High-flow Nasal Cannula Versus Conventional Oxygen During Awake Tracheal Intubation With Difficult Airways

High-Flow Nasal Cannula Versus Conventional Oxygen to Prevent Hypoxaemia During Awake Tracheal Intubation: A Multicentre, Open-Label, Randomised Controlled Trial (OXYOPTI-ATI)

Study Background Airway management is one of the most fundamental and critical technical procedures in anesthesiology, critical care, and emergency medicine. Difficult airway management remains a major challenge in these fields, particularly when a "cannot intubate, cannot ventilate" scenario occurs during the induction of general anesthesia. Such events can rapidly lead to hypoxemia, resulting in brain injury or even death, and have become a significant source of anesthesia-related severe complications and medical disputes.

Awake tracheal intubation (ATI) is considered the gold standard for airway management in patients with anticipated difficult airways, as it preserves spontaneous breathing and thereby reduces the risk of catastrophic airway failure during anesthesia induction. However, despite routine supplemental oxygen administration, hypoxemia remains one of the most common and potentially serious complications during ATI. When low-flow oxygen therapy (<30 L/min) is used, the reported incidence of hypoxemia (SpO₂ ≤ 90%) ranges from 12% to 29%. Once hypoxemia occurs during ATI, it may not only interrupt the procedure, increase the number of intubation attempts, and reduce the likelihood of successful intubation, but also trigger serious cardiovascular events, thereby compromising patient safety.

High-flow nasal cannula (HFNC) oxygen therapy can deliver heated and humidified gas at flow rates of up to 70 L/min and improve oxygenation and ventilation through mechanisms such as anatomical dead space washout, reduction of work of breathing, and generation of continuous positive airway pressure. HFNC has been shown to improve oxygenation in a variety of medical and procedural settings. However, evidence regarding the role of HFNC during awake tracheal intubation remains controversial and of low quality. There is an urgent need for well-designed multicenter randomized controlled trials specifically focused on the ATI setting, using hypoxemic events as the primary outcome and applying strictly standardized procedures, to provide high-quality evidence on the effectiveness and safety of HFNC during ATI. Such evidence is essential to inform clinical practice and support future updates of airway management guidelines.

Study Hypothesis This study hypothesizes that, in patients with anticipated difficult airways undergoing ATI, HFNC is more effective in preventing intubation-related hypoxemic events than conventional low-flow nasal cannula oxygen therapy.

Study Objectives

Primary Objective:

To evaluate the effectiveness of high-flow nasal cannula oxygen therapy compared with conventional low-flow nasal cannula oxygen therapy in preventing hypoxemia during ATI in patients with anticipated difficult airways.

Secondary Objectives:

To assess the effects of high-flow nasal cannula oxygen therapy versus conventional low-flow nasal cannula oxygen therapy on procedural outcomes of awake tracheal intubation, including the rate of interventions required after hypoxemia, first-attempt intubation success rate, number of intubation attempts, overall ATI success rate, intubation time, and the incidence of adverse events.

Study Methods This study is a multicenter, randomized controlled clinical trial. Adult patients undergoing ATI will be recruited from six tertiary hospitals in China. Participants will be randomly assigned to receive either high-flow nasal cannula oxygen therapy or conventional low-flow nasal cannula oxygen therapy throughout the intubation procedure. The study will compare the incidence of hypoxemia between the two groups and further evaluate intubation success rates, intubation time, the need for rescue interventions following hypoxemia, and the incidence of adverse events.

Study Overview

• Status: Recruiting
• Conditions: Difficult Airway; Awake Tracheal Intubation
• Intervention / Treatment: Device: High-Flow Nasal Cannula; Device: Ligh-Flow Nasal Cannula

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wenxian Li, PhD. MD.; Phone Number: +86 021 643 771 34; Email: wenxian.li@fdeent.org

Study Locations

• China
  • Gansu
    • Wuwei, Gansu, China
      • Recruiting
      • Wuwei People's Hospital
      • Contact: Xiaojuan Li, MD.; Phone Number: +86 18893755060; Email: 1123390492@qq.com
  • Guangzhou
    • Shenzhen, Guangzhou, China
      • Recruiting
      • South China Hospital of Shenzhen University
      • Contact: Yuancheng Hu, MD.; Phone Number: +86 13244723668; Email: 252203320@qq.com
  • Hebei
    • Baoding, Hebei, China
      • Not yet recruiting
      • Baoding NO.1 Central Hospital
      • Contact: Xiaonan Zhao, MD.; Phone Number: +86 15194969821; Email: zhaoxiaonan2005@126.com
  • Jiangsu
    • Pizhou, Jiangsu, China
      • Recruiting
      • Pizhou Hospital of Traditional Chinese Medicine
      • Contact: Yuanxin Yu, MD.; Phone Number: +86 15862146631; Email: 540160087@qq.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Eye & ENT Hospital of Fudan University
      • Contact: Yuan Han, PhD. MD.; Phone Number: +86 021 643 771 34; Email: yuan.han@fdeent.org
  • Sichuan
    • Neijiang, Sichuan, China
      • Not yet recruiting
      • The First People's Hospital of Neijiang
      • Contact: Fei Jiang, MD.; Phone Number: +86 18283236053; Email: 1277636690@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Presence of an anticipated difficult airway;
• Planned awake tracheal intubation;
• Age ≥ 18 years;
• Willingness to participate in the study and provision of written informed consent.

