British Journal of Anaesthesia, 128 (1): 207e213 (2022)

doi: 10.1016/j.bja.2021.09.016
Advance Access Publication Date: 20 October 2021
Respiration and the Airway

RESPIRATION AND THE AIRWAY

Efficacy of high-flow nasal oxygenation compared with tracheal

intubation for oxygenation during laryngeal microsurgery: a
randomised non-inferiority study
Se-Hee Min1,2, Heechul Yoon1, Gene Huh3, Seong K. Kwon3, Jeong-hwa Seo1 and Youn J. Cho1,*
1
Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University
College of Medicine, Seoul, Republic of Korea, 2Department of Anaesthesiology and Pain Medicine, Chung-Ang University
College of Medicine, Seoul, Republic of Korea and 3Department of Otorhinolaryngology-Head and Neck Surgery, Seoul
National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

*Corresponding author. E-mail: mingming7@gmail.com

Abstract
Background: Oxygenation via a high-flow nasal cannula (HFNC) can be an alternative to tracheal intubation during short
apnoeic procedures. This randomised, non-inferiority study assessed the efficacy of HFNC compared with tracheal
intubation in laryngeal microsurgery.
Methods: Patients (
20 yr old) undergoing laryngeal microsurgery under general anaesthesia and neuromuscular
blockade were randomised to either the HFNC or tracheal intubation groups. The primary endpoint was lowest pulse
oxygen saturation (SpO2) during the first 30 min of surgery. Secondary endpoints included incidence of desaturation
(SpO2 <95%), hypercarbia (transcutaneous carbon dioxide [CO2]
8.7 kPa), and rescue intervention.
Results: Amongst 130 patients randomised, 118 were included in the analysis. The lowest SpO2 was 100 (98e100)% in the
HFNC group (n¼56) and 100 (100e100)% in the tracheal intubation group (n¼62), with a mean difference of e1.4% (95%
confidence interval: e2.4% and e0.3%), failing to confirm non-inferiority with a non-inferiority margin of 2%. The peak
transcutaneous CO2 and end-tidal CO2 at the end of surgery were higher in the HFNC group compared with the tracheal
intubation group. Incidences of desaturation, hypercarbia, and rescue intervention were more frequent in patients
receiving HFNC compared with tracheal intubation.
Conclusions: HFNC oxygenation was not non-inferior to tracheal intubation for maintaining oxygen saturation during
laryngeal microsurgery. Considering more frequent desaturation, hypercarbia, and requirement for rescue intervention
compared with tracheal intubation, HFNC should be used with cautious monitoring even for short duration airway
surgery.
Clinical trial registration: NCT03629353.

Keywords: apnoea; high-flow nasal oxygenation; laryngeal microsurgery; oxygenation; tracheal intubation

Editor’s key points
 High-flow nasal oxygenation is potentially useful
during laryngeal microsurgery, but its efficacy has
not been compared formally with conventional
tracheal intubation.
 This randomised study shows that high-flow nasal
oxygenation may be as effective as tracheal intuba-
tion in oxygenation during laryngeal microsurgery.
 Nevertheless, the incidences of desaturation and
rescue intervention were more frequent for high-flow
nasal oxygenation than for tracheal intubation.

