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Patent ductus arteriosus in premature infants
Patent ductus arteriosus in premature infants Indications for surgery In order to establish more objective criteria for surgical intervention, the literature and our clinical experience with operative closure of patent ductus arteriosus in II premature infants was reviewed. A wide range of age at the time of operation underscored the spectrum of clinical presentation and the difficulty of interpreting the course of therapy. The presence of a typical continuous murmur established the diagnosis of patent ductus arteriosus in patients with respiratory distress syndrome. Cardiac catheterization confirmed the diagnosis and provided quantitation of the left-to-right shunt flow through the ductus arteriosus in 6 patients but did not influence the decision to operate. Progress of the clinical course as determined by the heart size on chest roentgenogram and the presence of hypercarbia (Pac<)2 > 60 mm. Hg) after respiratory assistance and medical decongestive measures were the two most helpful signs indicating the need for surgical intervention.
Edward A. Rittenhouse, M.D., Donald B. Doty, M.D., Ronald M. Lauer, M.D., and Johann L. Ehrenhaft, M.D., Iowa City, Iowa
An the normal term infant, physiological closure of the ductus arteriosus occurs within the first few hours of life. 1 ' 2 Anatomic obliteration is believed to take place several weeks later.3, 4 A higher incidence of delayed closure of the ductus arteriosus in babies born prematurely was reported by Burnard5 in 1959. Other investigators have confirmed that observation and documented an incidence in the range of seven to thirty-seven per cent. 6-11 With the development of the idiopathic respiratory distress syndrome, persistent patency occurs more frequently, possibly in as many as eighty-one per cent of the cases. Although the exact mechanism of delayed closure is not known, arterial hypoxemia and reduced responsiveness to oxygen of the ductus in the premature infant may be responsible. 10 - 13 In most of the infants, spontaneous closure of the ductus will eventually occur.8, 14, 15 Some patients, however, develop congestive heart failure and respiratory insufficiency from pulmonary overcirculation which does not respond to intensive medical therapy. From the Division of Thoracic and Cardiovascular Surgery, Department of Surgery, and the Division of Pediatric Cardiology, Department of Pediatrics, University of Iowa, Iowa City, Iowa. Received for publication April 14, 1975. Address for reprints: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University Hospitals, Iowa City, Iowa 52242.
Since most of the patients have the idiopathic respiratory distress syndrome, patent ductus arteriosus is a serious complicating feature.8' 16_18 Surgical closure of the ductus arteriosus may be necessary for these infants to survive, but previous reports have indicated a high postoperative mortality rate.14, 15, 17, 19_21 Indications for surgery have been based on physical and radiographic signs of severe congestive heart failure with hypoxia and respiratory insufficiency. Bouts with apnea and episodes of bradycardia requiring resuscitation have also been indications of the need for surgery. These signs, however, are subject to a wide range of clinical interpretation which could result in unnecessary ductus ligation or needless delay in patients who ultimately require operation. In order to develop more objective criteria for surgery, we reviewed the literature and analyzed our experience with ductus closure in premature infants. Clinical material and methods Eleven premature infants underwent surgical closure of a patent ductus arteriosus at this institution (Table I). There were 8 male and 3 female infants with an average gestational age of 31 weeks. The Apgar score averaged 4 at 1 minute and 6 at 5 minutes. The birth weight ranged from 950 to 1,927 grams (average 1,325 grams). Six of the babies developed evidence of the idiopathic respiratory distress syndrome, and chest 187
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Days 25 26 27
PH
Fig. 1. Alterations in Pa0a and PaC02 in 1 premature infant (Patient 1) undergoing ligation of patent ductus arteriosus. The level of Pa02 generally was maintained above 50 mm. Hg with an Fi02 of 0.35 to 0.40. Elevation of PaC02 necessitated initiation of respiratory assistance and ultimately surgery but was well controlled after ductal closure. C.P.A.P., Continuous positive airway pressure.
t
76! 7.574737.27.1-1
Preoperative
.70 .60 .50 .40 .30 Preoperative F j 0 z
Postoperative
.30 .40 5 0 .60 .70 Postoperative Fj 0 2
Fig. 2. Immediate preoperative and postoperative arterial pH, Pao2 and PaC02 in 9 premature infants undergoing ligation of the patent ductus arteriosus. Fi02 greater than 0.50 was required in only 2 patients, but PaC02 was greater than 50 mm. Hg in all in spite of respiratory assistance. Reduced pH and elevated PaC02 levels returned to normal after ductal closure.
roentgenograms revealed cardiac enlargement and increased pulmonary vasculature in all. An electrocardiogram was interpreted as showing left ventricular hypertrophy in 3 infants, right ventricular hypertrophy in 1, and combined ventricular hypertrophy in 6. Most of the patients had frequent episodes of apnea and bradycardia. Respiratory support with continuous positive airway pressure or a mechanical ventilator was necessary in all infants because of arterial hypoxemia and/or hypercarbia. The clinical diagnosis of patent ductus arteriosus was made in all cases when a typical continuous heart murmur was audible. Cardiac catheterization was performed prior to the operation in 6 patients, whereas 5 patients were operated upon on the basis of clinical findings alone. The hemodynamic studies showed an average aortic pressure of 66/36 mm. Hg and a pulmonary artery pressure of 37/14 mm. Hg. Pulmonary flow calculated by the Fick principle averaged 20.9 L. per minute per square meter and systemic flow 4.2 L. per minute per square meter; hence the pulmonary-systemic flow ratio was 5.5. The average pulmonary resistance was 2.0 mm. Hg per liter per minute per square meter and systemic resistance was 14 mm. Hg per liter per minute per square meter. Therefore, the ratio of pulmonary to systemic resistance remained low (average 0.18). The diagnosis of patent ductus arteriosus was confirmed from an increase in oxygen saturation in pulmonary artery blood and by angiocardiography. There were no complications from the cardiac catheterization, and none of the infants studied had associated cardiovascular anomalies. Surgery was performed an average of 42 days after birth, but this average is skewed by 2 babies who were operated upon very late. Eight of the 11 infants were operated upon during the first month of life. The babies weighed an average of 1,925 grams at the time of the operation. Endotracheal intubation and intravenous cannulation had been established as part of continuing medical care in the nursery, a practice which shortened required operating room time. Body temperature was maintained during the operation by overhead radiant heating. The surgical approach was through a standard left posterolateral thoracotomy. The ductus was ligated in 10 patients and divided in 1 patient. The surgical procedure was usually completed in less than 30 minutes. The typical course of immediate improvement in respiratory function following surgery is shown in 1 patient whose data are illustrated in Fig. 1. At 18 days of age the patient had an arterial partial pressure of oxygen (Pao2) of 35 mm. Hg and an arterial partial
Volume 71 Number 2 February, 1976
