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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 FailureThe HENIVOT Randomized Clinical Trial

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Key Points

Question  Among patients admitted to the intensive care unit with COVID-19–induced moderate to severe hypoxemic respiratory failure, does early continuous treatment with helmet noninvasive ventilation increase the number of days free of respiratory support at 28 days as compared with high-flow nasal oxygen?

Findings  In this randomized trial that included 109 patients, the median number of days free of respiratory support within 28 days was 20 days in the group that received helmet noninvasive ventilation and 18 days in the group that received high-flow nasal oxygen, a difference that was not statistically significant.

Meaning  Among critically ill patients with moderate to severe hypoxemic respiratory failure due to COVID-19, 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.

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

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Article Information

Corresponding Author: Domenico L. Grieco, MD, Department of Anesthesiology and Intensive Care Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Lgo F Vito, 00168, Rome, Italy (dlgrieco@outlook.it).

Accepted for Publication: March 12, 2021.

Published Online: March 25, 2021. doi:10.1001/jama.2021.4682

Author Contributions: Drs Grieco and Menga had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Grieco, Pintaudi, Dell'Anna, Bocci, De Pascale, Volta, Conti, Maggiore, Antonelli.

Acquisition, analysis, or interpretation of data: Grieco, Menga, Cesarano, Rosà, Spadaro, Bitondo, Montomoli, Falò, Tonetti, Cutuli, Pintaudi, Tanzarella, Piervincenzi, Bongiovanni, Dell’Anna, Delle Cese, Berardi, Carelli, Montini, Bello, Natalini, De Pascale, Velardo, Volta, Ranieri, Antonelli.

Drafting of the manuscript: Grieco, Menga, Cesarano, Pintaudi, Bongiovanni, Dell’Anna, Carelli, Bocci, Natalini, De Pascale, Antonelli.

Critical revision of the manuscript for important intellectual content: Grieco, Menga, Rosà, Spadaro, Bitondo, Montomoli, Falò, Tonetti, Cutuli, Pintaudi, Tanzarella, Piervincenzi, Bongiovanni, Delle Cese, Berardi, Montini, Bello, De Pascale, Velardo, Volta, Ranieri, Conti, Maggiore, Antonelli.

Statistical analysis: Grieco, Montini, De Pascale, Velardo.

Obtained funding: Grieco, Antonelli.

Administrative, technical, or material support: Grieco, Cesarano, Rosà, Spadaro, Bitondo, Pintaudi, Tanzarella, Piervincenzi, Bongiovanni, Dell’Anna, Bocci, Natalini, De Pascale, Antonelli.

Supervision: Grieco, Spadaro, Pintaudi, Piervincenzi, Bongiovanni, Dell’Anna, Bocci, Bello, De Pascale, Volta, Ranieri, Conti, Maggiore, Antonelli.

Conflict of Interest Disclosures: Dr Grieco reported receiving grants from the Italian Society of Anesthesia, Analgesia, and Intensive Care Medicine during the conduct of the study and grants from the European Society of Intensive Care Medicine and GE Healthcare and travel expenses from Maquet, Getinge, and Air Liquide outside the submitted work. Dr Montomoli reported receiving personal fees from Active Medica BV outside the submitted work. Dr Conti reported receiving payments for lectures from Chiesi Pharmaceuticals SpA. Dr Maggiore reported serving as the principal investigator of the RINO trial (ClinicalTrials.gov NCT02107183), which was supported by Fisher and Paykel Healthcare through an institutional grant, and receiving personal fees from Draeger Medical and GE Healthcare outside the submitted work. Dr Antonelli reported receiving personal fees from Maquet, Chiesi, and Air Liquide and grants from GE Healthcare outside the submitted work. No other disclosures were reported.

Funding/Support: The study was funded by a research grant (2017 Merck Sharp & Dohme SRL award) by the Italian Society of Anesthesia, Analgesia, and Intensive Care Medicine.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The COVID-ICU Gemelli Study Group members are listed in Supplement 4.

Data Sharing Statement: See Supplement 5.

