Short term evaluation of respiratory effort by premature infants supported with bubble nasal continuous airway pressure using Seattle-PAP and a standard bubble device

<div><p>Background</p><p>Almost one million prematurely born infants die annually from respiratory insufficiency, predominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continuous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breathing, estimated by esophageal pressure-rate products.</p><p>Methods</p><p>Infants born <32 weeks gestation and stable on Bn-CPAP with FiO₂ <0.30 were studied within 72 h following delivery. Esophageal pressures during spontaneous breathing were measured during 2 h on standard Bn-CPAP, then 2 h with Bn-CPAP using a modified bubble device presently termed Seattle-PAP, which produces a different pattern of pressure fluctuations and which provided greater respiratory support in preclinical studies, then 2 h on standard Bn-CPAP.</p><p>Results</p><p>All 40 infants enrolled completed the study and follow-up through 36 wks post menstrual age or hospital discharge, whichever came first. No infants were on supplemental oxygen at completion of follow-up. No infants developed pneumothoraces or nasal trauma, and no adverse events attributed to the study were observed. Pressure-rate products on the two devices were not different, but effort of breathing, assessed by areas under esophageal pressure-time curves, was lower with Seattle-PAP than with standard Bn-CPAP.</p><p>Conclusion</p><p>Use of Seattle-PAP to implement Bn-CPAP lowers the effort of breathing exerted even by relatively healthy spontaneously breathing premature neonates. Whether the lower effort of breathing observed with Seattle-PAP translates to improvements in neonatal mortality or morbidity will need to be determined by studies in appropriate patient populations.</p></div

GEE model fit of PRP, ΔP_es, RR, and AUCs, on time and epoch.

<p>GEE model fit of PRP, ΔP_es, RR, and AUCs, on time and epoch.</p

Areas under the P_es-time curve (AUC) per breath for individual infants.

<p>AUCs, more specifically the areas above the ΔP_es-time curves, were calculated for quiet breaths in one min segments in which at least 10 quiet breaths were observed and are averaged across all quiet breaths in that min interval; the data are presented as cmH₂O•min.</p

Areas under the curve (AUC) per min for individual infants.

<p>AUCs were calculated for quiet breaths in one min segments in which at least 10 quiet breaths were observed and normalized per min, using the RR derived from quiet breaths in that interval for the infant, with the data thus expressed as cmH₂O•min/min.</p

CONSORT flow chart for enrollment and study of infants.

<p>Due to the repeated measures design of the present study, enrollment of consecutive infants was neither intended nor attempted. Of the 42 sets of parents approached for enrollment, 40 agreed, and all of these infants completed the study, including follow-up to 36 weeks or discharge from hospital. Thus, follow-up and other data are comprehensive for all 40 of these infants. However, technical issues, many arising from the physical activities, such as body motion, swallowing, and similar actions of the unsedated infants interfering with efforts to record P_es, limited acquisition of interpretable data in 13 of the 40 infants.</p

Respiratory rates (RR) for individual infants.

<p>RRs were determined and are expressed similarly as for the ΔP_es data presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193807#pone.0193807.g003" target="_blank">Fig 3</a>.</p

Data summary by epoch and administration of antibiotics.

<p>Data summary by epoch and administration of antibiotics.</p

GEE model fit of PRP, ΔP_es, RR, and AUC per breath and per min.

<p>GEE model fit of PRP, ΔP_es, RR, and AUC per breath and per min.</p

PRP, ΔP_es, RR, and AUCs in individual infants, aggregated by receipt of ampicillin and gentamicin.

<p>The data presented in the respective figures in gray show the median values of each infant for his or her epochs. The dark black lines are the mean values over all medians. The blue lines are the mean values of the median values for infants who were given ampicillin and gentamicin, and the red lines are the respective mean values for the infants not treated similarly.</p

Demographic and clinical summary statistics for patients in the study.

<p>Demographic and clinical summary statistics for patients in the study.</p