Eur J Pediatr (1990) 149 : 727-729
EuropeanJournalof
Pediatrics
9 Springer-Verlag 1990
Surfactant treatment for respiratory distress syndrome following prolonged rupture of membranes T. R. J. Tubman 1 and H. L. Halliday 2 1NICU, Royal Maternity Hospital, 2Department of Child Health, Queen's University Belfast, Belfast BT12 6BJ, Northern Ireland Received May 4, 1989 / Accepted January 5, 1990
Abstract. Surfactant r e p l a c e m e n t for respiratory distress s y n d r o m e ( R D S ) following very p r o l o n g e d r u p t u r e of the m e m b r a n e s ( P R O M ) is of uncertain value. Seven p r e t e r m babies b o r n after P R O M ( m e d i a n 48 days, range 2 2 - 6 1 days) were c o m p a r e d with 14 babies without P R O M . All had clinical and radiological evidence of severe R D S , requiring mechanical ventilation with inspired o x y g e n concentrations __>60%. Indices of oxygenation and " c o m p l i a n c e " were c o m p a r e d before and serially up to 4 h after surfactant treatment. B e f o r e treatm e n t the P R O M babies had m o r e severe lung disease, based u p o n higher inspired o x y g e n c o n c e n t r a t i o n and m e a n airway pressure, and lower arterial/alveolar oxygen tension ratio and ventilator efficiency index. These indices were significantly worse in the P R O M g r o u p than the c o m p a r i s o n g r o u p at all times after treatment. T h e p o o r r e s p o n s e of the P R O M group, p e r h a p s because of p u l m o n a r y hypoplasia, suggests that surfactant r e p l a c e m e n t m a y not be beneficial for R D S in these babies.
Key words: Surfactant - P r o l o n g e d m e m b r a n e rupture P u l m o n a r y hypoplasia
Introduction T h e r e is c o n t r o v e r s y concerning the effect of p r o l o n g e d rupture of the m e m b r a n e s on the incidence of respiratory distress s y n d r o m e [7]. T h e r e is, h o w e v e r , an increased risk of congenital p n e u m o n i a or p u l m o n a r y hypoplasia, the latter particularly if o l i g o h y d r a m n i o s is present [11]. Offprint requests to: T. R. J. Tubman Abbreviations: a/A PO2 = arterial/alveolar oxygen tension
ratio; FiO2 = fraction of inspired oxygen; PROM = prolonged rupture of the membranes; RDS = respiratory distress syndrome; VEI = ventilator efficiency index
N a t u r a l surfactant r e p l a c e m e n t has b e e n shown to be an effective t r e a t m e n t in n e o n a t a l respiratory distress s y n d r o m e ( R D S ) , improving survival [2] and reducing ' the incidence of complications such as p n e u m o t h o r a x [2, 5] and intraventricular h a e m o r r h a g e [5]. T o determine the effect of surfactant in R D S following p r o l o n g e d rupture of m e m b r a n e s ( P R O M ) , we c o m p a r e d the responses of a group of these babies with those of babies whose m o t h e r s did not have P R O M .
