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Ligation of the patent ductus arteriosus in newborn respiratory failure
Ligation of the Patent Ductus Arteriosus in Newborn Respiratory Failure By Christopher Hubbard, Ralph W. Rucker, Fidel Realyvasquez, Donald R. Sperling, David A. Hicks, Carrie C. Worcester, Ragnar Amlie, Robert F. Huxtable, Robert H. Bartlett, and Alan B. Gazzaniga Irvine, California and Ann Arbor, Michigan • Patent ductus arteriosus (PDA) is commonly associated with respiratory disease in newborn infants and may require ligation. Surgical ligation of the PDA can be done in small infants with low operative risk and minimal complications. The outcome of patients after ligation depends primarily on the severity of the underlying pulmonary disease. One hundred fifty-one patients have undergone ligation in an eight-year period at this center. A simplified technique performed in the neonatal intensive care unit with the use of local anesthesia and conventional ventilator management is described. © 1986 by Grune & Stratton. Inc. INDEX WORDS: Patent ductus arteriosus; neonatal respiratory distress.
ductus arteriosus (PDA) is commonly p ATENT associated with severe respiratory failure in newborn infants. 1 If pulmonary vascular resistance is less than systemic vascular resistance, a PDA will result in excessive lung perfusion at the expense of systemic blood flow. This may result in metabolic acidosis, pulmonary edema, ventricular failure, and reduction in splanchnic and cerebral blood flow. These phenomena are added to the disorders of gas exchange associated with the primary lung disease. Although closure of the PDA usually occurs spontaneously in the full-term infant, there is a high incidence of continued patency in the premature baby. Surgical closure of a PDA is a major procedure, but the improvement in pulmonary function and peripheral perfusion justifies the risk. Several authors have reported successful series of PDA ligation. 2-5 It is now generally advised that the procedure be performed early in the course of respiratory and/or cardiac failure. 6 We have used surgical ligation of the PDA as an adjuct to management of respiratory failure in the newborn for the past ten years. Our initial procedure involved transport of the Patient to the operating room; however, for the past seven years we have used the neonatal intensive care unit as the location for surgery. This report describes our experience with ligation of PDA in the newborn with specific reference to methods and techniques. CASE REPORTS During the eight years between January 1975 and December 1982, 151 premature infants underwent PDA ligation. There were 89 male and 62 female patients. The estimated gestation of the patients was 29 weeks (range 23 to 34 wk), and the average weight at
Journal of Pediatric Surgery, Vol 21, No 1 (January),1986: pp 3-5
birth was 1,253 gm (range 540 to 3,515 gm; Table 1). During this time, approximately 2,500 infants were treated for respiratory failure in the neonatal intensive care units of the UCI Medical Center and Childrens Hospital of Orange County. PDA was diagnosed by typical murmur, wide pulse pressure, cardiomegaly, and evidence of excess pulmonary blood flow by radiographic examination. Indications for ligation included ventilator dependence, findings of pulmonary edema and left ventricular failure, metabolic acidosis, failure of indomethacin, and the need for increased nutritional support and fluids in an otherwise fluid-restricted infant. In recent years, as our technique was simplified, the time interval between surgery and date of birth was lessened (Table 2).