Received: 24 June 2021; Accepted: 21 September 2021

© 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com

207
 208 - Min et al.
During airway surgery, which requires inevitable apnoeic pe-
riods, tracheal intubation has been traditionally performed, and
the tracheal tube could be removed and reinserted repeatedly
for apnoeic procedures. Accordingly, repeated cessation of
oxygenation and ventilation exposes patients to desaturation
and hypercarbia, and increases the risk of hypoxaemia and
subsequent acidosis, and inadvertent airway injury.
Recently, oxygenation with a high-flow nasal cannula
(HFNC) has been used during the apnoeic period in various
clinical procedures.1 High-flow nasal oxygenation through
HFNC allows safe prolongation of the apnoeic period in pa-
tients requiring rapid sequence intubation or with difficult
airways.2,3 Moreover, HFNC does not disturb the surgical field,
and can therefore facilitate surgical procedures and shorten
the whole procedure time. However, carbon dioxide (CO2)
accumulation and progressive respiratory acidosis may occur
during apnoeic periods.4
Although there are several case reports on oxygenation
using HFNC during laryngeal or tracheal surgery,5,6 there is a
lack of randomised clinical trials on the efficacy of HFNC
compared with tracheal intubation in patients undergoing
laryngeal microsurgery under general anaesthesia and
neuromuscular block. We hypothesised that HFNC would be
not be inferior to tracheal intubation with regard to oxygena-
tion during surgery. To evaluate our hypothesis, we assessed
the oxygenation and ventilation of HFNC compared with
tracheal intubation in adult patients undergoing laryngeal
microsurgery.
Methods
This prospective, randomised, parallel-group, non-inferiority
study was approved by the Institutional Review Board of
Seoul National University Hospital (#1807-051-957; Youn
Joung Cho, principal investigator, on July 23, 2018), and was
registered at ClinicalTrials.gov (NCT03629353, on August 14,
2018) before patient enrolment. The study was conducted in
accordance with Good Clinical Practice guidelines and the
principles of the Declaration of Helsinki. All participants
provided written informed consent and could withdraw
consent at any time.
Eligible patients were adults (
20 yr) with ASA physical
status 1e3, scheduled for elective laryngeal microsurgery
requiring general anaesthesia and neuromuscular block in a
single tertiary centre (Seoul National University Hospital, Seoul,
Republic of Korea). The exclusion criteria were use of CO2 laser;
elevated intracranial pressure, skull base defect, chronic
obstructive pulmonary disease, or pulmonary hypertension;
requiring rapid sequence intubation; or lack of consent to
participation in the study. Each operation in a single patient
during the study period was treated as a separate patient.
After obtaining written informed consent, the subjects
were randomised to either the HFNC or tracheal intubation
group. Block randomisation (blocks of four) was performed
using a computer-generated randomisation program by an
independent researcher to allocate subjects in a 1:1 ratio.
Group allocation was concealed in opaque envelopes, and
subjects and researchers who collected and analysed the data
were blinded to the allocation.
Without premedication, the patients were monitored with
three-lead electrocardiogram, noninvasive blood pressure,
bispectral index, oxygen saturation measured by pulse oxime-
try (SpO2), transcutaneous CO2, and oxygen reserve index.
Transcutaneous CO2 was monitored with a sensor (V-Sign™
sensor 2; SenTec AG, Therwil, Switzerland) attached to the skin
of the forearm or anterior chest, which was connected to a
monitor (SenTec digital transcutaneous monitor; SenTec AG)
after calibration. Oxygen reserve index was monitored using a
sensor (Masimo SET® rainbow; Masimo Corporation, Irvine, CA,
USA) attached to a finger, connected to a monitor (Root; Masimo
Corporation). Oxygen reserve index was calculated from multi-
wave pulse co-oximetry, and can detect mild hypoxaemia even
in the range that cannot be detected based on SpO2.7
Without premedication, subjects were preoxygenated in a
30 head-up position for 3 min in both groups. Subjects were
preoxygenated with oxygen 100% (30e40 L min1) through
HFNC using a high-flow system (Optiflow™; Fisher & Paykel
Healthcare, Auckland, New Zealand) in the HFNC group, or
with oxygen 100% (10 L min1) via a face mask using an
anaesthesia machine (Primus; Dra € gerwerk AG & Co. KGaA,
Lübeck, Germany) in the tracheal intubation group.
After preoxygenation, general anaesthesia was induced
and maintained with TIVA using i.v. propofol (effect-site
concentration: 3e5 mg ml1) and remifentanil (effect-site
concentration: 2e6 ng ml1). Rocuronium 0.6 mg kg1 i.v. was
administered for neuromuscular block. Concentrations of
propofol and remifentanil were adjusted to maintain bispec-
tral index between 40 and 60 and adequate haemodynamics.
In the HFNC group, the oxygen flow rate was adjusted to 70 L
min1, and the fraction of inspired oxygen (FiO2) at 1.0
throughout the procedure. In patients receiving HFNC, the
surgical procedures were conducted in an apnoeic state
without setting the tidal volume or ventilatory frequency. In
the tracheal intubation group, a reinforced tracheal tube with
internal diameter of 5.0 or 5.5 mm (Mallinckrodt; Covidien,
