Background Non-invasive positive pressure ventilation (NPPV) is being used increasingly in the management of patients admitted to hospital with acute respiratory failure secondary to an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives To determine the efficacy of NPPV in the management of patients with respiratory failure due to an acute exacerbation of COPD. Search strategy An initial search was performed using the Cochrane Airways Group trials register and other relevant electronic databases. An updated search was conducted in September 2003 and another in April 2004. Selection criteria Randomised controlled trials comparing NPPV plus usual medical care (UMC) versus UMC alone were selected. Trials needed to recruit adult patients admitted to hospital with respiratory failure due to an exacerbation of COPD and with PaCO2 > 6 kPa (45 mmHg). Data collection and analysis Two reviewers independently selected articles for inclusion, evaluated methodological quality of the studies and abstracted the data. Main results Fourteen studies were included in the review. NPPV resulted in decreased mortality (Relative Risk 0.52; 95%CI 0.35 to 0.76), decreased need for intubation (RR 0.41; 95%CI 0.33 to 0.53), reduction in treatment failure (RR 0.48; 95%CI 0.37 to 0.63), rapid improvement within the first hour in pH (Weight Mean Difference 0.03; 95%CI 0.02 to 0.04), PaCO2 (WMD -0.40 kPa; 95%CI -0.78 to -0.03) and respiratory rate (WMD -3.08 bpm; 95%CI -4.26 to -1.89). In addition, complications associated with treatment (RR 0.38; 95%CI 0.24 to 0.60) and length of hospital stay (WMD -3.24 days; 95%CI -4.42 to -2.06) was also reduced in the NPPV group. Reviewers' conclusions Data from good quality randomised controlled trials show benefit of NPPV as first line intervention as an adjunct therapy to usual medical care in all suitable patients for the management of respiratory failure secondary to an acute exacerbation of COPD. NPPV should be considered early in the course of respiratory failure and before severe acidosis ensues, as a means of reducing the likelihood of endotracheal intubation, treatment failure and mortality.

Non‐invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease

Background
Non-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Objectives
To compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research.

Search methods
We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting abstracts. This update to the original review incorporates the results of database searches up to January 2017.

Selection criteria
All randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases.

Data collection and analysis
Two review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guidelines. Review authors undertook meta-analysis for data that were both clinically and statistically homogenous, and analysed data as both one overall pooled sample and according to two predefined subgroups related to exacerbation severity (admission pH between 7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit-based vs ward-based). We reported results for mortality, need for endotracheal intubation, and hospital length of stay in a 'Summary of findings' table and rated their quality in accordance with GRADE criteria.

Main results
We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient-reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.

Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) -3.39 days, 95% CI -5.93 to -0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO2) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO2 was observed, but this finding was not statistically significant (MD -4.62 mmHg, 95% CI -11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO2. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non-significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) -0.16, 95% CI -0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between-group differences.

Authors' conclusions
Data from good quality randomised controlled trials show that NIV is beneficial as a first-line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.

Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease

Changing Patterns in Long-term Noninvasive Ventilation: A 7-Year Prospective Study in the Geneva Lake Area

