The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome. Prospective, randomized, controlled pilot study of partial liquid ventilation in adult acute respiratory distress syndrome. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]. [Noninvasive positive pressure ventilation for acute respiratory failure in chronic obstructive pulmonary disease in a general respiratory ward]. High-frequency jet ventilation in the early management of respiratory distress syndrome is associated with a greater risk for adverse outcomes. Long-term controlled trial of nocturnal nasal positive pressure ventilation in patients with severe COPD. Impact of targeted-volume ventilation on lung inflammatory response in preterm infants with respiratory distress syndrome (RDS).
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 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. We evaluated the safety and efficacy of partial liquid ventilation (PLV) with perflubron in adult patients with acute lung injury and the acute respiratory distress syndrome (ARDS) in a multicenter, prospective, controlled, randomized exploratory clinical trial. Ninety adult patients with PaO2/FIO2 ratios > 60 and < 300 with ARDS for no more than 24 hours were randomized to receive PLV (n = 65) with administration of perflubron through an endotracheal tube sideport or conventional mechanical ventilation (CMV, n = 25) for a maximum of five days. Although a significant reduction in progression to ARDS was noted among patients with PLV, no significant differences in the number of days free from the ventilator at 28 days (CMV = 6.7 +/- 1.8, PLV = 6.3 +/- 1.0 days, p = 0.85), the incidence of mortality (CMV = 36%, PLV = 42%, p = 0.63), or any pulmonary-related parameter were observed. During a post hoc subgroup analysis, significantly more rapid discontinuation of mechanical ventilation (p = 0.045) and a trend toward an increase in the number of days free from the ventilator at 28 days (CMV = 3.2 +/- 1.9, PLV = 8.0 +/- 2.2 days, p = 0.06) were observed during PLV among those patients under 55 years of age with acute lung injury or ARDS. Episodes of hypoxia, respiratory acidosis, and bradycardia occurred more frequently in the PLV group, but these were transient and self-limited. Further evaluation of PLV is warranted to further define beneficial effects in well-defined groups of patients and also to gain additional information regarding safety. It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS).
                Randomized, controlled clinical trial.
                Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study).
                All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV.
                In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg.
                The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001).
                A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS. 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. In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), noninvasive ventilatory support (NPPV) with bilevel positive airway pressure (BiPAP) may improve clinical and physiological parameters. The present study used a randomized, prospective design to evaluate the possible benefits of NPPV plus standard therapy versus standard therapy alone in patients admitted with acute hypercapnic respiratory failure in a respiratory unit of a tertiary hospital.
                Forty-one patients were included in the study. Of them, 20 were randomly allocated to receive NPPV with a standard mask connected to a BiPAP ventilatory assist device (Respironics Inc, Murrysville, PA) and 21 to standard therapy. Both groups had similar characteristics upon their admission in the hospital.
                The use of noninvasive ventilation significantly reduced the respiratory rates and improved the conscious level within the first 2 h (p < 0.001). There were significant differences in PaCO2 and pH (p < 0.05) at 6 h of treatment. The need for intubation was 5% in the NPPV group vs 14% in the control group. The length of hospital stay was significantly shorter in the NPPV group (7 vs 10 days; p < 0.01). Nasal NPPV was well tolerated and complications were uncommon and mild.
                Early use of noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease leads to a more rapid improvement of physiological variables. Moreover, it is possible to apply this treatment in a general respiratory ward. The objective of this investigation was to determine if high-frequency jet ventilation (HFJV) used early in the treatment of premature infants with respiratory distress syndrome was effective in reducing pulmonary morbidity without increasing the occurrence of adverse neurologic outcomes.
                A total of 73 premature infants who met the inclusion criteria (gestational age of less than 33 weeks, birth weight of more than 500 g, age of less than 24 hours, need for assisted ventilation with peak inspiratory pressure of more than 16 and FIO2 more than 0.30, and roentgenographic evidence of respiratory distress syndrome) were randomized to either conventional (n = 36) or to high-frequency jet (n = 37) ventilation. Our goals were to maintain the infants on the assigned ventilator for at least 7 days unless they could either be extubated or meet crossover criteria. Univariate analyses were initially used to compare the two groups. Stepwise logistic regression was subsequently used to assess whether various factors independently influenced adverse outcomes.
