Late administration of surfactant replacement therapy increases surfactant protein-B content: A randomized pilot study

Department of Pediatrics, University of California San Francisco, San Francisco CA.
Pediatric Research (Impact Factor: 2.31). 10/2012; 72(6). DOI: 10.1038/pr.2012.136
Source: PubMed


Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. We conducted a multicenter randomized, blinded, pilot study to assess the safety and efficacy of late administration of doses of a surfactant protein-B (SP-B)-containing surfactant (calfactant) in combination with prolonged inhaled nitric oxide (iNO) in infants ≤1,000 g birth weight (BW).

We randomized 85 preterm infants ventilated at 7–14 d after birth to receive either late administration of surfactant (up to 5 doses) plus prolonged iNO or iNO alone. Large aggregate surfactant was isolated from daily tracheal aspirates (TAs) for measurement of SP-B content, total protein, and phospholipid (PL).

Late administration of surfactant had minimal acute adverse effects. Clinical status as well as surfactant recovery and SP-B content in tracheal aspirate were transiently improved as compared to the controls; these effects waned after 1 d. The change in SP-B content with surfactant dosing was positively correlated with SP-B levels during treatment (r = 0.50, P = 0.02).

Low SP-B values increased with calfactant administration, but the relationship of this response to SP-B levels suggests that degradation is a contributing mechanism for SP-B deficiency and surfactant dysfunction. We conclude that late therapy with surfactant in combination with iNO is safe and transiently increases surfactant SP-B content, possibly leading to improved short- and long-term respiratory outcomes.

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Available from: Rita Ryan, Nov 17, 2015
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    • "Moreover, Beresford and Shaw described how lower bronchoalveolar lavage SP-B and SP-D concentrations in preterm infants ventilated for respiratory distress syndrome were associated with worse clinical prognoses [29]. In this context, Keller et al. [30] demonstrated recently in preterm infants that late administration of a surfactant containing SP-B surfactant transiently increases SP-B content in the lung aspirates, possibly leading to improved short- and long-term respiratory outcomes. The diagnostic value of C-proSP-B in newborns in this context is still unknown and will require additional clinical studies. "
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    ABSTRACT: Background and objective: Mechanical ventilation via an endotracheal tube is a risk factor for bronchopulmonary dysplasia (BPD), one of the most common morbidities of very preterm infants. Our objective was to investigate the effect that strategies to avoid endotracheal mechanical ventilation (eMV) have on the incidence of BPD in preterm infants <30 weeks' gestational age (GA). Methods: In February 2013, we searched the databases Medline, Embase, and the Cochrane Central Register of Controlled Trials. Study selection criteria included randomized controlled trials published in peer-reviewed journals since the year 2000 that compared preterm infants <30 weeks' GA treated by using a strategy aimed at avoiding eMV with a control group in which mechanical ventilation via an endotracheal tube was performed at an earlier stage. Data were extracted and analyzed by using the standard methods of the Cochrane Neonatal Review Group. The authors independently assessed study eligibility and risk of bias, extracted data and calculated odds ratios and 95% confidence intervals, employing RevMan version 5.1.6. Results: We identified 7 trials that included a total of 3289 infants. The combined odds ratio (95% confidence interval) of death or BPD was 0.83 (0.71-0.96). The number needed to treat was 35. The study results were remarkably homogeneous. Avoiding eMV had no influence on the incidence of severe intraventricular hemorrhage. Conclusions: Strategies aimed at avoiding eMV in infants <30 weeks' GA have a small but significant beneficial impact on preventing BPD.
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