Respiratory distress syndrome (RDS) in preterm infants/Neonates

Prophylactic and early surfactant administration

Later surfactant administration

O: Reduced mortality and pulmonary complications (Bronchopulmonary dysplasia-BPD and other)

Surfactant therapy involves intervention via various methods like oxygen, CPAP, mechanical ventilation, and surfactant. Many ask if surfactant therapy works. They also ask what is the ideal dose and when to administer the dose. Too much and too late could cause problems versus early with a low dose. When surfactant was introduced in neonatology, it reduced VLBW infant deaths by 30%. Surfactant use two decades ago also led to an 80% decline in neonatal mortality in the United States.

However, surfactant can fail and normally does so because of certain factors like when infants are extremely preterm and developed poorly structured longs and when there an infant develops perinatal asphyxia. When those factors are not present, surfactant reduces incidence of PDA, sepsis pneumonia, and most importantly, reduces the need for mechanical ventilation. When there is absence of surfactant, infants may present with high distending pressures, airway distortion/stretch, cellular membrane disruption that could lead to edema or hyaline membrane formation, and other complications. From here it could advance to higher pressures/FiO2 and then eventually BPD, barotrauma.

Prophylactic treatment of infants during the first fifteen minutes of life seems more effective than later treatment. However, not all infants that show signs of developing RDS develop the condition. Overtreatment, especially with higher doses could expose infants to adverse effects, needlessly. In fact, multiple doses of surfactant, which has been a treatment of choice shown in the majority of trials may not be as helpful as thought. While functional inactivation of surfactant may be the reason why multiple doses are recommended, early treatment at low dose could be the best option.

Increased use of exogenous surfactant therapy is a better option when using extubation to NCPAP because it lessens the need for mechanical ventilation. When combined with early surfactant replacement therapy application, it greatly diminishes the probability of complications. Effective ventilatory management consists of rapid weaning and extubation to CPAP. While surfactant can be costly, the overall reduction in hospital and ancillary charges warrant early use of it.

Prophylactic and early surfactant replacement therapy minimizes pulmonary complications and mortality in ventilated infants that suffer from RDS or respiratory distress syndrome when compared to the same treat protocol administered later. While early treatment seems to reduce pulmonary complications and mortality, continued ventilation and post-surfactant intubation presents risks factors for BPD or bronchopulmonary dysplasia. In a 2010 review by Stevens, Blennow, Myers & Soll, the review compares results among two strategies of surfactant administration in RDS-afflicted infants.

The researchers examined early intervention of surfactant administration proceeded with quick extubation, and then compared results collected from this approach to later, selective use of surfactant administration proceeded with ongoing mechanical ventilation. Respiratory distress syndrome has remained a major problem for neonatal care. As the single most significant cause of mortality and morbidity in preterm infants, strategies must be changed in order to reduce infant mortality and development of pulmonary problems associated with continued ventilation and delayed treatment protocols. Evidence from clinical trials reveal surfactant replacement therapy in infants with RDS reduces mortality, improving clinical outcomes.

Reduction in mortality was identified by discovering the optimal dose, surfactant preparation, and time of administration. “For infants at high risk for RDS, prophylactic (pre- or post-ventilation) or early (< 2 hours of age) surfactant replacement therapy compared to later selective surfactant administration of established RDS significantly improves survival and reduces the incidence of bronchopulmonary dysplasia or death” (Stevens, Blennow, Myers & Soll, 2010, p. 3). This optimal method also reduces incidence of air leak proving to be an efficient and suitable means of treatment. Even with evidence of optimal dose and methods, BDP remains a prevalent issue and complication of RDS and preterm birth.

The Cochrane review states how earlier systematic reviews of surfactant replacement therapy assessed trials that utilized a different surfactant administration model consisting of surfactant administration, endotracheal intubation, IPPV (intermittent positive pressure ventilation), and stabilization proceeded by extubation when patients were on low respiratory support and stable. Lung injury has been seen with preterm infants with RDS when treated with IPPV. Lung injury increases the chances of developing BPD (bronchopulmonary dysplasia). Researchers also noted the positive effects of prolonged distending pressure for infants with RDS. Prolonged distending pressure comes from CPAP (continuous positive airway pressure) machines, especially when using nasal prongs or a nasopharyngeal tube. It removes the need for mechanical ventilation and provides treatment for RDS. They also identified that the same continuous pressure applied externally can have the same effect when placed to the thorax with a seal around the infant’s neck.

