The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. A prospective randomized comparison of conventional mechanical ventilation and very early high frequency oscillatory ventilation in extremely premature newborns with respiratory distress syndrome. Randomized, multicenter trial of conventional ventilation versus high-frequency oscillatory ventilation for the early management of respiratory failure in term or near-term infants in Colombia. Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]. HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Randomized study of high-frequency oscillatory ventilation in infants with severe respiratory distress syndrome. HiFO Study Group. Long term follow-up of very low birthweight infants from a neonatal volume versus pressure mechanical ventilation trial. Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn. Early versus delayed surfactant administration in extremely premature neonates with respiratory distress syndrome ventilated by high-frequency oscillatory ventilation. Volume guarantee versus high-frequency ventilation: lung inflammation in 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.
To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.
                A prospective randomized clinical trial.
                Three community-based level III neonatal intensive care units.
                A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.
                Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.
                No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.
                When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost. To compare the effectiveness and safety of very early high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) in treatment of the respiratory distress syndrome (RDS) and to evaluate their impact on the incidence of chronic pulmonary disease and early and late morbidity of very low-birthweight neonates.
                A prospective randomized clinical trial.
                Tertiary neonatal intensive care unit in the Perinatology Center in Prague.
                43 premature newborns, delivered in the Department of Obstetrics in the Perinatology Center, were randomly divided into two groups (HFOV and CMV) immediately after delivery; 2 patients in each group died, 2 fulfilled crossover criteria from CMV to HFOV, and 2 were excluded because of congenital malformations. Nineteen patients treated with HFOV were therefore compared with 18 infants in the CMV group.
                The two contrasting modes of ventilation were introduced immediately after intubation. Maintenance of optimal lung volume in HFOV to optimize oxygenation and the therapeutic administration of surfactant after fulfilling defined criteria are important points of the strategy and design of the study.
                Except for a higher proportion of males in the HFOV group (p<0.02), the basic clinical characteristics (gestational age, birthweight, Apgar score at 5 min, umbilical arterial pH), the two groups were similar. In the acute stage of RDS, infants treated with HFOV had higher proximal airway distending pressure with HFOV for 6 h after delivery (p<0.05). For a period of 12 h after delivery lower values for the alveolar-arterial oxygen difference (p<0.03) were noted. The number of patients who did not require surfactant treatment was higher in the HFOV group (11 vs. 1, p<0.001). In the HFOV group the authors found a lower roentgenographic score at 30 days of age (p<0.03) and a lower clinical score in the 36th postconceptional week (p<0.05), using these two scoring systems for assessing chronic lung disease according to Toce scale. The incidence of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage and retinopathy of prematurity in both groups was the same.
                HFOV, when applied early and when the clinical strategy of maintenance of optimal lung volume is used, improves oxygenation in the acute stage of RDS, reduces the need of surfactant administration, and can decrease the injury to lung tissue even in extremely immature newborns to whom surfactant is administered therapeutically. To determine the efficacy and safety of high-frequency oscillatory ventilation (HFOV) compared to conventional ventilation (CV) for the treatment of respiratory failure in term and near-term infants in Colombia.
                Eligible infants with moderate to severe respiratory failure were randomized to early treatment with CV or HFOV. Ventilator management and general patient care were standardized. The main outcome was neonatal death or pulmonary air leak.
                A total of 119 infants were enrolled (55 in the HFOV group; 64 in the CV group) during the study period. Six infants in the HFOV group (11%) and two infants in the CV group (3%) developed the primary outcome (RR: 3.6, 95% CI: 0.8-16.9). Five infants in the HFOV group (9%) and one infant in the CV (2%) died before 28 days of life (RR: 5.9 CI: 0.7-48.2). Secondary outcomes were similar between groups.
                HFOV may not be superior to CV as an early treatment for respiratory failure in this age group. Standardization of ventilator management and general patient care may have a greater impact on the outcome in Colombia than mode of ventilation.
                Journal of Perinatology (2005) 25, 720-724. doi:10.1038/sj.jp.7211386; published online 15 September 2005. To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome.
                Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol.
                Eight tertiary neonatal intensive care units.
                Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications.
                A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants.
                HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL. To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted.
                Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up.
                The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22-2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43-3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI.
                No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI. Ventilation strategies for preterm neonates may influence the severity of pulmonary dysfunction and later development of chronic lung disease. The objective of this report is to compare the effects of high-frequency oscillatory ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV) from the points of views of biochemical and functional variables.
                Randomized controlled trial.
                Third level NICU.
                Forty preterm neonates with a gestational age of 24-29 weeks were randomly assigned to one of the two above-mentioned ventilation strategies within 30 min from birth.
                At 1, 3, 5, and 7 days, the babies were monitored by means of ventilator indices, pulmonary function, and eight pro-inflammatory or anti-inflammatory cytokines measured in bronchoalveolar lavage fluid. The neonates assigned to the HFOV procedure benefited from early and sustained improvement in pulmonary mechanics and gas exchange-significantly higher dynamic respiratory compliance values, significantly lower expiratory airway resistance and oxygenation index values-with earlier extubation as compared to the neonates assigned to sIMV treatment, and showed significantly lower transforming growth factor-beta1 concentrations in bronchoalveolar lavage fluid.
                The results of this randomized clinical trial support the hypothesis that early and exclusive use of HFOV, combined with optimum volume strategy, has a beneficial effect during the acute phase of lung injury. We conducted a multicenter, prospective, noncrossover, randomized study to determine whether high-frequency oscillatory ventilation (HFOV) would decrease the development or progression of air leak syndrome in infants with severe respiratory distress syndrome. Air leak syndrome was defined as pulmonary interstitial emphysema or gross air leak such as pneumothorax. Infants were eligible for study entry if they were less than 48 hours of age and had severe respiratory distress syndrome, defined by peak inspiratory pressure or the presence of air leak syndrome. Infants who weighed > or = 0.5 kg at birth were randomly assigned to receive either conventional ventilation (CV) or HFOV. HFOV was provided by a ventilator that operated at 15 Hz, with a 1:2 inspiratory/expiratory ratio and no background tidal breaths. Severity of pulmonary interstitial emphysema was scored independently by two neonatologists unaware of the infants' ventilatory group. Gross air leak severity was scored according to the number of chest tubes required and duration of air leak. Eighty-six infants received HFOV; 90 received CV. During the first 24 hours of the study, patients in the HFOV group received significantly higher mean airway pressure and lower inspired oxygen concentration, had significantly lower arterial carbon dioxide tension, and had a higher ratio of arterial to alveolar oxygen tension. When the HFOV and CV groups were compared with control for birth weight strata, study site, and inborn versus outborn status, HFOV significantly reduced the development of air leak syndrome in those patients who entered the study without the syndrome. We conclude that HFOV, when the strategy employed in this study is used, provides effective ventilation, improves oxygenation, and significantly reduces the development of air leak syndrome in infants with severe respiratory distress syndrome. A previous randomised trial showed volume controlled ventilation (VCV) was efficacious in ventilating very preterm and extremely low birthweight babies.
                To compare long term survival, pulmonary morbidities and gross neurodevelopmental outcomes of babies randomised to either VCV or pressure limited ventilation (PLV) for treatment of respiratory distress syndrome.
                Masked evaluation of health status, including frequency of respiratory illness, use of medications, hospital admissions, and gross neurodevelopmental status were obtained using a structured parental questionnaire and verification from medical records.
                94 of 109 children (86%) survived to discharge. Three died after discharge (2 VCV, 1 PLV). Modality of ventilation did not affect overall mortality; seven VCV children died (12%) versus 11 PLV (21%) (OR 0.5 (95% CI 0.1 to 1.4), p = 0.13). Respiratory abnormalities were present in 32 (37%), and 26 (30%) required hospital readmission. There was no significant difference in readmission rates between the two groups: VC 13/45 (29%) and PLV 19/40 (47%) (OR 0.4 (0.1 to 1.1), p = 0.07). Modality of ventilation did not affect frequency of respiratory illness: VC 12 (27%) and PLV 14 (35%) (OR 0.46 (0.1 to 1.1), p = 0.09). However, significantly fewer VCV children (13%, n = 6) compared to PLV children (32%, n = 13) required treatment with inhaled steroids/bronchodilators (OR 0.3 (0.1 to 0.9), p = 0.04). Nine children had severe neurodevelopmental disability (cerebral palsy, blindness, deafness) (9.8%; 3 VCV, 6 PLV 6) (OR 0.4 (0.09 to 1.7)).