pressure of carbon dioxide (PaC02) of 85 mm. Hg which required endotracheal intubation and initiation of continuous positive-pressure ventilation. Oxygenation was well maintained (Pao2 53 to 62 mm. Hg) with a fraction of inspired oxygen (Fi02) of 0.40. However, PaCo2 again increased after a few days, reaching 68 mm. Hg immediately before the operation in spite of respiratory therapy. After ductus ligation, PaC02 and pH rapidly returned to normal. The inspired oxygen content was gradually reduced and oxygen saturation remained satisfactory as respiratory assistance was withdrawn. The alteration in arterial blood-gas analysis for 9 of the 11 patients undergoing ductus closure is illustrated in Fig. 2. Preoperatively, the pH averaged 7.29 (7.17 to 7.34); shortly after the operation, the average value was 7.44 (7.36 to 7.66). Preoperatively, arterial Pao2 was maintained above 55 mm. Hg in 6 of the 9 infants, and only 2 required an Fi02 greater than 0.5. These 2 patients required an Fi 02 of 0.7 to maintain a Pao2 of 45 and 56 mm. Hg, respectively. Immediately after the operation, the Pao2 averaged 72 mm. Hg (56 to 96 mm. Hg) with an Fi02 of 0.3 to 0.7. Despite respiratory assistance which appeared to supply clinically adequate alveolar ventilation, PaC02 was elevated in all patients preoperatively with an average of 74 mm. Hg (54 to 85 mm. Hg). In 7 of the 9 patients the PaC02 was 60 mm. Hg or greater. Within hours of the operation, the PaCo2 had decreased markedly in all patients, the value ranging from 32 to 58 mm. Hg (average 42 mm. Hg). Cardiac diameter was estimated, in retrospect, from the anteroposterior chest roentgenogram obtained in the supine position before and after surgery. The cardiothoracic ratio was calculated. In spite of recognized deficiencies in these measurements derived in this fashion, it was possible to document significant changes in heart size after the operation in every case. A dramatic decrease in heart size accompanied clinical improvement, but lung parenchymal signs of bronchopulmonary dysplasia and hyperinflation often persisted. The cardiothoracic ratio, as determined from the preoperative chest roentgenogram, averaged 0.65 (0.57 to 0.71). Approximately 6 weeks after the operation, the cardiothoracic ratio had decreased to an average of 0.57 (0.52 to 0.63) (Fig. 3). The patient with the lowest cardiothoracic ratio was the only infant who died of respiratory insufficiency early after the operation. This suggests the shunt flow through the patent ductus arteriosus was probably not a major contributing factor in the respiratory distress syndrome in this patient. Nine of the 11 patients lived, were discharged to
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Fig. 3. Change in cardiothoracic ratio before and after surgical closure of patent ductus arteriosus in the 11 premature infants. Cardiac enlargement was a consistent preoperative sign. their homes, and continue to thrive, for a survival rate of 82 per cent. One of the patients who died was an infant weighing 1,000 grams who was operated upon at 25 days of age. He showed marked improvement for the first 2 postoperative days, but during the second day, while on continuous positive airway pressure, the infant had a cardiopulmonary arrest. Resuscitation was not successful and, since autopsy was not granted, the cause of the sudden death was not clear. The second death occurred in an infant who underwent surgery at 13 days of age. The patient had severe hyaline membrane disease complicated by repeated episodes of aspiration of feedings. After a prolonged hospital course of respiratory insufficiency and aspiration pneumonitis, the infant died 2*/2 months after the operation. The autopsy showed marked right ventricular hypertrophy and bronchopulmonary dysplasia. Literature review Powell22 in 1963 was among the first to report surgical closure of a patent ductus arteriosus in a baby born prematurely. That patient developed congestive heart failure and underwent surgery at 5 months of age. In that same year, Decancq23 reported operative closure of a patent ductus arteriosus at 54 days of age in an infant weighing 1,417 grams. Both of these patients survived. In 1969, Siassi and associates24 reported improvement in respiratory distress after surgical ligation of patent ductus arteriosus in an infant 55 days after birth. Following these early reports, larger series have appeared in the literature mostly within the past 2
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Table I. Premature infants who underwent surgical closure of patent ductus arteriosus Patient No.
Gest. age (wk.j
1 2 3 4 5 6 7 8 9 10 11 Average
30 31 28 31 34 35 28 25 38 34 24 31
Sex M F M F M M M M F M M
Surgery
Birth weight (Cm.)
Age (da.)
Weight (Gm.)
1,100 1,480 990 1,077 1,927 1,501 1,090 950 1,870 1,400 1,190 1,325
23 170 25 30 18 15 13 20 44 25 74 42
1,300 5,250 1,000 1,400 1,900 1,390 1,200 1,200 2,650 1,650 2,240 1,925
years coincident with more frequent recognition of patent ductus arteriosus and improved survival rates in premature infants. 14-17 ' 19~21, 25> 26 Advancement in medical technology has permitted these infants to survive longer and has allowed the identification of congestive heart failure from a large left-to-right shunt through the ductus arteriosus as a major factor in the respiratory insufficiency of the respiratory distress syndrome. Pertinent data from the literature on ductus arteriosus ligation in premature infants are given in Table II. A total of 168 patients, including our series, has been reported in detail. The average gestational age ranged from 26 to 35 weeks. The average birth weight ranged from 1,181 to 1,400 grams in the seven series in which that information was given. The idiopathic respiratory distress syndrome was the most common clinical feature seen in 50 to 100 per cent of patients in the larger series. Multiple factors were used in selection of patients for operation for patent ductus arteriosus. Gupta and colleagues16 believed that inability to withdraw respiratory support was an indication for surgery. Horsley and associates20 based their indication for surgery on the demonstration of a large left-to-right shunt by cardiac catheterization. Others stated operation was required when severe congestive heart failure persisted in spite of intensive medical management as determined from physical examination and chest roentgenogram.14, 15' 17, 19, 26 Decreased pulmonary compliance,19 increased oxygen requirement,15, 17 frequent apneic episodes,14, 15, 17 bradycardia,15, 17 decreased Pao2,14, 19 and increased PaC0214, 17, 19, 21 have all been used as signs of heart failure due to patent
Complications Apnea, bradycardia Fever Pulmonary insufficiency
— — —
Aspiration pneumonia
— —
Atelectasis, pneumonia Bradycardia, apnea
Result Lived Lived Died Lived Lived Lived Died (3 mo.) Lived Lived Lived Lived
ductus arteriosus. Murphy14 suggested the most useful criteria were occurrence of frequent apneic spells and rising PaC02. Most of their patients developed a PaC02 greater than 60 mm. Hg prior to surgery. Kilman21 also showed that the PaCo2 was a useful indicator of the progress of therapy. Thibeault and associates25 have suggested two methods of establishing indications for surgery: the use of aortography to estimate the degree of left-to-right shunt through the ductus arteriosus and the use of chest x-ray films to estimate the degree of cardiac enlargement. Silverman and co-workers27 provided a method of noninvasive estimation of left atrial size by echocardiography from which the need for ductal closure in premature infants could be determined accurately. Surgery was usually performed within 6 weeks of birth and the average weight at the time of surgery ranged from 1,000 to 1,925 grams. Pulmonary complications were frequent before and after the operation. Atelectasis, pneumothorax, apnea, pneumonia, bronchospasm, and respiratory insufficiency were common in the postoperative period. Bradycardia, paralysis of the vocal cords, intracranial hemorrhage, paralysis of the diaphragm, and cardiac arrest were also noted. Repeated convulsions and meningitis complicated the course of 1 patient, and sepsis from other sources was reported. Fifty-nine of the 168 patients died, for an over-all mortality rate of 35 per cent. The mortality rate in the reported series ranged from 18 to 50 per cent. The causes of death after surgical closure of the patent ductus arteriosus are listed in Table III. Nearly two thirds of the infants died from pulmonary complications. Bronchopulmonary dysplasia with progressive
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Patent ductus arteriosus
19 1
Table II. Literature review of premature infants undergoing surgery for closure of patent ductus arteriosus Surgery
No. of Author Powell 22 (1963) Decancq 23 (1963) Siassi et al. 24 (1969) Gupta et al. 1 6 (1972) Gay et al. 1 9 (1973) Horsley et al. 2 0 (1973) Edmunds et al. 1 7 (1973) Murphy et al. 14 (1974) Zachman et al. 1 5 (1974)
Kilman et al. 21 (1974) Thibeault et al. 2 5 (1975) Neal et al. 26 (1975) Authors' series
Totals
cases
Average gest. age (wk.)
