Elective use of nasal continuous positive airways pressure following extubation of preterm infants. Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity. A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants. Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants. A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant. Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial. Early CPAP versus surfactant in extremely preterm infants. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure.
The aim of this study was to determine whether elective use of nasal continuous positive airways pressure (CPAP) following extubation of preterm infants was well tolerated and improved short- and long-term outcomes. A randomized comparison of nasal CPAP to headbox oxygen was undertaken and a meta-analysis performed including similar randomized trials involving premature infants less than 28 days of age. A total of 150 infants (median gestational age 30 weeks, range 24-34 weeks) were randomized in two centres. Fifteen nasal CPAP infants and 25 headbox infants required increased respiratory support post-extubation and 15 nasal CPAP infants and nine headbox infants required reintubation (non significant). Eight infants became intolerant of CPAP and were changed to headbox oxygen within 48 h of extubation; 19 headbox infants developed apnoeas and respiratory acidosis requiring rescue nasal CPAP, 3 ultimately were re-intubated. Seven other trials were identified, giving a total number of 569 infants. Overall, nasal CPAP significantly reduced the need for increased respiratory support (relative risk, 0.57, 95% CI 0.43-0.73), but not for re-intubation (relative risk 0.89, 95% CI 0.68-1.17). Nasal CPAP neither influenced significantly the intraventricular haemorrhage rate reported in four studies (relative risk 1.0, 95% CI 0.55, 1.82) nor that of oxygen dependency at 28 days reported in six studies (relative risk 1.0, 95% CI 0.8, 1.25). In two studies nasal CPAP had to be discontinued in 10% of infants either because of intolerance or hyperoxia.
                Elective use of nasal continuous positive airways pressure post-extubation is not universally tolerated, but does reduce the need for additional support. The efficacy of nasal intermittent positive pressure ventilation (NIPPV) in treating apnea of prematurity was evaluated. Apneic preterm infants were randomly assigned to receive either NIPPV or continuous positive airway pressure (NCPAP) for 4 hr when they failed to respond to conservative therapy. The amount of reduction in apneic spells and bradycardia in the two groups after treatment was compared. Thirty-four infants (18 with NIPPV, 16 with NCPAP) were enrolled. Their birth weights ranged from 590-1,880 g (mean, 1,021 g) and gestational ages from 25-32 weeks (mean, 27.6 weeks). The baseline characteristics were comparable in the two groups. Frequency of apnea and bradycardia was reduced during both forms of treatments. However, the infants receiving NIPPV had a greater reduction of apneic spells (P = 0.02) and a tendency to greater decrease in bradycardia (P = 0.09) than those receiving NCPAP. We conclude that NIPPV is more effective than NCPAP in reducing apnea in preterm infants. NIPPV may reduce bradycardia; however, this needs to be validated by a larger number of observations. To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome.
                Randomised controlled study.
                Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated.
                Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant.
                IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial. To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of <or=1,250 g.
                Preterm infants were randomized to CPAP generated via high flow cannula or the Infant Flow Nasal CPAP System (VIASYS, Conshohocken, PA, USA) at extubation. Primary outcome was incidence of reintubation within 7 days. Secondary outcomes included change in oxygen use and frequency of apnea and bradycardias postextubation.
                Forty neonates were randomized. Twelve of 20 infants randomized to high flow cannula CPAP were reintubated compared to three of 20 using Infant Flow (P=0.003). The high flow cannula group had increased oxygen use and more apneas and bradycardias postextubation.
                CPAP delivered by high flow nasal cannula failed to maintain extubation status among preterm infants <or=1,250 g as effectively as Infant Flow CPAP. To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode.
                Prospective, multicenter, randomized clinical trial.
                Level III neonatal intensive care units at three university children's hospitals.
                Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6.
                Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight).
                After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation. The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined.
                To evaluate the benefits and risks of prophylactic nCPAP in infants of 28-31 weeks gestation.
                Multicentre randomised controlled clinical trial.
                Seventeen Italian neonatal intensive care units.
                A total of 230 newborns of 28-31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP.
                Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome.
                Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks.
                Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids.
                In newborns of 28-31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4. There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants.
                We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).
                A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.
                The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
                2010 Massachusetts Medical Society We designed a multicenter randomized trial to compare 3 approaches to the initial respiratory management of preterm neonates: prophylactic surfactant followed by a period of mechanical ventilation (prophylactic surfactant [PS]); prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure (intubate-surfactant-extubate [ISX]) or initial management with bubble continuous positive airway pressure and selective surfactant treatment (nCPAP).
                Neonates born at 26 0/7 to 29 6/7 weeks' gestation were enrolled at participating Vermont Oxford Network centers and randomly assigned to PS, ISX, or nCPAP groups before delivery. Primary outcome was the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age.
                648 infants enrolled at 27 centers. The study was halted before the desired sample size was reached because of declining enrollment. When compared with the PS group, the relative risk of BPD or death was 0.78 (95% confidence interval: 0.59-1.03) for the ISX group and 0.83 (95% confidence interval: 0.64-1.09) for the nCPAP group. There were no statistically significant differences in mortality or other complications of prematurity. In the nCPAP group, 48% were managed without intubation and ventilation, and 54% without surfactant treatment.
                Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation. An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant. In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures.
                Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage.
                The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups.
                HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.
There is currently insufficient information to evaluate the effectiveness of prophylactic nasal CPAP in very preterm infants. Neither of the included studies reviewed showed evidence of benefit in reducing the use of IPPV. The tendency for some adverse outcomes to be increased is of concern and further multicentre randomized controlled trials are needed to clarify this.