Inhaling He/O2 did not result in a lower NIV failure rate than inhaling Air/O2 in COPD patients requiring noninvasive ventilation, in a randomized, controlled study.

In the study, known as the E.C.H.O.ICU trial , patients either received He/02 (a 78%/22% mixture blended with 100% O2) or a conventional Air/O2 mixture for up to 72 hours, during both noninvasive ventilation (NIV) and spontaneous breathing.

Previous research had demonstrated that during hypercapnic COPD exacerbations, the He/O2 mixture reduces airway resistance, partial pressure of carbon dioxide in arterial blood (PaCO2), intrinsic positive end-expiratory pressure, and work of breathing during both spontaneous breathing and NIV, compared with Air/O2, said Philippe Jolliet, MD, and his colleagues.

The two treatment groups in the E.C.H.O.ICU trial had similar NIV failure rates – defined as endotracheal intubation or death without intubation. The rates were 14.7% for the patients who received He/O2 and 14.5% for the patients who received Air/O2. The NIV failures for 31 the patients in the He/O2 group resulted in intubation; the remaining two patients who were classified as having NIV failure died. All 32 of the patients in the Air/O2 group who had NIV failures were intubated.

The length of ICU stay was also comparable between the two groups. In the subgroups of patients with severe acidosis (having a pH of less than 7.30) from both the He/O2 and Air/O2 groups, the NIV failure rates were again nearly identical (AJRCCM. 2016 Oct 13; doi: 10.1164/rccm.201601-0083OC).

The average times to NIV failure were 93 hours in the He/O2 group (N = 33) and 52 hours in the Air/O2 group (N = 32, P = .12). The He/O2 group achieved a significantly quicker improvement in respiratory acidosis, encephalopathy score, and respiratory rate.

Patients intubated following an NIV failure who had received He/O2 had a shorter ventilation duration and a shorter ICU stay than did the intubated patients who had received Air/O2 (7.4 days, vs. 13.6 days, P = .02, and 15.8 vs. 26.7 days, P = .01).

No significant differences appeared in the safety profile of the two groups, nor were significant differences seen in ICU, hospital, or 6-month mortality rates; or in 6-month hospital readmission rates.

“[The] study was stopped prematurely after a futility analysis due the low event rate identified by [an independent adjudication committee],” said Dr. Jolliet of the intensive care and burn unit at Le Centre Hospitalier Universitaire Vaudois (CHUV) , in Lausanne, Switzerland, and his fellow researchers.

The study included 445 patients from ICUs or intermediate care units in six countries. The inclusion criteria were presenting with current COPD exacerbation with hypercapnic acute respiratory failure, a PaCO2 of at least 45 mm Hg, an arterial pH of less than or equal to 7.35, and at least one of the following: respiration rate of at least 25 breaths per minute, a PaO2 less than or equal to 50 mm Hg, and an arterial oxygen saturation of less than or equal to 90%.

Half of the patients in each group were already receiving NIV prior to enrollment in the study. Males constituted two thirds of all enrolled patients.

HeO2 administration was limited to 72 hours for each patient and about a third of NIV failures occurred after the end of the HeO2 administration, the researchers said.

“The main reason for the absence of observed benefit on outcome in the He/O2 probably lies in the very low NIV failure rate now observed in both groups. One possible mechanism explaining the low intubation rate could be that some patients had received uncontrolled oxygen therapy prior to ICU admission, thereby worsening initial hypercapnia and acidosis, a problem that can easily be corrected by adequate titration,” the researchers said. “The 14.5% failure rate in the Air/O2 group was much lower than the 25% rate used in designing the study,” which was based on previous research.

The trial’s sponsor, Air Liquide Healthcare, provided input into the design and conduct of the study; oversaw the collection, management, and statistical analysis of data; and contributed to the manuscript’s preparation and review.


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