Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Comparison of nasal pressure support ventilation with nasal intermittent positive pressure ventilation in patients with nocturnal hypoventilation. A prospective randomized, controlled trial comparing synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as modes of extubation. A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants. Comparison of the acute effects on gas exchange of nasal ventilation and doxapram in exacerbations of chronic obstructive pulmonary disease. Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.
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. Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality. Nasal intermittent positive pressure ventilation (NIPPV) provides effective ventilatory support in patients with nocturnal hypoventilation. Nasal pressure support ventilation (NPSV), which only provides ventilation in response to patient triggering, may also be effective, simpler, and cheaper, but has not been evaluated. NIPPV and NPSV were compared in 12 patients with nocturnal hypoventilation, requiring domiciliary ventilatory support. The patients were studied on three consecutive nights, in random order: a control night without ventilation and a night on each mode of ventilatory support using the bilevel positive airway pressure (BiPAP) ventilator. Both NIPPV and NPSV significantly increased mean arterial oxygen saturation (SaO2) compared to the control night (NIPPV mean increase 4.1%; 95% confidence interval (CI) 2.2 to 6.1, NPSV 4.4%; CI 2.1 to 6.6) with no significant difference between the two modes. The percentage of the study night spent below 90% SaO2 was significantly reduced by both ventilator modes compared to the control night (median reduction on NIPPV 37%; CI -54 to -10, reduction on NPSV 31%; CI -53 to -9, with no significant difference between NPSV and NIPPV. NPSV was as effective as NIPPV in patients with nocturnal hypoventilation, which suggests that these patients are able to trigger the ventilator adequately. The lower cost of NPSV will make it accessible to more patients with chronic lung disease. To determine whether synchronized nasal intermittent positive pressure ventilation (SNIPPV) would decrease extubation failure compared with nasal continuous positive airway pressure (NCPAP) in preterm infants being ventilated for respiratory distress syndrome (RDS).
                Infants who were </=34 weeks' gestational age and who were ventilated for RDS were randomized to either SNIPPV or NCPAP after extubation. The criteria for extubation were peak inspiratory pressure of </=16 cm H(2)O, positive end expiratory pressure of </=5 cm H(2)O, intermittent mandatory ventilation rate of 15 to 25, and fraction of inspired oxygen </=0.35. Pulmonary function tests (PFT) were obtained before extubation. After extubation, blood gases were monitored for a minimum of 72 hours. Success was defined as remaining in the selected mode of treatment or demonstrating improvement (switching to oxyhood/nasal cannula/room air) by 72 hours.
                Thirty-two (94%) of 34 infants were extubated successfully with the use of SNIPPV versus 18 (60%) of 30 with the use of NCPAP (P <.01). There was no difference in apnea/bradycardia episodes in the 2 groups during the 72-hour study period. Among 55 infants who had PFT, 80% (8 of 10) with dynamic lung compliance of >/=0.5 mL/kg/cm H(2)O and expiratory airway resistance of </=70 cm H(2)O/L/s were extubated successfully. In infants with poor lung function (dynamic lung compliance: <0.5 mL/kg/cm H(2)O; expiratory airway resistance: >70 cm H(2)O/L/s), successful extubation was seen in 93% (27 of 29) in the SNIPPV group and 60% (15 of 25) in the NCPAP group. When weight was controlled for at the time of extubation, the odds of success in the SNIPPV group were 21.1 times higher (95% confidence interval: 3.4, 130.1) than that of the NCPAP group.
                SNIPPV is more effective than NCPAP in weaning infants with RDS from the ventilator. PFT may be useful in predicting successful extubation. 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. Nasal intermittent positive pressure ventilation (NIPPV) is useful in exacerbations of chronic obstructive pulmonary disease (COPD) complicated by ventilatory failure. The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure.
                Patients admitted with acute exacerbations of COPD and type 2 respiratory failure (Pao2 < 8 kPa and PaCO2 > 6.7 kPa) who did not improve with conventional treatment were randomised to receive either NIPPV or intravenous doxapram. Blood gas tensions were monitored for four hours.
                In nine patients who received NIPPV the arterial PaO2 improved from a mean (SE) of 5.9 (0.4) kPa to a maximum of 8.1 (0.6) kPa which was maintained at four hours. Eight patients who received doxapram had a similar baseline Pao2 of 5.6 (0.4) kPa which rose to a maximum of 7.3 (0.5) kPa but this was not maintained at four hours. The improvement in Pao2 in patients on NIPPV was accompanied by a fall in Paco2 but, in contrast, in those who received doxapram there was no improvement in Paco2.
                NIPPV may be more effective than doxapram in the management of acute ventilatory failure complicating COPD. Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV.
                Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacity<50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria.
                Peak nocturnal transcutaneous carbon dioxide tension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months.
                Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues. 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. Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed.
                To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater.
                Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%).
                We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.
Implications for practice: NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea that is frequent or severe. Its use appears to reduce the frequency of apneas more effectively than NCPAP. Additional safety and efficacy data are required before recommending NIPPV as standard therapy for apnea.
Implications for research: Future trials with sufficient power should assess the efficacy (reduction in failure of therapy) and safety (GI complications) of NIPPV. Outcomes should be assessed throughout the entire period during which the infant requires assisted ventilation. The recent ability to synchronise NIPPV with an infant's spontaneous respirations is a promising development requiring further assessment.