Deatns
Average birth weight (Gm.)
No. of cases of IRDS
Average age (da.)
Average weight (Gm.)
Per cent
—
— —
— —
Laryngospasm, tracheostomy
—
—
1
25
1 1
26 32
1,195 1,077
— —
150 54
1,417
1
35
2,470
1
55
—
4
30
—
2
31
1,000
Convulsion, meningitis
—
1,400
30
15
1,300
—
15
33
9
29
1,200
—
29
1,342
—
4
44
21
30
1,181
15
25
—
10
48
10
30
—
10
—
1,442
Atelectasis, vocal cord paralysis, bradycardia, bronchospasm Pneumothorax
5
50
27
30
1,400
22
15
—
9
33
12
29
—
—
Thoracic hemorrhage, pneumothorax, atelectasis, bradycardia, cardiac arrest, paralyzed diaphragm
21
29
1,060
21
5
—
1,260
11
31
1,325
45
—
No.
Morbidity
1,246
—
3
25
13
—
—
8
38
5
50
—
2
40
7
42
1,925
Bronchopulmonary dysplasia, intraventricular hemorrhage Apnea, bradycardia, atelectasis, pneumonia, respiratory insufficiency
2
18
59
35
168
14-56
Legend: IRDS. Idiopathic respiratory distress syndrome.
respiratory insufficiency was the most common cause. Intracranial hemorrhage was also a frequent cause of death and occurred in 10 per cent of the reported cases. Discussion Numerous reports over the past decade have documented delayed closure of the ductus arteriosus in premature infants. 5-7 ' 9 _ u ' 28 Most of the babies who developed a murmur of patent ductus arteriosus had spontaneous closure6 even if congestive heart failure developed.9-11 However, in some infants the ductus does not close, and these patients continue to have congestive heart failure with respiratory insufficiency, hypoxia, and hypercarbia. Apnea and bradycardia also occurred frequently. It has been suggested that administration of oxygen to these babies may facili-
tate closure of the ductus. 22 ' 29 However, the hazards of pulmonary damage and retrolental fibroplasia are great with that form of therapy.11 Definite criteria for operative intervention must be established since spontaneous closure does occur. However, these criteria must take into account the fact that ductus Hgation is often the definitive therapy for respiratory distress syndrome when heart failure is a predominant factor. An early diagnosis of patent ductus arteriosus in premature babies with respiratory distress syndrome must be established as the primary consideration. A typical continuous heart murmur in the clinical setting of respiratory distress syndrome virtually seals the diagnosis of patent ductus arteriosus. This will nearly always be associated with bounding peripheral pulses
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Table III. Causes of death among 168 premature infants undergoing surgical closure of patent ductus arteriosus Deaths Cause
No.
Progressive respiratory insufficiency Intracranial hemorrhage Management complications Miscellaneous Gastrointestinal complications Sepsis Total
38 6 5 4 3 3 59
and usually hepatomegaly. Unfortunately, some babies may have significant shunts through the ductus arteriosus and no ductal murmur26 or only a systolic murmur.25 Aortography, performed through an umbilical artery catheter, should be of great value under these circumstances in establishing the diagnosis. 25,27 Complete right and left heart cardiac catheterization is probably not necessary, as the risk is great in these critically ill infants and the procedure may not provide any additional useful information if the diagnosis can be established by other means. None of the 72 premature infants who underwent ductus ligation as reported by Gay,19 and Zachman,15 and their associates was subjected to cardiac catheterization. Only 1 patient was subsequently shown to have an associated cardiac anomaly. Significant complications were noted after catheterization in 2 of 16 patients reported upon by Kitterman's group8 and 9 of 12 patients described by Horsley's group.20 Cardiac catheterization was performed in 6 patients without complications in our series. The information was useful in confirming the diagnosis and quantitating the degree of shunt but was not essential for the decision to operate. Once the diagnosis of patent ductus arteriosus is confirmed, it is the clinical course of the patient which must be evaluated in determining the need for surgery. Obviously, all the patients should be receiving optimal respiratory support and medical decongestive measures. How long one should persist with these medical measures is unknown at present. Certain factors as observed in this and other retrospective studies are apparently more useful than others in following the clinical course to an ultimate operation. Apnea and bradycardiac episodes occurred frequently in all series. However, these signs are also present in many critically ill premature infants without
patent ductus arteriosus. Increased pulmonary vascular congestion may be difficult to determine from the chest roentgenograms. Arterial hypoxia is certainly a clear indication for surgical intervention, but, surprisingly, Pao2 was well maintained in these patients with an Fio2 which usually did not exceed 0.5. Apparently, oxygen transport across the alveolar capillary membrane is maintained by the oxygen and pressure gradients established by assisted ventilation. One of the most striking findings in this series was carbon dioxide retention despite what should have been adequate alveolar ventilation with either a ventilator or continuous positive airway pressure. The persistence of hypercarbia in the presence of apparently adequate ventilation would seem to be a most pressing indication for surgical intervention. This experience suggests that after maximum decongestive measures and respiratory support, persistence of aPa C02 greater than 60 mm. Hg indicates need for urgent surgical intervention. Following surgical closure of the patent ductus arteriosus, PaC02 was immediately improved in all these patients. It is clear from this series and that of Thibeault and associates25 that cardiomegaly is important in assessing the need for surgery. Certainly increasing heart size and perhaps increasing liver size on roentgenograms represent important indications for surgery. Echocardiography may also be an important tool in following the course of these babies and determining the need for operation. Using echocardiography, Silverman and associates27 have documented the normal diameters of the left atrium and