Noninvasive ventilation as a systematic extubation and weaning technique in acute-on-chronic respiratory failure: a prospective, randomized controlled study. The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics. Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn. [Noninvasive positive pressure ventilation for acute respiratory failure in chronic obstructive pulmonary disease in a general respiratory ward].
Prolonged duration of endotracheal mechanical ventilation (ETMV) is associated with an increased morbidity and mortality in intensive care unit (ICU) patients. The aim of this study was to assess the usefulness of noninvasive ventilation (NIV) as a systematic extubation and weaning technique to reduce the duration of ETMV in acute-on-chronic respiratory failure (ACRF). Among 53 consecutively intubated patients admitted for ACRF, we conducted a prospective, randomized controlled trial of weaning in 33 patients who failed a 2-h T-piece weaning trial (2 h-WT) although they met simple criteria for weaning. Conventional invasive pressure support ventilation (IPSV) was used as the control weaning technique in 16 patients (IPSV group), and NIV was applied immediately after extubation in 17 patients (NIV group). The two weaning groups were similar for type of chronic respiratory failure (CRF), pulmonary function data, age, Simplified Acute Physiology Score (SAPS II), and severity of ACRF on admission. The characteristics of the two groups were also similar at randomization. In the IPSV group, 12 of 16 patients (75%) were successfully weaned and extubated, versus 13 of 17 (76.5%) in the NIV group (p = NS). NIV like IPSV significantly and similarly improved gas exchange in relation to that achieved during 2 h-WT (p < 0.05). The duration of ETMV was significantly shorter in the NIV (4.56 +/- 1.85 d) than in the IPSV group (7.69 +/- 3.79 d) (p = 0. 004). NIV also reduced the mean period of daily ventilatory support, but increased the total duration of ventilatory support related to weaning (3.46 +/- 1.42 d, versus 11.54 +/- 5.24 d with NIV; p = 0. 0001). Most patients in the IPSV group developed complications related to ETMV and/or the weaning process, but the difference was not significant (nine of 16 versus six of 17). The durations of ICU and hospital stays and the 3-mo survival were similar in the two groups. In conclusion, NIV permits earlier removal of the endotracheal tube than with conventional IPSV, and reduces the duration of daily ventilatory support without increasing the risk of weaning failures. NIV should be considered as a new and useful systematic approach to weaning in patients with ACRF who are difficult to wean. 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. High-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) have been reported to improve oxygenation in children with acute hypoxemic respiratory failure (AHRF), but their roles in the treatment of AHRF remains unknown. The use of HFOV improves oxygenation by increasing lung recruitment. iNO can improve oxygenation in AHRF, but it may have limited efficacy in patients with poor lung inflation. Based on these findings, we hypothesized that the combined treatment of HFOV and inhalation of low-dose NO would improve oxygenation and survival in children with severe AHRF compared with children treated with conventional mechanical ventilation (CMV) or either treatment alone.
                Tertiary pediatric intensive care units at seven academic centers.
                Post hoc analysis of data from children enrolled in a multicenter, randomized, masked study of the use of iNO in the treatment of AHRF.
                A total of 108 pediatric patients with AHRF defined as an oxygenation index of >15 twice within 6 hrs. Mode of ventilation (HFOV or CMV) was determined by the patient's physician based on guidelines to maximize oxygenation. The patient was then randomized to treatment with or without iNO. Comparisons were made between patients who were treated with HFOV plus iNO (n = 14), HFOV alone (n = 12), CMV plus iNO (n = 35), and CMV alone (n = 38).
                Ventilation with CMV or HFOV with or without iNO.
                We found that the change in Pao /Fio ratio was greatest in the HFOV plus iNO group compared with the other treatment groups at 4 hrs (p =.02) and 12 hrs (p =.01). After 24 hrs of treatment, both HFOV plus iNO and HFOV alone resulted in greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.005). After 72 hrs, treatment with HFOV alone resulted in a greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.03). There was no difference in predefined treatment failures between treatment groups.