Patients and methods The study group consisted of seven preterm infants born following pregnancies complicated by PROM of greater than 3 weeks duration (median 48, range 22-61 days), where oligohydramnios had been diagnosed by ultrasound. They had been excluded from entry into the European Multicentre trial of surfactant replacement by virtue of PROM greater than 3 weeks [2]. However, they had all been given surfactant outside the trial in a non-randomised fashion in an attempt to improve their clinical condition. Response to surfactant within the subsequent 4h was compared with that of 14 preterm infants who had been treated in the trial. Two comparison babies were selected for each index case, one before and one after each PROM baby as they occurred in the trial. All babies had clinical and radiological signs suggestive of severe RDS due to surfactant deficiency, were aged between 2 and 15 h from birth and required mechanical ventilation with oxygen concentrations -->60% [2, 5]. Biochemical tests for fetal lung maturity were not performed. All but two of the comparison group had either been delivered by caesarean section before membrane rupture or had ruptured membranes for less than 24 h. In the two exceptions the membranes had been ruptured for 7 and 10 days respectively. After surfactant administration [2, 5], babies were assessed by arterial blood gases, ventilator settings and arterial/alveolar oxygen tension ratio (a/A PO2), which is an index of oxygenation. Changes in "lung compliance" were assessed using the ventilator efficiency index (VEI). This index is a semi-empirical analog of dynamic compliance, and has been shown to correlate reasonably well with it [10] (see appendix). Measurements were made before surfactant instillation and at 5, 15, 30, 60, 120 and 240min afterwards. Statistical analysis was performed using the Mann-Whitney U test, paired t test and
728 Table 1. Patient characteristics, ventilator settings and calculated indices before surfactant replacement
PROM group (~ = 7) Gestational agea (week) Birth weight (g)~ Male : Female Median age treated (h) (range) Maximum FiO2a Mean airway pressure (cm H20) a a/APO2 ~ VEI (ml/mmHg/kg) ~
Comparison group (~ = 14)
28.0 (1.3) 1084 (197) 4: 3
28.0 (2.2) 1169 (284) 8 :6
NS NS NS
5.5 (2-15) 0.97 (0.03)
5 (2-14) 0.79 (0.13)
NS , 0
0 0.4"
0.3
r(D 0
;=
0.2-
r
0.1-
t-.
; 1'530
b
60
120
Died
Autopsy Age at death
PROM group (n = 7) 4 3 10 h
a Mean (sd) FiO2 = fraction of inspired oxygen; a/APO2 = arterial/alveolar oxygen tension ratio; VEI = ventilator efficiency index, NS = not significant
O~
Table 2. Postmortem findings
240
9 days 20 days Comparison group (n = 14) 3a 2 56 h 16 days
Pulmonary findings
Lung: body weight ratio
Poorly developed, atelectatic Poorly aerated, fibrotic Consolidation
0.014
Hyaline membranes and haemorrhage Bronchopulmonary dysplasia
0.030 0.059 0.057 0.030
a All had membrane rupture < 24 h
between the two groups. Cultures of gastric aspirate taken at birth were positive in one baby from each group but neither of these had other evidence of sepsis such as abnormal white cell count or positive blood cultures. The P R O M group had m o r e severe disease before treatment, needing a significantly higher fraction of inspired oxygen (FiO2) and m e a n airway pressure, and having lower a/APO2 and V E I (Table 1). Both groups showed significant improvements in oxygenation after surfactant with increases in PaO2 and a/APO2 in the first 5 rain. These increases were greater in the comparison group (P < 0.001) and were not sustained beyond 5 min in the P R O M group (Fig. 1). By contrast, a/APO2 significantly improved in the comparison babies up to and including 4 h after treatment, indicating sustained beneficial changes in oxygenation. V E I was not affected in the P R O M babies and only began to show significant improvements in comparison babies from i h after treatment (P < 0.05). a/APO2 and V E I were significantly greater in the comparison group at all times up to and including four hours (Fig. 1). T h r e e of the P R O M group and 11 of the comparison babies survived. Of the survivors 2 P R O M babies and 3 of the comparison group developed bronchopulmonary dysplasia. Neither of these differences was statistically significant. Available p o s t m o r t e m detais are shown in Table 2.
Time (rain)
Fig. 1. Changes in arterial/alveolar oxygen tension ratio (a/APO2) (a) and ventilator efficiency index (VEI) (b) following surfactant replacement. (Mean + sem). A, PROM group; e, comparison group; *P < 0.01
Fisher's exact test where appropriate. P values where quoted are two-tailed.