MATERIALS AND METHODS Early in our experience ligation was performed in the operating room under general anesthesia. In 1976, we began performing the operation in the neonatal intensive care unit (NICU) under a radiant warmer. In 1977, we began using metal clips (Weck; Edward Week & Co, lnc, Triangle Park, NC) for ligation. The operating room staff brings all necessary equipment, instruments, and drapes to the NICU. The baby is positioned under the radiant warmer in the supine position with the left arm elevated above the head. The ventilator settings and monitoring systems (EKG, temperature, umbilical artery catheter, pressure wave display, and transcutaneous oxygen) remain unchanged from conventional intensive care unit monitoring. Fifty mL of packed cells are crossmatched and available in the unit. The baby then undergoes paralysis with pancuronium using 0.08 to 0.1 mg/kg. A grounding pad for electrocautery is placed under the buttocks and the chest is prepped with povidoneiodine (Betadine; The Purdue Frederick Co, Norwalk, Conn). Draping and gowning is done as in the operating room. Half percent lidocaine is injected into the skin and deeper structures of the left second intercostal space superior to the nipple. An anterolateral incision is made and the pectoralis and second intercostal muscles are divided with the cautery. A finger retractor is placed in the intercostal space and opened. It is important to remember that because the child is paralyzed, the rate and pressure of the ventilator may be increased. Pancuronium usually induces a tachycardia that is persistent throughout the procedure obviating the use of atropine for bradycardia. The lung is retracted with a brain retractor. Using the phrenic nerve, vagus nerve, and the aorta as landmarks,
From the Departments of Surgery and Pediatrics, University of California, Irvine; Childrens Hospital of Orange County, University of California Irvine Medical Center; and the Department of Surgery, University of Michigan, Ann Arbor. Presented at the Annual Meeting of the American College of Surgeons, Southern California Chapter, January 14-16, 1983, Rancho Mirage, Calif. Address reprint requests to Alan B. Gazzaniga, MD, Professor, Department of Surgery, University of California, Irvine, CA 92717. © 1986 by Grune & Stratton, Inc. 0022 3468/86/2101-0002503.00/0
3
4
HUBBARD ET AL
Table 1. Weight and Age at Operation and Outcome
Table 3. Cause of Death Following PDA Ligation
No. of Patients
Weight at Surgery (kg)
Mean Age at Surgery (Days)
% Died
49 62 18 14 8
<1.0 1.0-1.5 1.5-2.0 2.0-3.0 >3.0
3 7 4 7 6
35 23 44 25 33
Cause
the PDA is identified. The parietal pleura over the PDA posterior to the recurrent laryngeal or vagus nerve is incised. In some cases, it is necessary to cauterize and divide the highest intercostal vein. The fascia between the proximal PDA and the descending aorta is dissected and proves to be the most troublesome portion of the operation. The inferior portion of the PDA is easily dissected pushing the recurrent laryngeal nerve and vagus nerve medially. Care is taken to identify the aortic arch by tracing the left subclavian artery. Early in the series, small right angle clamps around the PDA were used but after several episodes of brisk bleeding, we began using metal clips and this problem has been eliminated. It is important to test the clip applier before it is used so the clip does not scissor and lacerate the ductus. A small Week clip is usually used in infants under 800 gm and a medium-sized clip in infants over 800 gin. A single clip is placed tightly across the duct; two clips may be used if the PDA is particularly long and easily dissected. During the period in which the lung is retracted, transcutaneous oxygen (Pt¢O2) is monitored. The PtcOz has frequently decreased. The lung is then released allowing the transcutaneous oxygen level to return to baseline. The average time of the surgical procedure is 10 to 15 minutes. If an umbilical artery catheter is in place, there frequently is a sharp rise in systolic blood pressure following ligation with a subsequent drop in blood pressure back to baseline levels over the following 24 hours. Chest closure is done with 2-0 chromic (usually one or two in the intercostal space) and the pleural space is drained with a #10 or #12 chest tube. The pectoralis muscles are closed with absorbable sutures, and the skin with a plastic suture. Postoperatively, the patient is returned to routine ventilator management. RESULTS
There were no intraoperative deaths in this series. In one patient there was a laceration of the aorta because the Week clip scissored when it was applied. This was repaired, but the baby died four days postoperatively from intracranial hemorrhage and renal failure. There were 106 (70%) survivors and 45 (30%) babies died. In the patients who survived, the average days on assisted ventilation preoperatively was six and Table 2. Number of PDA Ligations Per Year
Year
1975 1976 1977 1978 1979 1980 1981 1982
No. of Patients
14 11 13 15 25 31 25 17
Mean Age at Surgery(Days)
No. Died
% Died
14 14 14 20 14 7 7 . 7
4 3 5 7 11 7 5 3
29 27 39 47 44 23 2O 17
No. of Deaths
Respiratory distress syndrome (hyaline membrane disease) 8ronchopulmonary dysplasia Congestive heart failure Intracranial hemorrhage Renal failure Hepatic failure
21 13 2 5 3 1
12 days postoperatively. In the group of infants who died, the average day of death was 55 days postoperatively. These babies were on the ventilator an average of 44 days postoperatively. The causes of death included respiratory distress syndrome (hyaline membrane disease), 21 patients; bronchopulmonary dysplasia, 13 patients; congestive heart failure, two patients; central nervous system bleeding, five patients; renal failure, three patients; and hepatic failure, one patient (Table 3). Postoperative complications included pneumothorax in 34 patients, which resolved in an average of four days. Phrenic nerve paralysis occurred in five patients. This was related to retraction of the mediastinum. Since recognition of this complication, the mediastinum is not retracted. There were no misdiagnoses, wound infections, or chylothorax. DISCUSSION
The value of ligation of the patent ductus arteriosus in the premature infant with respiratory distress syndrome was first proposed by Powell. 7 Since then, others have reported their experience, 2-5 and all agree that the procedure can be done with a very low operative risk. Although the risk of operation is slight, it still is not clear which premature infants with respiratory distress syndrome should undergo PDA ligation. Premature infants who are candidates for ligation generally fall into three categories. One category is those patients with minimal lung disease and congestive heart failure. These infants usually do well after ligation and have a marked improvement in their clinical course. In the second category are those patients with moderate lung disease and congestive heart failure. It is often difficult to distinguish which is contributing most to the patient's problem. The results in this group are often variable. The third category of patients are those who clearly have severe lung disease and the PDA only represents a small part of the problem. The results in this group have been the poorest. In our early experience, ligation was done after all forms of medical therapy, including ventilator management, diuretics, digitalization, indomethacin, and
PDA LIGATION
5
fluid restriction had been tried. However, it became apparent that doing ligation as a final effort was not increasing patient salvage. The age at which the infant underwent ligation progressively decreased (Table 2). The average age of ligation is now seven days and the mortality in the early ligation group has dropped (Table 2). Early ligation has the potential benefit of reducing barotrauma due to positive pressure ventilation. Additionally, with the P D A ligated, fluid restriction is a less critical problem and nutritional support can proceed at a higher level. Severity of the results of apneic bradycardia spells is potentially decreased. Transporting a sick premature infant to the operating room is stressful to the infant. Because of this we began ligation in the intensive care unit in 1977, and the infants have tolerated it well. The potential disadvantages, which included infection, cramped quarters with inadequate light, suction and cautery, and departure from the usual operating room schedule and routines, have been more theoretical than real. It is far easier to schedule a P D A ligation in the neonatal intensive care unit than to interrupt a busy operating room schedule. The use of head lamps and magnification has made this a rather simple operation. We have experienced no wound infections as a result of operating in the noncontrolled environment of the intensive care unit. Our current practice of using existing ventilator settings and conventional neonatal monitoring during the procedure has evolved from our early experience with an anesthesiologist standing by. Any surgical
team that adopts this procedure would be well advised to include an experienced neonatal anesthesiologist for the first several procedures. Ligation with metal clips was first called to our attention by Printup in his discussion of the paper by Nelson et al. 8 It was later supported by the report from Traugott et al. 9 Use of the clip obviates the need for circumferential dissection of the PDA, which is the most hazardous part of the operation. W e experienced one early complication related to the use of metal clips that was caused by scissoring due to nonalignment of the clip applier and laceration of the duct. Ligation has been shown to raise systemic arterial pressure, m and we have also seen this repeatedly. Since sudden ligation of the P D A may lead to intraventricular bleeding, gradual occlusion of the P D A has been advocated. 1° A W e c k clip is ideally suited for gradual occlusion if this theory is correct. In our series, however, there were only five deaths related to intracranial bleeding and three of these had occurred prior to P D A ligation. A subgroup of patients (12 in our series) who are born with severe hyaline membrane disease and have such significant lung problems that their clinical course is serious within the first 24 hours, have not done well with P D A ligation in our series. These infants required 100% oxygen, high ventilator pressures, have interstitial air seen on chest roentgenogram, and metabolic acidosis. Ligation has not helped this group of infants who usually die as a result of their lung disease a n d / o r intracranial bleeding.
REFERENCES
1. Neal WA, Bessinger FB, Hunt CE, et al: Patent ductus arteriosus complicating respiratory distress syndrome. J Pediatr 86:127-131, 1975 2. Horsley BL, Lerbert DB, Allen AC, et al: Respiratory distress from patent ductus arteriosus in the premature newborn. Ann Surg 177:806-810, 1973 3. Gay JH, Daily WJR, Meyer BHP, et al: Ligation of the patent ductus arteriosus in premature infants: Report of 45 cases. J Pediatr Surg 8:677-683, 1973 4. Brandt B, Marvin WJ, Ehrenhaft JL, et al: Ligation of patent ductus arteriosus in premature infants. Ann Thorac Surg 32:167 172, 1981 5. Gomez R, Moreno F, Burgueros M, et al: Management of patent ductus arteriosus in preterm babies. Ann Thorac Surg 29:459-463, 1980
6. Mikhail M, Lee W, Toews W, et al: Surgical and medical experience with 734 premature infants with patent ductus arteriosus. J Thorac Cardiovasc Surg 83:349-357, 1982 7. Powell ML: Patent ductus arteriosus in premature infants. Med J Aust 2:58-61, 1963 8. Nelson R J, Thibeault DW, Emmanouilides GC, et al: Improving the results of ligation of patent ductus arteriosus in small preterm infants. J Thorac Cardiovasc Surg 71 : 169-178, 1976 9. Traugott RC, Will R J, Schuchmann GF, et al: A simplified method of ligation of patent ductus arteriosus in premature infants. Ann Thorac Surg 29:263, 1978 10. Marshall TA, Marshall F, Reddy PP: Physiologic changes associated with ligation of the ductus arteriosus in preterm infants. J Pediatr 101:749 753, 1982
ductus arteriosus (PDA) is commonly p ATENT associated with severe respiratory failure in newborn infants. 1 If pulmonary vascular resistance is less than systemic vascular resistance, a PDA will result in excessive lung perfusion at the expense of systemic blood flow. This may result in metabolic acidosis, pulmonary edema, ventricular failure, and reduction in splanchnic and cerebral blood flow. These phenomena are added to the disorders of gas exchange associated with the primary lung disease. Although closure of the PDA usually occurs spontaneously in the full-term infant, there is a high incidence of continued patency in the premature baby. Surgical closure of a PDA is a major procedure, but the improvement in pulmonary function and peripheral perfusion justifies the risk. Several authors have reported successful series of PDA ligation. 2-5 It is now generally advised that the procedure be performed early in the course of respiratory and/or cardiac failure. 6 We have used surgical ligation of the PDA as an adjuct to management of respiratory failure in the newborn for the past ten years. Our initial procedure involved transport of the Patient to the operating room; however, for the past seven years we have used the neonatal intensive care unit as the location for surgery. This report describes our experience with ligation of PDA in the newborn with specific reference to methods and techniques. CASE REPORTS During the eight years between January 1975 and December 1982, 151 premature infants underwent PDA ligation. There were 89 male and 62 female patients. The estimated gestation of the patients was 29 weeks (range 23 to 34 wk), and the average weight at
Journal of Pediatric Surgery, Vol 21, No 1 (January),1986: pp 3-5
birth was 1,253 gm (range 540 to 3,515 gm; Table 1). During this time, approximately 2,500 infants were treated for respiratory failure in the neonatal intensive care units of the UCI Medical Center and Childrens Hospital of Orange County. PDA was diagnosed by typical murmur, wide pulse pressure, cardiomegaly, and evidence of excess pulmonary blood flow by radiographic examination. Indications for ligation included ventilator dependence, findings of pulmonary edema and left ventricular failure, metabolic acidosis, failure of indomethacin, and the need for increased nutritional support and fluids in an otherwise fluid-restricted infant. In recent years, as our technique was simplified, the time interval between surgery and date of birth was lessened (Table 2).
