Effect of Bias Gas Flow on Tracheal Cytokine Concentrations in Ventilated Extremely Preterm Infants: A Randomized Controlled Trial.

BACKGROUND: The objective of this study was to determine whether ventilator bias gas flow affects tracheal aspirate (TA) cytokine concentrations in ventilated extremely preterm infants. METHODS: This is a randomized controlled trial in a tertiary neonatal unit in New Zealand. Preterm infants (<28 weeks' gestation/<1,000 g) requiring intubation in the first 7 days after birth were randomized to bias gas flows of 4 or 10 L/min. Cytokine concentrations in TA and plasma were measured at 24, 72, and 120 h after the onset of ventilation. The primary outcome measure was concentration of interleukin (IL)-8 in TA 24 h after the onset of mechanical ventilation. RESULTS: Baseline demographics were similar in babies randomized to 4 (n = 50) and 10 (n = 45) L/min bias gas flow. TA IL-8 concentrations were not different between groups. Plasma IL-8 concentrations decreased over time (p < 0.05). Respiratory support and incidence of bronchopulmonary dysplasia at 36 weeks' corrected gestational age were similar between groups. Fewer babies ventilated at 4 L/min developed necrotizing enterocolitis (NEC) ≥ stage 2 (n = 0 vs. n = 5; p = 0.02) and fewer died (n = 1 vs. n = 5, p = 0.06). CONCLUSIONS: Lower bias gas flow in ventilated extremely preterm infants did not alter TA cytokine concentrations but the lower incidence of NEC and mortality warrants further investigation.

Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences.

BACKGROUND: Preterm infants ≤32 weeks' gestation are increasingly being managed on continuous positive airway pressure (CPAP), without prior intubation and surfactant therapy. Some infants treated in this way ultimately fail on CPAP and require intubation and ventilation. OBJECTIVES: To define the incidence, predictors and consequences of CPAP failure in preterm infants managed with CPAP from the outset. METHODS: Preterm infants 25-32 weeks' gestation were included in the study if inborn and managed with CPAP as the initial respiratory support, with division into two gestation ranges and grouping according to whether they were successfully managed on CPAP (CPAP-S) or failed on CPAP and required intubation <72 h (CPAP-F). Predictors of CPAP failure were sought, and outcomes compared between the groups. RESULTS: 297 infants received CPAP, of which 65 (22%) failed, with CPAP failure being more likely at lower gestational age. Most infants failing CPAP had moderate or severe respiratory distress syndrome radiologically. In multivariate analysis, CPAP failure was found to be predicted by the highest FiO2 in the first hours of life. CPAP-F infants had a prolonged need for respiratory support and oxygen therapy, and a higher risk of death or bronchopulmonary dysplasia at 25-28 weeks' gestation (CPAP-F 53% vs. CPAP-S 14%, relative risk 3.8, 95% CI 1.6, 9.3) and a substantially higher risk of pneumothorax at 29-32 weeks. CONCLUSION: CPAP failure in preterm infants usually occurs because of unremitting respiratory distress syndrome, is predicted by an FiO2 ≥0.3 in the first hours of life, and is associated with adverse outcomes.

Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure.

OBJECTIVE: To evaluate the applicability and potential effectiveness of a technique of minimally-invasive surfactant therapy (MIST) in preterm infants on continuous positive airway pressure (CPAP). METHODS: An open feasibility study of MIST was conducted at two sites. Infants were eligible for MIST if needing CPAP pressure ≥7 cm H(2)O and FiO(2) ≥0.3 (25-28 weeks gestation, n=38) or ≥0.35 (29-32 weeks, n=23). Without premedication, a narrow-bore catheter was inserted through the vocal cords under direct vision. Surfactant (100 or 200 mg/kg Curosurf) was then instilled, followed by reinstitution of CPAP. Outcomes were compared between surfactant-treated infants and historical controls achieving the same CPAP and FiO(2) thresholds. RESULTS: Surfactant was successfully administered via MIST in all cases, with a rapid and sustained reduction in FiO(2) thereafter. For infants at 25-28 weeks gestation, need for intubation <72 h was diminished after MIST compared with controls (32% vs 68%; OR 0.21, 95% CI 0.083 to 0.55), with a similar trend at 29-32 weeks (22% vs 45%; OR 0.34, 95% CI 0.11 to 1.1). Duration of ventilation and incidence of bronchopulmonary dysplasia were similar, but infants receiving MIST had a shorter duration of oxygen therapy. CONCLUSION: Surfactant delivery via a narrow-bore tracheal catheter is feasible and potentially effective, and deserves further investigation in clinical trials.

High bias gas flows increase lung injury in the ventilated preterm lamb.

BACKGROUND: Mechanical ventilation of preterm babies increases survival but can also cause ventilator-induced lung injury (VILI), leading to the development of bronchopulmonary dysplasia (BPD). It is not known whether shear stress injury from gases flowing into the preterm lung during ventilation contributes to VILI. METHODS: Preterm lambs of 131 days' gestation (term = 147 d) were ventilated for 2 hours with a bias gas flow of 8 L/min (n = 13), 18 L/min (n = 12) or 28 L/min (n = 14). Physiological parameters were measured continuously and lung injury was assessed by measuring mRNA expression of early injury response genes and by histological analysis. Control lung tissue was collected from unventilated age-matched fetuses. Data were analysed by ANOVA with a Tukey post-hoc test when appropriate. RESULTS: High bias gas flows resulted in higher ventilator pressures, shorter inflation times and decreased ventilator efficiency. The rate of rise of inspiratory gas flow was greatest, and pulmonary mRNA levels of the injury markers, EGR1 and CTGF, were highest in lambs ventilated with bias gas flows of 18 L/min. High bias gas flows resulted in increased cellular proliferation and abnormal deposition of elastin, collagen and myofibroblasts in the lung. CONCLUSIONS: High ventilator bias gas flows resulted in increased lung injury, with up-regulation of acute early response genes and increased histological lung injury. Bias gas flows may, therefore, contribute to VILI and BPD.

Ventilator gas flow rates affect inspiratory time and ventilator efficiency index in term lambs.

BACKGROUND: Despite increasing survival in the smallest preterm infants, the incidence of chronic lung disease has not decreased. Research into ventilatory strategies has concentrated on minimising barotrauma, volutrauma and atelectotrauma, but little attention has been paid to the role of bias gas flow rates and the potential for rheotrauma or shear stress injury. Ventilated preterm infants frequently receive relatively high gas flow rates. OBJECTIVES: We hypothesised that altering bias gas flow rates would change the efficiency of ventilation and thereby affect ventilatory parameters. METHODS: We tested this hypothesis using an artificial lung followed by ventilation of 8 term lambs. RESULTS: Between flows of 2 and 15 l/min, inflation time (Ti) in the artificial lung was inversely related to the bias gas flow rate. In the ventilated lambs, Ti was inversely related to flow rates up to 10 l/min, with no statistically significant effect at flow rates >10 l/min. There were no adverse effects on gas exchange or cardiovascular parameters until a flow rate of 3 l/min was used, when inadequate gas exchange occurred. CONCLUSIONS: Ti is inversely associated with the bias gas flow rate. Flow rates much lower than those used in many neonatal units seem to provide adequate ventilation. We suggest that the role of ventilator gas flow rates, which may potentially influence shear stress in ventilator-induced lung injury, merits further investigation.