aortic root and have established the ratio of these values (left atrium-aorta) to be 0.86 ± 0.10. Babies who required surgical ligation of ductus arteriosus all had left atrium-aorta ratios above 1.15. Changes in this ratio appeared to correlate well with the effects of medical and surgical therapy. Whether timing of the operation was appropriate in these patients cannot be determined from this retrospective study. It could be argued that the average age of 42 days represented unnecessary delay, but 8 of the 11 babies were 30 days of age or less at the time of operation. Similarly, allowing respiratory insufficiency to deteriorate to the point of hypercarbia could be criticized, but only 1 of the 11 died early after the operation. This is a very acceptable survival rate in these critically ill babies. Finally, the question of whether earlier surgery may prevent pulmonary damage remains unanswered. Heart size is reduced but pulmonary changes may persist after ductal ligation. The over-all mortality rate following patent ductus ligation in premature infants appears to be closely
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related to the degree of reversibility of pulmonary insufficiency. The single late death in this series was related to respiratory failure. Furthermore, nearly two thirds of the deaths in the cases recorded in the literature were due to progressive respiratory insufficiency. Several investigators have suggested that early ductus ligation in premature infants with severe respiratory distress and a large left-to-right shunt may prevent the development of bronchopulmonary dysplasia. 15 ' 16, 1 9 , 2 4 A prospective, randomized study will be required to confirm this hypothesis. Addendum Since submission of this manuscript we have closed the ductus arteriosus in an additional 13 premature infants with three postoperative deaths. Two babies who died were operated upon in the first week of life in an attempt to improve their severe respiratory insufficiency. However, the heart was not greatly enlarged on chest x-ray films, which underscores the importance of cardiomegaly in predicting the contribution of the patent ductus arteriosus to respiratory insufficiency. 1 2
3 4 5 6 7 8
9 10
REFERENCES Moss, A. J., Emmanuoilides, G. C , and Duffie, E. R., Jr.: Closure of the Ductus Arteriosus in the Newborn Infant, Pediatrics 32: 25, 1963. Rudolph, A. M., Drorbaugh, J. E., Auld, P. A. M., Rudolph, A. J., Nadas, A. S., Smith, C. A., and Hubbell, J. P.: Studies on the Circulation in the Neonatal Period: The Circulation in the Respiratory Distress Syndrome, Pediatrics 27: 551, 1961. Mitchell, S. C : The Ductus Arteriosus in the Neonatal Period, J. Pediatr. 51: 12, 1957. Eldridge, F. L., and Hultgren, H. N.: The Physiological Closure of the Ductus Arteriosus in the Newborn Infant, J. Clin. Invest. 34: 987, 1955. Burnard, E. D.: A Murmur That May Arise From the Ductus Arteriosus in the Human Baby, Proc. R. Soc. Med. 52: 77, 1959. Hallidie-Smith, K. A.: Murmur of Persistent Ductus Arteriosus in Premature Infants, Arch. Dis. Child. 47: 725, 1972. Clarkson, P. M., and Orgill, A. A.: Continuous Murmurs in Infants of Low Birth Weight, J. Pediatr. 84: 208, 1974. Kitterman, J. A., Edmunds, L. H., Gregory, G. A., Heymann, M. A., Tooley, W. H., and Rudolph, A. M.: Patent Ductus Arteriosus in Premature Infants: Incidence, Relation to Pulmonary Disease and Management, N. Engl. J. Med. 287:473, 1972. Auld, P. A. M.: Delayed Closure of the Ductus Arteriosus, J. Pediatr. 69: 61, 1966. Danilowicz, D., Rudolph, A. M., and Hoffman, J. I. E.: Delayed Closure of the Ductus Arteriosus in Premature Infants, Pediatrics 37: 74, 1966.
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11 Girling, D. J., and Hallidie-Smith, K. A.: Persistent Ductus Arteriosus in 111 and Premature Babies, Arch. Dis. child. 46: 177, 1971. 12 Blanco, C. E., Siassi, B., and Cabal, L. A.: Persistent Patency of Ductus Arteriosus in Premature Newborn Infants (Abstr.), Am. J. Cardiol. 31: 121, 1973. 13 Moss, A. J., Emmanouilides, G. C , Adams, F. H., and Chuang, K.: Response of Ductus Arteriosus and Pulmonary and Systemic Arterial Pressure to Changes in Oxygen Environment in Newborn Infants, Pediatrics 33: 937, 1964. 14 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.
15 Zachman, R. D., Steinmetz, G. P., Botham, R. J., Graven, S. N., and Ledbetter, M. K.: Incidence and Treatment of the Patent Ductus Arteriosus in the 111 Premature Neonate, Am. Heart J. 87: 697, 1974. 16 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:
17
18
19
20
21
22 23 24
25
642,
1972. Edmunds, L. H., Gregory, G. A., Heymann, M. A., Kitterman, J. A., Rudolph, A. M., and Tooley, S. H.: Surgical Closure of the Ductus Arteriosus in Premature Infants, Circulation 48: 856, 1973. Jegier, W., Karn, G., and Stern, L.: Operative Treatment of Patent Ductus Arteriosus Complicating Respiratory Distress Syndrome of the Premature Infant (Abstr.), Can. Med. Assoc. J. 98: 105, 1968. 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 Forty-five Cases, J. Pediatr. Surg. 8: 677, 1973. Horsley, B. L., Terberg, 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. Kilman, J. W., Kakos, G. S., Williams, T. E., Jr., Craenen, J., and Hosier, D. M.: Ligation of Patent Ductus Arteriosus for Persistent Respiratory Distress Syndrome in Premature Infants, J. Pediatr. Surg. 9: 277, 1974. Powell, M. L.: Patent Ductus Arteriosus in Premature Infants, Med. J. Aust. 2: 58, 1963. Decancq, H. G., Jr.: Repair of Patent Ductus Arteriosus in a 1,417 Gram Infant, Am. J. Dis. Child. 106: 402, 1963. 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. Thibeault, D. W., Emmanouilides, G. C , Nelson, R. J., Lackman, R. S., Rosengart, R. M., and Oh, W.: Patent Ductus Arteriosus Complicating the Respiratory Distress Syndrome in Preterm Infants, J. Pediatr. 86: 120, 1975.
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26 Neal, W. A., Bessinger, F. B., Hunt, C. E., and Lucas, R. V.: Patent Ductus Arteriosus Complicating Respiratory Distress Syndrome, J. Pediatr. 86: 127, 1975. 27 Silveiman, N. H., Lewis, A. B., Heymann, M. A., and Rudolph, A. M.: Echocardiographic Assessment of Ductus Arteriosus Shunt in Premature Infants, Circulation 50: 821, 1974.