Exclusion Criteria:

• Contraindications to HFNC use, such as severe nasal obstruction or deformity, recent (within 3 months) nasal or skull base surgery, skull base fracture, or active epistaxis;
• Hemodynamic instability, defined as a mean arterial pressure (MAP) < 65 mmHg or the need for vasoactive medications to maintain blood pressure;
• Pregnancy;
• Current participation in another interventional clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HFNC group; During awake tracheal intubation, participants receive heated and humidified high-flow nasal cannula oxygen therapy at a flow rate of 40 L/min, FiO₂ of 100%, and a temperature of 37 °C, starting before the procedure and continuing until successful intubation is confirmed by the presence of end-tidal carbon dioxide.	Device: High-Flow Nasal Cannula; A heated and humidified high-flow nasal oxygen therapy device（Fisher & Paykel，East Tamaki，New Zealand） set at a flow rate of 40 L/min, an inspired oxygen fraction (FiO₂) of 100%, and a temperature of 37 °C.
Active Comparator: LFNC group; During awake tracheal intubation, participants receive oxygen via a disposable nasal cannula at a flow rate of 4 L/min, starting before the procedure and continuing until successful intubation is confirmed by the presence of end-tidal carbon dioxide.	Device: Ligh-Flow Nasal Cannula; Low-flow oxygen delivered via a disposable nasal cannula at a flow rate of 4 L/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of hypoxemia（SpO₂≤ 90%）	From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of SpO₂ ≤ 80%		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Lowest SpO₂		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Cumulative duration of hypoxemia		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Area under the curve (AUC) for SpO₂ ≤ 90%		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Number of hypoxemic episodes per participant (defined as the first occurrence of SpO₂ ≤ 90% after preoxygenation counted as one episode; subsequent episodes counted if SpO₂ returns to normal and then decreases again)		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
SpO₂ at the time of successful intubation		At the time of successful intubation up to 24 hours
End-tidal carbon dioxide (EtCO₂) at the time of successful intubation		At the time of successful intubation up to 24 hours
Proportion of participants requiring rescue interventions after the occurrence of hypoxemia		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
First-attempt intubation success rate		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Awake tracheal intubation success rate		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Intubation time	Defined as the duration from initiation of ATI to confirmation of successful intubation by end-tidal carbon dioxide	From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.
Incidence of adverse events		From initiation of awake tracheal intubation to completion of successful tracheal intubation confirmed by end-tidal carbon dioxide (EtCO₂), assessed up to 30 minutes.

Collaborators and Investigators

• Sponsor: Wenxian Li

Publications and helpful links

General Publications

• Cook TM, Woodall N, Frerk C; Fourth National Audit Project. Major complications of airway management in the UK: results of the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1: anaesthesia. Br J Anaesth. 2011 May;106(5):617-31. doi: 10.1093/bja/aer058. Epub 2011 Mar 29.
• Badiger S, John M, Fearnley RA, Ahmad I. Optimizing oxygenation and intubation conditions during awake fibre-optic intubation using a high-flow nasal oxygen-delivery system. Br J Anaesth. 2015 Oct;115(4):629-32. doi: 10.1093/bja/aev262. Epub 2015 Aug 7.
• Heidegger T. Management of the Difficult Airway. N Engl J Med. 2021 May 13;384(19):1836-1847. doi: 10.1056/NEJMra1916801. No abstract available.
• Cascio RS, Kilmon CA. Pervasive developmental disorder, not otherwise specified: primary care perspectives. Nurse Pract. 1997 Jul;22(7):11, 15-6, 18 passim.
• Law JA, Morris IR, Brousseau PA, de la Ronde S, Milne AD. The incidence, success rate, and complications of awake tracheal intubation in 1,554 patients over 12 years: an historical cohort study. Can J Anaesth. 2015 Jul;62(7):736-44. doi: 10.1007/s12630-015-0387-y. Epub 2015 Apr 24.
• Ho AM, Chung DC, To EW, Karmakar MK. Total airway obstruction during local anesthesia in a non-sedated patient with a compromised airway. Can J Anaesth. 2004 Oct;51(8):838-41. doi: 10.1007/BF03018461.
• Vourc'h M, Huard D, Le Penndu M, Deransy R, Surbled M, Malidin M, Mahe PJ, Guitton C, Roquilly A, Malard O, Feuillet F, Rozec B, Asehnoune K. High-flow oxygen therapy versus facemask preoxygenation in anticipated difficult airway management (PREOPTI-DAM): an open-label, single-centre, randomised controlled phase 3 trial. EClinicalMedicine. 2023 May 22;60:101998. doi: 10.1016/j.eclinm.2023.101998. eCollection 2023 Jun.
• Mangan CE, Borow L, Burtnett-Rubin MM, Egan V, Giuntoli RL, Mikuta JJ. Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings. Obstet Gynecol. 1982 Mar;59(3):315-9.
• Kinsella SM, Winton AL, Mushambi MC, Ramaswamy K, Swales H, Quinn AC, Popat M. Failed tracheal intubation during obstetric general anaesthesia: a literature review. Int J Obstet Anesth. 2015 Nov;24(4):356-74. doi: 10.1016/j.ijoa.2015.06.008. Epub 2015 Jun 30.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2026
• Primary Completion (Actual): February 4, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: February 2, 2026
• First Posted (Actual): February 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: hypoxemia; High-flow nasal cannula; Difficult airway; Awake tracheal intubation
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypoxia
• Other Study ID Numbers: EENTFudan 2025155-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No