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Ann Thorac Surg 2006;81:231-234
© 2006 The Society of Thoracic Surgeons
a Service de Chirurgie, Polyclinique du Bois; Lille, France
b Service de Chirurgie Cardiaque, CHRU de Lille; Lille, France
c Service de Médecine Néonatale, CHRU de Lille, Lille, France
Accepted for publication March 16, 2005.
* Address correspondence to Dr Jaillard, Service de Chirurgie, Polyclinique du Bois, Lille, 59000 France (Email: sjaillard{at}wanadoo.fr).
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentReferences |
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METHODS: We retrospectively studied 58 infants less than 28 weeks gestational age who underwent surgical closure of ductus arteriosus between January 1997 and December 2002. Nine infants with intrauterine growth restriction and major congenital malformation were excluded from the study. Criteria for surgical closure of ductus arteriosus were: (1) medical treatment failure (ie, indomethacin or ibuprofen) and (2) hemodynamically patent ductus arteriosus: systemic arterial pressure less than gestational age in mm Hg, heart failure, left atrial-aortic root ratio greater than 1.6, mean velocity in the left pulmonary artery greater than 0.6 m/s, and ductus arteriosus diameter greater than 3 mm. Infants were divided into two groups: (1) the early group who had surgery before 21 days of life (n = 31), and (2) the late group who had surgery after 21 days of life (n = 27). Preoperative and postoperative criteria were compared between the two groups (ie, gestational age, birth weight, hemodynamic, ventilatory, and echographic [left atrial-aortic root ratio, mean velocity in the left pulmonary artery] parameters).
RESULTS: Preoperative gestational age and birth weight did not differ between the two groups. In the early group, gestational age was 26 weeks (range, 23 to 28 weeks and birth weight was 800 g (range, 630 to 1,240 g). In the late group, gestational age was 26 weeks (range, 24 to 28 weeks) and birth weight was 840 g (530 to 1,130 g). Hemodynamic, ventilatory, and echographic parameters were similar in both groups. Rate of bronchopulmonary dysplasia was similar in both groups. However, at 24 hours post surgery, median FiO 2 was higher in the late group (28% [range, 21% to 65%]) than in early group (21% [range, 21% to 60%]) (p < 0.05). Furthermore, full oral feeding was acquired later in the late group (57 days of life [range, 30 to 136 days]) than in the early group (37 days of life [range, 27 to 84 days]) (p < 0.01), and body weight at 36 weeks of post-conceptional age was higher in the early group at 1,800 g (range, 1,250 to 2,750 g) than in the late group at 1,607 g (1,274 to 2,200 g) (p < 0.05).
CONCLUSIONS: Our findings show that early surgical closure of the ductus arteriosus (< 3 weeks of life) is associated with shortened delay for full oral feeding and improved body growth when compared with late surgical closure (> 3 weeks of life).
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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In these extremely premature neonates, the rate of patent ductus arteriosus (PDA) is close to 30% [2]. The management of PDA in these high-risk infants remains an area of controversy, and optimal management of the PDA in neonates weighing less than 800 g is still under debate.
In the 1980s, early surgical ligation was advocated as the optimal therapy for PDA because it ensured definitive ductal closure with minimal morbidity and mortality [3]. Advocates of early surgical ligation argued that this approach may decrease the incidence of pulmonary complications associated with prolonged mechanical ventilation [4].
Concurrently, the introduction of indomethacin for pharmacological constriction of the ductus arteriosus [5] stimulated further studies, which showed that indomethacin therapy can be effective in closing the ductus arteriosus in preterm infants [6].
Early detection of persistent ductus arteriosus is proposed and criteria to use early indomethacin therapy have now been better defined. Although surgical versus pharmacological closure of the PDA was a past area of avid debate, there is little information on the best timing when both medical and surgical treatment are successively required. Our purpose was to determine the influence of delay of surgical closure of the ductus arteriosus on respiratory and digestive outcome in the most immature newborn infants.
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Patients and Methods |
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Criteria for surgical closure of the ductus arteriosus were: (1) failure of two courses of medical treatment (ie, indomethacin or ibuprofen), and (2) hemodynamically PDA assessed by systemic arterial pressure (mean arterial pressure) less than gestational age (weeks); heart failure symptoms; and echocardiographic data of the left atrial-aortic root ratio > 1.6, the mean velocity in the left pulmonary artery > 0.6m/s, and the ductus arteriosus diameter > 3 mm. All infants had an exclusively left-right shunting through the ductus arteriosus.