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28 Krovetz, L. J., and Rowe, R. D.: Patent Ductus, Prematurity and Pulmonary Disease, N. Engl. J. Med. 287: 513, 1972. 29 Dunn, P. M., and Speidel, B. D.: Use of Oxygen to Close Patent Ductus Arteriosus in Preterm Infants, Lancet 1: 333, 1973.
Edward A. Rittenhouse, M.D., Donald B. Doty, M.D., Ronald M. Lauer, M.D., and Johann L. Ehrenhaft, M.D., Iowa City, Iowa
An the normal term infant, physiological closure of the ductus arteriosus occurs within the first few hours of life. 1 ' 2 Anatomic obliteration is believed to take place several weeks later.3, 4 A higher incidence of delayed closure of the ductus arteriosus in babies born prematurely was reported by Burnard5 in 1959. Other investigators have confirmed that observation and documented an incidence in the range of seven to thirty-seven per cent. 6-11 With the development of the idiopathic respiratory distress syndrome, persistent patency occurs more frequently, possibly in as many as eighty-one per cent of the cases. Although the exact mechanism of delayed closure is not known, arterial hypoxemia and reduced responsiveness to oxygen of the ductus in the premature infant may be responsible. 10 - 13 In most of the infants, spontaneous closure of the ductus will eventually occur.8, 14, 15 Some patients, however, develop congestive heart failure and respiratory insufficiency from pulmonary overcirculation which does not respond to intensive medical therapy. From the Division of Thoracic and Cardiovascular Surgery, Department of Surgery, and the Division of Pediatric Cardiology, Department of Pediatrics, University of Iowa, Iowa City, Iowa. Received for publication April 14, 1975. Address for reprints: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University Hospitals, Iowa City, Iowa 52242.
Since most of the patients have the idiopathic respiratory distress syndrome, patent ductus arteriosus is a serious complicating feature.8' 16_18 Surgical closure of the ductus arteriosus may be necessary for these infants to survive, but previous reports have indicated a high postoperative mortality rate.14, 15, 17, 19_21 Indications for surgery have been based on physical and radiographic signs of severe congestive heart failure with hypoxia and respiratory insufficiency. Bouts with apnea and episodes of bradycardia requiring resuscitation have also been indications of the need for surgery. These signs, however, are subject to a wide range of clinical interpretation which could result in unnecessary ductus ligation or needless delay in patients who ultimately require operation. In order to develop more objective criteria for surgery, we reviewed the literature and analyzed our experience with ductus closure in premature infants. Clinical material and methods Eleven premature infants underwent surgical closure of a patent ductus arteriosus at this institution (Table I). There were 8 male and 3 female infants with an average gestational age of 31 weeks. The Apgar score averaged 4 at 1 minute and 6 at 5 minutes. The birth weight ranged from 950 to 1,927 grams (average 1,325 grams). Six of the babies developed evidence of the idiopathic respiratory distress syndrome, and chest 187
The Journal of Thoracic and Cardiovascular Surgery
1 8 8 Rittenhouse et al.
Days 25 26 27
PH
Fig. 1. Alterations in Pa0a and PaC02 in 1 premature infant (Patient 1) undergoing ligation of patent ductus arteriosus. The level of Pa02 generally was maintained above 50 mm. Hg with an Fi02 of 0.35 to 0.40. Elevation of PaC02 necessitated initiation of respiratory assistance and ultimately surgery but was well controlled after ductal closure. C.P.A.P., Continuous positive airway pressure.
t
76! 7.574737.27.1-1
Preoperative
.70 .60 .50 .40 .30 Preoperative F j 0 z
Postoperative
.30 .40 5 0 .60 .70 Postoperative Fj 0 2
Fig. 2. Immediate preoperative and postoperative arterial pH, Pao2 and PaC02 in 9 premature infants undergoing ligation of the patent ductus arteriosus. Fi02 greater than 0.50 was required in only 2 patients, but PaC02 was greater than 50 mm. Hg in all in spite of respiratory assistance. Reduced pH and elevated PaC02 levels returned to normal after ductal closure.
roentgenograms revealed cardiac enlargement and increased pulmonary vasculature in all. An electrocardiogram was interpreted as showing left ventricular hypertrophy in 3 infants, right ventricular hypertrophy in 1, and combined ventricular hypertrophy in 6. Most of the patients had frequent episodes of apnea and bradycardia. Respiratory support with continuous positive airway pressure or a mechanical ventilator was necessary in all infants because of arterial hypoxemia and/or hypercarbia. The clinical diagnosis of patent ductus arteriosus was made in all cases when a typical continuous heart murmur was audible. Cardiac catheterization was performed prior to the operation in 6 patients, whereas 5 patients were operated upon on the basis of clinical findings alone. The hemodynamic studies showed an average aortic pressure of 66/36 mm. Hg and a pulmonary artery pressure of 37/14 mm. Hg. Pulmonary flow calculated by the Fick principle averaged 20.9 L. per minute per square meter and systemic flow 4.2 L. per minute per square meter; hence the pulmonary-systemic flow ratio was 5.5. The average pulmonary resistance was 2.0 mm. Hg per liter per minute per square meter and systemic resistance was 14 mm. Hg per liter per minute per square meter. Therefore, the ratio of pulmonary to systemic resistance remained low (average 0.18). The diagnosis of patent ductus arteriosus was confirmed from an increase in oxygen saturation in pulmonary artery blood and by angiocardiography. There were no complications from the cardiac catheterization, and none of the infants studied had associated cardiovascular anomalies. Surgery was performed an average of 42 days after birth, but this average is skewed by 2 babies who were operated upon very late. Eight of the 11 infants were operated upon during the first month of life. The babies weighed an average of 1,925 grams at the time of the operation. Endotracheal intubation and intravenous cannulation had been established as part of continuing medical care in the nursery, a practice which shortened required operating room time. Body temperature was maintained during the operation by overhead radiant heating. The surgical approach was through a standard left posterolateral thoracotomy. The ductus was ligated in 10 patients and divided in 1 patient. The surgical procedure was usually completed in less than 30 minutes. The typical course of immediate improvement in respiratory function following surgery is shown in 1 patient whose data are illustrated in Fig. 1. At 18 days of age the patient had an arterial partial pressure of oxygen (Pao2) of 35 mm. Hg and an arterial partial
Volume 71 Number 2 February, 1976