Additional Contributions: We are grateful to all intensive care unit physicians, residents, nurses, and personnel from the participating centers, whose sacrifice, efforts, devotion to patients, and passion have made possible this timely report. We are grateful to Jean-Pierre Frat, MD, PhD (Poitiers, France), Oriol Roca, MD, PhD (Barcelona, Spain), and Jordi Mancebo, MD, PhD (Barcelona, Spain), for their contribution as members of the adjudication committee for endotracheal intubation. We are grateful to Cristina Cacciagrano, Emiliano Tizi, and Alberto Noto, MD, for their contribution to study organization. We are grateful to Gabriele Esposito, PD, for Figure 1 drafting. Drs Frat, Roca, and Velardo received a personal fee for their contribution to the study; all others listed did not receive compensation.

Additional Information: The study was endorsed by the Insufficienza Respiratoria Acuta e Assistenza Respiratoria study group of the Italian Society of Anesthesia, Analgesia, and Intensive Care Medicine.

References
1.
Rochwerg  B , Brochard  L , Elliott  MW ,  et al.  Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure.   Eur Respir J. 2017;50(2):1602426. doi:10.1183/13993003.02426-2016 PubMedGoogle Scholar
2.
Yoshida  T , Fujino  Y , Amato  MBP , Kavanagh  BP .  Fifty years of research in ARDS: spontaneous breathing during mechanical ventilation: risks, mechanisms, and management.   Am J Respir Crit Care Med. 2017;195(8):985-992. doi:10.1164/rccm.201604-0748CPPubMedGoogle ScholarCrossref
3.
Grieco  DL , Menga  LS , Eleuteri  D , Antonelli  M .  Patient self-inflicted lung injury: implications for acute hypoxemic respiratory failure and ARDS patients on non-invasive support.   Minerva Anestesiol. 2019;85(9):1014-1023. doi:10.23736/S0375-9393.19.13418-9 PubMedGoogle ScholarCrossref
4.
Bellani  G , Laffey  JG , Pham  T ,  et al; LUNG SAFE Investigators; ESICM Trials Group.  Noninvasive ventilation of patients with acute respiratory distress syndrome: insights from the LUNG SAFE Study.   Am J Respir Crit Care Med. 2017;195(1):67-77. doi:10.1164/rccm.201606-1306OC PubMedGoogle ScholarCrossref
5.
Franco  C , Facciolongo  N , Tonelli  R ,  et al.  Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia.   Eur Respir J. 2020;56(5):2002130. doi:10.1183/13993003.02130-2020 PubMedGoogle Scholar
6.
Grasselli  G , Zangrillo  A , Zanella  A ,  et al; COVID-19 Lombardy ICU Network.  Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.   JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394 PubMedGoogle ScholarCrossref
7.
COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators.  Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study.   Intensive Care Med. 2021;47(1):60-73. doi:10.1007/s00134-020-06294-x PubMedGoogle ScholarCrossref
8.
Rochwerg  B , Einav  S , Chaudhuri  D ,  et al.  The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.   Intensive Care Med. 2020;46(12):2226-2237. doi:10.1007/s00134-020-06312-y PubMedGoogle ScholarCrossref
9.
Mellado-Artigas  R , Ferreyro  BL , Angriman  F ,  et al; COVID-19 Spanish ICU Network.  High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure.   Crit Care. 2021;25(1):58. doi:10.1186/s13054-021-03469-w PubMedGoogle ScholarCrossref
10.
Patel  BK , Wolfe  KS , Pohlman  AS , Hall  JB , Kress  JP .  Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial.   JAMA. 2016;315(22):2435-2441. doi:10.1001/jama.2016.6338 PubMedGoogle ScholarCrossref
11.
Ferreyro  BL , Angriman  F , Munshi  L ,  et al.  Association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: a systematic review and meta-analysis.   JAMA. 2020;324(1):57-67. doi:10.1001/jama.2020.9524 PubMedGoogle ScholarCrossref