MATERIALS AND METHODS Early in our experience ligation was performed in the operating room under general anesthesia. In 1976, we began performing the operation in the neonatal intensive care unit (NICU) under a radiant warmer. In 1977, we began using metal clips (Weck; Edward Week & Co, lnc, Triangle Park, NC) for ligation. The operating room staff brings all necessary equipment, instruments, and drapes to the NICU. The baby is positioned under the radiant warmer in the supine position with the left arm elevated above the head. The ventilator settings and monitoring systems (EKG, temperature, umbilical artery catheter, pressure wave display, and transcutaneous oxygen) remain unchanged from conventional intensive care unit monitoring. Fifty mL of packed cells are crossmatched and available in the unit. The baby then undergoes paralysis with pancuronium using 0.08 to 0.1 mg/kg. A grounding pad for electrocautery is placed under the buttocks and the chest is prepped with povidoneiodine (Betadine; The Purdue Frederick Co, Norwalk, Conn). Draping and gowning is done as in the operating room. Half percent lidocaine is injected into the skin and deeper structures of the left second intercostal space superior to the nipple. An anterolateral incision is made and the pectoralis and second intercostal muscles are divided with the cautery. A finger retractor is placed in the intercostal space and opened. It is important to remember that because the child is paralyzed, the rate and pressure of the ventilator may be increased. Pancuronium usually induces a tachycardia that is persistent throughout the procedure obviating the use of atropine for bradycardia. The lung is retracted with a brain retractor. Using the phrenic nerve, vagus nerve, and the aorta as landmarks,
From the Departments of Surgery and Pediatrics, University of California, Irvine; Childrens Hospital of Orange County, University of California Irvine Medical Center; and the Department of Surgery, University of Michigan, Ann Arbor. Presented at the Annual Meeting of the American College of Surgeons, Southern California Chapter, January 14-16, 1983, Rancho Mirage, Calif. Address reprint requests to Alan B. Gazzaniga, MD, Professor, Department of Surgery, University of California, Irvine, CA 92717. © 1986 by Grune & Stratton, Inc. 0022 3468/86/2101-0002503.00/0
3
4
HUBBARD ET AL
Table 1. Weight and Age at Operation and Outcome
Table 3. Cause of Death Following PDA Ligation
No. of Patients
Weight at Surgery (kg)
Mean Age at Surgery (Days)
% Died
49 62 18 14 8
<1.0 1.0-1.5 1.5-2.0 2.0-3.0 >3.0
3 7 4 7 6
35 23 44 25 33
Cause
the PDA is identified. The parietal pleura over the PDA posterior to the recurrent laryngeal or vagus nerve is incised. In some cases, it is necessary to cauterize and divide the highest intercostal vein. The fascia between the proximal PDA and the descending aorta is dissected and proves to be the most troublesome portion of the operation. The inferior portion of the PDA is easily dissected pushing the recurrent laryngeal nerve and vagus nerve medially. Care is taken to identify the aortic arch by tracing the left subclavian artery. Early in the series, small right angle clamps around the PDA were used but after several episodes of brisk bleeding, we began using metal clips and this problem has been eliminated. It is important to test the clip applier before it is used so the clip does not scissor and lacerate the ductus. A small Week clip is usually used in infants under 800 gm and a medium-sized clip in infants over 800 gin. A single clip is placed tightly across the duct; two clips may be used if the PDA is particularly long and easily dissected. During the period in which the lung is retracted, transcutaneous oxygen (Pt¢O2) is monitored. The PtcOz has frequently decreased. The lung is then released allowing the transcutaneous oxygen level to return to baseline. The average time of the surgical procedure is 10 to 15 minutes. If an umbilical artery catheter is in place, there frequently is a sharp rise in systolic blood pressure following ligation with a subsequent drop in blood pressure back to baseline levels over the following 24 hours. Chest closure is done with 2-0 chromic (usually one or two in the intercostal space) and the pleural space is drained with a #10 or #12 chest tube. The pectoralis muscles are closed with absorbable sutures, and the skin with a plastic suture. Postoperatively, the patient is returned to routine ventilator management. RESULTS
