribution of each factor may vary from infant to infant and from series to series. These factors include the initial surfactant abnormality, other abnormalities of the immature lung and heart, and varying degrees of left-to-right shunting through the PDA. As results are analyzed, one must be very careful to note what sort of infants were included in the series. We agree with Dr. McGough that the preparation of the infant for surgery is quite important. We do not have the facilities in our NICU to operate in the unit, and therefore we have elected to improve our technique of bringing the infant to the operating room. With regard to the technique of operation, I would like to emphasize that early in our series we attempted to expand areas of atelectatic lung and found that we have a very high incidence of pneumomediastinum and occasionally subpleural pneumothorax. We now feel that overzealous attempts to expand atelectatic lung at the time of surgery must be avoided unless there are problems with the arterial blood-gas levels. Dr. Meyer has commented upon the use of echocardiography, which may be a very significant advance in the noninvasive diagnostic evaluation of these infants. As this technique is used more commonly, it is going to be important that the results be correlated with the clinical course of the infant. With regard to other cardiac abnormalities at the time of autopsy, we have found none. However, I think that one must be very wary and, if there is any doubt about the diagnosis, one must subject these infants to a more formal cardiac catheterization.