Results
Clinical characteristics of the two groups are shown in Table 1. There were no differences in m e a n birthweight, gestational age, male : female ratio or age when treated,
Discussion
Babies in the P R O M group were born after an average of 6 weeks ruptured membranes. Oligohydramnios was present in these pregnancies and three babies were born with limb contractures. It is therefore likely that all of them had developed some degree of pulmonary hypoplasia. Pulmonary hypoplasia may develop after severe oligohydramnios even if m e m b r a n e rupture has been of relatively short duration [12], but it is difficult to diagnose even at autopsy. Three of the four P R O M babies who died had an autopsy p e r f o r m e d (Table 2); two of these had a lung: body weight ratio greater than 0.022 suggesting normally developed lungs [1], but lung weight
729 m a y increase following the onset of mechanical ventilation [4]. Radial alveolar count m a y be a m o r e accurate indicator of pulmonary hypoplasia than weight ratios [1], but was not p e r f o r m e d in this study. Non-compliant lungs m a y have b e e n caused by congenital pneumonia, but only one of the P R O M babies had a positive gastric aspirate and none had positive blood cultures or leucocytosis. At autopsy only one baby, who died at 20 days had evidence of pneumonia. Babies delivered without P R O M showed striking improvements in oxygenation following surfactant. This was not unexpected [2] and m a y be due to correction of ventilation-perfusion inequalities [3]. The very brief i m p r o v e m e n t in the P R O M group is m o r e difficult to explain. Surfactant deficiency has been demonstrated in the lungs of babies born after oligohydramnios [8, 13], and this could have been temporarily corrected by exogenous surfactant. Alternatively, i m p r o v e m e n t m a y have been due to some unknown factor present in the surfactant. Rapid i m p r o v e m e n t in oxygenation of the comparison babies was not matched by concomitant changes in lung compliance as represented by VEI. In a n u m b e r of studies where p r e t e r m animals have been given surfactant, compliance also changed less rapidly than oxygenation [9]. However, changes in transthoracic impedance following surfactant administration, suggest that compliance m a y improve as rapidly as changes in oxygenation [3]. In this study, delay in changes in V E I may have been due to later reduction in distending pressure, m a d e in line with the protocol of the E u r o p e a n multicentre trial [2]. As V E I is an index calculated from ventilator settings, it can be low in situations where a p e a k pressure higher than necessary is applied. Lung compliance could then be under-estimated in an over-ventilated baby, who m a y actually have improved after treatment. V E I did not change within the 4 h study period in the P R O M group, and these babies continued to need high m e a n inspiratory pressures. This suggests that the p r e d o m i n a n t pathology after prolonged rupture of m e m b r a n e s is hypoplasia rather than surfactant deficiency, or "dry lung syndrome" which is perhaps due to airway collapse [6]. We have found in a small non-randomized study that R D S following very prolonged m e m b r a n e rupture does not respond to surfactant replacement by sustained improvements in either oxygenation or lung compliance. This form of treatment m a y not therefore be appropriate for respiratory distress in these circumstances. However, this should be addressed further in a randomized controlled study to determine whether all such babies should be excluded f r o m surfactant replacement therapy in the future.
Acknowledgements.The surfactant was prepared in Stockholm by Dr.T. Curstedt and Dr.B.Robertson, supported by the Swedish Medical Research Council (Project number 3351) and the Swedish National Association against Heart and Chest Diseases. Dr. T. R. J Tubman was supported by a grant from the Perinatal Trust fund of Northern Ireland. We thank Lynda Thompson for typing the manuscript.