                The two groups of infants were similar in all obstetrical, perinatal, and neonatal demographic characteristics. The mean birth weight and gestational age in the conventional group were 930 g and 26.6 weeks and in the HFJV group, 961 g and 26.9 weeks. The infants were randomized at similar ages (7.1 and 7.3 hours of life, respectively). Their prerandomization ventilator settings and arterial blood gases were nearly identical. There were no differences in pulmonary outcomes (occurrence of air leaks, need for oxygen or ventilation at 36 weeks postconception), and there were no differences in the mean number of days oxygen was required, number of days ventilated, or length of hospital stay. Infants ventilated with HFJV were significantly more likely to develop cystic periventricular leukomalacia (10 vs 2, P = .022) or to have a poor outcome (grade IV hemorrhage, cystic periventricular leukomalacia, or death) (17 vs 7, P = .016). Logistic regression analysis revealed HFJV to be a significant independent predictor of both cystic periventricular leukomalacia and a poor outcome. The presence of hypocarbia was not an independently significant predictor of adverse outcomes.
                With the HFJV treatment strategy that we used, use of the high-frequency jet ventilator in the early management of premature infants with respiratory distress syndrome resulted in significantly more adverse outcomes than in those treated with conventional mechanical ventilation. To determine the 1-year efficacy of noninvasive positive pressure ventilation (NPPV) added to long-term oxygen therapy (LTOT) in patients with stable severe COPD. PATIENT SELECTION AND METHODS: We prospectively randomized 52 patients with severe COPD (FEV(1) < 45%) to either NPPV plus "standard care" (96% patients with LTOT) or to standard care alone (93% patients with LTOT). The outcomes measured included the following: rate of acute COPD exacerbations; hospital admissions; intubations; and mortality at 3 months, 6 months, and 12 months. The patients were also evaluated at 3 months and 6 months for dyspnea using the Medical Research Council and Borg scales, gas exchange, hematocrit, pulmonary function, cardiac function with echocardiogram, and neuropsychological performance.
                One-year survival was similar in both groups (78%). The number of acute exacerbations was similar at all time points in patients receiving NPPV, compared with control subjects. The number of hospital admissions was decreased at 3 months in the NPPV group (5% vs 15% of patients, p < 0.05), but this difference was not seen at 6 months (18% vs 19%, respectively). The only beneficial differences were observed in the Borg dyspnea rating, which dropped from 6 to 5 (p < 0.039), and in one of the neuropsychological tests (psychomotor coordination) for the NPPV group at 6 months.
                Our study indicates that over 1 year, NPPV does not affect the natural course of the disease and is of marginal benefit in outpatients with severe COPD who are in stable condition. Volutrauma and pulmonary inflammation are thought to be the most important predisposing factors of chronic lung disease (CLD), a major complication of prematurity. A new option in patient-triggered ventilation (PTV), the volume guarantee (VG), a volume-targeted ventilation, seems to be a promising approach in reducing the risk of CLD, by limiting lung inflammatory injury and volutrauma. Our aim was to evaluate lung inflammatory response in preterm infants with respiratory distress syndrome (RDS), mechanically ventilated with and without VG, as measured by proinflammatory cytokines (IL-6, IL-8, and TNF-alpha) in tracheobronchial aspirate (TA) fluid. Fifty-three preterm infants (GA = 25-32 weeks) with RDS were randomized at birth to be ventilated using pressure support ventilation (PSV) with VG (Vt = 5 ml/kg) (n = 30) and without VG (n = 23) (Draeger Babylog 8000 Plus, 5.n). IL-6, IL-8, and TNF-alpha were determined by ELISA in TA samples on days 1, 3, and 7 of life. We observed a significant difference (ANOVA) in IL-8 and IL-6 levels on day 3 between the two groups (P < 0.05), and an increasing significative trend in IL-8 values in PSV group (P < 0.05). Mechanical ventilation lasted longer in the PSV group (12.3 +/- 3 vs. 8.8 +/- 3 days) (P = no significance). In conclusion, these preliminary data suggest a role for volume-targeted ventilatory strategy in reducing acute inflammatory response in preterm infants with RDS. Further studies are required in order to define whether this ventilatory strategy prevents lung injury.
                Copyright 2004 Wiley-Liss, Inc.
The overall analysis shows a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern is the significant increase in acute brain injury in one trial which used lower mean airway pressures when ventilating with HFJV. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials.