Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. A preliminary evaluation of a prospective study of pulmonary function studies and symptoms of hypoventilation in ALS/MND patients. Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis. Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial. Effects of nocturnal noninvasive mechanical ventilation on heart rate variability of patients with advanced COPD. [Application of sequential noninvasive following invasive mechanical ventilation in COPD patients with severe respiratory failure by investigating the appearance of pulmonary-infection-control-window]. Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease.
Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial.
                92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured.
                NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit.
                In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage. 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. There is still no consensus as to which physiologic marker should be used as a trigger for the initiation of non-invasive positive pressure ventilation (NPPV) in patients with amyotrophic lateral sclerosis (ALS). Current practice parameters recommend that the decision to begin treatment be based upon forced vital capacity (FVC) measurements. A prospective, randomized study was performed in 20 ALS patients who had an FVC of 70-100%. Patients received baseline assessments including: ALS functional rating scale-respiratory version (ALSFRS-R), pulmonary symptom scale, Short form 36 (SF-36), FVC%, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and nocturnal oximetry. Patients were randomized to receive NPPV based upon nocturnal oximetry studies suggesting oxygen desaturation <90% for one cumulative minute ("early intervention") or a FVC <50% ("standard of care"). At enrollment, there was no significant correlation between FVC% and the ALSFRS-R, symptom score, MEP, MIP, or duration of nocturnal desaturation <90%. An increase in the vitality subscale of the SF-36 was demonstrated in 5/6 patients randomized to "early intervention" with NPPV. Our data indicate that FVC% correlates poorly with respiratory symptoms and suggests that MIP and nocturnal oximetry may be more sensitive measures of early respiratory insufficiency. In addition, intervention with NPPV earlier than our current standard of care may result in improved quality of life. The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg).
                In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity.
                Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2.
                6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival. Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD.
                A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (PaCO2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood.
                144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour.
                Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life.
                ACTRN12605000205639. Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD.
                A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months.
                After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013).
                NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients. To evaluate the application of sequential noninvasive following invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients with severe respiratory failure by investigating the appearance of pulmonary-infection-control-window.
                From November 2001 to October 2004, 76 case of COPD patients with severe respiratory failure due to pulmonary infection were intubated and recruited in the study. When the pulmonary infection was significantly controlled (the time of pulmonary infection control was called PIC window) by the antibiotic and comprehensive therapy, all cases were randomized into noninvasive veatiation group (NIV) and control group. The early extubation was conducted and followed by noninvasive mechanical ventilation via facial mask with bilevel positive airway pressure mode immediately in the NIV group. Conventional invasive synchronized intermittent mandatory ventilation (SIMV) plus pressure support ventilation (PSV) was used as the weaning technique in the control group.
                Thirty eight cases among 76 patients were in the NIV group, and the rest in the control group. The NIV group and the control group had similar age, sex, APACHE scores, RR, HR, MAP, PaO2 and PaCO2 at the time of commencement and PIC window (P > 0.05). The time of PIC window was (7.5 +/- 1.9) d in the NIV group, and (8.0 +/- 2.5) d in the control group (P > 0.05). In the NIV group, the durations of invasive mechanical ventilation (MV) and total MV were (7.5 +/- 1.9) d and (12.5 +/- 4.0) d respectively, while the durations were (23.5 +/- 9.5) d in the control group (P < 0.05). The durations of RICU stay and hospital stay were shorter than that in the control group. The incidence of ventilation associated pneumonia (VAP) was 18.4% (7/38) in the NIV group, 39.5% (15/38) in the control group respectively (P < 0.05). The incidence of reintubation was 13.2% (5/38) in the NIV group, 34.2% (13/38) in the control group respectively (P < 0.05). Hospital mortality was 7.9% (3/38) in the NIV group, and 28.9% (11/38) in the control group (P < 0.05).
                In those COPD patients requiring intubation and mechanical ventilantion who have severe respiratory failure due to pulmonary infection, sequential noninvasive following invasive mechanical ventilation at the appearance of PIC window can significantly reduce the MV duration, the length of RICU stay and hospital stay, and decrease the occurrence of VAP, reintubation and hospital mortality as well. So it is an efficient strategy to be generalized. 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. 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.
Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Future studies should examine the health economics of NIV and factors influencing access to NIV. We need to understand the factors, personal and socioeconomic, that determine access to NIV.