Appendix Calculation of indices of oxygenation and compliance Arterial/alveolar PO2 ratio (a/A PO2): a/A PO2 = PaOz/[(FiO2 • 713) - (PaCO2/0.8)] Ventilator efficiency index (VEI): VEI
3800
=
(PIP - P E E P ) • f • PaCO2 PIP
= p e a k inspiratory pressure, m m H g
P E E P = p e a k and-expiratory pressure, m m H g f
= ventilator rate
References 1. Askenazi SS, Perlman M (1979) Pulmonary hypoplasia: lung weight and radial alveolar count as criteria of diagnosis. Arch Dis Child 54 : 614-618 2. Collaborative European Multicentre Study Group (1988) Surfactant replacement therapy in severe neonatal respiratory distress syndrome; an international randomised clinical trial. Pediatrics 82 : 683-691 3. Halliday HL, McCord FB, McClure BG, Reid MMcC (1989) Acute effects of instillation of surfactant in severe respiratory distress syndrome. Arch Dis Child 64:13-16 4. Hislop A, Wigglesworth JS, Desai R, Aber V (1987) The effects of preterm delivery and mechanical ventilation on human lung growth. Early Hum Dev 15 : 147-164 5. McCord FB, Curstedt T, Halliday HL, McClure BG, Reid MMcC, Robertson B (1988) Surfactant treatment and incidence of intraventricular haemorrhage in severe respiratory distress syndrome. Arch Dis Child 63 : 10-16 6. McIntosh N (1988) Dry lung syndrome after oligohydramnios. Arch Dis Child 63 : 190-193 7. Mead PB (1983) Premature rupture of the membranes. In: Chiswick ML (ed) Recent advances in perinatal medicine, vol. 1. Churchill Livingstone, Edinburgh, pp 77-84 8. Nakamura Y, Yamamoto I, Funatsu Y, Motomura K, Fukuda S, Hashimoto T, Morimatsu M (1988) Decreased surfactant level in the lung with oligohydramnios: a morphometric and biochemical study. J Pediatr 112 : 471-474 9. Noack G, Berggren P, Curstedt T, Grossman G, Herin P, Mortensson W, Nilson R, Robertson B (1987) Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant. Acta Paediatr Scand 76 : 697-705 10. Notter RH, Egan EA, Kwong MS, Holm BA, Shapiro DL (1985) Lung surfactant replacement in premature lambs with extracted lipids from bovine lung lavage: effects of dose, dispersion technique, and gestational age. Pediatr Res 19:569577 11. Perlman M, Williams J, Hirsch M (1976) Neonatal pulmonary hypoplasia after prolonged leakage of amniotic fluid. Arch Dis Child 51 : 349-353 12. Thibeault DW, Beatty EC, Hall RT, Bowen SK, O'Neill DH (1985) Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios. J Pediatr 107: 273-277 13. Wigglesworth JS, Desai R, Guerrini P (1981) Fetal lung hypoplasia: biochemical and structural variations and their possible significance. Arch Dis Child 56 : 606-615
EuropeanJournalof
Pediatrics
9 Springer-Verlag 1990
Surfactant treatment for respiratory distress syndrome following prolonged rupture of membranes T. R. J. Tubman 1 and H. L. Halliday 2 1NICU, Royal Maternity Hospital, 2Department of Child Health, Queen's University Belfast, Belfast BT12 6BJ, Northern Ireland Received May 4, 1989 / Accepted January 5, 1990
Abstract. Surfactant r e p l a c e m e n t for respiratory distress s y n d r o m e ( R D S ) following very p r o l o n g e d r u p t u r e of the m e m b r a n e s ( P R O M ) is of uncertain value. Seven p r e t e r m babies b o r n after P R O M ( m e d i a n 48 days, range 2 2 - 6 1 days) were c o m p a r e d with 14 babies without P R O M . All had clinical and radiological evidence of severe R D S , requiring mechanical ventilation with inspired o x y g e n concentrations __>60%. Indices of oxygenation and " c o m p l i a n c e " were c o m p a r e d before and serially up to 4 h after surfactant treatment. B e f o r e treatm e n t the P R O M babies had m o r e severe lung disease, based u p o n higher inspired o x y g e n c o n c e n t r a t i o n and m e a n airway pressure, and lower arterial/alveolar oxygen tension ratio and ventilator efficiency index. These indices were significantly worse in the P R O M g r o u p than the c o m p a r i s o n g r o u p at all times after treatment. T h e p o o r r e s p o n s e of the P R O M group, p e r h a p s because of p u l m o n a r y hypoplasia, suggests that surfactant r e p l a c e m e n t m a y not be beneficial for R D S in these babies.
