Surfactant for RDS: When and how?

June 2004 issue of The Journal of Pediatrics contains two articles about surfactant therapy for respiratory distress syndrome (RDS). The big picture is that surfactant treatments for RDS are safe and very effective and are the standard of care. However, considerable controversy remains about when to treat infants at risk for or with RDS, how to give those treatments, and what sort of ventilatory support is best and for how long. Variables generating uncertainty are timing of treatment (at delivery/after initial stabilization), ventilatory support before and after treatment (continuous positive airway pressure [CPAP]/mechanical ventilation and type of mechanical ventilation), techniques for treatment (pharyngeal at delivery, number and volumes of boluses for each treatment, management after treatment). Each variable is further complicated by the gestational age/birth weight of each infant and the clinical status of the infant at birth. The Texas Neonatal Research Group performed a multicenter randomized trial to ask if larger infants with RDS and an oxygen requirement of would benefit from immediate intubation and surfactant treatment compared with expectant management with surfactant treatment if the respiratory disease progressed. For this group of infants, an early intervention with surfactant treatment was of no benefit. This result supports the current clinical trend to use CPAP therapy for larger infants with RDS. Kaiser, Gauss, and Williams evaluated the effect of surfactant treatment on cerebral blood flow in very-low-birth-weight (VLBW) infants using continuous monitoring. They demonstrate that routine surfactant treatments result in a peak increase in Pco2 of about 20 mm Hg 15 minutes after the surfactant treatment. The increase in Pco2 is associated with an increase in cerebral blood flow velocity, demonstrating intact autoregulation of cerebral blood flow in these VLBW infants. The peak increase in Pco2 at 15 minutes probably results from airway occlusion with the surfactant suspension. The importance of the study is that it points out that surfactant therapy does cause transient physiologic changes that need to be balanced against benefit. For example, the decision to treat an infant on CPAP with surfactant requires intubation followed by surfactant instillation. Both procedures cause physiologic abnormalities that need to be recognized. Strategies for when to treat which patient and how remain hot topics in neonatology.

Early surfactant for neonates with mild to moderate RDS
Objective The researchers studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiring mechanical ventilation.
Study design A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight 1250 grams, gestational age weeks, postnatal age 4 to 24 hours, FIO2 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n=65) or expectant management (n=67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation.
Results Infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P=.001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk=0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes).
Conclusions Routine elective intubation for administration of surfactant to preterm infants 1250 grams with mild to moderate RDS is not recommended.
( The Journal of Pediatrics, June 2004 • Volume 144 • Number 6 )

Surfactant administration acutely affects cerebral and systemic hemodynamics and gas exchange in very-low-birth-weight infants
Objectives To determine whether surfactant administration affects cerebral and systemic hemodynamics and gas exchange in very low birth weight infants and to determine the predominant factor influencing changes in mean cerebral blood flow velocity (mCBFv) after surfactant instillation.
Study design Fourteen very low birth weight infants with respiratory distress syndrome had continuous monitoring of mCBFv, PaCO2, mean arterial blood pressure (MABP), and PaO2 before, during, and after the second dose of surfactant. Peak values and relative changes of the 4 variables for 45 minutes after surfactant were calculated. Logistic regression was used to determine the predominant factor influencing changes in mCBFv after surfactant.
Results Birth weight was 832 ± 162 grams and gestational age was 25.7 ± 1.5 weeks. The time from birth to monitoring was 6.9 ± 1.0 hours. Mean CBFv increased 75.7% ± 51.6% after surfactant and peaked at 14.4 ± 5.9 minutes. PaCO2 was highly associated (OR=107.3, P < .0001) with mCBFv; as PaCO2 increased, mCBFv increased. In contrast, MABP (OR=6.7, P=.047) had less impact on mCBFv. PaO2 was not associated with mCBFv.
Conclusions The increases in mCBFv after surfactant administration were predominantly due to increases in PaCO2 and not changes in MABP.
( Kaiser, Gass et al.in The Journal of Pediatrics, June 2004 •Volume144 •Number 6)

