Bubble continuous positive airway pressure enhances lung volume and gas exchange in preterm lambs

Abstract

Rationale: The technique used to provide continuous positive airway pressure (CPAP) to the newborn may influence lung function and breathing efficiency.

Objectives: To compare differences in gas exchange physiology and lung injury resulting from treatment of respiratory distress with either bubble or constant pressure CPAP and to determine if the applied flow influences short-term outcomes.

Methods: Lambs (133 d gestation; term is 150 d) born via cesarean section were weighed, intubated, and treated with CPAP for 3 hours. Two groups were treated with 8 L/minute applied flow using the bubble (n = 12) or the constant pressure (n = 12) technique. A third group (n = 10) received the bubble method with 12 L/minute bias flow. Measurements at study completion included arterial blood gases, oxygraphy, capnography, tidal flow, multiple breath washout, lung mechanics, static pressure-volume curves, and bronchoalveolar lavage fluid protein.

Measurements and main results: Birth weight and arterial gas variables at 15 minutes were comparable. Flow (8 or 12 L/min) did not influence the 3-hour outcomes in the bubble group. Bubble technique was associated with a higher pH, Pa(O2), oxygen uptake, and area under the flow-volume curve, and a decreased alveolar protein, respiratory quotient, Pa(CO2), and ventilation inhomogeneity compared with the constant pressure group.

Conclusions: Compared with constant pressure technique, bubble CPAP promotes enhanced airway patency during treatment of acute postnatal respiratory disease in preterm lambs and may offer protection against lung injury.

Figure 1.

Time course of changes in arterial blood gas values. The values for umbilical arterial pH (A), partial pressure of carbon dioxide (Pa_CO2, B), and partial pressure of oxygen (Pa_O2, C) are shown for the first 150 minutes of the study, up to the point of pulmonary physiological assessments. There were significant differences between the constant pressure (open symbols) and 8-L/minute bias flow bubble (closed symbols) continuous positive airway pressure group for pH, Pa_CO2, and Pa_O2. *p < 0.05; **p < 0.01. Specific p values are not included in the graph, for clarity, but are provided in Table E2 of the online supplement.

Figure 2.

Indirect calorimetry. Oxygen (O₂) extraction and carbon dioxide (CO₂) removal rates were calculated from the product of the breath-to-breath changes in inspired and expired O₂ and CO₂ and the minute volume (corrected for dry weight). Bubble continuous positive airway pressure (CPAP) animals extracted O₂ more efficiently than constant pressure CPAP animals (p = 0.041). The significantly higher respiratory quotient (RQ) of the constant pressure CPAP group is suggestive of respiratory failure (p = 0.005).

Figure 3.

Tidal breathing. Measurements of (A) tidal volume (Vt), (B) respiratory rate (RR), (C) minute volume (MV), and (D) area under the flow–volume curve (AFV) obtained from 30-second recordings of regular breathing in quiet sleep. There was a significant increase in AFV (p = 0.008) for the bubble CPAP group as a whole, and increased Vt (p = 0.044) and MV (p = 0.041) in the 12-L/minute bubble CPAP group.

Figure 4.

Multiple breath washout and forced oscillatory mechanics. Measurements of (A) functional residual capacity (FRC) and (B) lung clearance index (LCI) were derived from multiple breath washouts using approximately 4% SF₆ as the tracer gas. The higher LCI in the constant pressure group (p = 0.022) implies more inhomogeneous ventilation. The low-frequency forced oscillation technique was used to obtain partitioned measurements of the airway and tissue mechanics, including (C) airway resistance (Raw), (D) lower respiratory system tissue damping (tissue resistance, G_lrs), and (E) lower respiratory system tissue compliance (C_lrs). There was a trend to increased compliance in the bubble CPAP group.

Figure 5.

Deflation pressure–volume curves, saturated phosphatidylcholine (Sat PC), and alveolar protein. (A) The deflation limb of the static pressure–volume relationship obtained post mortem in unventilated (open circles), constant pressure CPAP (gray squares), and 8-L/minute bubble CPAP (black triangles) lamb groups. Sat PC levels (B) and differences in alveolar protein levels (C) isolated from alveolar wash samples are shown for unventilated controls (dark gray bars), constant pressure CPAP (CP, white bars), and 8-L/minute (light gray bars) and 12-L/min (black bars) bubble (B) CPAP groups. **p < 0.0001 for constant pressure and bubble CPAP versus unventilated control animals.