Key words: Surfactant - P r o l o n g e d m e m b r a n e rupture P u l m o n a r y hypoplasia
Introduction T h e r e is c o n t r o v e r s y concerning the effect of p r o l o n g e d rupture of the m e m b r a n e s on the incidence of respiratory distress s y n d r o m e [7]. T h e r e is, h o w e v e r , an increased risk of congenital p n e u m o n i a or p u l m o n a r y hypoplasia, the latter particularly if o l i g o h y d r a m n i o s is present [11]. Offprint requests to: T. R. J. Tubman Abbreviations: a/A PO2 = arterial/alveolar oxygen tension
ratio; FiO2 = fraction of inspired oxygen; PROM = prolonged rupture of the membranes; RDS = respiratory distress syndrome; VEI = ventilator efficiency index
N a t u r a l surfactant r e p l a c e m e n t has b e e n shown to be an effective t r e a t m e n t in n e o n a t a l respiratory distress s y n d r o m e ( R D S ) , improving survival [2] and reducing ' the incidence of complications such as p n e u m o t h o r a x [2, 5] and intraventricular h a e m o r r h a g e [5]. T o determine the effect of surfactant in R D S following p r o l o n g e d rupture of m e m b r a n e s ( P R O M ) , we c o m p a r e d the responses of a group of these babies with those of babies whose m o t h e r s did not have P R O M .
Patients and methods The study group consisted of seven preterm infants born following pregnancies complicated by PROM of greater than 3 weeks duration (median 48, range 22-61 days), where oligohydramnios had been diagnosed by ultrasound. They had been excluded from entry into the European Multicentre trial of surfactant replacement by virtue of PROM greater than 3 weeks [2]. However, they had all been given surfactant outside the trial in a non-randomised fashion in an attempt to improve their clinical condition. Response to surfactant within the subsequent 4h was compared with that of 14 preterm infants who had been treated in the trial. Two comparison babies were selected for each index case, one before and one after each PROM baby as they occurred in the trial. All babies had clinical and radiological signs suggestive of severe RDS due to surfactant deficiency, were aged between 2 and 15 h from birth and required mechanical ventilation with oxygen concentrations -->60% [2, 5]. Biochemical tests for fetal lung maturity were not performed. All but two of the comparison group had either been delivered by caesarean section before membrane rupture or had ruptured membranes for less than 24 h. In the two exceptions the membranes had been ruptured for 7 and 10 days respectively. After surfactant administration [2, 5], babies were assessed by arterial blood gases, ventilator settings and arterial/alveolar oxygen tension ratio (a/A PO2), which is an index of oxygenation. Changes in "lung compliance" were assessed using the ventilator efficiency index (VEI). This index is a semi-empirical analog of dynamic compliance, and has been shown to correlate reasonably well with it [10] (see appendix). Measurements were made before surfactant instillation and at 5, 15, 30, 60, 120 and 240min afterwards. Statistical analysis was performed using the Mann-Whitney U test, paired t test and
728 Table 1. Patient characteristics, ventilator settings and calculated indices before surfactant replacement
PROM group (~ = 7) Gestational agea (week) Birth weight (g)~ Male : Female Median age treated (h) (range) Maximum FiO2a Mean airway pressure (cm H20) a a/APO2 ~ VEI (ml/mmHg/kg) ~
Comparison group (~ = 14)
28.0 (1.3) 1084 (197) 4: 3
28.0 (2.2) 1169 (284) 8 :6
NS NS NS
5.5 (2-15) 0.97 (0.03)
5 (2-14) 0.79 (0.13)
NS , 0
0 0.4"
0.3
r(D 0
;=
0.2-
r
0.1-
t-.
