Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial

Abstract

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, setting, and participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55).

Main outcomes and measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay.

Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99).

Conclusions and relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation.

Trial registration: ClinicalTrials.gov Identifier: NCT04502576.

Figure 1.. Noninvasive Helmet Ventilation as Used in the Trial

The patient intervention is illustrated on the left with a mock-up of the control panel on the right. Sources of pressurized oxygen and air, typically through piped gasses, are not illustrated. Settings illustrated were the initial settings used in the trial. Listed monitoring and intubation criteria are those used in the trial. Fio₂ indicates fraction of inspired oxygen; Paco₂, partial pressure of arterial carbon dioxide; Pao₂, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure; PSV, pressure support ventilation; and Spo₂, peripheral oxygen saturation as measured by pulse oximetry.

Figure 2.. Selection and Randomization of Patients in a Study of Noninvasive Helmet Ventilation vs High-Flow Nasal Oxygen

Fio₂ indicates fraction of inspired oxygen; NYHA, New York Heart Association; Paco₂, partial pressure of arterial carbon dioxide; and Pao₂, partial pressure of arterial oxygen. ^aMajor protocol violations included crossover between study protocols and assigned treatment not provided due to any reason.

Figure 3.. Cumulative Incidence of Intubation Over Time in the Helmet Noninvasive Ventilation and High-Flow Nasal Oxygen Groups to Day 28

The hazard ratio for endotracheal intubation in the helmet noninvasive ventilation is 0.49 (95% CI, 0.27-0.89). Follow-up was completed to 60 days after randomization for all patients.

Figure 4.. Physiologic Variables Over the First 48 Hours in the Helmet Noninvasive Ventilation and High-Flow Nasal Oxygen Groups

Patients were censored from the analysis after intubation. Comparisons between groups were performed with 1-way analysis of variance. Box plots are shown where the middle line represents the median observed value, boxes represent the interquartile range, whiskers extend to the most extreme observed values with 1.5 times the interquartile range of the nearer quartile, and dots represent observed values outside that range. The plus signs indicate mean values. VAS indicates visual analog scale.