In COPD, Carbon Dioxide Is Often Overlooked

Aaron B. Holley, MD


January 06, 2020

When it comes to outcome targets for chronic obstructive pulmonary disease (COPD), carbon dioxide is often overlooked.

Most pulmonary and internal medicine physicians know oxygen therapy can improve mortality for patients with COPD and hypoxia. Anecdotally, they'll be quick to tell you that hypoxia leads to exercise intolerance and pulmonary arterial hypertension, and supplemental oxygen improves quality of life and functional status in patients. What about carbon dioxide, though? If the oxygen level is normalized, does carbon dioxide matter? Is it worth targeting for reduction?

Recently published European Respiratory Society guidelines for using noninvasive positive pressure ventilation (NPPV) in chronic COPD tackled this question head on (please note: we're not talking about acute exacerbations here). It's been a controversial topic for some time. After a multicenter, randomized controlled trial (RCT) published in 2014 reported a mortality benefit with nighttime NPPV in selected patients with COPD, the discussion shifted back toward a more aggressive approach. Before 2009, most NPPV studies for COPD were negative, so an explanation for the positive findings from the RCT was sought. Enter high-intensity NPPV (HIN) targeting carbon dioxide elimination.

Monitoring Carbon Dioxide More Closely

What is HIN? Well, it doesn't require specific NPPV settings, nor does it have an official definition. It simply denotes a more aggressive approach to carbon dioxide reduction. The logic holds that the magnitude of reduction, and perhaps the high baseline carbon dioxide levels among the patients enrolled, is what drove the marked mortality improvement with NPPV in the 2014 RCT. So if you're looking to achieve the same benefit for your patients, you'll need to follow carbon dioxide levels closely.

Apparently, the European guideline authors bought in to this approach. Although all their recommendations are conditional and based on low-quality evidence, they advocate NPPV for stable, hypercapnic patients with COPD, using fixed pressure settings and targeting carbon dioxide reduction. Lastly, they suggest using long-term NPPV for patients with COPD who are recovering from acute hypercapnic respiratory failure. In the body of the paper, they clarify this indication and recommend it only if the patient remains hypercapnic several weeks (~2-4) after recovery from their acute event.

I think there are two ways to view these developments. On the one hand, the mortality and quality of life benefits demonstrated in some long-term COPD NPPV trials are impressive. It's not often that physicians have the opportunity to make such a large impact treating a chronic disease. We shouldn't kid ourselves about the cost and resources required, though. The 2014 RCT admitted their patients for an average of 5.6 days while they titrated their machines. HIN involves inspiratory pressures in the 20-30 cm H2O range, and although some have argued these settings won't affect compliance or sleep, extrapolated data from obesity hypoventilation syndrome say otherwise, and I remain skeptical. Lastly, a back-up rate may be needed to ensure carbon dioxide reduction, which in some health systems and countries can triple the cost of NPPV.

With the more recent data and this new guideline, physicians caring for hypercapnic patients with COPD should consider placing them on NPPV. Those with high partial pressure of carbon dioxide, usually > 50 mm Hg, are most likely to benefit, and close follow-up will be required. Management will be similar to what's done in most sleep clinics for patients with sleep apnea using continuous positive airway pressure. It'll require mask checks and switches, managing leaks, eliminating obstructive breathing events, and ensuring good sleep. Oh, and rechecking carbon dioxide and overnight oximetry. How many pulmonary clinics do all that? Mine doesn't.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.

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