This prospective, single-centre, randomized controlled trial was performed at Severance Hospital, Yonsei University Health System, Seoul, South Korea.This study was approved by the institutional review board of Severance Hospital, Seoul, South Korea (#4-2019-1336). Written informed consent was obtained from all individuals participating in the trial. The trial was registered prior to patient enrolment at clinicaltrials.gov (Registration number: NCT04291339, Principal investigator: Hyun Joo Kim, Date of registration: March 2, 2020). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
Inclusion and exclusion criteria
Patients aged ≥20 years who were scheduled to undergo orotracheal intubation for general anesthesia from November 2020 to January 2021 were enrolled in this study. Patients with cranial fractures or craniofacial malformations that prevented oxygen delivery through the nostrils, those who could not cooperate due to impaired consciousness, and those who could not fast prior to surgery or were at risk of aspiration of gastric contents due to gastroesophageal disease were excluded from the study. Patients who required awake intubation were also excluded.
A computer-generated randomisation table (available at https://www.randomizer.org/form.htm) was used to randomly assign patients to the HFNO group or the FMV group at a 1:1 ratio. Due to differences in the appearance of the preoxygenation devices, the patients and anesthesiologists could not be blinded to group allocation once the induction process was initiated. Prior to surgery, group allocations were concealed in sequentially numbered, sealed, opaque envelopes. Randomisation was performed after enrolment but before the start of the study protocol by Hyun Joo Kim.
Anesthetic management and measurements
In the operating room, patients were placed in a supine position with a pillow behind their head. An electrocardiogram was obtained, and blood pressure, oxygen saturation, and brain function (SedLine®, Masimo Corp., Irvine, CA, USA) were monitored non-invasively. Each patient’s pulse oximetry was measured using the RD Rainbow SET®-2 Neo sensor (Massimo Corp.) attached to the patient’s finger and covered with a light-shielding black bag. The ORI was monitored using the Rainbow SET Radial-7 Pulse CO-Oximeter (software version 188.8.131.52, Masimo Corp.).
Prior to initiating anesthesia induction, an airway assessment was performed, including assessments for obstructive sleep apnoea, snoring while sleeping, interincisor distance, hyomental distance, and head and neck movement. The modified Mallampati and upper lip bite test scores were also determined.
In the HFNO group, the Optiflow (Fisher & Paykel Healthcare, Auckland, New Zealand) nasal cannula was placed on the patient’s nares. Preoxygenation was performed for 3 minutes at 40 L/min at an FiO2 of 1.0. During the preoxygenation period, the patient was asked to rate whether they were comfortable with the oxygen administration method using a four-level scale (comfortable, acceptable, uncomfortable, intolerable). If the patient complained of nasal discomfort, the oxygen flow rate was reduced in increments of 5 L/minto a minimum of 30 L/min.
After preoxygenation, anesthesia induction was accomplished intravenously using propofol (1–2 mg/kg). Neuromuscular blockade was induced using intravenous rocuronium (0.6 mg/kg) after the patient lost consciousness in both groups. Oxygen was administered via nasal cannula at 70 L/min for 3 minutes, and the patient’s jaw was lifted using the operator’s hands to maintain upper airway patency. At 3 minutes after rocuronium administration, endotracheal intubation was attempted using a videolaryngoscope and an endotracheal tube. The high-flow nasal cannula was used to continuously supply oxygen at 70 L/min during intubation attempts until the endotracheal tube was placed.
In the FMV group, the facemask was placed in contact with the patient’s nose and mouth, and oxygen was supplied at 10 L/min at an FiO2 of 1.0 for 3 minutes. During preoxygenation, the patient’s comfort level was assessed using the same scale as that used in the HFNO group. If discomfort was reported, the oxygen flow rate was lowered in increments of 1 L/min to a minimum flow rate of 6 L/min. When the patient lost consciousness, FMV was continued for 3 minutes using the volume-controlled mode of the mechanical ventilator with an oxygen flow rate of 2 L/min, tidal volume of 8 mL/kg, respiratory rate of 15 breaths per minute, peak end-expiratory pressure of 0 cmH2O, and FiO2 of 1.0. A two-handed jaw thrust manoeuvre was performed to maintain upper airway patency. Endotracheal intubation was performed using a videolaryngoscope at 3 minutes after the administration of rocuronium. The facemask was removed from the patient’s face, and oxygenation was discontinued during intubation attempts.
The ORI was continuously monitored until the endotracheal intubation was completed. ORI and SpO2 values were collected at 10 time points: at baseline (before preoxygenation), at 1, 2, and 3 minutes of preoxygenation, during the propofol and rocuronium injections, at 1 and 2 minutes after the rocuronium injection, and at the initiation and completion of intubation.
Patient characteristics such as age, sex, height, weight, and the American Society of Anesthesiologists physical class were recorded. The number of intubation attempts, intubation time, and Cormack–Lehane grade were recorded. The primary outcome was the highest ORI value achieved by oxygenation. The secondary outcome was the time required to reach the highest ORI observed during the induction of anesthesia.
Sample size calculation
Data from previous studies were used to calculate the sample size. The highest mean ORI value during anesthesia induction was estimated as 0.5 ± 0.11 (mean ± standard deviation), and a significant difference of 0.05 was assumed between the two groups. The estimated sample size was 76 patients per group with a power of 80% and type-1 error of 0.05. As this was a novel study to monitor the ORI throughout the anesthesia induction period, and because the ORI is a new parameter and the risks of data collection failure, inter-individual variability, and patient dropout are high, the sample size was increased to 100 patients per group.
Continuous variables are reported as mean ± standard deviation, and categorical variables are reported as numbers (percentages). Continuous variables were analysed using Student’s t-test or Mann–Whitney U test, as appropriate. Categorical variables were analysed using the chi-square test or Fisher’s exact test. ORI and SpO2 during the induction process were analysed using Student’s t-test. All analyses were performed using R package version 4.1.0 statistical software (http://www.R-project.org, The R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was defined as a two-sided P-value < 0.05.