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Aspiration of bile as a cause of respiratory distress in the newborn infant
ASPIRATION OF BILE AS A CAUSE OF RESPIRATORY DISTRESS IN THE NEWBORN INFANT VANESSA ELLISON, MBCHB, KEI LUI, FRACP, MD, AND PETER A. DARGAVILLE, MBBS, FRACP, MD
Early-onset respiratory distress and a radiographic appearance of an aspiration syndrome occurred in two neonates with gastroschisis who had evidence of inhalation of bile. Hypoxemic respiratory failure developed in both infants, contributing to death or prolonged respiratory morbidity. Bile aspiration syndrome should be considered whenever there is early-onset respiratory distress in a neonate with high intestinal obstruction. (J Pediatr 2004;144:389-90)
espiratory distress in the newborn infant can occur after aspiration of a number of different amniotic fluid contaminants, including meconium,1 vernix caseosa,2 cellular debris,3 and blood.4 Although aspiration of bile or bile-containing fluid is recognized as injurious to the pulmonary epithelium,5-7 to date, bile aspiration in the neonate has only been reported in the context of a tracheobiliary fistula.8 We report two neonates in whom inhalation of bile was associated with significant respiratory distress and radiographic features of an aspiration syndrome.
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CASE REPORTS Case 1 A female infant weighing 1690 g was born at 34 weeks’ gestation to an 18-year-old mother via spontaneous vaginal delivery. An antenatal diagnosis of gastroschisis had been made after an ultrasound performed at 19 weeks and was confirmed postnatally. Membranes were ruptured 35 minutes before delivery, with green nonparticulate discoloration of the liquor. There was no suggestion of meconium passage before delivery. APGAR scores were 3 at 1 minute and 7 at 5 minutes, and the infant required intubation and positive pressure ventilation in the delivery suite because of severe respiratory distress. Copious amounts of green nonparticulate fluid were suctioned from below the vocal cords, both in the delivery room, and after admission to the neonatal intensive care unit. A single dose of exogenous surfactant was administered with no improvement. Chest radiography showed uniform widespread nongranular opacification. The infant underwent partial surgical repair of the gastroschisis, with formation of a Silastic sleeve on day 1. Postoperatively, assisted ventilation requirements increased, and high-frequency oscillatory ventilation was used with 20 parts per million of nitric oxide. There was further deterioration on day 5 with progressive respiratory failure, and the infant died on day 8 from intractable hypoxemia and hypotension. There was no growth on cultures.
Case 2 A male infant weighing 3440 g was born at 38 weeks’ gestation to an 18-year-old primigravida. A diagnosis of gastroschisis had been made on an antenatal ultrasound at 18 weeks’ gestation and was confirmed postnatally. Membranes were ruptured three hours before delivery, with the liquor noted to be green in color. Delivery was by vacuum extraction because of concerns of fetal distress. There was no evidence of meconium passage before delivery. Histopathological examination revealed bile staining of the placental membranes. APGAR scores were 2 at 1 minute and 3 at 5 minutes. At 3 minutes, the infant began vomiting bilious fluid and became apneic and bradycardic, requiring intubation and positive pressure ventilation. Large amounts of bile were suctioned from the oro-gastric tube. The infant was given conventional ventilation. The initial chest radiograph showed poorly expanded lung fields and a widespread pattern of patchy interstitial opacification
From the Department of Neonatology, Royal Children’s Hospital, Melbourne, the Department of Newborn Care, Royal Hospital for Women, Sydney, and Murdoch Children’s Research Institute, Melbourne, Australia. Submitted for publication Sept 8, 2003; accepted Nov 25, 2003. Reprint requests: Peter Dargaville, MBBS, FRACP, MD, Department of Neonatology, Royal Children’s Hospital, Flemington Road, Parkville, VIC 3052, Australia. E-mail: peter. [email protected]. 022-3476/$ - see front matter Copyright ª 2004 Elsevier Inc. All rights reserved. 10.1016/j.jpeds.2003.11.026
389
Figure. Case 2: Chest radiograph at 10 hours of age showing patchy opacification typical of an aspiration syndrome.
