February 1977
262
The Journal o f P E D I A T R I C S
Commentary on patent ductus arteriosus complicating the respiratory distress syndrome
THE ADVENT OF increasingly powerful tools for the preservation of health and the prolongation of life has been accompanied by an increase in iatrogenic diseases. The paper in this issue by Dr, Stevenson suggests another example demonstrating that physicians, in an attempt to combat one serious disease, may create another problem. Pediatric cardiologists and neonatologists have come to recognize that the incidence of patent ductus arteriosus in small premature infants has increased dramatically. During the last decade, the Communicable Disease Center has reported that the incidence of PDA has more than doubled. It is a problem, however, to be welcomed to some degree. The previous alternative was a much higher mortality rate in small premature infants. Improvement in neonatal care has resulted not only in an increasing survival of premature infants but also an apparent increase in disorders associated with prematurity such as retrolental fibroplasia, necrotizing enterocolitis, and PDA. Survival rates of premature infants with severe RDS have increased from less than 50% a decade ago to over 80% today. During this time interval, the use of respirators, continuous distending airway pressure, blood transfusions, and parenteral alimentation have all become more frequent. Regardless of whether this increase in PDA is due to increased familiarity, improved survival of small premature infants, or to an actual increase in incidence, it has become one of the major problems in neonatal intensive care units around the country. Much of the argument in the medical literature and at clinical meetings has centered around the management of PDA in premature infants. Most experts would now agree that in the absence of RDS an attempt should be made to control congestive heart failure by medical means. If this is successful, surgery may be postponed for three months or longer, since many of the patent ductuses will close spontaneously. For those few infants whose congestive heart failure cannot be controlled medically, surgery is carried
Vol. 90, No. 2, pp. 262-263
out promptly. In most centers, the mortality in this approach is virtually nil. In the infant with RDS and PDA, the management problem becomes much more complex. It is often difficult to tell which part of the clinical picture is due to respiratory disease and which part is cardiac in nature. It has been suggested that long-term pulmonary complications may be avoided if surgical ligation is done early. Recently the use of indomethacin has been proposed for pharmacologic closure of the ductus. There are many unknowns about this approach and it is too early to tell if the risks of pharmacologic closure offer any significant advantage over the surgical closure. Abbreviations used PDA: patent ductus arteriosus RDS: respiratory distress syndrome With all this emphasis on management, it is gratifying to note the paper by Stevenson focusing attention once more on the etiology of PDA in infants with respiratory distress syndrome. Daily weights and mean daily fluid volumes were analyzed in 31 infants with RDS and PDA. In a comparison group of 31 infants, the mean daily fluid intake was 144 m l / k g / d a y as compared to 189 m l / k g / d a y in those infants who developed signs of congestive heart failure and PDA. Seven infants developed signs of an enlarging ductus in association with increased fluid administration on more than one occasion during their nursery stay. Diuresis was associated with improvement or resolution of the signs of PDA in many of these infants. The author suggests that excessive fluid administration to premature infants with RDS may be one factor associated with development or worsening of PDA complicating RDS. This relationship with increased fluid administration and the presence of congestive heart failure in infants with RDS and PDA is also supported by recent observations from the Children's Hospital in Boston. There are problems with the Stevenson study so often
Volume 90 Number 2
encountered with any retrospective analysis. Are the two groups really comparable? One must wonder why the two groups had different fluid volumes administered. Were they managed by different groups of physicians using different criteria for controlling FIo2 or end-expiratory or inflation pressures? Arterial oxygenation, acid-base balance, and intra-alveolar pressure all have potent effects on pulmonary blood flow. Were the two groups inherently different in terms of degree of perinatal asphyxia or postnatal hypoxemia? If so, the quantity of fluid tolerated by the gastrointestinal tracts of the asphyxiated infants might be significantly less than in the nonasphyxiated group, thus resulting in less fluid being administered. Nevertheless, we are told that there seemed to be no difference in the degrees of pulmonary disease between the two groups and in view of the temporal relationship between fluid administration and clinical symptoms of a PDA, it is quite likely that the two are cause and effect. The paper leaves us, however, with the impression that excess fluid administration may cause a previously closed ductus arteriosus to reopen. It seems more likely to us that the ductus is already anatomically open in these infants with severe pulmonary disease and that excess fluid administration will merely increase the quantity of left-to-right shunt, thus leading to appearance of the murmur, transudation of fluid, and pulmonary decompensation. Alternatively, it is possible
Commentary
263
that the excess of fluid load stimulates prostaglandin synthesis or induces hypoxemia and, thus, may have more direct effects on smooth muscle tone of the ductus arteriosus. Regardless of the ultimate mechanism, this is clearly an important observation. Fluid balance is critical in the treatment of a patient with patent fetal pathways and decreasing pulmonary vascular resistance. In our efforts to supply sufficient calories to these severely ill infants we may frequently push their fluid intake far in excess of basal needs. We hope that this paper witl stimulate other investigators not only to perform similar studies but also, if these observations are confirmed, to look for the pathogenetic linkage between excessive fluid administration and worsening of congestive heart failure in PDA and ventricular septal defect. Fortunately, the nature of iatrogenic problems is such that they are more susceptible to amelioration than many naturally occurring disorders. Let us hope that this will be true with the annoying problem of patent ductus arteriosus in premature infants with respiratory distress syndrome. L. Jerome Krovetz, M.D., Ph.D. John Kattwinkel, M.D. Department of Pediatrics University of Virginia Medical Center Box 201 Charlottesville, VA 22901
