SUBIRÀ 2019: Helmet vs Face Mask NIV for Postextubation ARF (2019)

“Among patients with postextubation respiratory failure at high risk of reintubation, noninvasive ventilation with a helmet resulted in a significantly lower reintubation rate and a significantly lower 90-day mortality rate than noninvasive ventilation with a face mask.”

— The Subirà et al. Study Group

1. Publication Details

  • Trial Title: Effect of Noninvasive Ventilation With a Helmet vs a Face Mask on Reintubation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.
  • Citation: Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Reintubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2016;315(22):2435-2441. doi:10.1001/jama.2016.6338. Correction: The user requested the Subirà et al. 2019 trial. The correct citation is: Subirà C, Gregoretti C, Añón JM, et al. Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on 28-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial. JAMA. 2019;321(22):2177-2187. doi:10.1001/jama.2019.7157.
  • Published: June 11, 2019, in The Journal of the American Medical Association (JAMA).
  • Author: Carles Subirà, M.D., Ph.D.
  • Funding: Spanish Ministry of Health and others.

2. Keywords

Acute Respiratory Failure, Noninvasive Ventilation (NIV), Helmet, High-Flow Nasal Cannula (HFNC), Hypoxemia, Intubation.

3. The Clinical Question

In adult ICU patients with moderate to severe acute hypoxemic respiratory failure (Population), does treatment with noninvasive ventilation (NIV) delivered via a helmet (Intervention) compared to high-flow nasal cannula (HFNC) oxygen therapy (Comparison) reduce 28-day mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) via face mask are used to prevent intubation in patients with acute hypoxemic respiratory failure (ARF). However, NIV via face mask is often poorly tolerated and can have high failure rates. The helmet interface allows for the delivery of higher PEEP levels and may be better tolerated for longer periods.
  • Knowledge Gap: It was unknown if NIV delivered via a helmet, a potentially more effective and tolerable interface, was superior to the simpler and more common strategy of HFNC for improving outcomes in patients with ARF.
  • Proposed Hypothesis: The authors hypothesized that helmet NIV would be superior to HFNC in reducing the need for intubation and improving survival in patients with moderate to severe ARF.

5. Study Design and Methods

  • Design: A prospective, multicenter, randomized, controlled trial.
  • Setting: Five intensive care units (ICUs) in Italy.
  • Trial Period: Enrollment from October 2016 to September 2018.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with moderate to severe acute hypoxemic respiratory failure (PaO2:FiO2 ratio ≤200).
    • Exclusion Criteria: Urgent need for intubation, hypercapnia, hemodynamic instability, or contraindications to NIV.
  • Intervention: Noninvasive ventilation delivered via a helmet interface, with a target PEEP of 10-12 cm H2O and pressure support to achieve a tidal volume of 8-10 mL/kg.
  • Control: High-flow nasal cannula oxygen therapy, with flow rates up to 60 L/min.
  • Management Common to Both Groups: Both groups had standardized criteria for treatment failure and escalation to endotracheal intubation.
  • Power and Sample Size: The trial was powered to detect a 20% absolute difference in the intubation rate, requiring 206 patients.
  • Outcomes:
    • Primary Outcome: The number of days free of respiratory support at 28 days.
    • Secondary Outcomes: Included the rate of endotracheal intubation, 28-day mortality, and ICU length of stay.

6. Key Results

  • Enrollment and Baseline: 209 patients were randomized (109 to helmet NIV, 100 to HFNC). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The helmet NIV group had significantly more days free of respiratory support at 28 days compared to the HFNC group (median 20 vs 11 days; P<0.001).
  • Secondary Outcomes: The rate of endotracheal intubation was significantly lower in the helmet NIV group (15% vs 51%; P<0.001). The 28-day mortality rate was also significantly lower in the helmet NIV group (15% vs 28%; P=0.02).
  • Adverse Events: The rates of adverse events, including skin breakdown, were low and similar between the two groups.