Mansfield, MA, USA) was inserted, and the subjects lungs were
ventilated with a tidal volume of 6e8 ml kg1, ventilatory
frequency of 10e20 bpm, FiO2 at 0.4, and PEEP of 5 cm H2O. The
surgery was performed in the supine position in both groups.
During the operation, a tooth guard and a laryngoscope
were used to visualise and approach to the glottis and peri-
glottic structures. In the tracheal intubation group, the
tracheal tube was temporarily removed and reinserted
repeatedly during the operation as needed by surgeons.
During surgery, if SpO2 decreased <95% or transcutaneous
CO2 increased
8.7 kPa, the operating surgeon and the
anaesthesiologist determined whether to provide rescue
intervention. As rescue intervention, the trachea was intu-
bated and the lungs were ventilated with an anaesthesia ma-
chine to ensure adequate SpO2 and end-tidal CO2 in the HFNC
group. In the tracheal intubation group, FiO2 was adjusted up
to 1.0, and bag-and-mask ventilation was applied. If the
tracheal tube was removed because of surgical necessity,
reintubation was performed. Alveolar recruitment was per-
formed at the discretion of the attending anaesthesiologists.
At completion of the surgery, sugammadex 4 mg kg1 i.v.
was administered to reverse neuromuscular block. A supra-
glottic airway device was used to facilitate elimination of CO2
and emergence from anaesthesia in the HFNC group. After
removing the supraglottic airway or tracheal tube, the patients
were monitored in the PACU before transfer to general wards.
Data on the baseline characteristics of the included pa-
tients; comorbidities; diagnosis; durations of anaesthesia,
surgery, and apnoea; and durations of PACU and postoperative
hospital stay were collected. Parameters of oxygenation and
ventilation, including SpO2, transcutaneous CO2, and oxygen
reserve index, were recorded during surgery. End-tidal CO2 at
the end of the procedure and requirement for rescue
 High-flow nasal cannula in laryngeal microsurgery
Screened for eligibility
(n=287)
Enrolment
Enrolled to the study
(n=126)
Allocation
Allocated to high-flow nasal cannula
(n=63)
Excluded
Use of CO2 laser
(n=7)
Completed the study
Follow-up
(n=56)
Analysed
Analysis
(n=56)
Fig 1. Consolidated Standards of Reporting Trials (CONSORT) diagram.
intervention were assessed. Any significant arrhythmia or ST-
segment changes on electrocardiogram were recorded.
Study endpoints and sample size calculation
The primary endpoint was the lowest SpO2 during the first 30
min of the surgery in the two groups. The secondary endpoints
included the peak transcutaneous CO2, lowest oxygen reserve
index, end-tidal CO2 at the end of the procedure, incidences of
desaturation (defined as SpO2 <95%) or hypercarbia (trans-
cutaneous CO2
8.7 kPa), and the requirement of rescue
intervention.
To calculate sample size, we conducted a pilot study with 20
patients undergoing laryngeal microsurgery in our institution.
In the pilot study, the lowest SpO2 was 97% (4%) during the 30
min of the surgery under general anaesthesia using tracheal
intubation. To test the non-inferiority of HFNC compared with
tracheal intubation regarding the lowest SpO2 during surgery,
63 subjects per group (a total of 126 patients) were required for a
non-inferiority margin of 2%, which was chosen by clinical
acceptance, with one-sided level of significance of 0.025 and
power of 80%, including a dropout rate of 5%.
Statistical analysis
The normality of the data was tested using Kolmo
goroveSmirnov tests. According to the distribution of the data,
continuous variables are presented as the mean (standard
- 209
Excluded (n=161)
Planned to use CO2 laser (n=133)
Required rapid sequence induction (n=1)
Refused to participate (n=27)
Allocated to tracheal intubation
(n=63)
Excluded
Use of CO2 laser
(n=1)
Completed the study
(n=62)
Analysed
(n=62)
deviation) or median (inter-quartile range [IQR]). The mean dif-
ferences between the groups were compared using the inde-
pendent t-test or the ManneWhitney U-test according to the
normality of the variables.
For comparison of the lowest SpO2 between the two groups,
the non-inferiority test was performed using a non-inferiority
margin of 2% for this study. For repeated measures variables, a
linear mixed model with Bonferroni correction was per-
formed. In the mixed model, the group, measurement time,
and the interaction between time and group were regarded as
fixed effects, and subject was regarded as a random effect. The
normality assumption for the model residuals was checked
using histograms and quantileequantile plots of residuals.
Plots of residuals vs fitted values were assessed to check that
the error terms (residuals) had a mean of zero and constant
variance. If the interaction between time and group was sig-
nificant, between-group comparisons were performed at each
measurement time point using the independent t-test or
ManneWhitney U-test with Bonferroni correction for multiple
comparison. To evaluate the diagnostic value of apnoea time
using HFNC for adequate oxygenation and ventilation, a
receiver operating characteristic (ROC) curve analysis was
performed, and the area under the ROC (AUC) was calculated
with 95% confidence intervals (CIs). The best cut-off point was
determined as the value maximising Youden’s index (sum of
sensitivity and specificity). In this ROC analysis, patients with
obesity (BMI
30 kg m2) were excluded.
 210 - Min et al.

