Objective

To determine whether noninvasive ventilation (NIV) delivered by helmet improves intubation rate among patients with acute respiratory distress syndrome (ARDS).

Introduction

Noninvasive ventilation allows patients to remain animated while in the ICU and is a strategy now used by many ICU physicians. NIV using a face mask can reduce the requirement for endotracheal intubation and improve mortality in patients with acute respiratory failure. However, about half of patients with hypoxaemia, particularly those with ARDS, are not helped by face mask ventilation. An alternative is to deliver NIV via a helmet—a transparent hood that covers the entire head of the patient with a soft collar neck seal. Advantages over a face mask include improved tolerability and lower likelihood of air leakage.

Study design

Single-centre, randomized clinical trial.

Patients and methods

The study was carried out at the University of Chicago, USA, between 3 October 2012 and 21 September 2015. Patients were included if they had ARDS (Berlin criteria 2012) requiring NIV delivered by face mask for at least 8 h. After 8 h, patients were randomly assigned to continue face mask NIV or to switch to a helmet. Positive end-expiratory pressure, fraction of inspired oxygen, and driving pressure titration were managed with the same protocol in both groups. The primary outcome was the proportion of patients who required endotracheal intubation. Exploratory secondary outcomes included 28-day invasive ventilator–free days (days alive without mechanical ventilation), duration of ICU and hospital stay, and hospital and 90-day mortality. Adverse events were prespecified to include factors specific to mask or helmet use (for the helmet this included skin ulceration at the neck seal, claustrophobia, and helmet deflation).

Results

The planned enrollment was 206 patients (103 per group), but the trial was stopped early based on predefined criteria for efficacy, so only 44 patients randomized to the helmet group and 39 to the face mask group were included in the analysis. Baseline characteristics were similar between the two groups. The intubation rate was 61.5% (n=24) for the face mask group vs. 18.2% (n=8) for the helmet group (absolute difference: −43.3%; 95% CI: −62.4 to −24.3; p<0.001). The most common reason for intubation in the face mask group was respiratory failure (83.3% [n=20] for face mask vs. 37.5% [n=3] for helmet; absolute difference: −45.3; 95% CI: −82.5 to −9.1; p=0.01). In contrast, neurologic failure was the most common reason for intubation in the helmet group (62.5% [n=5] for helmet vs. 4.2% [n=1] for face mask; absolute difference: 58.3; 95% CI: 24.8 to 92.8; p=0.001). The number of ventilator-free days was significantly higher in the helmet group (28 vs. 12.5; p<0.001). The helmet group spent less time in the ICU (4.7 days vs. 7.8 days; absolute difference: −2.76; 95% CI: −6.07 to 0.54; p=0.04) and there was a numerical trend toward less time in the hospital (10.1 days for the helmet group vs. 15.2 days for the face mask group; absolute difference: −2.92 days; 95% CI: −8.47 to 2.63; p=0.16). At 90 days, 56.4% (n=22) of the face mask group had died vs. 34.1% (n=15) of the helmet group (absolute difference: −22.3%; 95% CI: −43.3 to −1.4; p=0.02). The incidence of adverse events was low; 7.6% in the face mask group had nose ulcers and 6.8% in the helmet group had neck ulcers.

Discussion

In this single-centre, randomized clinical trial, NIV delivered by helmet significantly reduced the intubation rate among patients with ARDS compared with the patients receiving NIV by face mask. The helmet also was associated with improved ventilator-free days and significantly reduced ICU length of stay and reduced 90-day mortality. The authors point out that multicentre studies are needed to replicate these findings.

Strengths and Weaknesses

We use a lot of NIV by face mask in our ICU but mostly in patients with chronic obstructive pulmonary disease (COPD) or hypoxic respiratory failure due to atelectasis, pulmonary oedema, or (in postoperative patients) after extubation to avoid re-intubation. We rarely use it in full-blown ARDS because (depending on the underlying cause,) the natural history of this disease will not resolve in a couple of days. Hence putting the patient at risk for exhaustion and inadvertent emergency intubation. The idea of the present study is straightforward and the hypothesis raised promising however there are some major limitations:

• First, with 83 patients recruited, the number of patients studied is very small. The authors acknowledge this but the data monitoring committee stopped the trial early when they felt that it was clear that there was a benefit to the helmet therapy. Maybe the results could have been different when a proper power analysis was taken into account.
• Second, many eligible patients were not included into the study and on average only 1 in 10 patients was randomised. This raises concerns with regard to the generalisability of the study results.
• Third, the study took more than 3 years (!) to include only 83 patients (and to get prematurely stopped). Within this time-period a lot of practices may have changed impacting the results, and hence having introduced a bias.
• Fourth, for obvious reasons the study was not-blinded which could have introduced another bias.
• Fifth, with a value of 10, the fragility index (for intubation as endpoint) is surprisingly good, almost too good to be true on such small numbers. As we learned from the past in critical care trials, the reader must be cautious when looking at single centre studies with large treatment effects.
• Sixth, the authors used the updated Berlin ARDS definitions that have been subject to a lot of criticism as these definitions are too vague/unspecific, still allowing a heterogeneous population. The reason behind is that the Berlin definitions do not discriminate between the presence or not of extravascular lung water, the hallmark of ARDS.
• Seventh, there are some very interesting differences in the baseline demographics of the control and interventional group. In the facemask group there were more patients with solid organ malignancy, aspiration pneumonia, and extra pulmonary ARDS. Whereas there were more patients with pneumonia in the helmet group. This could also have had an impact on the results.
• Eight, there are some very interesting differences in the treatment modality with the patients in the helmet group receiving on average 8 vs 5 cmH2O PEEP. This could be due to an issue of tolerance but confirms that the 2 groups were treated differently after randomisation. There were more patients with extrapulmonary ARDS (eg abdominal catastrophe with increased abdominal pressures) that could have benefitted from higher PEEP levels.
• Ninth, the criterion for deciding when to intubate was unclear and left to the discretion of the attending physicians.This increases the chance of bias, especially in an un-blinded trial.
• Tenth, the authors claim that hospital and 90-day mortality were significantly lower in the helmet group. However, when recalculating the p-value with the more appropriate Fisher’s exact test the p-value turns out to be 0.068 (nonsignificant) resulting in a Fragility index of 0 (http://www.fragilityindex.com/). Similarly the p-value for 90-day mortality should be 0.04 instead of 0.02, resulting in a fragility index of 1. It is therefore misleading to list such hard outcomes (mortality) in a study with such small numbers.

THM: Take home message

Albeit the fact that the findings of this study look promising, the results should be interpreted with caution and cannot be extrapolated to the general medical ICU population. Before the use of helmets can be advocated in medical patients with ARDS, the present findings need to be confirmed in a larger multicentre trial.

Reference

Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. JAMA 2016;315:2435–2441. View on PubMed - Download PDF
Trial registration number: NCT01680783.
PMID: 27179847 PMCID: PMC4967560 DOI: 10.1001/jama.2016.6338