                The efficacy of VCV in very preterm and low birth babies appears to be maintained on longer term evaluation. We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV).
                Single-center, prospective, randomized, controlled trial.
                Newborn intensive care unit of a tertiary care teaching hospital.
                We studied infants with a gestational age of > or =34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (PaO2 < or =100 mm Hg on FIO2 = 1.0), despite optimal medical management Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded.
                The treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted.
                Primary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively; p = .007). Mortality did not differ with treatment assignment.
                Among infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease. To determine whether early surfactant administration is superior to selective delayed treatment in terms of improving survival and/or reducing chronic lung disease in extremely premature neonates with respiratory distress syndrome (RDS) treated by high-frequency oscillatory ventilation (HFOV).
                Prospective randomized clinical trial.
                Tertiary neonatal intensive care unit (NICU) in the Perinatology Center of Prague.
                Forty-three extremely premature infants who needed artificial ventilation within 3 h after delivery.
                Patients were randomly assigned to either early ( n=21) or delayed (n=22) administration of surfactant. All were ventilated by HFOV as the primary mode of ventilation using the high volume strategy aimed at optimizing lung volume. Curosurf at a dose of 100 mg/kg was given as a single bolus via the endotracheal tube within 1 min immediately after intubation in the early group (EARL), or during HFOV only when defined criteria were reached in the delayed (DEL) group.
                No differences were noted in demographic data between the two groups. Fewer infants randomized to the EARL group required oxygen use or died at 36 weeks (combined outcome 29% vs 64%, p=0.021), and there was a lower incidence of any intraventricular hemorrhage in this group (43 vs 82%, p=0.008).
                When compared to delayed dosing, early administration of surfactant followed by HFOV facilitates and accelerates respiratory stabilization during the acute phase of severe RDS, may reduce the incidence of chronic lung disease or death and may positively influence the incidence of severe intracranial pathology in extremely premature infants with primary surfactant insufficiency. Appropriate ventilation together with improvement of clinical care of premature babies can contribute to reducing lung inflammation, known to represent the "primum movens" of bronchopulmonary dysplasia (BPD). High-frequency oscillatory ventilation (HFOV) and volume-guarantee (VG) ventilation are effective in the treatment of neonatal respiratory distress syndrome (RDS).
                To assess the potential of HFOV and VG to prevent BPD in the acute phase of RDS, by a randomised clinical study evaluating lung inflammation in premature infants. Study design: Forty infants (gestational age 25-32 weeks) with RDS were assigned to assist-control ventilation plus VG (Vt = 5 ml/kg) or HFOV (both with a Dräger Babylog 8000 plus ventilator). Levels of interleukin (IL) 6, IL8 and tumour necrosis factor were determined in tracheal aspirate on days 1, 3 and 7 of life.
                In the HFOV group IL6 levels were significantly higher on day 3 (0.5 (0.2) vs assisted-control ventilation plus VG group 0.1 (0.2) ng/ml) and oxygen dependency was significantly longer (36 (23) vs assisted-control ventilation plus VG group 19 (11) days).
                VG ventilation is an effective lung-protective strategy to be used in acute RDS, inducing a lower expression of early inflammation markers than HFOV. Whether the use of this initial ventilatory strategy contributes to the prevention of BPD requires further studies. 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.
There is no clear evidence that elective HFOV offers important advantages over CV when used as the initial ventilation strategy to treat preterm infants with acute pulmonary dysfunction. There may be a small reduction in the rate of CLD with HFOV use, but the evidence is weakened by the inconsistency of this effect across trials and the overall borderline significance. Future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm infants), compare different strategies for generating HFOV and CV, and report important long-term neurodevelopmental outcomes.