Exacerbations of chronic obstructive pulmonary disease (COPD) cause morbidity, hospital admissions, and mortality, and strongly influence health-related quality of life. Some patients are prone to frequent exacerbations, which are associated with considerable physiologic deterioration and increased airway inflammation. About half of COPD exacerbations are caused or triggered primarily by bacterial and viral infections (colds, especially from rhinovirus), but air pollution can contribute to the beginning of an exacerbation. Type 1 exacerbations involve increased dyspnea, sputum volume, and sputum purulence; Type 2 exacerbations involve any two of the latter symptoms, and Type 3 exacerbations involve one of those symptoms combined with cough, wheeze, or symptoms of an upper respiratory tract infection. Exacerbations are more common than previously believed (2.5-3 exacerbations per year); many exacerbations are treated in the community and not associated with hospital admission. We found that about half of exacerbations were unreported by the patients, despite considerable encouragement to do so, and, instead, were only diagnosed from patients' diary cards. COPD patients are accustomed to frequent symptom changes, and this may explain their tendency to underreport exacerbations. COPD patients tend to be anxious and depressed about the disease and some might not seek treatment. At the beginning of an exacerbation physiologic changes such as decreases in peak flow and forced expiratory volume in the first second (FEV(1)) are usually small and therefore are not useful in predicting exacerbations, but larger decreases in peak flow are associated with dyspnea and the presence of symptomatic upper-respiratory viral infection. More pronounced physiologic changes during exacerbation are related to longer exacerbation recovery time. Dyspnea, common colds, sore throat, and cough increase significantly during prodrome, indicating that respiratory viruses are important exacerbation triggers. However, the prodrome is relatively short and not useful in predicting onset. As colds are associated with longer and more severe exacerbations, a COPD patient who develops a cold should be considered for early therapy. Physiologic recovery after an exacerbation is often incomplete, which decreases health-related quality of life and resistance to future exacerbations, so it is important to identify COPD patients who suffer frequent exacerbations and to convince them to take precautions to minimize the risk of colds and other exacerbation triggers. Exacerbation frequency may vary with the severity of the COPD. Exacerbation frequency may or may not increase with the severity of the COPD. As the COPD progresses, exacerbations tend to have more symptoms and take longer to recover from. Twenty-five to fifty percent of COPD patients suffer lower airway bacteria colonization, which is related to the severity of COPD and cigarette smoking and which begins a cycle of epithelial cell damage, impaired mucociliary clearance, mucus hypersecretion, increased submucosal vascular leakage, and inflammatory cell infiltration. Elevated sputum interleukin-8 levels are associated with higher bacterial load and faster FEV(1) decline; the bacteria increase airway inflammation in the stable patient, which may accelerate disease progression. A 2-week course of oral corticosteroids is as beneficial as an 8-week course, with fewer adverse effects, and might extend the time until the next exacerbation. Antibiotics have some efficacy in treating exacerbations. Exacerbation frequency increases with progressive airflow obstruction; so patients with chronic respiratory failure are particularly susceptible to exacerbation.

http://rc.rcjournal.com/content/respcare/48/12/1204.full.pdf

Exacerbations of Chronic Obstructive Pulmonary Disease

Background: Non-invasive ventilation (NIV) has been shown to reduce intubation and in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF). However, little information exists on the outcomes following discharge. A study was undertaken to examine the rates of readmission, recurrent AHRF, and death following discharge and the risk factors associated with them. 

Methods: A cohort of COPD patients with AHRF who survived after treatment with NIV in a respiratory high dependency unit was prospectively followed from July 2001 to October 2002. The times to readmission, first recurrent AHRF, and death were recorded and analysed against potential risk factors collected during the index admission. 

Results: One hundred and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after NIV during the study period. One year after discharge 79.9% had been readmitted, 63.3% had another life threatening event, and 49.1% had died. Survivors spent a median of 12% of the subsequent year in hospital. The number of days in hospital in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the MRC dyspnoea score (p<0.001) predicted early death. 

Conclusions: COPD patients with AHRF who survive following treatment with NIV have a high risk of readmission and life threatening events. Further studies are urgently needed to devise strategies to reduce readmission and life threatening events in this group of patients.

https://thorax.bmj.com/content/thoraxjnl/59/12/1020.full.pdf

Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure

BACKGROUND—There is increasing interest in the use of non-invasive nocturnal intermittent positive pressure ventilation (NIPPV) in the management of patients with chronic hypercapnoeic (type II) respiratory failure. Although this treatment enables patients requiring mechanical ventilatory support to be treated more readily at home, few studies have been done to demonstrate its long term benefits in chronic obstructive pulmonary disease (COPD) and the application of NIPPV in these circumstances remains controversial.
METHODS—Eleven patients in severe stable chronic type II respiratory failure due to COPD who were unresponsive to conventional treatments experienced symptomatic hypercapnia when receiving sufficient supplementary oxygen to result in an arterial oxygen saturation (SaO2) of >90%. They were assessed for treatment with NIPPV, and its effects were observed for over two years using arterial blood gas tensions, spirometric parameters and body mass index (BMI), survival, hospital admissions, use of general practitioner resources, and patient satisfaction.
RESULTS—Hospital admissions and GP consultations were halved after one year compared with the year before NIPPV and there was a sustained improvement in arterial blood gas tensions at 12 and 24 months when breathing air, despite progressive deterioration in ventilatory function. BMI did not change during the period of observation. The median survival was 920 days, with no patient dying within the first 500days.
CONCLUSIONS—Domiciliary NIPPV results in improvements in arterial blood gas tensions which are sustained after two years of treatment and reduces both hospital admissions and general practitioner visits by patients with severe COPD in hypercapnoeic respiratory failure. It is well tolerated and, although there was no control group, survival appears to be prolonged when these results are compared with those of the NOTT and MRC (LTOT) trials.

https://thorax.bmj.com/content/thoraxjnl/53/6/495.full.pdf

Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long term follow up and effect on survival

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Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long term follow up and effect on survival