Age at the time of surgery was independent of the conditions of the infant, and was chosen only on the time schedule of the surgeons and anesthesiologists and on the availability of the operating room. The infants were operated on in a specially dedicated room under general anesthesia and by endotracheal intubation. High-frequency oscillatory ventilation was applied if required. A left posterolateral mini-thoracotomy (< 4 cm long on the third intercostal space) and a transpleural approach were performed. Either two surgical ligatures or two medium hemoclips were used to close the ductus arteriosus. A chest tube was inserted only in selected high-risk cases and at the surgeon's discretion.
Infants were divided into two groups: (1) an early group for which surgery was performed before 21 days of life, and (2) a late group for which surgery was performed after 21 days of life.
In each group, preoperative data were recorded (ie, gestational age, birth weight, weight at surgery, delay from birth to surgery, hemodynamic parameters, respiratory and ventilatory parameters, and echocardiographic measurements).
Hemodynamic parameters were noted postoperatively. Ventilatory parameters (ie, ventilation mode [controlled, non invasive, nasal cannulas, room air]) and required FiO2 were recorded at 6, 12, 24, and 48 hours and at 7 and 28 days postoperatively, and then at 36 weeks of post-conceptional age. Bronchopulmonary dysplasia was defined as any requirement for supplemental oxygen at 36 weeks of conceptional age. Nutritional status was evaluated using age at full oral feeding and body weight at 36 weeks of post-conceptional age.
Mortality and respiratory morbidity were systematically recorded. Statistical analysis was performed using 
2 or Fisher's exact test for difference of proportions, and the Mann-Whitney U test to compare the two groups. Results are expressed as median and range. P values < 0.05 were considered significant.
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Results |
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Preoperatively
The clinical characteristics of the infants were similar between both groups at birth (Table 1). Postnatal age and body weight at surgery were in agreement with the design of the study (Table 1). No difference was found for ventilatory requirement, hemodynamic, and echocardiographic parameters between the 2 groups (Table 1). One necrotizing enterocolitis occurred in the early group and two in the late group after one course of indomethacin. Subsequently, surgery was conducted after the first course for these infants.
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Early morbidity consisted of three persistent air leakages (more than 2 days and less than 5 days) secondary to lung and pleural surgical injury. Later morbidity consisted of one superficial wound infection and two recurrent nerve injuries. Because only infants with stridor, hoarseness, and difficult weaning from nasal continuous positive airway pressure underwent evaluation for vocal cord paralysis in this study, additional unrecognized recurrent nerve injuries may have occurred.
Hemodynamic, ventilatory, and echographic parameters were similar in both groups after the surgery (Table 2). Duration of ventilatory support, O2 need, and rate of bronchopulmonary dysplasia did not differ between the groups. However, median FiO 2 was higher in the late group than in the early group at 24 hours postoperatively (Table 2). Furthermore, full oral feeding was acquired later in the late group than in the early group (57 days of life [range, 30 to 136 days] vs 37 days of life [range, 27 to 84 days]) (p<0.01). Body weight at 36 weeks post-conceptional age was higher in the early group (1,800 g [range, 1,250 to 2,750 g]) than in the late group (1,607 g [range, 1,274 to 2,200]) (p < 0.05).
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Comment |
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Improved obstetrical and neonatal interventions and aggressive resuscitation techniques have gradually improved the survival of preterm infants and lowered the viability threshold [7]. However, management of PDA remains a challenge in the most immature infants. It has been suggested that early ductal ligation resulted in a shorter duration of mechanical ventilation in infants weighing less than 1,500 g [8, 9]. On the contrary, early ligation was not found to influence the oxygen dependency if O2 was required before the surgery [9]. Moreover, Coster and colleagues [10] demonstrated that tube feeding could be started shortly after the surgery and have proposed that early ductal surgical closure may have beneficial impacts on the nutritional status. Our study further supports this hypothesis and provides new information. Indeed, we found that early surgical closure of PDA is associated with earlier full oral feeding and increased body weight gain. Despite a lower body weight at the time of surgery in the late surgery group, the weight at 36 weeks post-conceptional age was greater in the early surgery group. Patent ductus arteriosus decreases the systemic blood flow and reduces intestinal O2 delivery. Thus we speculate that early surgery may improve intestinal function and feeding tolerance. Furthermore, O2 need was lower when surgical closure of the ductus arteriosus was performed before 21 days of life. Patent ductus arteriosus rises pulmonary blood flow resulting in alveolar edema and in intrapulmonary shunt. We further speculate that delayed surgery may progressively impair pulmonary function and may explain the increase in O2 need in the post surgery period.
The 5% mortality rate in the series seems to be unrelated to the surgical procedure, but rather to the underlying diseases and complications of prematurity. This mortality, which occurred after 36 weeks of post-conceptional age, did not bias our results because follow-up criteria were recorded until 36 weeks post-conceptional age. The age at surgery was not determined by the infant's conditions, including gestational age or complications, and was related only to logistical considerations such as the availability of the operating room. This explains why the two groups were similar before the surgery in term of hemodynamic, respiratory, and echocardiographic parameters except body weight at surgery. Other confusion factors, such as differences in practices between the five neonatal intensive care units in the area and in the outborn or inborn status, can be ruled out because the number of infants from each different center and the rate of inborn and outborn infants were similar in the two groups. Moreover, none of the ductus arteriosus closed spontaneously in each study group after the decision was taken to ligate the ductus arteriosus. In a recent study regarding the lack of response to multiples courses of indomethacin, Keller and Clyman [11] reported that premature newborns older than 28 weeks with persistent or recurrent Doppler flow in the ductus arteriosus after completion of an initial course of indomethacin rarely responded to multiple courses of indomethacin.
There are two limitations to our study. First, this was a retrospective study conducted during 5 years in which neonatal practices might have been different. Nevertheless, such a bias is attenuated by the fact that infants born during the same period belong to one group or another. Second, nowadays, in a surgical study of 58 low birth-weight infants with PDA, it might seem improper not to refer to the use of video-assisted thoracoscopic surgery, because it has been recently documented as a safe and effective method of closing PDA even in very low birth-weight infants [12–14]. Despite this fact, the video-assisted thoracoscopic surgery technique is not a current practice in our unit. On the other hand, infants were systematically operated in the neonatal intensive care unit of which benefits have been recently published [15]. Currently we use a limited thoracotomy (less than 4 cm) that allows us to perform a safe surgical closure of the ductus arteriosus lasting less than 20 minutes. Nevertheless, we are concerned about possible advantages of video-assisted thoracoscopic surgery in comparison with the open technique.
In conclusion, surgical closure of the PDA in the neonatal intensive care unit is safe and efficient in very premature infants. We showed that infants operated on earlier after failure of medical treatment had improved: 1) short-term ventilatory parameter, 2) the delay for full oral feeding, and 3) the body weight gain at 36 weeks of post-conceptional age. These findings associated with recent data of the literature urge us to propose an early evaluation of the ductus arteriosus after a first course of medical treatment to prevent the delay in surgical closure of the ductus arteriosus in extremely preterm newborn infants [11].
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This article has been cited by other articles:
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  J. C. Madan, D. Kendrick, J. I. Hagadorn, I. D. Frantz III, and the National Institute of Child Health and Human D Patent Ductus Arteriosus Therapy: Impact on Neonatal and 18-Month Outcome Pediatrics, February 1, 2009; 123(2): 674 - 681. [Abstract] [Full Text] [PDF]
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 S. Tschuppert, C. Doell, R. Arlettaz-Mieth, O. Baenziger, V. Rousson, C. Balmer, R. Pretre, and A. Dodge-Khatami The effect of ductal diameter on surgical and medical closure of patent ductus arteriosus in preterm neonates: Size matters J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 78 - 82. [Abstract] [Full Text] [PDF]
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N. Chorne, C. Leonard, R. Piecuch, and R. I. Clyman Patent Ductus Arteriosus and Its Treatment as Risk Factors for Neonatal and Neurodevelopmental Morbidity Pediatrics, June 1, 2007; 119(6): 1165 - 1174. [Abstract] [Full Text] [PDF]
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 M. H. Hines Invited commentary Ann. Thorac. Surg., January 1, 2006; 81(1): 234 - 235. [Full Text] [PDF]
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