Acute Exacerbation of COPD: Effects of Noninvasive Ventilation and Oxygen on Readmission and Mortality

Andrew Shorr, MD, MPH


September 11, 2017

This is Andy Shorr, from MedStar Washington Hospital Center, with the Pulmonary and Critical Care Literature Update.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) remain a leading reason for admission to medical services in both US and European hospitals.

It's important to realize that many patients with COPD have acute hypercapnic respiratory failure and require treatment with noninvasive ventilation (NIV). They also have prolonged hospital stays, which consume substantial resources. More important, these patients have a high risk for short-term hospital readmission, and we often hear that 20%-30% are readmitted within 90 days. That's why, from the US perspective, this area is a major target for quality improvement and is something that the Centers for Medicare & Medicaid Services is looking at in terms of reimbursement issues.

At the recent American Thoracic Society's annual meeting, held in May 2017, Murphy and colleagues presented a very interesting randomized controlled trial looking at high-risk COPD patients and the use of nocturnal NIV to improve outcomes compared with supplemental oxygen alone. This article was published in JAMA simultaneously in print and online, and is available on the JAMA website.[1]

All participants in this trial were high-risk patients with COPD who had persistent hypercapnic respiratory failure while they were admitted and required supplemental oxygen. After patients had been stable for 2-4 weeks, they were randomized to either continue on supplemental oxygen alone or to initiate NIV in addition to supplemental oxygen.

Again, all of the patients selected to participate in the study had persistent hypercarbia but no longer had acute hypercarbia, based on arterial blood gas measurement. They also had to demonstrate a pH >7.3 on arterial blood gas sample. After these criteria were met, the patients were randomized to receive nocturnal NIV with supplemental oxygen or supplemental oxygen alone.

The investigators followed all study participants for 1 year, looking at issues related to COPD exacerbations, mortality, and quality of life (QOL). In this study of 116 patients, the authors showed that the time to the pooled endpoint—which was either readmit, exacerbation, or death—was substantially increased in the NIV plus supplemental oxygen group compared with those who received supplemental oxygen alone.

It is important to note that thousands of patients were screened and excluded from this study. The authors screened such a large number of patients to eliminate those who were obese, had preexisting sleep apnea, or had other conditions requiring nocturnal ventilation. Needless to say, because this was a very cumbersome study, a large number of patients dropped out during the screening process for other reasons.

This cohort of 116 patients showed a substantial reduction in the time to the first exacerbation or mortality. The study also showed that the average number of exacerbations per year for patients receiving NIV was reduced from about four to three. Though these numbers may not seem large, this means that instead of being hospitalized four times a year, these patients were hospitalized only three times a year. Therefore, this number is substantial given the duration and expense associated with these hospitalizations.

As I mentioned previously, this was a pooled endpoint looking at time to first exacerbation and mortality. When broken down in terms of time to first exacerbation or time to mortality, the authors showed that there is no impact on mortality over the 12-month study for this intervention.

There were about 60 patients in each arm of the study, which is very underpowered. However, one important point that I don't believe the authors stressed is that the crude mortality rate in these 116 patients over 1 year is around 30%. As intensivists caring for patients with COPD who have had exacerbations and FEV1s of around 600 cc, and as pulmonologists seeing these patients in clinic, we need to discuss end-of-life care, palliative care, and goals of care with them.

I think the authors should be commended on performing this very cumbersome study. All of the patients in this study had to undergo nocturnal titration studies and required high levels of driving pressure. This trial was very challenging, especially given that other previous studies were done in patients with less hypercapnia, or less severe hypercapnia. In this study, patients had severe hypercapnia, with pCO2s of 59 or 60.

The authors persisted, completed the trial, and proved that outcomes could be improved in a super high-risk group of patients—improved their disease-free interval, for lack of a better term.

Regarding patient QOL, there was no QOL penalty associated with NIV. You might suspect that there would actually be a penalty for these patients because now they have nocturnal NIV in addition to supplemental oxygen, which might neutralize the benefit of being out of the hospital. This, however, was not the case. In fact, there was some improvement in QOL—not as substantial as one might have hoped, but certainly no suggestion of harm to patient QOL.

Again, this RCT, published online in JAMA, explores the role of NIV in patients with chronic hypercapnia, recent COPD exacerbations, and hospitalization.

This is Andy Shorr from Washington, DC.


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