There were no intraoperative deaths in this series. In one patient there was a laceration of the aorta because the Week clip scissored when it was applied. This was repaired, but the baby died four days postoperatively from intracranial hemorrhage and renal failure. There were 106 (70%) survivors and 45 (30%) babies died. In the patients who survived, the average days on assisted ventilation preoperatively was six and Table 2. Number of PDA Ligations Per Year
Year
1975 1976 1977 1978 1979 1980 1981 1982
No. of Patients
14 11 13 15 25 31 25 17
Mean Age at Surgery(Days)
No. Died
% Died
14 14 14 20 14 7 7 . 7
4 3 5 7 11 7 5 3
29 27 39 47 44 23 2O 17
No. of Deaths
Respiratory distress syndrome (hyaline membrane disease) 8ronchopulmonary dysplasia Congestive heart failure Intracranial hemorrhage Renal failure Hepatic failure
21 13 2 5 3 1
12 days postoperatively. In the group of infants who died, the average day of death was 55 days postoperatively. These babies were on the ventilator an average of 44 days postoperatively. The causes of death included respiratory distress syndrome (hyaline membrane disease), 21 patients; bronchopulmonary dysplasia, 13 patients; congestive heart failure, two patients; central nervous system bleeding, five patients; renal failure, three patients; and hepatic failure, one patient (Table 3). Postoperative complications included pneumothorax in 34 patients, which resolved in an average of four days. Phrenic nerve paralysis occurred in five patients. This was related to retraction of the mediastinum. Since recognition of this complication, the mediastinum is not retracted. There were no misdiagnoses, wound infections, or chylothorax. DISCUSSION
The value of ligation of the patent ductus arteriosus in the premature infant with respiratory distress syndrome was first proposed by Powell. 7 Since then, others have reported their experience, 2-5 and all agree that the procedure can be done with a very low operative risk. Although the risk of operation is slight, it still is not clear which premature infants with respiratory distress syndrome should undergo PDA ligation. Premature infants who are candidates for ligation generally fall into three categories. One category is those patients with minimal lung disease and congestive heart failure. These infants usually do well after ligation and have a marked improvement in their clinical course. In the second category are those patients with moderate lung disease and congestive heart failure. It is often difficult to distinguish which is contributing most to the patient's problem. The results in this group are often variable. The third category of patients are those who clearly have severe lung disease and the PDA only represents a small part of the problem. The results in this group have been the poorest. In our early experience, ligation was done after all forms of medical therapy, including ventilator management, diuretics, digitalization, indomethacin, and
PDA LIGATION
5
fluid restriction had been tried. However, it became apparent that doing ligation as a final effort was not increasing patient salvage. The age at which the infant underwent ligation progressively decreased (Table 2). The average age of ligation is now seven days and the mortality in the early ligation group has dropped (Table 2). Early ligation has the potential benefit of reducing barotrauma due to positive pressure ventilation. Additionally, with the P D A ligated, fluid restriction is a less critical problem and nutritional support can proceed at a higher level. Severity of the results of apneic bradycardia spells