Treat underlying lung disease: The logical first step is to optimise lung function and treat all potential aggravating conditions.
Oxygen therapy: Long term, continuous (>15h/day) oxygen therapy to treat chronic hypoxaemia prolongs survival of patients with COPD, presumably by reducing pulmonary hypertension (Medical Research Council Working Party 1981, Nocturnal Oxygen Therapy Trial Group 1980, Weitzenblum 1985, Gorecka 1997, Zielinski 1998) (For a detailed description of oxygen therapy in COPD, see section P10).
Ventilatory support: 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 IPAP 13cmH2O, EPAP5cmH2O. 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 22cmH2O, EPAP 5cmH2O. 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 19cmH2O, EPAP 5cmH2O. Mean reduction in PaCO2 was 3.8mmHg.
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 subjects 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. Referral for specialist opinion at an institution with expertise in this area should be sought.
Diuretics: Diuretics may reduce right ventricular filling pressure and oedema, but excessive volume depletion must be avoided. Volume status can be monitored by measuring serum creatinine and urea levels. Diuretics may cause metabolic alkalosis resulting in suppression of ventilatory drive.
Digoxin: Digoxin is not indicated in the treatment of cor pulmonale and may increase the risk of arrhythmia when hypoxaemia is present (Global Initiative for Chronic Obstructive Lung Disease 2016). It may be used to control the rate of atrial fibrillation.
Vasodilators: Vasodilators (hydralazine, nitrates, nifedipine, verapamil, diltiazem, angiotensin-converting enzyme [ACE] inhibitors) do not produce sustained relief of pulmonary hypertension in patients with COPD (Barbera 1996, Jones 1997). They can worsen oxygenation (by increasing blood flow through poorly ventilated lung) and result in systemic hypotension. However, a cautious trial may be used in patients with severe or persistent pulmonary hypertension not responsive to oxygen therapy. Some vasodilators (eg, dihydropyrodine calcium antagonists) have been shown to reduce right ventricular pressure with minimal side effects and increased well-being, at least in the short term (Sajkov 1993, Sajkov 1997). Nitric oxide worsens V/Q mismatching and is therefore contraindicated in patients with COPD (Barbera 1996, Jones 1997).< Prev Next >