Effect of different CPAP levels on ultrasound-assessed lung aeration and gas exchange in neonates

Abstract

Background: Respiratory distress syndrome (RDS) and transient tachypnoea (TTN) are the two commonest neonatal respiratory disorders. The optimal continuous positive airway pressure (CPAP) to treat them is unknown. We aim to clarify the effect of different CPAP levels on lung aeration and gas exchange in patients with RDS and TTN.

Methods: Prospective, observational, pragmatic, physiological cohort study. CPAP was sequentially increased from 4 to 6 and 8 cmH₂O and backwards, with interposed wash-out periods. Lung aeration was assessed with a validated neonatal lung ultrasound score. Gas exchange was non-invasively evaluated with transcutaneous monitoring. Ultrasound score and PtcO₂/FiO₂ ratio were the co-primary outcomes. PtcCO₂ and other oxygenation metrics were the secondary outcomes.

Results: 30 neonates with RDS and 30 with TTN were studied. Each CPAP increment significantly (overall always p < 0.001) improved both lung aeration and oxygenation, but the increase from 6 to 8 cmH₂O achieved a small absolute benefit. In RDS patients, the absolute improvements were small and the diagnosis of TTN was significantly associated with greater improvement of lung aeration (β= -1.4 (95%CI: -2.4; -0.3), p = 0.01) and oxygenation (β = 39.6 (95%CI: 4.1; 75.1), p = 0.029). Aeration improved in 16 (53.3%) and 27 (90%) patients in the RDS and TTN groups, respectively (p = 0.034). Lung aeration showed significant hysteresis in TTN patients. Secondary outcomes gave similar results.

Conclusions: Increasing CPAP from 4 to 8 cmH₂O improves ultrasound-assessed lung aeration and oxygenation in RDS and TTN. The absolute improvements are small when CPAP is beyond 6 cmH₂O or for RDS patients.

Keywords: Infant; Respiratory distress syndrome; Surfactant; Transient tachypnoea of the neonate.

Fig. 1

Co-primary outcomes: absolute values of lung aeration (panel A) and oxygenation (panel B). Open circles and T-bars represent means and standard deviations, respectively. p-values in the right upper corner refer to the overall results of RM-ANOVA; dotted horizontal lines indicate pairwise within-patient post-hoc comparisons. Results for the whole population (ALL) and for the RDS and TTN cohorts are shown. eLUS and PtcO₂/FiO₂ are dimensionless variables. Abbreviations: CPAP: continuous positive airway pressure; eLUS: extended lung ultrasound score; FiO₂: inspired oxygen fraction; PtcO₂: transcutaneous partial pressure of oxygen; RDS: respiratory distress syndrome; TTN: transient tachypnoea of the neonate

Fig. 2

Distribution of ultrasound patterns of lung aeration. Panels A and B depict changes of lung aeration patterns with increasing CPAP in patients with RDS and TTN, respectively. Data are expressed as a percentage of scanned chest areas. Green, yellow, and orange columns represent, respectively, the percentage of chest zones with normal (A-pattern), alveolar-interstitial (B-pattern) and severe alveolar-interstitial (severe B-pattern) lung ultrasound appearance, respectively. The width of diagonal bands depicts how many chest zones were changed by a given CPAP increment and p-values of significant changes are indicated within the bands (McNemar-Bowker test for pairwise multi-class nominal data, with Bonferroni correction). Panels C and D show illustrative cases of RDS and TTN, respectively. In the latter, with increasing CPAP level, the shift from a severe B- to a B- and an A-pattern is more evident than in the former. Images were captured on the right upper chest zone after 5’ of (4, 6 and 8 cmH₂O) CPAP application, in a transversal view with a high frequency, micro-linear, “hockey stick”-shaped probe placed between the ribs; technical details are available in [31]. Abbreviations: CPAP: continuous positive airway pressure

Fig. 3

Ultrasound-assessed lung aeration during CPAP increment (i.e. inflation) and decrement (i.e. deflation) in TTN patients. Data were obtained on a subset of neonates with TTN (n = 9). Black and hatched lines represent inflation and deflation, respectively. Black circles and T-bars represent means and standard deviations, respectively. Symbols represents the paired comparison of lung aeration between inflation and deflation at the same CPAP level (^#p = 0.029; *p = 0.015). Abbreviations: CPAP: continuous positive airway pressure; eLUS: extended lung ultrasound score; TTN: transient tachypnoea of the neonate