pressure of carbon dioxide (PaC02) of 85 mm. Hg which required endotracheal intubation and initiation of continuous positive-pressure ventilation. Oxygenation was well maintained (Pao2 53 to 62 mm. Hg) with a fraction of inspired oxygen (Fi02) of 0.40. However, PaCo2 again increased after a few days, reaching 68 mm. Hg immediately before the operation in spite of respiratory therapy. After ductus ligation, PaC02 and pH rapidly returned to normal. The inspired oxygen content was gradually reduced and oxygen saturation remained satisfactory as respiratory assistance was withdrawn. The alteration in arterial blood-gas analysis for 9 of the 11 patients undergoing ductus closure is illustrated in Fig. 2. Preoperatively, the pH averaged 7.29 (7.17 to 7.34); shortly after the operation, the average value was 7.44 (7.36 to 7.66). Preoperatively, arterial Pao2 was maintained above 55 mm. Hg in 6 of the 9 infants, and only 2 required an Fi02 greater than 0.5. These 2 patients required an Fi 02 of 0.7 to maintain a Pao2 of 45 and 56 mm. Hg, respectively. Immediately after the operation, the Pao2 averaged 72 mm. Hg (56 to 96 mm. Hg) with an Fi02 of 0.3 to 0.7. Despite respiratory assistance which appeared to supply clinically adequate alveolar ventilation, PaC02 was elevated in all patients preoperatively with an average of 74 mm. Hg (54 to 85 mm. Hg). In 7 of the 9 patients the PaC02 was 60 mm. Hg or greater. Within hours of the operation, the PaCo2 had decreased markedly in all patients, the value ranging from 32 to 58 mm. Hg (average 42 mm. Hg). Cardiac diameter was estimated, in retrospect, from the anteroposterior chest roentgenogram obtained in the supine position before and after surgery. The cardiothoracic ratio was calculated. In spite of recognized deficiencies in these measurements derived in this fashion, it was possible to document significant changes in heart size after the operation in every case. A dramatic decrease in heart size accompanied clinical improvement, but lung parenchymal signs of bronchopulmonary dysplasia and hyperinflation often persisted. The cardiothoracic ratio, as determined from the preoperative chest roentgenogram, averaged 0.65 (0.57 to 0.71). Approximately 6 weeks after the operation, the cardiothoracic ratio had decreased to an average of 0.57 (0.52 to 0.63) (Fig. 3). The patient with the lowest cardiothoracic ratio was the only infant who died of respiratory insufficiency early after the operation. This suggests the shunt flow through the patent ductus arteriosus was probably not a major contributing factor in the respiratory distress syndrome in this patient. Nine of the 11 patients lived, were discharged to
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Fig. 3. Change in cardiothoracic ratio before and after surgical closure of patent ductus arteriosus in the 11 premature infants. Cardiac enlargement was a consistent preoperative sign. their homes, and continue to thrive, for a survival rate of 82 per cent. One of the patients who died was an infant weighing 1,000 grams who was operated upon at 25 days of age. He showed marked improvement for the first 2 postoperative days, but during the second day, while on continuous positive airway pressure, the infant had a cardiopulmonary arrest. Resuscitation was not successful and, since autopsy was not granted, the cause of the sudden death was not clear. The second death occurred in an infant who underwent surgery at 13 days of age. The patient had severe hyaline membrane disease complicated by repeated episodes of aspiration of feedings. After a prolonged hospital course of respiratory insufficiency and aspiration pneumonitis, the infant died 2*/2 months after the operation. The autopsy showed marked right ventricular hypertrophy and bronchopulmonary dysplasia. Literature review Powell22 in 1963 was among the first to report surgical closure of a patent ductus arteriosus in a baby born prematurely. That patient developed congestive heart failure and underwent surgery at 5 months of age. In that same year, Decancq23 reported operative closure of a patent ductus arteriosus at 54 days of age in an infant weighing 1,417 grams. Both of these patients survived. In 1969, Siassi and associates24 reported improvement in respiratory distress after surgical ligation of patent ductus arteriosus in an infant 55 days after birth. Following these early reports, larger series have appeared in the literature mostly within the past 2
190
The Journal of Thoracic and Cardiovascular Surgery
Rittenhouse et al.
Table I. Premature infants who underwent surgical closure of patent ductus arteriosus Patient No.
Gest. age (wk.j
1 2 3 4 5 6 7 8 9 10 11 Average
30 31 28 31 34 35 28 25 38 34 24 31
Sex M F M F M M M M F M M
Surgery
Birth weight (Cm.)
Age (da.)
Weight (Gm.)
1,100 1,480 990 1,077 1,927 1,501 1,090 950 1,870 1,400 1,190 1,325
23 170 25 30 18 15 13 20 44 25 74 42
1,300 5,250 1,000 1,400 1,900 1,390 1,200 1,200 2,650 1,650 2,240 1,925
years coincident with more frequent recognition of patent ductus arteriosus and improved survival rates in premature infants. 14-17 ' 19~21, 25> 26 Advancement in medical technology has permitted these infants to survive longer and has allowed the identification of congestive heart failure from a large left-to-right shunt through the ductus arteriosus as a major factor in the respiratory insufficiency of the respiratory distress syndrome. Pertinent data from the literature on ductus arteriosus ligation in premature infants are given in Table II. A total of 168 patients, including our series, has been reported in detail. The average gestational age ranged from 26 to 35 weeks. The average birth weight ranged from 1,181 to 1,400 grams in the seven series in which that information was given. The idiopathic respiratory distress syndrome was the most common clinical feature seen in 50 to 100 per cent of patients in the larger series. Multiple factors were used in selection of patients for operation for patent ductus arteriosus. Gupta and colleagues16 believed that inability to withdraw respiratory support was an indication for surgery. Horsley and associates20 based their indication for surgery on the demonstration of a large left-to-right shunt by cardiac catheterization. Others stated operation was required when severe congestive heart failure persisted in spite of intensive medical management as determined from physical examination and chest roentgenogram.14, 15' 17, 19, 26 Decreased pulmonary compliance,19 increased oxygen requirement,15, 17 frequent apneic episodes,14, 15, 17 bradycardia,15, 17 decreased Pao2,14, 19 and increased PaC0214, 17, 19, 21 have all been used as signs of heart failure due to patent
Complications Apnea, bradycardia Fever Pulmonary insufficiency
— — —
Aspiration pneumonia
— —
Atelectasis, pneumonia Bradycardia, apnea
Result Lived Lived Died Lived Lived Lived Died (3 mo.) Lived Lived Lived Lived
ductus arteriosus. Murphy14 suggested the most useful criteria were occurrence of frequent apneic spells and rising PaC02. Most of their patients developed a PaC02 greater than 60 mm. Hg prior to surgery. Kilman21 also showed that the PaCo2 was a useful indicator of the progress of therapy. Thibeault and associates25 have suggested two methods of establishing indications for surgery: the use of aortography to estimate the degree of left-to-right shunt through the ductus arteriosus and the use of chest x-ray films to estimate the degree of cardiac enlargement. Silverman and co-workers27 provided a method of noninvasive estimation of left atrial size by echocardiography from which the need for ductal closure in premature infants could be determined accurately. Surgery was usually performed within 6 weeks of birth and the average weight at the time of surgery ranged from 1,000 to 1,925 grams. Pulmonary complications were frequent before and after the operation. Atelectasis, pneumothorax, apnea, pneumonia, bronchospasm, and respiratory insufficiency were common in the postoperative period. Bradycardia, paralysis of the vocal cords, intracranial hemorrhage, paralysis of the diaphragm, and cardiac arrest were also noted. Repeated convulsions and meningitis complicated the course of 1 patient, and sepsis from other sources was reported. Fifty-nine of the 168 patients died, for an over-all mortality rate of 35 per cent. The mortality rate in the reported series ranged from 18 to 50 per cent. The causes of death after surgical closure of the patent ductus arteriosus are listed in Table III. Nearly two thirds of the infants died from pulmonary complications. Bronchopulmonary dysplasia with progressive
Volume 71 Number 2 February, 1976
Patent ductus arteriosus
19 1
Table II. Literature review of premature infants undergoing surgery for closure of patent ductus arteriosus Surgery
No. of Author Powell 22 (1963) Decancq 23 (1963) Siassi et al. 24 (1969) Gupta et al. 1 6 (1972) Gay et al. 1 9 (1973) Horsley et al. 2 0 (1973) Edmunds et al. 1 7 (1973) Murphy et al. 14 (1974) Zachman et al. 1 5 (1974)
Kilman et al. 21 (1974) Thibeault et al. 2 5 (1975) Neal et al. 26 (1975) Authors' series
Totals
cases
Average gest. age (wk.)
