Intensive Care Medicine

, Volume 45, Issue 4, pp 447–458 | Cite as

Nasal high-flow preoxygenation for endotracheal intubation in the critically ill patient: a randomized clinical trial

  • Christophe GuittonEmail author
  • Stephan Ehrmann
  • Christelle Volteau
  • Gwenhael Colin
  • Adel Maamar
  • Vanessa Jean-Michel
  • Pierre-Joachim Mahe
  • Mickael Landais
  • Noelle Brule
  • Cedric Bretonnière
  • Olivier Zambon
  • Mickael Vourc’h



Preoxygenation with high-flow therapy by nasal cannulae (HFNC) is now widespread in the intensive care unit (ICU). However, no large randomized study has assessed its relevance in non-severely hypoxemic patients. In a randomized controlled trial (PROTRACH study), we aimed to evaluate preoxygenation with HFNC vs. standard bag-valve mask oxygenation (SMO) in non-severely hypoxemic patients during rapid sequence intubation (RSI) in the ICU.


Randomized controlled trial including non-severely hypoxemic patients requiring intubation in the ICU. Patients received preoxygenation by HFNC or SMO during RSI. HFNC was maintained throughout the intubation procedure whereas SMO was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry (SpO2) throughout the intubation procedure. Secondary outcomes included drop in SpO2, adverse events related to intubation, and outcome in the ICU.


A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC n = 95; SMO n = 89), the median [IQR] lowest SpO2 was 100% [97; 100] for HFNC and 99% [95; 100] for the SMO group (P = 0.30). Mild desaturation below 95% was more frequent with SMO (23%) than with HFNC (12%) (RR 0.51, 95% CI 0.26–0.99, P = 0.045). There were fewer adverse events in the HFNC group (6%) than in the SMO group (19%) (RR 0.31, 95% CI 0.13–0.76, P = 0.007), including fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and SMO (RR 0.38, 95% CI 0.15–0.95, P = 0.03).


Compared with SMO, preoxygenation with HFNC in the ICU did not improve the lowest SpO2 during intubation in the non-severely hypoxemic patients but led to a reduction in intubation-related adverse events.

Trial registration

Clinical trial Submission: 7 March 2016. Registry name: Benefits of high-flow nasal cannulae oxygen for preoxygenation during intubation in non-severely hypoxemic patients: the PROTRACH study. identifier: NCT02700321. Eudra CT: 2015-A00145-44. CPP: 15/13-975 (Comité de protection des personnes de Rennes). URL registry:


Preoxygenation High-flow oxygen therapy by nasal cannulae Intubation Apneic oxygenation Intensive care unit 



Collaborators and additional contributions: We are grateful to all medical staff, nurses, and research staff at the seven sites for inclusion and data collection. We thank Caroline Postnikoff (University Hospital of Nantes) for administrative and logistic support and Marion Rigot (University Hospital of Nantes) for creating the electronic Case Report Form and Dr. Anne Chiffoleau, MD for safety monitoring (University Hospital of Nantes). The safety board was composed of Dr. Christophe Girault (University Hospital of Rouen), Prof. Gilles Capellier (University Hospital of Besancon) and Prof. Antoine Roch (University Hospital of Marseille).

Data sharing statements: Deidentified data collected for the study, including individual participant data and a data dictionary defining each field, in the set will be made available to others. Study protocol, statistical analysis plan, informed consent form, and record of the primary outcome will be made available on reasonable request by addressing an email to the corresponding author in the 5 years following publication with investigator support.

Author contributions

CG and MV had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: MV, CG, OZ, CB, and SE. Data acquisition: all of the authors participated in data collection and acquisition. Data analysis and interpretation: CG, MV, CB, SE, and CV. Drafting of the manuscript: CG, MV, CB, OZ, and SE. Critical revision of the manuscript for important intellectual content: All of the authors. Statistical analysis: CV. Funding obtained: CG and OZ. Administrative, technical, or material support: All of the clinician authors. Study supervision: MV and CG.

Financial and material support for the research and the grant support, funding source, and provision of equipment and supplies

This study was supported by the French Ministry of Health (Interregional French Clinical Hospital Research Program Grant; PHRCi 2014—API12/N/077) in addition to a grant for research & innovation missions allocated to the University Hospital of Nantes and by Fisher & Paykel Healthcare. The University Hospital of Nantes was the sponsor of the study. The equipment was loaned by Fisher & Paykel Healthcare whereas nasal cannulae were bought with the funds of PHRCi.

Fisher & Paykel participation was inferior to 5% of the total budget (3500 €). Fisher & Paykel did not participate in the design and conduct of the study, nor in data collection, management, analysis and interpretation of the data, nor in the preparation, review, approval, and decision to submit the manuscript for publication.

Compliance with ethical standards

Conflicts of interest

Christelle Volteau, Colin Gwenaël, Adel Maamar, Vanessa Jean-Michel, Pierre Joachim Mahe, Mickaël Landais, Noëlle Brule, Cedric Bretonnière, Olivier Zambon, and Christophe Guitton declare no conflict of interest. Stephan Ehrmann declares receiving consultancy fees from Aerogen Ltd, La Diffusion Technique Française, and Baxter healthcare and unrestricted research support from Fisher and Paykel, Aerogen Ltd, and Hamilton Medical. Mickael Vourc’h declares personal fees from MSD, Pfizer, Baxter, Grants from Fisher Paykel, outside the submitted work.

Ethical approval

The appropriate ethics committee approved this study protocol in September 11 2015 (15/13-975).

Supplementary material

134_2019_5529_MOESM1_ESM.docx (141 kb)
Supplementary material 1 (DOCX 140 kb)
134_2019_5529_MOESM2_ESM.pdf (609 kb)
Supplementary material 2 (PDF 609 kb)
134_2019_5529_MOESM3_ESM.docx (71 kb)
Supplementary material 3 (DOCX 70 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Christophe Guitton
    • 1
    Email author
  • Stephan Ehrmann
    • 2
  • Christelle Volteau
    • 3
  • Gwenhael Colin
    • 4
  • Adel Maamar
    • 5
  • Vanessa Jean-Michel
    • 6
  • Pierre-Joachim Mahe
    • 7
  • Mickael Landais
    • 1
  • Noelle Brule
    • 8
  • Cedric Bretonnière
    • 8
  • Olivier Zambon
    • 8
  • Mickael Vourc’h
    • 8
  1. 1.Service de Réanimation Médico Chirurgicale, USCCentre Hospitalier du MansLe Mans Cedex 9France
  2. 2.Médecine Intensive Réanimation, INSERM CIC 1415, Centre Hospitalier Universitaire de Tours, Centre d’Etude des Pathologies Respiratoires INSERM U1100, Tours UniversityToursFrance
  3. 3.Plateforme de Méthodologie et de BiostatistiqueCentre Hospitalier Universitaire de NantesNantesFrance
  4. 4.Médecine Intensive RéanimationCentre Hospitalier de La Roche sur YonLa Roche-Sur-YonFrance
  5. 5.Médecine Intensive RéanimationCentre Hospitalier Universitaire de RennesRennesFrance
  6. 6.Médecine Intensive RéanimationCentre Hospitalier Universitaire de BrestBrestFrance
  7. 7.Service d’Anesthésie-Réanimation ChirurgicaleHôtel-Dieu, Centre Hospitalier Universitaire de NantesNantesFrance
  8. 8.Médecine Intensive RéanimationHôtel-Dieu, Centre Hospitalier Universitaire de NantesNantesFrance

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