Does Heliox Help in COPD Exacerbations?

Abstract & Commentary

By Andrew M. Luks, MD, Pulmonary and Critical Care Medicine, University of Washington, Seattle Dr. Luks reports no financial relationship to this field of study. This article originally appeared in the March 2010 issue of Critical Care Alert. It was edited by David J. Pierson, MD, and peer reviewed by William Thompson, MD. Dr. Pierson is Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, and Dr. Thompson is Staff Pulmonologist, VA Medical Center; Associate Professor of Medicine, University of Washington; they both report no financial relationships relevant to this field of study.

Synopsis: In this prospective, multicenter, randomized trial, addition of a helium-oxygen gas mixture to non-invasive positive pressure ventilation in the treatment of COPD exacerbations did not decrease the need for intubation when compared to non-invasive positive pressure ventilation alone.

Source: Maggiore SM, et al. A multicenter randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease. Crit Care Med. 2010;38:145-151.

Previous studies have shown that addition of a helium-oxygen mixture (HeO2) to non-invasive ventilation (NIV) in patients with COPD exacerbation improves dyspnea, work of breathing, and carbon dioxide elimination, but have yet to establish whether this approach is associated with improvements in other important clinical outcomes. Using a prospective, multicenter randomized study design, Maggiore and colleagues sought to address this gap in the literature and test the hypothesis that NIV combined with HeO2 was associated with decreased need for intubation during COPD exacerbations when compared to NIV alone.

Patients were included in the study if they were between 18 and 85 years of age; had known or suspected COPD based on pulmonary function tests, blood gases, clinical history, or chest radiograph; had worsening dyspnea for two weeks or less; had PaCO2 > 45 mm Hg; and had two or more of the following: respiratory rate > 24, pH < 7.35, and PaO2 < 50 mm Hg on room air. Patients were excluded if they had respiratory arrest or need for immediate intubation, pneumothorax, a short life expectancy (< 1 month), high oxygen requirements, and a variety of other criteria.

Enrolled patients were randomized to receive NIV plus HeO2 or air-oxygen in addition to conventional medical treatment. All patients were treated with an FIO2 of 0.35 and were started on an inspiratory pressure (IPAP) of 12-15 cm H2O and an expiratory pressure (EPAP) of 5 cm H2O with subsequent changes based on clinical status and blood gas results. NIV was not applied continuously and was, instead, applied intermittently for > 6 hours/day with clinicians free to decide how long and how often to use NIV each day. NIV was gradually discontinued when the total duration of NIV was < 6 hours/day. The decision to perform endotracheal intubation was based on pre-specified criteria that were well-defined in the study. The primary endpoint was the need for endotracheal intubation while secondary endpoints included total duration of NIV and invasive mechanical ventilation, length of ICU and hospital stay, 28-day mortality, and the incidence of adverse events.

A total of 204 patients were included in the study (102 per group). Sixty-four percent of the patients had a prior diagnosis of COPD, while the remaining 36% were suspected of having the diagnosis at the time of admission. Patients in both groups received an average IPAP of 15.1 ± 4 cm H2O and EPAP of 3.3 ± 2.0 cm H2O. The total duration of NIV in the first 48 hours of admission did not differ between the two groups, with the HeO2-treated patients receiving an average of 17.7 ± 9.8 hours compared to 18.8 ± 11.3 hours in the control group. A total of 56 patients in the study (27%) required intubation. The intubation rate was lower in the HeO2 group (24.5%) compared to the control group (30.4%), but this difference was not statistically significant (p = 0.35). Statistically significant differences favoring HeO2 were seen, however, in the subgroup of patients who required NIV for < 4 days (31% vs. 53%). There were no statistically significant differences in the duration of mechanical ventilation, ICU and hospital length of stay, and mortality. Observed complications included facial skin necrosis, eye irritation, gastric distention, and nosocomial pneumonia, but there were no observed differences in the incidence of these complications between the two study groups.

Commentary

Non-invasive positive pressure ventilation is now the standard treatment for patients who present with severe COPD exacerbations, as the treatment modality has been shown to decrease the need for intubation, shorten ICU length of stay, and improve mortality in such patients. The question is: Can we do better? The addition of HeO2 to treatment regimens in these patients certainly makes physiologic sense — the less dense and slightly more viscous HeO2 mixture leads to more laminar flow in obstructed airways and requires less pressure to drive ventilation — and has been shown to improve symptom-based and physiologic outcomes. Unfortunately, we still lack evidence that the therapy provides benefits over NIV alone with regard to other more important outcomes, including the need for intubation. Maggiore et al did show a trend toward improvement in this outcome measure but, as with a previous study that looked at this issue,1 these results were not statistically significant. They did show a significant improvement in those patients who required NIV for < 4 days, but the utility of this finding is questionable, as it is very difficult to predict a priori the duration of therapy that will be required in a given patient.

Both of these studies share a problem in that they were small and likely underpowered and, as a result, potentially subject to Type II errors. The study by Maggiore and colleagues likely also suffered from their overly broad inclusion criteria that might have captured patients who did not truly have COPD (e.g., prior pulmonary function testing was not required for diagnosis and relatively young patients unlikely to have COPD were eligible for inclusion) and the fact that NIV practices and other aspects of care were not standardized across study sites. It is also unclear whether the choice of HeO2 mixture (65% helium, 35% oxygen) was appropriate and, in particular, whether mixtures with a lower FIO2 and, therefore, lower density, might have yielded more benefit. The choice of this mixture is somewhat odd in that the observed hypoxemia in COPD exacerbations is typically due to areas of low ventilation-perfusion ratios rather than shunt and usually responds to only small increases in the FIO2 well below the 35% level used in this study.

The fact that this and the prior study showed a trend toward improvement does provide a reasonable justification for conducting a larger trial to address this question, but until the results of such a trial are available, we should not be wheeling the heliox tanks to the bedsides of our COPD patients. Although the therapy is relatively benign in terms of the side effect profile, it is not cheap. At our institution, each K-sized tank costs roughly $150 and, depending on the intensity of use in a given patient, several tanks may be required each day. Granted, this expense may be offset by savings associated with decreased hospital and ICU length of stay, but before we embark on wholesale use of the therapy we should really wait for better evidence of benefit in important clinical outcomes.

Reference

1. Jolliet P, et al. Helium-oxygen versus air-oxygen noninvasive pressure support in decompensated chronic obstructive disease. Crit Care Med. 2003;31:878-884.