Deatns
Average birth weight (Gm.)
No. of cases of IRDS
Average age (da.)
Average weight (Gm.)
Per cent
—
— —
— —
Laryngospasm, tracheostomy
—
—
1
25
1 1
26 32
1,195 1,077
— —
150 54
1,417
1
35
2,470
1
55
—
4
30
—
2
31
1,000
Convulsion, meningitis
—
1,400
30
15
1,300
—
15
33
9
29
1,200
—
29
1,342
—
4
44
21
30
1,181
15
25
—
10
48
10
30
—
10
—
1,442
Atelectasis, vocal cord paralysis, bradycardia, bronchospasm Pneumothorax
5
50
27
30
1,400
22
15
—
9
33
12
29
—
—
Thoracic hemorrhage, pneumothorax, atelectasis, bradycardia, cardiac arrest, paralyzed diaphragm
21
29
1,060
21
5
—
1,260
11
31
1,325
45
—
No.
Morbidity
1,246
—
3
25
13
—
—
8
38
5
50
—
2
40
7
42
1,925
Bronchopulmonary dysplasia, intraventricular hemorrhage Apnea, bradycardia, atelectasis, pneumonia, respiratory insufficiency
2
18
59
35
168
14-56
Legend: IRDS. Idiopathic respiratory distress syndrome.
respiratory insufficiency was the most common cause. Intracranial hemorrhage was also a frequent cause of death and occurred in 10 per cent of the reported cases. Discussion Numerous reports over the past decade have documented delayed closure of the ductus arteriosus in premature infants. 5-7 ' 9 _ u ' 28 Most of the babies who developed a murmur of patent ductus arteriosus had spontaneous closure6 even if congestive heart failure developed.9-11 However, in some infants the ductus does not close, and these patients continue to have congestive heart failure with respiratory insufficiency, hypoxia, and hypercarbia. Apnea and bradycardia also occurred frequently. It has been suggested that administration of oxygen to these babies may facili-
tate closure of the ductus. 22 ' 29 However, the hazards of pulmonary damage and retrolental fibroplasia are great with that form of therapy.11 Definite criteria for operative intervention must be established since spontaneous closure does occur. However, these criteria must take into account the fact that ductus Hgation is often the definitive therapy for respiratory distress syndrome when heart failure is a predominant factor. An early diagnosis of patent ductus arteriosus in premature babies with respiratory distress syndrome must be established as the primary consideration. A typical continuous heart murmur in the clinical setting of respiratory distress syndrome virtually seals the diagnosis of patent ductus arteriosus. This will nearly always be associated with bounding peripheral pulses
The Journal of Thoracic and Cardiovascular Surgery
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Table III. Causes of death among 168 premature infants undergoing surgical closure of patent ductus arteriosus Deaths Cause
No.
Progressive respiratory insufficiency Intracranial hemorrhage Management complications Miscellaneous Gastrointestinal complications Sepsis Total
38 6 5 4 3 3 59
and usually hepatomegaly. Unfortunately, some babies may have significant shunts through the ductus arteriosus and no ductal murmur26 or only a systolic murmur.25 Aortography, performed through an umbilical artery catheter, should be of great value under these circumstances in establishing the diagnosis. 25,27 Complete right and left heart cardiac catheterization is probably not necessary, as the risk is great in these critically ill infants and the procedure may not provide any additional useful information if the diagnosis can be established by other means. None of the 72 premature infants who underwent ductus ligation as reported by Gay,19 and Zachman,15 and their associates was subjected to cardiac catheterization. Only 1 patient was subsequently shown to have an associated cardiac anomaly. Significant complications were noted after catheterization in 2 of 16 patients reported upon by Kitterman's group8 and 9 of 12 patients described by Horsley's group.20 Cardiac catheterization was performed in 6 patients without complications in our series. The information was useful in confirming the diagnosis and quantitating the degree of shunt but was not essential for the decision to operate. Once the diagnosis of patent ductus arteriosus is confirmed, it is the clinical course of the patient which must be evaluated in determining the need for surgery. Obviously, all the patients should be receiving optimal respiratory support and medical decongestive measures. How long one should persist with these medical measures is unknown at present. Certain factors as observed in this and other retrospective studies are apparently more useful than others in following the clinical course to an ultimate operation. Apnea and bradycardiac episodes occurred frequently in all series. However, these signs are also present in many critically ill premature infants without
patent ductus arteriosus. Increased pulmonary vascular congestion may be difficult to determine from the chest roentgenograms. Arterial hypoxia is certainly a clear indication for surgical intervention, but, surprisingly, Pao2 was well maintained in these patients with an Fio2 which usually did not exceed 0.5. Apparently, oxygen transport across the alveolar capillary membrane is maintained by the oxygen and pressure gradients established by assisted ventilation. One of the most striking findings in this series was carbon dioxide retention despite what should have been adequate alveolar ventilation with either a ventilator or continuous positive airway pressure. The persistence of hypercarbia in the presence of apparently adequate ventilation would seem to be a most pressing indication for surgical intervention. This experience suggests that after maximum decongestive measures and respiratory support, persistence of aPa C02 greater than 60 mm. Hg indicates need for urgent surgical intervention. Following surgical closure of the patent ductus arteriosus, PaC02 was immediately improved in all these patients. It is clear from this series and that of Thibeault and associates25 that cardiomegaly is important in assessing the need for surgery. Certainly increasing heart size and perhaps increasing liver size on roentgenograms represent important indications for surgery. Echocardiography may also be an important tool in following the course of these babies and determining the need for operation. Using echocardiography, Silverman and associates27 have documented the normal diameters of the left atrium and aortic root and have established the ratio of these values (left atrium-aorta) to be 0.86 ± 0.10. Babies who required surgical ligation of ductus arteriosus all had left atrium-aorta ratios above 1.15. Changes in this ratio appeared to correlate well with the effects of medical and surgical therapy. Whether timing of the operation was appropriate in these patients cannot be determined from this retrospective study. It could be argued that the average age of 42 days represented unnecessary delay, but 8 of the 11 babies were 30 days of age or less at the time of operation. Similarly, allowing respiratory insufficiency to deteriorate to the point of hypercarbia could be criticized, but only 1 of the 11 died early after the operation. This is a very acceptable survival rate in these critically ill babies. Finally, the question of whether earlier surgery may prevent pulmonary damage remains unanswered. Heart size is reduced but pulmonary changes may persist after ductal ligation. The over-all mortality rate following patent ductus ligation in premature infants appears to be closely