; 1'530
b
60
120
Died
Autopsy Age at death
PROM group (n = 7) 4 3 10 h
a Mean (sd) FiO2 = fraction of inspired oxygen; a/APO2 = arterial/alveolar oxygen tension ratio; VEI = ventilator efficiency index, NS = not significant
O~
Table 2. Postmortem findings
240
9 days 20 days Comparison group (n = 14) 3a 2 56 h 16 days
Pulmonary findings
Lung: body weight ratio
Poorly developed, atelectatic Poorly aerated, fibrotic Consolidation
0.014
Hyaline membranes and haemorrhage Bronchopulmonary dysplasia
0.030 0.059 0.057 0.030
a All had membrane rupture < 24 h
between the two groups. Cultures of gastric aspirate taken at birth were positive in one baby from each group but neither of these had other evidence of sepsis such as abnormal white cell count or positive blood cultures. The P R O M group had m o r e severe disease before treatment, needing a significantly higher fraction of inspired oxygen (FiO2) and m e a n airway pressure, and having lower a/APO2 and V E I (Table 1). Both groups showed significant improvements in oxygenation after surfactant with increases in PaO2 and a/APO2 in the first 5 rain. These increases were greater in the comparison group (P < 0.001) and were not sustained beyond 5 min in the P R O M group (Fig. 1). By contrast, a/APO2 significantly improved in the comparison babies up to and including 4 h after treatment, indicating sustained beneficial changes in oxygenation. V E I was not affected in the P R O M babies and only began to show significant improvements in comparison babies from i h after treatment (P < 0.05). a/APO2 and V E I were significantly greater in the comparison group at all times up to and including four hours (Fig. 1). T h r e e of the P R O M group and 11 of the comparison babies survived. Of the survivors 2 P R O M babies and 3 of the comparison group developed bronchopulmonary dysplasia. Neither of these differences was statistically significant. Available p o s t m o r t e m detais are shown in Table 2.
Time (rain)
Fig. 1. Changes in arterial/alveolar oxygen tension ratio (a/APO2) (a) and ventilator efficiency index (VEI) (b) following surfactant replacement. (Mean + sem). A, PROM group; e, comparison group; *P < 0.01
Fisher's exact test where appropriate. P values where quoted are two-tailed.
Results
Clinical characteristics of the two groups are shown in Table 1. There were no differences in m e a n birthweight, gestational age, male : female ratio or age when treated,
Discussion
Babies in the P R O M group were born after an average of 6 weeks ruptured membranes. Oligohydramnios was present in these pregnancies and three babies were born with limb contractures. It is therefore likely that all of them had developed some degree of pulmonary hypoplasia. Pulmonary hypoplasia may develop after severe oligohydramnios even if m e m b r a n e rupture has been of relatively short duration [12], but it is difficult to diagnose even at autopsy. Three of the four P R O M babies who died had an autopsy p e r f o r m e d (Table 2); two of these had a lung: body weight ratio greater than 0.022 suggesting normally developed lungs [1], but lung weight
729 m a y increase following the onset of mechanical ventilation [4]. Radial alveolar count m a y be a m o r e accurate indicator of pulmonary hypoplasia than weight ratios [1], but was not p e r f o r m e d in this study. Non-compliant lungs m a y have b e e n caused by congenital pneumonia, but only one of the P R O M babies had a positive gastric aspirate and none had positive blood cultures or leucocytosis. At autopsy only one baby, who died at 20 days had evidence of pneumonia. Babies delivered without P R O M showed striking improvements in oxygenation following surfactant. This was not unexpected [2] and m a y be due to correction of ventilation-perfusion inequalities [3]. The very brief i m p r o v e m e n t in the P R O M group is m o r e difficult to explain. Surfactant deficiency has been demonstrated in the lungs of babies born after oligohydramnios [8, 13], and this could have been temporarily corrected by exogenous surfactant. Alternatively, i m p r o v e m e n t m a y have been due to some unknown factor present in the surfactant. Rapid i m p r o v e m e n t in oxygenation of the comparison babies was not matched by concomitant changes in lung compliance as represented by VEI. In a n u m b e r of studies where p r e t e r m animals have been given surfactant, compliance also changed less rapidly than oxygenation [9]. However, changes in transthoracic impedance following surfactant administration, suggest that compliance m a y improve as rapidly as changes in oxygenation [3]. In this study, delay in changes in V E I may have been due to later reduction in distending pressure, m a d e in line with the protocol of the E u r o p e a n multicentre trial [2]. As V E I is an index calculated from ventilator settings, it can be low in situations where a p e a k pressure higher than necessary is applied. Lung compliance could then be under-estimated in an over-ventilated baby, who m a y actually have improved after treatment. V E I did not change within the 4 h study period in the P R O M group, and these babies continued to need high m e a n inspiratory pressures. This suggests that the p r e d o m i n a n t pathology after prolonged rupture of m e m b r a n e s is hypoplasia rather than surfactant deficiency, or "dry lung syndrome" which is perhaps due to airway collapse [6]. We have found in a small non-randomized study that R D S following very prolonged m e m b r a n e rupture does not respond to surfactant replacement by sustained improvements in either oxygenation or lung compliance. This form of treatment m a y not therefore be appropriate for respiratory distress in these circumstances. However, this should be addressed further in a randomized controlled study to determine whether all such babies should be excluded f r o m surfactant replacement therapy in the future.
