SURFACTANT THERAPY IN NEONATAL CARE [Review Article]

2005

PEDIATRICS, 2008

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes indications, administration, formulations, and outcomes for surfactant-replacement therapy. The impact of antenatal steroids and continuous positive airway pressure on outcomes and surfactant use in preterm infants is reviewed. Because respiratory insufficiency may be a component of multiorgan dysfunction, preterm and term infants receiving surfactant-replacement therapy should be managed in facilities with technical and clinical expertise to administer surfactant and provide multisystem support. BACKGROUND Surfactant replacement was established as an effective and safe therapy for immaturity-related surfactant deficiency by the early 1990s. 1-21 Systematic reviews of randomized, controlled trials have confirmed that surfactant replacement reduces initial inspired oxygen and ventilation requirements as well as the incidence of respiratory distress syndrome, death, pneumothorax, and pulmonary interstitial emphysema (Table 1). 2-4,13 After the initial surfactant efficacy and safety trials were conducted, additional studies led to refinements in treatment strategies, 5-7,10,11,13,22-36 choice of preparations, 37-54 techniques for administration, 55-65 and indications other than respiratory distress syndrome. 66-87 The preponderance of evidence indicates that surfactant replacement increases survival rates without an increase in risk of disabilities. Thus, surfactant replacement is associated with an absolute increase in the number of preterm infants who survive with and without disabilities. 88-112 However, the risk of long-term disability remains uncertain, because few follow-up studies at school age and adolescence for preterm infants treated with surfactant have been reported.* Antenatal steroid use to stimulate structural maturation and surfactant synthesis in the fetal lung increased significantly after completion of the pivotal surfactant trials. 113-127 Investigations powered to assess the benefit of antenatal steroid exposure combined with surfactant replacement have not been reported, although secondary analyses of surfactant trials, 113,114,116 animal studies, 125-127 and clinical experience have indicated that, together, the 2 therapies have an additive effect. Preliminary studies of either continuous positive airway pressure alone or exogenous surfactants and rapid extubation to continuous positive airway pressure have suggested that the need for surfactant replacement and incidence of bronchopulmonary dysplasia in extremely preterm infants may be reduced. 128-144 The purpose of this clinical report is to update and expand our previous statement about surfactant replacement in newborn infants. 1 Specifically, the topics reviewed include efficacy in preterm infants, prophylactic versus rescue surfactant replacement, surfactant preparations and administration techniques, effects of surfactant on short-term and long-term outcomes, and surfactant replacement for respiratory disorders other than respiratory distress syndrome. The impact of antenatal steroid exposure and continuous positive airway

Journal of Perinatology, 2006

Many different surfactant preparations derived from animal sources, as well as synthetic surfactants, are available for the treatment of preterm infants with respiratory distress syndrome (RDS). Natural, modified surfactants containing surfactant-associated proteins appear to be more effective than non-protein-containing synthetic surfactants. Comparative trials with poractant alfa at a higher initial dose of 200 mg/kg appear to be associated with rapid weaning of FiO 2 , less need for additional doses, and decreased mortality in infants <32 weeks gestation when compared with beractant. Early rescue (<30 min of age) surfactant therapy is an effective method to minimize over treatment of some preterm infants who may not develop RDS. Surfactant therapy followed by rapid extubation to nasal ventilation appears to be more beneficial than continued mechanical ventilation. In near-term or term newborns with acute RDS, surfactant therapy has been shown to be 70% effective in improving respiratory failure.

The Journal of Pediatrics, 1991

A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (I) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full t reatmenl protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was _<2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of >0.5, and mean airway pressure was >__7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic' and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.48) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p= 0.0004). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment. Adverse effects (transient hypoxemia to 60% saturation) occurred in 4.5% of the infants treated with surfactant in the rescue group. Among preterm infants aged 24 to 29 weeks in this study, 19% did not have RDS. We conclude that surfactant treatment at 2 to 4 hours after birth (but after the onset of severe RDS) is as efficacious as treatment at birth. (J PEDIATR 1991;118:581-94)

Journal of Pediatric and Neonatal Individualized Medicine, 2013

Late preterm (LPT) neonates are at a high risk for respiratory distress soon after birth due to respiratory distress syndrome (RDS), transient tachypnea of the newborn, persistent pulmonary hypertension, and pneumonia along with an increased need for surfactant replacement therapy, continuous positive airway pressure, and ventilator support when compared with the term neonates. In the past, studies on outcomes of infants with respiratory distress have primarily focused on extremely premature infants, leading to a gap in knowledge and understanding of the developmental biology and mechanism of pulmonary diseases in LPT neonates. Surfactant deficiency is the most frequent etiology of RDS in very preterm and moderately preterm infants, while cesarean section and lung infection play major roles in RDS development in LPT infants. The clinical presentation and the response to surfactant therapy in LPT infants may be different than that seen in very preterm infants. Incidence of pneumonia and occurrence of pneumothorax are significantly higher in LPT and term infants. High rates of pneumonia in these infants may result in direct injury to the type II alveolar cells of the lung with decreasing synthesis, release, and processing of surfactant. Increased permeability of the alveolar capillary membrane to both fluid and solutes is known to result in entry of plasma proteins into the alveolar hypophase, further inhibiting the surface properties of surfactant. However, the oxygenation index value do not change dramatically after ventilation or surfactant administration in LPT infants with RDS compared to very preterm infants. These finding may indicate a different pathogenesis of RDS in late preterm and term infants. In conclusion, surfactant therapy may be of significant benefit in LPT infants with serious respiratory failure secondary to a number of insults. However, optimal timing and dose of administration are not so clear in this group. Additional randomized, controlled studies and evidence-based guidelines are needed for optimal surfactant therapy in these infants.