(Figure). Ventilatory requirements were high in the first 72 hours and improved after initiation of high-frequency oscillatory ventilation on day 3. The infant had partial repair of the gastroschisis with a Silastic sleeve fixed around margins of the defect on the first day of life. Definitive closure was at eight days later. The infant remained ventilator-dependent for 18 days. There were signs of persistent upper intestinal obstruction, and a laparotomy performed at 56 days revealed unrecognized small bowel atresia, which was excised. The infant was finally discharged at day 84 with no residual respiratory distress.
DISCUSSION We report two neonates with clinical features, radiographic findings, and ventilatory progress consistent with an aspiration syndrome, contributing to death in one case and resulting in significant respiratory morbidity in the second case. In both infants, there was evidence of aspiration of bilecontaminated fluid, with bile-stained material suctioned from the endotracheal tube in the first case, and respiratory deterioration after bilious vomiting in the second. In both cases, there was efflux of large volumes of bile-stained fluid from the stomach, indicative of high intestinal obstruction associated with gastroschisis. In case 1, bile aspiration appears to have occurred prenatally, as indicated by the immediate onset of respiratory distress after birth, and the recovery of bile-stained fluid from the trachea in the delivery suite. In a second case, a discrete
390
Ellison, Lui, and Dargaville
episode of aspiration occurred after delivery, but in view of the fetal distress and bile-stained liquor, there may well have been bile inhalation before birth. The discoloration of amniotic fluid in these infants was probably due to efflux of bile-stained fluid from the fetal intestine, as has been noted before in gastroschisis.9 Neither infant appeared to have passed meconium before delivery. The amniotic fluid contamination was nonparticulate, and there was associated bile staining of the placental membranes in case 2. There is laboratory evidence that exposure to bile causes significant injury to the pulmonary epithelium. Oelberg et al found that in cultured pneumocytes, the addition of bile salts to the culture medium resulted in altered cell permeability, indicating a cytotoxic effect.5 In experimental animals, intratracheal administration of bile results in severe compromise of oxygenation and lung function,6,7 which is frequently lethal.6 The lung dysfunction is potentiated by the addition of hydrochloric acid,7 but even at neutral pH, the injury is more pronounced than that caused by gastric acid alone.6 In human neonates, exposure of the pulmonary epithelium to bile has been seen to cause lung inflammation and respiratory failure in the context of a congenital tracheobiliary fistula.8 In this situation, pure bile flows directly to the lung through the fistulous opening. The clinical course and radiographic changes seen in our cases suggest that aspiration of bile-containing fluid via the trachea can have pronounced effects on the neonatal lung. Bile aspiration should be considered whenever there is early onset of respiratory distress in an infant with high intestinal obstruction.
REFERENCES 1. Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues. Pediatr Clin North Am 1993; 40:955-81. 2. Ohlsson A, Cumming W, Najjar H. Neonatal aspiration syndrome due to vernix caseosa. Pediatr Radiol 1985;15:193-5. 3. Perlman M, Bar-Ziv J. Congenital ichthyosis and neonatal pulmonary disease. Pediatrics 1974;53:573-5. 4. Gordon E, South M, McDougall PN, Dargaville PA. The blood aspiration syndrome as a cause of respiratory distress in the newborn. J Pediatr 2003;142:200-2. 5. Oelberg DG, Downey SA, Flynn MM. Bile salt-induced intracellular Ca++ accumulation in type II pneumocytes. Lung 1990;168:297-308. 6. Henderson RD, Fung K, Cullen JB, Milne EN, Marryatt G. Bile aspiration: an experimental study in rabbits. Can J Surg 1975;18:64-9. 7. Porembka D, Kier A, Sehlorst S, Boyce S, Orlowski JP, Davis K. The pathophysiologic changes following bile aspiration in a porcine lung model. Chest 1993;104:919-24. 8. Tekant GA, Joseph VT, Cheah SL. Congenital tracheobiliary fistula. J Pediatr Surg 1994;29:594-5. 9. Dixon JC, Penman DM, Soothill PW. The influence of bowel atresia in gastroschisis on fetal growth, cardiotocograph, abnormalities, and amniotic fluid staining. Br J Obstet Gynecol 2000;107:572-5.