12.
Antonelli  M , Conti  G , Pelosi  P ,  et al.  New treatment of acute hypoxemic respiratory failure: noninvasive pressure support ventilation delivered by helmet: a pilot controlled trial.   Crit Care Med. 2002;30(3):602-608. doi:10.1097/00003246-200203000-00019 PubMedGoogle ScholarCrossref
13.
Morais  CCA , Koyama  Y , Yoshida  T ,  et al.  High positive end-expiratory pressure renders spontaneous effort noninjurious.   Am J Respir Crit Care Med. 2018;197(10):1285-1296. doi:10.1164/rccm.201706-1244OC PubMedGoogle ScholarCrossref
14.
Yoshida  T , Grieco  DL , Brochard  L , Fujino  Y .  Patient self-inflicted lung injury and positive end-expiratory pressure for safe spontaneous breathing.   Curr Opin Crit Care. 2020;26(1):59-65. doi:10.1097/MCC.0000000000000691 PubMedGoogle ScholarCrossref
15.
Grieco  DL , Menga  LS , Raggi  V ,  et al.  Physiological comparison of high-flow nasal cannula and helmet noninvasive ventilation in acute hypoxemic respiratory failure.   Am J Respir Crit Care Med. 2020;201(3):303-312. doi:10.1164/rccm.201904-0841OC PubMedGoogle ScholarCrossref
16.
Grieco  DL , Toni  F , Santantonio  MT ,  et al.  Comfort during high-flow oxygen therapy through nasal cannula in critically ill patients: effects of gas temperature and flow.  Presented at the 26th Annual Congress of the European Society of Intensive Medicine; October 5-9, 2013; Paris, France.
17.
Muriel  A , Peñuelas  O , Frutos-Vivar  F ,  et al.  Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis.   Intensive Care Med. 2015;41(9):1586-1600. doi:10.1007/s00134-015-3854-6 PubMedGoogle ScholarCrossref
18.
Coppo  A , Bellani  G , Winterton  D ,  et al.  Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study.   Lancet Respir Med. 2020;8(8):765-774. doi:10.1016/S2213-2600(20)30268-X PubMedGoogle ScholarCrossref
19.
Frat  J-P , Thille  AW , Mercat  A ,  et al; FLORALI Study Group; REVA Network.  High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.   N Engl J Med. 2015;372(23):2185-2196. doi:10.1056/NEJMoa1503326 PubMedGoogle ScholarCrossref
20.
Antonelli  M , Conti  G , Rocco  M ,  et al.  A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure.   N Engl J Med. 1998;339(7):429-435. doi:10.1056/NEJM199808133390703 PubMedGoogle ScholarCrossref
21.
Fan  E , Del Sorbo  L , Goligher  EC ,  et al; American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine.  An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome.   Am J Respir Crit Care Med. 2017;195(9):1253-1263. doi:10.1164/rccm.201703-0548ST PubMedGoogle ScholarCrossref
22.
Boles  J-M , Bion  J , Connors  A ,  et al.  Weaning from mechanical ventilation.   Eur Respir J. 2007;29(5):1033-1056. doi:10.1183/09031936.00010206 PubMedGoogle ScholarCrossref
23.
Maggiore  SM , Idone  FA , Vaschetto  R ,  et al.  Nasal high-flow versus Venturi mask oxygen therapy after extubation: effects on oxygenation, comfort, and clinical outcome.   Am J Respir Crit Care Med. 2014;190(3):282-288. doi:10.1164/rccm.201402-0364OC PubMedGoogle ScholarCrossref
24.
Menga  LS , Cese  LD , Bongiovanni  F ,  et al.  High failure rate of noninvasive oxygenation strategies in critically ill subjects with acute hypoxemic respiratory failure due to COVID-19.   Respir Care. 2021;(March):respcare.08622. doi:10.4187/respcare.08622 PubMedGoogle Scholar
25.
Carrillo  A , Gonzalez-Diaz  G , Ferrer  M ,  et al.  Non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure.   Intensive Care Med. 2012;38(3):458-466. doi:10.1007/s00134-012-2475-6 PubMedGoogle ScholarCrossref