Neonatology, 2013

not specifically for surfactant dosage) within the first 2 h of life versus delayed selective surfactant administration to infants with established RDS were considered for review. Data Collection and Analysis: Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on type of surfactant preparation, gestational age, and exposure to prenatal steroids. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group. Main Results: Six randomized controlled trials met selection criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and four utilized animal-derived surfactant preparations. The meta-analyses demonstrate significant reductions in the risk of neonatal mortality (typical risk ratio (RR) 0.84; 95% confidence interval (CI) 0.74-0.95; typical risk difference (RD)-0.04; 95% CI-0.06 to-0.01; 6 studies; 3,577 infants), chronic lung disease (typical RR 0.69; 95% CI 0.55-0.86; typical RD-0.04; 95% CI-0.06 to-0.01; 3 studies; 3,041 infants), and chronic lung disease or death at 36 weeks (typical RR 0.83; 95% CI 0.75-0.91; typical RD-0.06; 95% CI-0.09 to-0.03; 3 studies; 3,050 infants) associated with early treatment of intubated infants with RDS. Intubated infants randomized to early selective surfactant administration also demonstrated a decreased risk of acute lung injury including a decreased risk of pneumothorax (typical RR 0.69; 95% CI 0.59-0.82; typical RD-0.05; 95% CI-0.08 to-0.03; 5 studies; 3,545 infants), pulmonary interstitial emphysema (typical RR 0.60; 95% CI 0.41-0.89; typical RD-0.06; 95% CI-0.10 to-0.02; 3 studies; 780 infants), and overall air leak syndromes (typical RR 0.61; 95% CI 0.48-0.78; typical RD-0.18; 95% CI-0.26 to-0.09; 2 studies; 463 infants). A trend

Journal of Pulmonary and Respiratory Medicine, 2013

Exogenous surfactant treatment of premature infants with Respiratory Distress Syndrome (RDS) has been the standard of care for more than two decades. There are now many studies comparing various surfactant preparations. Data are clear that the synthetic surfactants without surfactant proteins are inferior to animal derived surfactant preparations. In the United States, commercially available surfactants are beractant, calfactant, poractant alfa, and lucinactant. Relative efficacy of the various available animal derived surfactants in the United States appear to favor poractant alfa, the surfactant preparation with the highest concentrations of phospholipids and high concentration of surfactant proteins, allowing a higher initial dose of phospholipids in preterm infants less than 32 weeks. A new synthetic surfactant with a surfactant protein analog, lucinactant, has been recently been approved for use in the United States. Synthetic surfactants hold the possibility of surfactant treatments without potential animal-born infectious agents or animal proteins that could induce an immune response in fragile premature infants with multiple medical problems. New surfactant administration strategies are described, complimenting new respiratory support strategies, designed to minimize invasive mechanical ventilation and decrease the frequency of chronic lung disease. Minimally invasive surfactant administration strategies are being developed to accommodate these new respiratory support strategies. The goal of this manuscript is to review the available surfactant preparations and their administration strategies.

Medical Journal Armed Forces India, 2011

Pediatrics International, 2002

Background: Chronic lung disease (CLD) is generally known to develop among preterm infants who have severe respiratory distress syndrome (RDS) at birth. Many clinical trials have established the efficacy of surfactant replacement therapy to treat RDS at birth with differing doses. In this study, the preterm infants diagnosed to have RDS at birth and treated with one or two doses of surfactant, depending on the severity of the RDS, were studied to evaluate the effect of surfactant on the later development of CLD. Methods: A retrospective examination of case records of preterm infants who were born at ≤28 weeks gestation period were studied. The subjects received a natural surfactant product (survanta) between

The Turkish journal of pediatrics

A significant ratio of late preterm infants receives surfactant therapy (ST) for respiratory distress syndrome (RDS) and for other neonatal lung diseases characterized by surfactant inactivation or dysfunction. We aimed to investigate the clinical and therapeutic characteristics and outcomes of late preterm infants who received ST in the last 10 years in our neonatal intensive care unit. During the 10-year period, 77 late preterm infants received ST. The underlying lung diseases were RDS in 51 (66.2%), congenital pneumonia in 15 (19.5%), congenital diaphragmatic hernia in 4 (5.2%), pulmonary edema due to hydrops fetalis in 4 (5.2%), and acute respiratory distress syndrome (ARDS) in 3 (3.9%) infants. Pulmonary hypertension was a significant predictive factor for mortality. Although RDS was the main cause of respiratory failure in late preterm infants, other lung diseases leading to surfactant dysfunction were not rare; therefore, ST should be considered as a life-saving treatment.