                We conclude that the combination of HFOV with iNO causes a greater improvement in oxygenation than either treatment strategy alone in children with severe AHRF. We speculate that the enhanced lung recruitment by HFOV enhances the effects of low dose iNO on gas exchange. A prospective controlled randomized study of the use of extracorporeal membrane oxygenation to treat newborns with respiratory failure was carried out using the "randomized play-the-winner" statistical method. In this method the chance of randomly assigning an infant to one treatment or the other is influenced by the outcome of treatment of each patient in the study. If one treatment is more successful, more patients are randomly assigned to that treatment. A group of 12 infants with birth weight greater than 2 kg met objective criteria for high mortality risk. One patient was randomly assigned to conventional treatment (that patient died); 11 patients were randomly chosen for extracorporeal membrane oxygenation (all survived). Intracerebral hemorrhage occurred in one of 11 surviving children. Extracorporeal membrane oxygenation allows lung rest and improves survival compared to conventional ventilator therapy in newborn infants with severe respiratory failure. Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients. Avoiding intubation is a major goal in the management of respiratory failure, particularly in immunosuppressed patients. Nevertheless, there are only limited data on the efficacy of noninvasive ventilation in these high-risk patients.
                We conducted a prospective, randomized trial of intermittent noninvasive ventilation, as compared with standard treatment with supplemental oxygen and no ventilatory support, in 52 immunosuppressed patients with pulmonary infiltrates, fever, and an early stage of hypoxemic acute respiratory failure. Periods of noninvasive ventilation delivered through a face mask were alternated every three hours with periods of spontaneous breathing with supplemental oxygen. The ventilation periods lasted at least 45 minutes. Decisions to intubate were made according to standard, predetermined criteria.
                The base-line characteristics of the two groups were similar; each group of 26 patients included 15 patients with hematologic cancer and neutropenia. Fewer patients in the noninvasive-ventilation group than in the standard-treatment group required endotracheal intubation (12 vs. 20, P=0.03), had serious complications (13 vs. 21, P=0.02), died in the intensive care unit (10 vs. 18, P=0.03), or died in the hospital (13 vs. 21, P=0.02).
                In selected immunosuppressed patients with pneumonitis and acute respiratory failure, early initiation of noninvasive ventilation is associated with significant reductions in the rates of endotracheal intubation and serious complications and an improved likelihood of survival to hospital discharge. Within the intensive-care unit, non-invasive ventilation (NIV) can prevent the need for intubation and the mortality associated with severe episodes of chronic obstructive pulmonary disease (COPD). The aim of this study was to find whether the introduction of NIV, early after the admission on a general respiratory ward, was effective at reducing the need for intubation and the mortality associated with acute exacerbations of COPD.
                We did a prospective multicentre randomised controlled study comparing NIV with standard therapy in patients with mild to moderate acidosis. NIV was administered on the ward with a simple non-invasive ventilator and a standardised predefined protocol. Patients were recruited from 14 UK hospitals over 22 months.
                236 patients were recruited, 118 received standard therapy alone and 118 additional NIV. The two groups had similar characteristics at enrolment. The use of NIV significantly reduced the need for intubation as defined by the failure criteria. 32/118 (27%) of the standard group failed compared with 18/118 (15%) of the NIV group (p=0.02). In-hospital mortality was also reduced by NIV, 24/118 (20%) died in the standard group compared with 12/118 (10%) in the NIV group (p=0.05). In both groups pH, PaCO2, and respiratory rate improved at 4 h (p<0.01). However, NIV led to a more rapid improvement in pH in the first hour (p=0.02) and a greater fall in respiratory rate at 4 h (p=0.035). The duration of breathlessness was also reduced by NIV (p=0.025).
                The early use of NIV for mildly and moderately acidotic patients with COPD in the general ward setting leads to more rapid improvement of physiological variables, a reduction in the need for invasive mechanical ventilation (with objective criteria), and a reduction in in-hospital mortality. 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. 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.
There are a lack of well-designed, controlled experiments of non-invasive modes of respiratory support in children with AHRF. Studies assessing outcomes of mortality and avoidance of intubation and its associated complications, hospital stay and patient comfort are needed.