Nasal High-Flow Preoxygenation for Endotracheal Intubation in the Critically Ill Patient: A Randomized Clinical Trial

Background: Although performed daily, intubation in intensive care units (ICU) remains a critical procedure with life-threatening adverse events. High-flow therapy by nasal cannulae (HFNC) is now widespread in the operating room and in the ICU, especially for preoxygenation before intubation in non-hypoxemic patients. However, no large randomized study has assessed its relevance in this population. Methods: The PROTRACH study is a randomized, multicenter open-labelled, controlled trial, including non-severely hypoxemic patients requiring intubation in medical or surgical ICU. Patients were randomly allocated to receive 4-minute preoxygenation delivered by HFNC or standard high-flow face mask (HFFM) before intubation. HFNC was maintained throughout the intubation procedure whereas HFFM was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry throughout the intubation procedure. Secondary outcomes included drop in pulse oximetry, adverse events related to intubation, and outcome in the ICU. Main Findings: A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC n = 95; HFFM n = 89), the median [IQR] lowest pulse oximetry was 100% [97;100] for HFNC and 99 % [95;100] for the HFFM group (P = 0.30). Mild desaturation below 95% was more frequent with HFFM (23%) than with HFNC (12%) (relative risk 0.51, CI 95% [0.26 to 0.99], P = 0.045). There were fewer adverse events in the HFNC group (6%) than in the HFFM group (19%) (relative risk 0.31, CI 95% [0.13 to 0.76], P = 0.007), including significantly fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and HFFM (relative risk 0.38, CI 95% [0.15 to 0.95], P = 0.03). There was no difference in the outcome in the ICU with a mortality rate of 27% in both groups (P = 0.90). Interpretation: Compared with HFFM, preoxygenation with HFNC in the ICU did not improve the lowest level of pulse oximetry during intubation in the non-severely hypoxemic patients but led to a reduction in severe and moderate intubation-related adverse events. Clinical Trial Number: Clinicaltrials.gov identifier: NCT02700321, Eudra CT: 2015-A00145-44 Funding Statement: The French Ministry of Health (Interregional French Clinical Hospital Research Program grant (PHRCi 2014 - API12/N/077), a grant for research & innovation missions (University Hospital of Nantes) and by Fisher & Paykel Healthcare. Declaration of Interests: Declaration of Interest: Christelle Volteau, Gwenael Colin, Adel Maamar, Vanessa Jean Michel, Pierre Joachim Mahe, Mickael Landais, Noelle Brule, Cedric Bretonniere, Olivier Zambon and Christophe Guitton declare no conflict of interest. Stephan Ehrmann declares receiving consultancy fees from Aerogen Ltd, La Diffusion Technique Francaise 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. Ethics Approval Statement: Three methods of consent were available. When possible, capable patients were included after written informed consent. Most patients were included after the written informed consent of their next-of-kin or following an emergency inclusion procedure if not available at the time of inclusion. Then, consent was obtained from all patients as soon as possible after recovery. The appropriate ethics committee (Comite de Protection des Personnes, Rennes, France) approved this study protocol in September 2015 (15/13-975).