The Journal of Pediatrics March 2004
Early-onset respiratory distress and a radiographic appearance of an aspiration syndrome occurred in two neonates with gastroschisis who had evidence of inhalation of bile. Hypoxemic respiratory failure developed in both infants, contributing to death or prolonged respiratory morbidity. Bile aspiration syndrome should be considered whenever there is early-onset respiratory distress in a neonate with high intestinal obstruction. (J Pediatr 2004;144:389-90)
espiratory distress in the newborn infant can occur after aspiration of a number of different amniotic fluid contaminants, including meconium,1 vernix caseosa,2 cellular debris,3 and blood.4 Although aspiration of bile or bile-containing fluid is recognized as injurious to the pulmonary epithelium,5-7 to date, bile aspiration in the neonate has only been reported in the context of a tracheobiliary fistula.8 We report two neonates in whom inhalation of bile was associated with significant respiratory distress and radiographic features of an aspiration syndrome.
R
CASE REPORTS Case 1 A female infant weighing 1690 g was born at 34 weeks’ gestation to an 18-year-old mother via spontaneous vaginal delivery. An antenatal diagnosis of gastroschisis had been made after an ultrasound performed at 19 weeks and was confirmed postnatally. Membranes were ruptured 35 minutes before delivery, with green nonparticulate discoloration of the liquor. There was no suggestion of meconium passage before delivery. APGAR scores were 3 at 1 minute and 7 at 5 minutes, and the infant required intubation and positive pressure ventilation in the delivery suite because of severe respiratory distress. Copious amounts of green nonparticulate fluid were suctioned from below the vocal cords, both in the delivery room, and after admission to the neonatal intensive care unit. A single dose of exogenous surfactant was administered with no improvement. Chest radiography showed uniform widespread nongranular opacification. The infant underwent partial surgical repair of the gastroschisis, with formation of a Silastic sleeve on day 1. Postoperatively, assisted ventilation requirements increased, and high-frequency oscillatory ventilation was used with 20 parts per million of nitric oxide. There was further deterioration on day 5 with progressive respiratory failure, and the infant died on day 8 from intractable hypoxemia and hypotension. There was no growth on cultures.
Case 2 A male infant weighing 3440 g was born at 38 weeks’ gestation to an 18-year-old primigravida. A diagnosis of gastroschisis had been made on an antenatal ultrasound at 18 weeks’ gestation and was confirmed postnatally. Membranes were ruptured three hours before delivery, with the liquor noted to be green in color. Delivery was by vacuum extraction because of concerns of fetal distress. There was no evidence of meconium passage before delivery. Histopathological examination revealed bile staining of the placental membranes. APGAR scores were 2 at 1 minute and 3 at 5 minutes. At 3 minutes, the infant began vomiting bilious fluid and became apneic and bradycardic, requiring intubation and positive pressure ventilation. Large amounts of bile were suctioned from the oro-gastric tube. The infant was given conventional ventilation. The initial chest radiograph showed poorly expanded lung fields and a widespread pattern of patchy interstitial opacification
From the Department of Neonatology, Royal Children’s Hospital, Melbourne, the Department of Newborn Care, Royal Hospital for Women, Sydney, and Murdoch Children’s Research Institute, Melbourne, Australia. Submitted for publication Sept 8, 2003; accepted Nov 25, 2003. Reprint requests: Peter Dargaville, MBBS, FRACP, MD, Department of Neonatology, Royal Children’s Hospital, Flemington Road, Parkville, VIC 3052, Australia. E-mail: peter. [email protected]. 022-3476/$ - see front matter Copyright ª 2004 Elsevier Inc. All rights reserved. 10.1016/j.jpeds.2003.11.026
389
Figure. Case 2: Chest radiograph at 10 hours of age showing patchy opacification typical of an aspiration syndrome.