Early Extubation and Nasal Continuous Positive Airway Pressure After Surfactant Treatment for Respiratory Distress Syndrome Among Preterm Infants <30 Weeks’ Gestation Objective. To test the hypothesis that preterm infants with infant respiratory distress syndrome who are treated with nasal continuous positive airway pressure (NCPAP) and surfactant administration followed by immediate extubation and NCPAP application (SURF-NCPAP group) demonstrate less need for mechanical ventilation (MV), compared with infants who receive MV after surfactant administration (SURF-
Methods. A prospective randomized study was conducted, in which infants <30 weeks’ gestation were randomized to the SURF-NCPAP group or the SURF-MV group.
Results. At 7 days of life, no patient in the SURF-NCPAP group but 6 patients (43%) in the SURF-MV group still were undergoing MV. The duration of oxygen therapy, NCPAP, and MV, the need for a second dose of surfactant, and the length of stay in the intensive care unit were significantly greater in the SURF-MV group.
Conclusions. The immediate reinstitution of NCPAP after surfactant administration for infants with infant respiratory distress syndrome is safe and beneficial, as indicated by the lesser need for MV and the briefer requirement for respiratory supports, compared with the institution of MV after surfactant treatment. Moreover, this strategy contributed to reducing the need for surfactant treatment and reducing the time and costs involved in keeping the infants in the neonatal intensive care unit.( PEDIATRICS Vol. 113 No. 6 June 2004, pp. e560-e563)

Timing of Initial Surfactant Treatment for Infants 23 to 29 Weeks’ Gestation: Is Routine Practice Evidence Based?
Objective. To describe the timing of initial surfactant treatment for high-risk preterm infants in routine practice and compare these findings with evidence from randomized trials and published guidelines.
Methods. Data from the Vermont Oxford Network Database for infants who were born from 1998 to 2000 and had birth weights 401 to 1500 g and gestational ages of 23 to 29 weeks were analyzed to determine the time after birth at which the initial dose of surfactant was administered.
Conclusion. Although the time after birth at which the first dose of surfactant is administered to infants 23 to 29 weeks’ gestation decreased from 1998 to 2000, in 2000 many infants still received delayed treatment, and delivery room surfactant administration was not routinely practiced at most units. The researchers conclude that there is a gap between evidence from randomized controlled trials that supports prophylactic or early surfactant administration and what is actually done in routine practice at many units.( PEDIATRICS Vol. 113 No. 6 June 2004, pp. 1593-1602)


Other News :
Measurement of Interleukin 8 in Combination With CRP Reduced Unnecessary Antibiotic Therapy in Newborns
Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement.
Methods. Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation.
Results. In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group.
Conclusions. The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe. (PEDIATRICS Vol. 114 No. 1 July 2004, pp. 1-8)

Early enteral feeding and nosocomial sepsis in very low birthweight infants
The interrelations between early enteral feeding, necrotising enterocolitis (NEC), and nosocomial sepsis (NS) remain unclear.
Objective: To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight (VLBW< 1500 g) infants.
Methods: Data were collected on the pattern of enteral feeding and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995–2001. Enteral feeding was compared between infants with and without NS and/or NEC.
Results: The study sample included 385 infants. Of these, 163 (42%) developed NS and 35 (9%) developed NEC. Enteral feeding was started at a significantly earlier mean (SD) age in infants who did not develop nosocomial sepsis (2.8 (2.6) v 4.8 (3.7) days, p  =  0.0001). Enteral feeding was introduced at the same age in babies who did or did not develop NEC (3.1 (2) v 3.7 (3) days, p  =  0.28). Over the study period, the mean annual age at the start of enteral feeding fell consistently, and this correlated with the mean annual incidence of NS (r2  =  0.891, p  =  0.007). Multiple logistic regression analysis showed age at start of enteral feeding, respiratory distress syndrome, and birth weight to be the most significant predictors of risk of NS (p  =  0.0005, p  =  0.024, p  =  0.011).
Conclusions: Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC in VLBW infants. These findings support the use of early enteral feeding in this high risk population, but this needs to be confirmed in a large randomised controlled trial.
(Archives of Disease in Childhood Fetal and Neonatal Edition 2004;89:F289)