Volume 71 Number 2 February, 1976
related to the degree of reversibility of pulmonary insufficiency. The single late death in this series was related to respiratory failure. Furthermore, nearly two thirds of the deaths in the cases recorded in the literature were due to progressive respiratory insufficiency. Several investigators have suggested that early ductus ligation in premature infants with severe respiratory distress and a large left-to-right shunt may prevent the development of bronchopulmonary dysplasia. 15 ' 16, 1 9 , 2 4 A prospective, randomized study will be required to confirm this hypothesis. Addendum Since submission of this manuscript we have closed the ductus arteriosus in an additional 13 premature infants with three postoperative deaths. Two babies who died were operated upon in the first week of life in an attempt to improve their severe respiratory insufficiency. However, the heart was not greatly enlarged on chest x-ray films, which underscores the importance of cardiomegaly in predicting the contribution of the patent ductus arteriosus to respiratory insufficiency. 1 2
3 4 5 6 7 8
9 10
REFERENCES Moss, A. J., Emmanuoilides, G. C , and Duffie, E. R., Jr.: Closure of the Ductus Arteriosus in the Newborn Infant, Pediatrics 32: 25, 1963. Rudolph, A. M., Drorbaugh, J. E., Auld, P. A. M., Rudolph, A. J., Nadas, A. S., Smith, C. A., and Hubbell, J. P.: Studies on the Circulation in the Neonatal Period: The Circulation in the Respiratory Distress Syndrome, Pediatrics 27: 551, 1961. Mitchell, S. C : The Ductus Arteriosus in the Neonatal Period, J. Pediatr. 51: 12, 1957. Eldridge, F. L., and Hultgren, H. N.: The Physiological Closure of the Ductus Arteriosus in the Newborn Infant, J. Clin. Invest. 34: 987, 1955. Burnard, E. D.: A Murmur That May Arise From the Ductus Arteriosus in the Human Baby, Proc. R. Soc. Med. 52: 77, 1959. Hallidie-Smith, K. A.: Murmur of Persistent Ductus Arteriosus in Premature Infants, Arch. Dis. Child. 47: 725, 1972. Clarkson, P. M., and Orgill, A. A.: Continuous Murmurs in Infants of Low Birth Weight, J. Pediatr. 84: 208, 1974. Kitterman, J. A., Edmunds, L. H., Gregory, G. A., Heymann, M. A., Tooley, W. H., and Rudolph, A. M.: Patent Ductus Arteriosus in Premature Infants: Incidence, Relation to Pulmonary Disease and Management, N. Engl. J. Med. 287:473, 1972. Auld, P. A. M.: Delayed Closure of the Ductus Arteriosus, J. Pediatr. 69: 61, 1966. Danilowicz, D., Rudolph, A. M., and Hoffman, J. I. E.: Delayed Closure of the Ductus Arteriosus in Premature Infants, Pediatrics 37: 74, 1966.
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11 Girling, D. J., and Hallidie-Smith, K. A.: Persistent Ductus Arteriosus in 111 and Premature Babies, Arch. Dis. child. 46: 177, 1971. 12 Blanco, C. E., Siassi, B., and Cabal, L. A.: Persistent Patency of Ductus Arteriosus in Premature Newborn Infants (Abstr.), Am. J. Cardiol. 31: 121, 1973. 13 Moss, A. J., Emmanouilides, G. C , Adams, F. H., and Chuang, K.: Response of Ductus Arteriosus and Pulmonary and Systemic Arterial Pressure to Changes in Oxygen Environment in Newborn Infants, Pediatrics 33: 937, 1964. 14 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,
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15 Zachman, R. D., Steinmetz, G. P., Botham, R. J., Graven, S. N., and Ledbetter, M. K.: Incidence and Treatment of the Patent Ductus Arteriosus in the 111 Premature Neonate, Am. Heart J. 87: 697, 1974. 16 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:
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1972. Edmunds, L. H., Gregory, G. A., Heymann, M. A., Kitterman, J. A., Rudolph, A. M., and Tooley, S. H.: Surgical Closure of the Ductus Arteriosus in Premature Infants, Circulation 48: 856, 1973. Jegier, W., Karn, G., and Stern, L.: Operative Treatment of Patent Ductus Arteriosus Complicating Respiratory Distress Syndrome of the Premature Infant (Abstr.), Can. Med. Assoc. J. 98: 105, 1968. 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 Forty-five Cases, J. Pediatr. Surg. 8: 677, 1973. Horsley, B. L., Terberg, 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. Kilman, J. W., Kakos, G. S., Williams, T. E., Jr., Craenen, J., and Hosier, D. M.: Ligation of Patent Ductus Arteriosus for Persistent Respiratory Distress Syndrome in Premature Infants, J. Pediatr. Surg. 9: 277, 1974. Powell, M. L.: Patent Ductus Arteriosus in Premature Infants, Med. J. Aust. 2: 58, 1963. Decancq, H. G., Jr.: Repair of Patent Ductus Arteriosus in a 1,417 Gram Infant, Am. J. Dis. Child. 106: 402, 1963. 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. Thibeault, D. W., Emmanouilides, G. C , Nelson, R. J., Lackman, R. S., Rosengart, R. M., and Oh, W.: Patent Ductus Arteriosus Complicating the Respiratory Distress Syndrome in Preterm Infants, J. Pediatr. 86: 120, 1975.
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26 Neal, W. A., Bessinger, F. B., Hunt, C. E., and Lucas, R. V.: Patent Ductus Arteriosus Complicating Respiratory Distress Syndrome, J. Pediatr. 86: 127, 1975. 27 Silveiman, N. H., Lewis, A. B., Heymann, M. A., and Rudolph, A. M.: Echocardiographic Assessment of Ductus Arteriosus Shunt in Premature Infants, Circulation 50: 821, 1974.
The Journal of Thoracic and Cardiovascular Surgery
28 Krovetz, L. J., and Rowe, R. D.: Patent Ductus, Prematurity and Pulmonary Disease, N. Engl. J. Med. 287: 513, 1972. 29 Dunn, P. M., and Speidel, B. D.: Use of Oxygen to Close Patent Ductus Arteriosus in Preterm Infants, Lancet 1: 333, 1973.