262
The Journal o f P E D I A T R I C S
Commentary on patent ductus arteriosus complicating the respiratory distress syndrome
THE ADVENT OF increasingly powerful tools for the preservation of health and the prolongation of life has been accompanied by an increase in iatrogenic diseases. The paper in this issue by Dr, Stevenson suggests another example demonstrating that physicians, in an attempt to combat one serious disease, may create another problem. Pediatric cardiologists and neonatologists have come to recognize that the incidence of patent ductus arteriosus in small premature infants has increased dramatically. During the last decade, the Communicable Disease Center has reported that the incidence of PDA has more than doubled. It is a problem, however, to be welcomed to some degree. The previous alternative was a much higher mortality rate in small premature infants. Improvement in neonatal care has resulted not only in an increasing survival of premature infants but also an apparent increase in disorders associated with prematurity such as retrolental fibroplasia, necrotizing enterocolitis, and PDA. Survival rates of premature infants with severe RDS have increased from less than 50% a decade ago to over 80% today. During this time interval, the use of respirators, continuous distending airway pressure, blood transfusions, and parenteral alimentation have all become more frequent. Regardless of whether this increase in PDA is due to increased familiarity, improved survival of small premature infants, or to an actual increase in incidence, it has become one of the major problems in neonatal intensive care units around the country. Much of the argument in the medical literature and at clinical meetings has centered around the management of PDA in premature infants. Most experts would now agree that in the absence of RDS an attempt should be made to control congestive heart failure by medical means. If this is successful, surgery may be postponed for three months or longer, since many of the patent ductuses will close spontaneously. For those few infants whose congestive heart failure cannot be controlled medically, surgery is carried
Vol. 90, No. 2, pp. 262-263
out promptly. In most centers, the mortality in this approach is virtually nil. In the infant with RDS and PDA, the management problem becomes much more complex. It is often difficult to tell which part of the clinical picture is due to respiratory disease and which part is cardiac in nature. It has been suggested that long-term pulmonary complications may be avoided if surgical ligation is done early. Recently the use of indomethacin has been proposed for pharmacologic closure of the ductus. There are many unknowns about this approach and it is too early to tell if the risks of pharmacologic closure offer any significant advantage over the surgical closure. Abbreviations used PDA: patent ductus arteriosus RDS: respiratory distress syndrome With all this emphasis on management, it is gratifying to note the paper by Stevenson focusing attention once more on the etiology of PDA in infants with respiratory distress syndrome. Daily weights and mean daily fluid volumes were analyzed in 31 infants with RDS and PDA. In a comparison group of 31 infants, the mean daily fluid intake was 144 m l / k g / d a y as compared to 189 m l / k g / d a y in those infants who developed signs of congestive heart failure and PDA. Seven infants developed signs of an enlarging ductus in association with increased fluid administration on more than one occasion during their nursery stay. Diuresis was associated with improvement or resolution of the signs of PDA in many of these infants. The author suggests that excessive fluid administration to premature infants with RDS may be one factor associated with development or worsening of PDA complicating RDS. This relationship with increased fluid administration and the presence of congestive heart failure in infants with RDS and PDA is also supported by recent observations from the Children's Hospital in Boston. There are problems with the Stevenson study so often
Volume 90 Number 2
encountered with any retrospective analysis. Are the two groups really comparable? One must wonder why the two groups had different fluid volumes administered. Were they managed by different groups of physicians using different criteria for controlling FIo2 or end-expiratory or inflation pressures? Arterial oxygenation, acid-base balance, and intra-alveolar pressure all have potent effects on pulmonary blood flow. Were the two groups inherently different in terms of degree of perinatal asphyxia or postnatal hypoxemia? If so, the quantity of fluid tolerated by the gastrointestinal tracts of the asphyxiated infants might be significantly less than in the nonasphyxiated group, thus resulting in less fluid being administered. Nevertheless, we are told that there seemed to be no difference in the degrees of pulmonary disease between the two groups and in view of the temporal relationship between fluid administration and clinical symptoms of a PDA, it is quite likely that the two are cause and effect. The paper leaves us, however, with the impression that excess fluid administration may cause a previously closed ductus arteriosus to reopen. It seems more likely to us that the ductus is already anatomically open in these infants with severe pulmonary disease and that excess fluid administration will merely increase the quantity of left-to-right shunt, thus leading to appearance of the murmur, transudation of fluid, and pulmonary decompensation. Alternatively, it is possible
Commentary
263
that the excess of fluid load stimulates prostaglandin synthesis or induces hypoxemia and, thus, may have more direct effects on smooth muscle tone of the ductus arteriosus. Regardless of the ultimate mechanism, this is clearly an important observation. Fluid balance is critical in the treatment of a patient with patent fetal pathways and decreasing pulmonary vascular resistance. In our efforts to supply sufficient calories to these severely ill infants we may frequently push their fluid intake far in excess of basal needs. We hope that this paper witl stimulate other investigators not only to perform similar studies but also, if these observations are confirmed, to look for the pathogenetic linkage between excessive fluid administration and worsening of congestive heart failure in PDA and ventricular septal defect. Fortunately, the nature of iatrogenic problems is such that they are more susceptible to amelioration than many naturally occurring disorders. Let us hope that this will be true with the annoying problem of patent ductus arteriosus in premature infants with respiratory distress syndrome. L. Jerome Krovetz, M.D., Ph.D. John Kattwinkel, M.D. Department of Pediatrics University of Virginia Medical Center Box 201 Charlottesville, VA 22901