(Figure). Ventilatory requirements were high in the first 72 hours and improved after initiation of high-frequency oscillatory ventilation on day 3. The infant had partial repair of the gastroschisis with a Silastic sleeve fixed around margins of the defect on the first day of life. Definitive closure was at eight days later. The infant remained ventilator-dependent for 18 days. There were signs of persistent upper intestinal obstruction, and a laparotomy performed at 56 days revealed unrecognized small bowel atresia, which was excised. The infant was finally discharged at day 84 with no residual respiratory distress.
DISCUSSION We report two neonates with clinical features, radiographic findings, and ventilatory progress consistent with an aspiration syndrome, contributing to death in one case and resulting in significant respiratory morbidity in the second case. In both infants, there was evidence of aspiration of bilecontaminated fluid, with bile-stained material suctioned from the endotracheal tube in the first case, and respiratory deterioration after bilious vomiting in the second. In both cases, there was efflux of large volumes of bile-stained fluid from the stomach, indicative of high intestinal obstruction associated with gastroschisis. In case 1, bile aspiration appears to have occurred prenatally, as indicated by the immediate onset of respiratory distress after birth, and the recovery of bile-stained fluid from the trachea in the delivery suite. In a second case, a discrete
390
Ellison, Lui, and Dargaville
episode of aspiration occurred after delivery, but in view of the fetal distress and bile-stained liquor, there may well have been bile inhalation before birth. The discoloration of amniotic fluid in these infants was probably due to efflux of bile-stained fluid from the fetal intestine, as has been noted before in gastroschisis.9 Neither infant appeared to have passed meconium before delivery. The amniotic fluid contamination was nonparticulate, and there was associated bile staining of the placental membranes in case 2. There is laboratory evidence that exposure to bile causes significant injury to the pulmonary epithelium. Oelberg et al found that in cultured pneumocytes, the addition of bile salts to the culture medium resulted in altered cell permeability, indicating a cytotoxic effect.5 In experimental animals, intratracheal administration of bile results in severe compromise of oxygenation and lung function,6,7 which is frequently lethal.6 The lung dysfunction is potentiated by the addition of hydrochloric acid,7 but even at neutral pH, the injury is more pronounced than that caused by gastric acid alone.6 In human neonates, exposure of the pulmonary epithelium to bile has been seen to cause lung inflammation and respiratory failure in the context of a congenital tracheobiliary fistula.8 In this situation, pure bile flows directly to the lung through the fistulous opening. The clinical course and radiographic changes seen in our cases suggest that aspiration of bile-containing fluid via the trachea can have pronounced effects on the neonatal lung. Bile aspiration should be considered whenever there is early onset of respiratory distress in an infant with high intestinal obstruction.
REFERENCES 1. Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues. Pediatr Clin North Am 1993; 40:955-81. 2. Ohlsson A, Cumming W, Najjar H. Neonatal aspiration syndrome due to vernix caseosa. Pediatr Radiol 1985;15:193-5. 3. Perlman M, Bar-Ziv J. Congenital ichthyosis and neonatal pulmonary disease. Pediatrics 1974;53:573-5. 4. Gordon E, South M, McDougall PN, Dargaville PA. The blood aspiration syndrome as a cause of respiratory distress in the newborn. J Pediatr 2003;142:200-2. 5. Oelberg DG, Downey SA, Flynn MM. Bile salt-induced intracellular Ca++ accumulation in type II pneumocytes. Lung 1990;168:297-308. 6. Henderson RD, Fung K, Cullen JB, Milne EN, Marryatt G. Bile aspiration: an experimental study in rabbits. Can J Surg 1975;18:64-9. 7. Porembka D, Kier A, Sehlorst S, Boyce S, Orlowski JP, Davis K. The pathophysiologic changes following bile aspiration in a porcine lung model. Chest 1993;104:919-24. 8. Tekant GA, Joseph VT, Cheah SL. Congenital tracheobiliary fistula. J Pediatr Surg 1994;29:594-5. 9. Dixon JC, Penman DM, Soothill PW. The influence of bowel atresia in gastroschisis on fetal growth, cardiotocograph, abnormalities, and amniotic fluid staining. Br J Obstet Gynecol 2000;107:572-5.
The Journal of Pediatrics March 2004