Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth

RESEARCH ARTICLE Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth Melissa L. Siew1*, Jeroen J. van Vonderen2, Stuart B. Hooper1, Arjan B. te Pas2 1 The Ritchie Centre, MIMR-PHI, Monash University, Clayton, Australia, 2 Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands * Abstract Objective OPEN ACCESS Citation: Siew ML, van Vonderen JJ, Hooper SB, te Pas AB (2015) Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth. PLoS ONE 10(6): e0129592. doi:10.1371/journal. pone.0129592 Academic Editor: Olivier Baud, Hôpital Robert Debré, FRANCE Received: December 23, 2014 Accepted: May 10, 2015 To investigate the differences in breathing pattern and effort in infants at birth who failed or succeeded on continuous positive airway pressure (CPAP) during the first 48 hours after birth. Methods Respiratory function recordings of 32 preterm infants were reviewed of which 15 infants with a gestational age of 28.6 (0.7) weeks failed CPAP and 17 infants with a GA of 30.1 (0.4) weeks did not fail CPAP. Frequency, duration and tidal volumes (VT) of expiratory holds (EHs), peak inspiratory flows, CPAP-level and FiO2-levels were analysed. Published: June 8, 2015 Copyright: © 2015 Siew et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data are available upon request from the authors for researchers who meet the criteria for access to confidential data as determined by the local IRB of the Leiden University Medical Center. Funding: A.B. te Pas is recipient of a Veni-grant, the Netherlands Organisation for Health Research and Development (ZonMw), part of the Innovational Research Incentives Scheme Veni-Vidi-Vici, projectnumber 91612027. J.J. van Vonderen is recipient of a Willem-Alexander Children’s Foundation scholarship. M.L. Siew was funded by the David Henderson-Smart Travel Scholarship. The Results EH incidence increased <6 minutes after birth and remained stable thereafter. EH peak inspiratory flows and VT were similar between CPAP-fail and CPAP-success infants. At 9-12 minutes, CPAP-fail infants more frequently used smaller VTs, 0-9 ml/kg and required higher peak inspiratory flows. However, CPAP-success infants often used large VTs (>9 ml/kg) with higher peak inspiratory flows than CPAP-fail infants (71.8 ± 15.8 vs. 15.5 ± 5.2 ml/kg.s, p <0.05). CPAP-fail infants required higher FiO2 (0.31 ± 0.03 vs. 0.21 ± 0.01), higher CPAP pressures (6.62 ± 0.3 vs. 5.67 ± 0.26 cmH2O) and more positive pressure-delivered breaths (45 ± 12 vs. 19 ± 9%) (p <0.05) Conclusion At 9-12 minutes after birth, CPAP-fail infants more commonly used lower VTs and required higher peak inspiratory flow rates while receiving greater respiratory support. VT was less variable and larger VT was infrequently used reflecting early signs of fatigue. PLOS ONE | DOI:10.1371/journal.pone.0129592 June 8, 2015 1 / 15 Respiratory Patterns after Failing CPAP at Birth funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Introduction Continuous positive airway pressure (CPAP) is progressively replacing intubation and mechanical ventilation as the first choice of respiratory support for premature infants at birth. However a considerable number of infants, who are initially stabilised with CPAP, will develop worsening respiratory failure and eventually require intubation for mechanical ventilation and the administration of surfactant.[1–6] If early identification of preterm infants who fail CPAP is possible this could be used to optimise the timing of surfactant treatment to early administration (within 2 hours) [7], decrease pulmonary damage and improve outcomes. Many measurements have been investigated for their ability to predict CPAP failure in infants such as FiO2, PaO2, A-aDO2, a/A ratio, PaO2/FiO2 and the stable micro bubble test as soon as possible after birth.[8–13] To date, the respiratory pattern and effort at birth have not been investigated although they are a major determinant of lung gas volumes [14] and may correlate with respiratory distress severity and predict CPAP failure.[15] As the preterm infant’s chest wall is highly compliant and transiently expands immediately after birth [16], it has limited capacity to oppose lung recoil.[17] As such, these infants must utilise their breathing pattern to develop and maintain functional residual capacity (FRC) immediately after birth. Expiratory holds (EHs), which are breaths characterised by a period of zero flow during expiration and prolonged duration of expiratory [18–20], help to maintain FRC.[14,18,21] Studies in newborn rabbits, lambs and infants suggest that the use of EHs is influenced by changes in lung gas volumes and airway pressure.[14,19,22,23] Although it is uncertain whether EHs can indicate absolute lung gas volumes, we have previously shown a strong relationship between the incidence of EHs and FRC in newborn rabbits.[14] Large tidal volumes (VTs) at birth promote lung liquid clearance by generating transpulmonary pressures that move liquid from the airspace into the peri-alveolar interstitial tissue. [14,16] There is a positive relationship between VT and FRC with large VTs resulting in larger immediate FRC accumulation in the first breaths after birth.[24] A similar relationship is observed regarding inspiratory effort and FRC development.[24] Clearly, VT and inspiratory flow can influence end-expiratory lung gas volumes. As preterm infants are commonly surfactant deficient and have a highly compliant chest, they commonly have lower than normal resting lung gas volumes.[25,26] It is possible that infants with the lowest lung gas volumes represent those most likely to develop severe respiratory distress syndrome (RDS) and thus require more respiratory support than CPAP initiated at birth. Indeed, up to 80% of infants who fail CPAP demonstrate moderate-severe RDS.[1,27] As such, preterm infants who fail to establish a good breathing pattern and effort immediately after birth are more likely to be unable to maintain their FRC and eventually require increased respiratory support. We hypothesized that the breathing pattern and effort at birth is different in infants who failed CPAP within 48 hours after birth than in infants where CPAP was successful. Methods The local institutional review boards (IRBs) of the Leiden University Medical Center (Commissie Medische Ethiek, Leids Universitair Medisch Centrum) and Royal Women’s Hospital (the Human Research Ethics Committee, Royal Woman’s Hospital) approved physiological- and video recordings at birth in the delivery roo (...truncated)