CPAP has been touted since the early 1970’s as being an effective means of treating RDS and lessening the need for mechanical ventilation. Since prolonged use of mechanical ventilation increases risk, CPAP can be a means of removing the need for mechanical ventilation. There was even speculation that greater use of CPAP would reduce risk of development of BPD. “A recent observational study comparing the prevalence of chronic lung disease (CLD, oxygen at 36 weeks’ postmenstrual age) at three large NICUs identified initiation of mechanical ventilation as the major risk factor associated with an increased risk of CLD among very low birth weight infants” (Stevens, Blennow, Myers & Soll, 2010, p. 3).

This review assesses the effect of a strategy involving surfactant administration through endotracheal instillation in conjunction with a less than one hour planned and brief period of monitored mechanical ventilation proceeded by extubation compared to a more conventional strategy involving selective surfactant administration proceeded by continuous extubation and mechanical ventilation from low respiratory support within previous RDS-afflicted non-intubated infants. By comparing two treatment models for RDS, “early surfactant administration with brief mechanical ventilation (less than one hour) followed by early extubation vs. later selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support in previously non-intubated infants with RDS” (Stevens, Blennow, Myers & Soll, 2010, p. 3), the review identified which strategy works best. The types of participants included in the studies reviewed were all infants less than thirty-seven weeks’ old that presented signs of RDS. The studies also included infants less than thirty-two weeks’ old that were considered high risk for RDS.

The review authors searched and selected six randomized trials from 1994 to 2006 that fit the selected criteria. Results from the randomized trials revealed the strategy of early surfactant administration in conjunction with extubation and then transitioning to NCPAP provided major decreases in the infant’s need for mechanical ventilation. Less use of mechanical ventilation led to fewer air leak syndromes as well as lower incidence of BPD. The other strategy did not fare well and increased changes for pulmonary complications. “The findings suggest that a lower treatment threshold (oxygen requirement < 0.45) confers greater advantage than does a higher treatment threshold (oxygen requirement > 0.45)” (Stevens, Blennow, Myers & Soll, 2010, p. 3). While no infants endured complications from surfactant administration in the reviewed clinical trials, surfactant therapy strategy generated a prevalence of PDA (patent ductus arteriosus).

In conclusion, this systematic review provided evidence from six randomized clinical trials that early intervention through surfactant administration helped reduce the need for infants at high risk for RDS or that have RDS to continue mechanical ventilation. NCPAP in combination with surfactant replacement therapy reduces need for mechanical ventilation and thus reduces the likely of developing pulmonary complications and development of BPD. Prolonged mechanical ventilation increases the likelihood of developing BPD and other kinds of pulmonary complications. Measures taken to reduce mechanical ventilation will decrease chances of infants developing such pulmonary complications.

The review also helped identify gaps in information such as time to regain birth weight, need for analgesia/sedation, chronic lung disease, total duration of respiratory support, and neurodevelopmental outcome. These things may contribute to the overall health of the infant and should be studied. New evidence discovered through the review reveals lower FiO2 in the beginning of treatment is associated with major reduction in occurrence of BPD and leak syndromes. Moreover, higher FiO2 led to increased occurrence of PDA. Using a low treatment threshold early for infants with initial symptoms and signs of RDS is preferable than later treatment at a higher dosage.

Surfactant therapy is the best option for infants but it has to be administered early on to get the best outcomes. Mechanical ventilation does not help and the sooner it can be removed, the better. This is because mechanical ventilation has been shown to increase the likelihood of infants developing pulmonary complications. Since there does exist an optimal dose and time for administration, hospitals should use this information to reduce some health complications in infants.

References

Stevens, T., Blennow, M., Myers, E., & Soll, R. (2010). Cochrane review: Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Evid.-Based Child Health, 5(1), 82-115. http://dx.doi.org/10.1002/ebch.519

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