Artificial ventilation of the newborn infant is the foundation of neonatology. Early practitioners included pediatricians, anesthesiologists, cardiologists, respiratory therapists, and engineers. The discovery of surfactant, followed by the death of Patrick Kennedy, jump-started the new area, with investment and research rapidly expanding. The ever more complex design of mechanical ventilators necessitated a more thorough understanding of newborn pulmonary physiology in order to provide support with minimal associated injury. This piece briefly reviews and highlights this history.

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Objective To determine if preterm infants with moderate respiratory distress syndrome on continuous positive airway pressure (CPAP) who received surfactant via a laryngeal mask airway (LMA) would have a decreased rate of intubation and mechanical ventilation compared with those on CPAP who did not receive surfactant. Study design In this prospective, multicenter, randomized controlled trial, 103 premature infants 28(0/7)-35(6/7) weeks gestation, >= 1250 g and <= 36 hours old on CPAP requiring fraction of inspired oxygen 0.30-0.40 were assigned to receive surfactant administered through an LMA then placed back on CPAP (LMA group) or maintained on CPAP with no surfactant administered (control group). The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life. Results Surfactant administration through an LMA (n = 50) significantly decreased the rate of intubation and mechanical ventilation compared with controls (n = 53): 38% vs 64%, respectively, OR 0.30 (95% CI 0.13, 0.70), P = .006, number needed to treat: 4). There were no serious adverse events associated with placement of the LMA or surfactant administration. Conclusions In premature neonates with moderate respiratory distress syndrome, surfactant administered through an LMA decreased the rate of intubation and mechanical ventilation. This intervention may have significant impact on clinical care in both high and low resource settings.

Objective To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (<= 28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxidealone (control).Study design Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in >= 3 surveys).Results Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 +/- 1.2 weeks' gestation and 713 +/- 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM.Conclusion Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity.

OBJECTIVE:To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD).STUDY DESIGN:Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction.RESULTS:A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks.CONCLUSION:Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing.TRIAL REGISTRATION:ClinicalTrials.gov: NCT01022580.

Real-time pulmonary graphics now enable clinicians to view lung mechanics and patient-ventilator interactions on a breath-to-breath basis. Displays of pressure, volume, and flow waveforms, pressure-volume and flow-volume loops, and trend screens enable clinicians to customize ventilator settings based on the underlying pathophysiology and responses of the individual patient. This article reviews the basic concepts of pulmonary graphics and demonstrates how they contribute to our understanding of respiratory physiology and the management of neonatal respiratory failure.

Aim We hypothesised that short-term application of bi-level nasal continuous positive airway pressure CPAP (SiPAP) compared with conventional nasal CPAP (nCPAP) at the same mean airway pressure in infants with persistent oxygen need recovering from respiratory distress syndrome would improve CO2 removal with no change in oxygen requirement.Design Non-blinded, randomised, observational four-period crossover study.Setting/population Level III NICU; low-birthweight infants requiring CPAP and oxygen while recovering from respiratory distress syndrome.Methods Infants requiring nasal CPAP for >24h prior to study enrolment, and fraction of inspired oxygen requirement (FiO(2)) of 0.25-0.5, were randomised to either nCPAP or SiPAP. A crossover design with four 1 h treatment periods was used such that each infant received both treatments twice. Oxygen saturations (SaO(2)), transcutaneous CO2 (tcCO(2)) and vital signs were monitored continuously. Polysomnographic recordings were analysed for apnoea, bradycardia and oxygen desaturation.Results Twenty low-birthweight infants receiving 0.30.04% supplemental oxygen on CPAP of 6 cm H2O were studied at an average of 33days of age (23days, SD). There were no differences in tcCO(2) or other physiological parameters except mean blood pressure, which was lower during nCPAP (52.3 +/- 8.3 vs 54.4 +/- 9.1mmHg; +/- SD; p<0.01). No differences in short or prolonged apnoea, bradycardia or significant desaturation events were observed.Conclusions At similar mean airway pressures, SiPAP does not improve CO2 removal, oxygenation or other studied physiological parameters with the exception of mean blood pressure, which was not clinically significant.Trial registration number NCT01053455.

Background/aims The pathogenesis of BPD is multifactorial. In preterm infants ≤28 wk GA requiring ventilation at 7–14 days, >60% have surfactant dysfunction. Survival without BPD in these infants is <25%. Inhaled nitric oxide (iNO) may improve outcome in some infants (Schreiber, NEJM 2003, Ballard NEJM, 2006). Methods Preterm infants ≤28 wk GA requiring mechanical ventilation at 7–14 days were enrolled in a RCT at 25 US centres. All infants received iNO and were randomised to receive surfactant (Infasurf) or sham instillation behind a screen every 1–2 days; maximum of 5 doses. Infants were evaluated by physiologic oxygen/flow reduction at 36 and 40 wk. Pulmonary outcome to 18 months is being collected. Results Between January 2010 and September 2013, 511 of the planned 524 infants were enrolled. There was no difference between groups in mean BW (701 ± 164 grams), GA (25.2 ± 1.2 wk), percentage under 26 wk (70.6%), race, gender, severity of disease at enrollment or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 wk (31.3% vs.31.7%; relative benefit 0.98 (0.75, 1.28 p = 0.89) or 40 wk (58.7% vs. 54.1%; relative benefit 1.08 (0.92, 1.27 p = 0.33). Overall survival without BPD at 36wk in African Americans was better than whites (37.2% vs. 25.4%p = 0.008). Conclusions Late treatment with surfactant in ventilated preterm infants did not improve survival without BPD at 36 or 40 weeks PMA. Overall better outcome in African-American infants may be due to a racial response to iNO. Pulmonary and neurodevelopmental assessment are on-going.