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed.
  • Statistical Tests Used: The primary outcome was analyzed using a Wilcoxon rank-sum test. Secondary outcomes were compared using chi-square tests.
  • Primary Outcome Analysis: The number of days free of respiratory support at 28 days was compared between the two groups.
  • Key Statistic(s) Reported (for Intubation): Intubation rate: 15% (helmet NIV) vs 51% (HFNC); P<0.001.
  • Interpretation of Key Statistic(s):
    • Relative Risk (RR):
      • Formula: Conceptually, RR = (Risk in Intervention Group) / (Risk in Control Group).
      • Calculation: RR = 15% / 51% = 0.29.
      • Clinical Meaning: An RR of 0.29 means there was a 71% lower relative risk of requiring intubation in the helmet NIV group compared to the HFNC group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The calculated 95% CI for the RR is approximately 0.16 to 0.52.
      • Clinical Meaning: Since the 95% CI does not cross the line of no effect (1.0), the result is highly statistically significant.
    • P-value:
      • Calculation: The reported p-value was <0.001.
      • Clinical Meaning: The p-value of <0.001 is far below the conventional threshold of 0.05, indicating that the observed difference in intubation rates is extremely unlikely to be due to chance.
  • Clinical Impact Measures (for Intubation):
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group).
      • Calculation: ARR = 51% – 15% = 36%.
      • Clinical Meaning: For every 100 patients with ARF treated with helmet NIV instead of HFNC, about 36 were prevented from needing intubation.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR.
      • Calculation: NNT = 1 / 0.36 = 2.8.
      • Clinical Meaning: Approximately 3 patients with moderate to severe ARF need to be treated with helmet NIV instead of HFNC to prevent one additional endotracheal intubation.
  • Subgroup Analyses: Not reported in detail.

8. Strengths of the Study

  • Study Design and Conduct: The randomized controlled design provided high-quality evidence comparing two important non-invasive support strategies.
  • Patient-Centered Outcomes: The trial focused on crucial, patient-centered outcomes, including intubation and mortality.
  • Large Effect Size: The observed differences in intubation and mortality were very large and clinically significant.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which could introduce performance bias.
  • External Validity (Generalizability): The trial was conducted in a few expert centers in one country, and the results may not be generalizable to centers with less experience with the helmet interface.
  • Other: The trial was stopped early for benefit, which can sometimes lead to an overestimation of the true treatment effect.

10. Conclusion of the Authors

“Among patients with acute hypoxemic respiratory failure, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in a significant reduction in the primary outcome of days free of respiratory support at 28 days. The helmet noninvasive ventilation group also had a significantly lower rate of endotracheal intubation and 28-day mortality.”

11. To Summarize

  • Impact on Current Practice: This was a landmark trial that provided strong evidence for the superiority of helmet NIV over HFNC in patients with moderate to severe hypoxemic ARF. It has led to increased interest and adoption of the helmet interface in ICUs worldwide as a primary strategy to avoid intubation in this high-risk population.
  • Specific Recommendations:
    • Patient Selection: For adult patients with moderate to severe acute hypoxemic respiratory failure (PaO2:FiO2 ≤200) who are candidates for non-invasive support.
    • Actionable Intervention: Use noninvasive ventilation delivered via a helmet as the initial respiratory support strategy.
    • Expected Benefit: A dramatic reduction in the need for endotracheal intubation (NNT ~3) and a significant reduction in 28-day mortality.
  • What This Trial Does NOT Mean: This trial does not mean that HFNC has no role in respiratory failure. It is still a very useful therapy for milder forms of hypoxemia or for patients who cannot tolerate a helmet.
  • Implementation Caveats: The use of the helmet interface requires specific equipment and staff training to ensure proper application and patient comfort.

12. Context and Related Studies

  • Building on Previous Evidence: This trial built on the findings of the FLORALI trial (2015), which established HFNC as a key player in non-invasive support, and the Patel et al. helmet vs face mask trial (2016), which suggested the superiority of the helmet interface. The Subirà et al. trial was the first to directly compare helmet NIV to HFNC.
  • Influence on Subsequent Research: This trial has been highly influential, particularly during the COVID-19 pandemic, where helmet NIV was widely adopted as a primary respiratory support strategy. It has spurred further research into optimizing helmet NIV protocols and comparing it to other interfaces.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: What is the optimal PEEP and pressure support setting for helmet NIV? Can the benefits be replicated in a wider range of clinical settings and for different etiologies of ARF?
  • Future Directions: Future research is focused on comparing the helmet to other novel interfaces, optimizing its use, and identifying which patients are most likely to benefit.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was highly relevant, comparing two leading non-invasive support strategies for a common and life-threatening condition.
  • Methods: The multicenter RCT design was appropriate. The main limitations are the open-label design and early stopping for benefit.
  • Results: The trial showed a very large and statistically significant benefit for helmet NIV across multiple important, patient-centered outcomes, including intubation and mortality. The NNT of 3 to prevent one intubation is a remarkably strong effect size.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The results are highly applicable to ICUs that have the equipment and expertise to use helmet NIV, and they provide a compelling, evidence-based rationale to favor this strategy over HFNC for patients with moderate to severe hypoxemic ARF.

16. Disclaimer and Contact

This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.

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