Acknowledgements.The surfactant was prepared in Stockholm by Dr.T. Curstedt and Dr.B.Robertson, supported by the Swedish Medical Research Council (Project number 3351) and the Swedish National Association against Heart and Chest Diseases. Dr. T. R. J Tubman was supported by a grant from the Perinatal Trust fund of Northern Ireland. We thank Lynda Thompson for typing the manuscript.
Appendix Calculation of indices of oxygenation and compliance Arterial/alveolar PO2 ratio (a/A PO2): a/A PO2 = PaOz/[(FiO2 • 713) - (PaCO2/0.8)] Ventilator efficiency index (VEI): VEI
3800
=
(PIP - P E E P ) • f • PaCO2 PIP
= p e a k inspiratory pressure, m m H g
P E E P = p e a k and-expiratory pressure, m m H g f
= ventilator rate
References 1. Askenazi SS, Perlman M (1979) Pulmonary hypoplasia: lung weight and radial alveolar count as criteria of diagnosis. Arch Dis Child 54 : 614-618 2. Collaborative European Multicentre Study Group (1988) Surfactant replacement therapy in severe neonatal respiratory distress syndrome; an international randomised clinical trial. Pediatrics 82 : 683-691 3. Halliday HL, McCord FB, McClure BG, Reid MMcC (1989) Acute effects of instillation of surfactant in severe respiratory distress syndrome. Arch Dis Child 64:13-16 4. Hislop A, Wigglesworth JS, Desai R, Aber V (1987) The effects of preterm delivery and mechanical ventilation on human lung growth. Early Hum Dev 15 : 147-164 5. McCord FB, Curstedt T, Halliday HL, McClure BG, Reid MMcC, Robertson B (1988) Surfactant treatment and incidence of intraventricular haemorrhage in severe respiratory distress syndrome. Arch Dis Child 63 : 10-16 6. McIntosh N (1988) Dry lung syndrome after oligohydramnios. Arch Dis Child 63 : 190-193 7. Mead PB (1983) Premature rupture of the membranes. In: Chiswick ML (ed) Recent advances in perinatal medicine, vol. 1. Churchill Livingstone, Edinburgh, pp 77-84 8. Nakamura Y, Yamamoto I, Funatsu Y, Motomura K, Fukuda S, Hashimoto T, Morimatsu M (1988) Decreased surfactant level in the lung with oligohydramnios: a morphometric and biochemical study. J Pediatr 112 : 471-474 9. Noack G, Berggren P, Curstedt T, Grossman G, Herin P, Mortensson W, Nilson R, Robertson B (1987) Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant. Acta Paediatr Scand 76 : 697-705 10. Notter RH, Egan EA, Kwong MS, Holm BA, Shapiro DL (1985) Lung surfactant replacement in premature lambs with extracted lipids from bovine lung lavage: effects of dose, dispersion technique, and gestational age. Pediatr Res 19:569577 11. Perlman M, Williams J, Hirsch M (1976) Neonatal pulmonary hypoplasia after prolonged leakage of amniotic fluid. Arch Dis Child 51 : 349-353 12. Thibeault DW, Beatty EC, Hall RT, Bowen SK, O'Neill DH (1985) Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios. J Pediatr 107: 273-277 13. Wigglesworth JS, Desai R, Guerrini P (1981) Fetal lung hypoplasia: biochemical and structural variations and their possible significance. Arch Dis Child 56 : 606-615
