Effects of bovine lipid extract surfactant administration in preterm infants treated for respiratory distress syndrome

Abstract Aim To review the initial effectiveness of bovine lipid extract surfactant (BLES) for the treatment of respiratory distress syndrome in preterm infants. Methods and results A retrospective review of data collected from infants born <37‐week gestation with respiratory distress syndrome treated with BLES between February 1, 2015 and March 1, 2016. Data were analyzed to determine the timing of initial dose, the length of time to wean the fraction of inspired oxygen (FiO2) concentration to 0.21 following initial dose, and the number of repeated doses given during hospital admission. Infants were subgrouped by gestational age stratum, 230 to 276 weeks (group 1), 280 to 316 weeks (group 2), and 320 to 366 weeks (group 3). Ninety‐eight infants received the surfactant during the study period. After applying exclusion criteria, 77 infants were analyzed. Mean (SD) gestational age was 28 (4) weeks, and mean (SD) birth weight was 1250 (602) g. Initial dose of BLES was given at a median (interquartile range) time of 29 (19‐43) minutes in group 1, 150 (20‐615) minutes in group 2, and 990 (53‐2025) minutes in group 3. Median (interquartile range) length of time to wean the FiO2 concentration to 0.21 was 14 (5‐56) minutes, 10 (5‐53) minutes, and 10 (5‐38) minutes in groups 1, 2, and 3, respectively. Ten infants required repeated doses. Conclusion Given the rapid response of BLES in all the groups, careful monitoring of ventilator parameters is paramount to allow for rapid weaning and early extubation to avoid lung injury associated with mechanical ventilation.

The local evidence-based practice guideline for the management of RDS was followed to determine which infants received BLES. 13 The guideline includes all infants born less than 37-week gestation at risk of developing RDS. Infants are resuscitated according to the Neonatal Resuscitation Program guidelines. 14 Following resuscitation, each infant is assessed to determine which respiratory management strategy is the most appropriate.

| Data collection
The data were collected for each infant who received BLES either in the resuscitation room or in the NICU, by respiratory therapists. The following characteristics were collected from each infant: gestational age, birth weight (grams), clinical diagnosis, initial timing of BLES administration (minutes from birth), length of time to wean the FiO 2 concentration to 0.21 following initial dose of surfactant replacement therapy, and number of repeated doses given during hospital admission. Only infants who were able to wean the FiO 2 concentration to 0.21 after their initial dose were included in the main data analysis.
Maternal characteristics were unavailable and were not collected.

| Statistical analysis
The statistical analysis was performed using SPSS v.24 (IBM Corp, Armonk, New York). The data were presented as mean ± standard deviation (SD), median ± interquartile range (IQR), and number of infants (%). Comparisons between gestational age subgroups were evaluated using Kruskal-Wallis test. Statistical significance was defined as a P value < .05.

The study was approved by the Research Ethics Board at Western
University, London, Ontario, Canada. Individual signed consent is not required to be obtained from patients/guardians for retrospective data/chart review, according to the Research Ethics Board guidelines.
The data were extracted anonymously, with no identifiers. All parents are made aware on admission that our institution is a teaching/academic hospital and that their infant's data may be used for research.

| RESULTS
Ninety-eight infants born between 23 0and 36 6 -week gestation with a diagnosis of RDS were treated with BLES during the study period ( Figure 1). Twenty-one infants were excluded in the initial analysis.
Sixteen infants had incomplete data collected. Five infants had ongoing oxygen requirements and were unable to wean the FiO 2 concentration to 0.21 following their initial dose of BLES; their mean (SD) gestational age was 28 (3) weeks, and the mean (SD) birth weight was 1342 (425) g.
Data from 77 infants were analyzed. Mean (SD) gestational age was 28 (4) weeks, and the mean (SD) birth weight was 1250  Our review of data had some methodological limitations. First, this was a retrospective descriptive review, lacking a comparable control group. We also had a small sample size, which may result in lower statistical power to detect differences between groups. Finally, we did not analyze significant characteristics of the studied participants, such as sex, multiple gestation, perinatal asphyxia, Apgar scores, and maternal risk factors (preterm prolonged rupture of membrane, chorioamnionitis, mode of delivery, and prenatal steroids); these factors may have affected our results.

| CONCLUSION
Extreme preterm infants received their initial dose of BLES earlier in their RDS management. Fast onset of action with rapid weaning of the FiO 2 concentration to 0.21 was described in all 3 groups of preterm infants following the administration of BLES for the treatment of RDS. Careful monitoring of ventilator parameters following BLES administration is therefore paramount to allow for rapid weaning and early extubation onto noninvasive ventilator support, to prevent lung injury associated with mechanical ventilation.

ACKNOWLEDGEMENT/FUNDING
No acknowledgement or funding.

CONFLICT OF INTERESTS
BLES Biochemical Inc did not fund the study nor had any influence in the design, data collection, and interpretation of the results. The surfactant maker did not review or revised the manuscript submitted for publication.