is potentially decreased. Transporting a sick premature infant to the operating room is stressful to the infant. Because of this we began ligation in the intensive care unit in 1977, and the infants have tolerated it well. The potential disadvantages, which included infection, cramped quarters with inadequate light, suction and cautery, and departure from the usual operating room schedule and routines, have been more theoretical than real. It is far easier to schedule a P D A ligation in the neonatal intensive care unit than to interrupt a busy operating room schedule. The use of head lamps and magnification has made this a rather simple operation. We have experienced no wound infections as a result of operating in the noncontrolled environment of the intensive care unit. Our current practice of using existing ventilator settings and conventional neonatal monitoring during the procedure has evolved from our early experience with an anesthesiologist standing by. Any surgical
team that adopts this procedure would be well advised to include an experienced neonatal anesthesiologist for the first several procedures. Ligation with metal clips was first called to our attention by Printup in his discussion of the paper by Nelson et al. 8 It was later supported by the report from Traugott et al. 9 Use of the clip obviates the need for circumferential dissection of the PDA, which is the most hazardous part of the operation. W e experienced one early complication related to the use of metal clips that was caused by scissoring due to nonalignment of the clip applier and laceration of the duct. Ligation has been shown to raise systemic arterial pressure, m and we have also seen this repeatedly. Since sudden ligation of the P D A may lead to intraventricular bleeding, gradual occlusion of the P D A has been advocated. 1° A W e c k clip is ideally suited for gradual occlusion if this theory is correct. In our series, however, there were only five deaths related to intracranial bleeding and three of these had occurred prior to P D A ligation. A subgroup of patients (12 in our series) who are born with severe hyaline membrane disease and have such significant lung problems that their clinical course is serious within the first 24 hours, have not done well with P D A ligation in our series. These infants required 100% oxygen, high ventilator pressures, have interstitial air seen on chest roentgenogram, and metabolic acidosis. Ligation has not helped this group of infants who usually die as a result of their lung disease a n d / o r intracranial bleeding.
REFERENCES
1. Neal WA, Bessinger FB, Hunt CE, et al: Patent ductus arteriosus complicating respiratory distress syndrome. J Pediatr 86:127-131, 1975 2. Horsley BL, Lerbert DB, Allen AC, et al: Respiratory distress from patent ductus arteriosus in the premature newborn. Ann Surg 177:806-810, 1973 3. Gay JH, Daily WJR, Meyer BHP, et al: Ligation of the patent ductus arteriosus in premature infants: Report of 45 cases. J Pediatr Surg 8:677-683, 1973 4. Brandt B, Marvin WJ, Ehrenhaft JL, et al: Ligation of patent ductus arteriosus in premature infants. Ann Thorac Surg 32:167 172, 1981 5. Gomez R, Moreno F, Burgueros M, et al: Management of patent ductus arteriosus in preterm babies. Ann Thorac Surg 29:459-463, 1980
6. Mikhail M, Lee W, Toews W, et al: Surgical and medical experience with 734 premature infants with patent ductus arteriosus. J Thorac Cardiovasc Surg 83:349-357, 1982 7. Powell ML: Patent ductus arteriosus in premature infants. Med J Aust 2:58-61, 1963 8. Nelson R J, Thibeault DW, Emmanouilides GC, et al: Improving the results of ligation of patent ductus arteriosus in small preterm infants. J Thorac Cardiovasc Surg 71 : 169-178, 1976 9. Traugott RC, Will R J, Schuchmann GF, et al: A simplified method of ligation of patent ductus arteriosus in premature infants. Ann Thorac Surg 29:263, 1978 10. Marshall TA, Marshall F, Reddy PP: Physiologic changes associated with ligation of the ductus arteriosus in preterm infants. J Pediatr 101:749 753, 1982