26.
Hilbert  G , Gruson  D , Vargas  F ,  et al.  Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure.   N Engl J Med. 2001;344(7):481-487. doi:10.1056/NEJM200102153440703 PubMedGoogle ScholarCrossref
27.
Ferrer  M , Esquinas  A , Leon  M , Gonzalez  G , Alarcon  A , Torres  A .  Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial.   Am J Respir Crit Care Med. 2003;168(12):1438-1444. doi:10.1164/rccm.200301-072OC PubMedGoogle ScholarCrossref
28.
Demoule  A , Chevret  S , Carlucci  A ,  et al; oVNI Study Group; REVA Network (Research Network in Mechanical Ventilation).  Changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries.   Intensive Care Med. 2016;42(1):82-92. doi:10.1007/s00134-015-4087-4 PubMedGoogle ScholarCrossref
29.
Demoule  A , Girou  E , Richard  J-C , Taille  S , Brochard  L .  Benefits and risks of success or failure of noninvasive ventilation.   Intensive Care Med. 2006;32(11):1756-1765. doi:10.1007/s00134-006-0324-1 PubMedGoogle ScholarCrossref
30.
Ferrer  M , Esquinas  A , Arancibia  F ,  et al.  Noninvasive ventilation during persistent weaning failure: a randomized controlled trial.   Am J Respir Crit Care Med. 2003;168(1):70-76. doi:10.1164/rccm.200209-1074OC PubMedGoogle ScholarCrossref
31.
Brochard  L , Slutsky  A , Pesenti  A .  Mechanical ventilation to minimize progression of lung injury in acute respiratory failure.   Am J Respir Crit Care Med. 2017;195(4):438-442. doi:10.1164/rccm.201605-1081CP PubMedGoogle ScholarCrossref
32.
Goligher  EC , Dres  M , Patel  BK ,  et al.  Lung- and diaphragm-protective ventilation.   Am J Respir Crit Care Med. 2020;202(7):950-961. doi:10.1164/rccm.202003-0655CP PubMedGoogle ScholarCrossref
33.
Tonelli  R , Fantini  R , Tabbì  L ,  et al.  Early inspiratory effort assessment by esophageal manometry predicts noninvasive ventilation outcome in de novo respiratory failure: a pilot study.   Am J Respir Crit Care Med. 2020;202(4):558-567. doi:10.1164/rccm.201912-2512OC PubMedGoogle ScholarCrossref
34.
Antonelli  M , Conti  G , Esquinas  A ,  et al.  A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome.   Crit Care Med. 2007;35(1):18-25. doi:10.1097/01.CCM.0000251821.44259.F3 PubMedGoogle ScholarCrossref
35.
Carteaux  G , Millán-Guilarte  T , De Prost  N ,  et al.  Failure of noninvasive ventilation for de novo acute hypoxemic respiratory failure: role of tidal volume.   Crit Care Med. 2016;44(2):282-290. doi:10.1097/CCM.0000000000001379 PubMedGoogle ScholarCrossref
36.
Demoule  A , Vieillard Baron  A , Darmon  M ,  et al.  High-flow nasal cannula in critically iii patients with severe COVID-19.   Am J Respir Crit Care Med. 2020;202(7):1039-1042. doi:10.1164/rccm.202005-2007LE PubMedGoogle ScholarCrossref
37.
Zucman  N , Mullaert  J , Roux  D , Roca  O , Ricard  J-D ; Contributors.  Prediction of outcome of nasal high flow use during COVID-19–related acute hypoxemic respiratory failure.   Intensive Care Med. 2020;46(10):1924-1926. doi:10.1007/s00134-020-06177-1 PubMedGoogle ScholarCrossref
38.
Goligher  EC , Fan  E , Herridge  MS ,  et al.  Evolution of diaphragm thickness during mechanical ventilation: impact of inspiratory effort.   Am J Respir Crit Care Med. 2015;192(9):1080-1088. doi:10.1164/rccm.201503-0620OC PubMedGoogle ScholarCrossref
39.
Herridge  MS , Cheung  AM , Tansey  CM ,  et al; Canadian Critical Care Trials Group.  One-year outcomes in survivors of the acute respiratory distress syndrome.   N Engl J Med. 2003;348(8):683-693. doi:10.1056/NEJMoa022450 PubMedGoogle ScholarCrossref
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