P11 Long-term home non-invasive ventilation

For patients with COPD who also have sleep apnoea or hypoventilation, ventilatory support with continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) may be more appropriate than oxygen therapy (for more details see section X3.2). A 2013 Cochrane meta-analysis comparing nocturnal NIV to standard care alone in patients with stable COPD and hypercapnia found no benefit. There was no significant change to gas exchange, exercise tolerance, quality of life, lung function, respiratory muscle strength or sleep efficiency (Struik 2013). The authors concluded that there is insufficient evidence to support widespread NIV use in stable COPD [evidence level I]. This meta-analysis included data from an Australian trial of hypoxaemic COPD patients with hypercapnia (n=144) randomised to long term oxygen therapy alone or with NIV. McEvoy et al found a small mortality benefit in the NIV group, at the expense of worse quality of life (McEvoy 2009) [evidence level II]. Mean pressures used were inspiratory positive airways pressure (IPAP) 13 cmH2O, EPAP 5 cmH2O. No significant reduction in PaCO2 was observed.

In 2014 two further randomised controlled trials of long term NIV in patients with COPD were published. A major difference from the McEvoy trial is the significantly higher inspiratory positive pressures used. Kohnlein et al (Kohnlein 2014) randomised 195 patients with clinically stable, severe COPD and hypercapnia to NIV or usual care. Both groups were admitted to hospital every 3 months for 1 year for ‘treatment optimisation’. NIV was titrated to target a reduction in PaCO2 by 20% or achieve PaCO2 of less than 48mmHg. There was a significant reduction in 1-year mortality. 12% mortality in the intervention group and 33% in the control group was reported; hazard ratio 0·24 (95% CI 0·11–0·49; p=0·0004) [evidence level II]. Mean pressures used were IPAP 22 cmH2O, EPAP 5 cmH2O. Mean reduction in PaCO2 was 7mmHg. In direct contrast to this finding, Struik et al 2014 found no mortality or exacerbation rate difference in a 12 month randomised controlled trial (n =201) of NIV and usual care in patients with severe COPD who had been admitted to hospital with an exacerbation of COPD and hypercapnia (Struik 2014). Mean pressures used were IPAP 19 cmH2O, EPAP 5 cmH2O. Mean reduction in PaCO2 was 3.8mmHg.

In 2017, Murphy et al reported on a trial of long term NIV in patients who remained hypercapnic and hypoxic two to four weeks after resolution of respiratory acidosis due to an exacerbation of COPD (Murphy 2017). Murphy excluded patients with a BMI >35 kg/mand patients with obstructive sleep apnoea. 116 patients were randomised to continuous home oxygen or continuous home oxygen plus home NIV. It should be noted that over 2,000 patients were screened for inclusion. Similar to Kohnlein, high NIV pressures were used with a median IPAP pressure of 24 cmH2O and a median EPAP pressure of 4 cmH2O. Median NIV adherence at 12 months was high at 7.6hrs. The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group versus 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI 0.1 to 34%). There was no mortality difference at 12 months.

Comparison between the trials above is difficult as they used different treatment algorithms and NIV pressure settings. Furthermore, inclusion criteria and patient characteristics also differed significantly. For example, McEvoy et al performed a baseline diagnostic sleep study and excluded patients with OSA. A baseline PSG was not performed in the other trials. It is also unclear if the results from the Kohnlein trial are generalisable to an Australasian patient population given that all participants were electively admitted three monthly. A meta-analysis of 21 RCTs of domiciliary NIV trials included the three trials referred to above (Dretzke 2016). The authors concluded that domiciliary NIV does not reduce mortality in patients with stable COPD or in patients post admission for an exacerbation of COPD. The authors noted significant differences in patient populations and trial designs.

With such significant heterogeneity of results, patient characteristics and methodology, it remains unclear if long term NIV should be recommended for patients with severe stable COPD and hypercapnia.  The trial by Murphy et al demonstrates that in highly selected patients who remain hypercapnic and hypoxic several weeks after an episode of acute hypercapnic respiratory failure, home NIV delivered at very high pressures significantly reduces hospital re-admissions.  Referral for specialist opinion at an institution with expertise in this area should be sought.