Table 1 Baseline characteristics of subjects undergoing

a laryngeal microsurgery. Data are median (inter-quartile
Oxygen saturation measured by

range), n (%), or mean (standard deviation). HFNC, high-flow

100 nasal cannula. *Other diagnoses included periglottic leuco-
plakia, ulcer, or lesions on pyriform sinus or tongue base.
pulse oximetry (%)

98 HFNC Tracheal
(n¼56) intubation
(n¼62)
96
Age (yr) 59 58
(range: 20e84) (range: 25e78)
94 Female, n (%) 15 (27) 18 (29)
Height (cm) 167 (7) 166 (8)
Weight (kg) 63.7 (60.0e73.3) 65.8 (59.0e77.2)
92
BMI (kg m2) 23.8 (3.5) 24.7 (3.0)
ASA physical
b status, n (%)
11 1 12 (21) 23 (37)
* 2 39 (70) 38 (61)
Transcutaneous carbon

10 * 3 5 (9) 1 (2)
* Comorbidities, n (%)
9
dioxide (kPa)

* Hypertension 23 (41) 22 (36)

8 * Diabetes mellitus 7 (13) 14 (23)
Asthma 0 (0) 2 (3)
7 * Chronic liver 4 (7) 3 (5)
* disease
6
Diagnosis, n (%)
5 Benign mass 21 (37) 44 (71)
Malignant tumour 10 (18) 9 (15)
4 Subglottic stenosis 15 (27) 1 (2)
Tracheal stenosis 5 (9) 4 (6)
c Others* 5 (9) 4 (6)

1.0
Oxygen reserve index

0.8
All analyses were conducted in a modified intention-to-
0.6 treat manner, which includes all randomised patients who
received treatment without cessation during the study period.
0.4 IBM SPSS Statistics (version 21.0; IBM Corp., Armonk, NY, USA)
and R software (version 3.4.3; R Development Core Team,
0.2 Vienna, Austria) for Microsoft Windows were used. In all an-
alyses, P<0.05 was taken to indicate statistical significance.
0.0

Results
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10 in
15 in
20 in
2 5 in

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yg lin

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m
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at

Of 287 patients screened, 126 patients were randomised to the

ox ase

0
5
B

HFNC or tracheal intubation group (each n¼63) between

During laryngeal microsurgery August 17, 2018 and January 20, 2020. After randomisation,
re
rp

eight patients were excluded because of unplanned use of a

te

High-flow nasal cannula

Af

Tracheal intubation
Fig 2. (a) Oxygen saturation by pulse oximetry, (b) trans-
cutaneous carbon dioxide, and (c) oxygen reserve index at
baseline, after preoxygenation, at 0, 5, 10, 15, 20, 25, and 30 min
of laryngeal microsurgery. Repeated measures variables were
compared using a linear mixed model with Bonferroni correc-
tion. The interactions between time and group were significant
for pulse oximetry, transcutaneous carbon dioxide, and oxygen
reserve index (P¼0.017, <0.001, and 0.014, respectively). As the
interactions between time and group were significant, between-
group comparisons were performed at each measurement time
point using the ManneWhitney U-test with Bonferroni correc-
tion for multiple comparison. Data points are means and error
bars are standard deviations.
CO2 laser (Fig. 1). These patients were excluded from the
modified intention-to-treat population because they met the
exclusion criteria. In total, 56 subjects in the HFNC group and
62 subjects in the tracheal intubation group were included in
the analysis.
The patient characteristics are presented in Table 1. The
BMI ranges of the patients were 16.4e34.1 kg m2 in the HFNC
group and 17.4e32.7 kg m2 in the tracheal intubation group.
The median (IQR) operation time was 20 (10e26) min, and that
for anaesthesia duration was 40 (30e50) min. At baseline and
at the end of surgery, SpO2, transcutaneous CO2, and oxygen
reserve index were comparable between the two groups.
Duration of total anaesthesia was longer in the tracheal intu-
bation group than in the HFNC group (Table 2).
For the primary outcome, HFNC was not confirmed to be
non-inferior to tracheal intubation, with the lowest SpO2
during the first 30 min of the surgery being median (IQR) 100
 High-flow nasal cannula in laryngeal microsurgery - 211

Table 2 Perioperative variables of oxygenation and ventilation in subjects who received oxygen supply using high-flow nasal cannula
or tracheal intubation during laryngeal microsurgery. Data are median (inter-quartile range) or n (%). CO2, carbon dioxide; HFNC, high-
flow nasal cannula; NA, not available; SpO2, pulse oxygen saturation.

HFNC (n¼56) Tracheal intubation P-value

(n¼62)

SpO2 (%)
Baseline 99 (97e100) 98 (97e100) 0.363
At the end of surgery 100 (100e100) 100 (100e100) 0.350
Lowest SpO2 (%) 100 (98e100) 100 (100e100) 0.050
Incidence of SpO2 <95%, n (%) 6 (11) 1 (2) 0.037
Incidence of SpO2 <90%, n (%) 3 (5) 0 (0) 0.104
Transcutaneous CO2 (kPa)
Baseline 5.0 (4.5e5.5) 5.2 (4.7e5.6) 0.038
At the end of surgery 6.5 (5.8e7.0) 6.2 (5.6e6.6) 0.068
Peak transcutaneous CO2 (kPa) 7.8 (6.7e8.6) 6.1 (5.7e6.4) <0.001
Incidence of transcutaneous CO2
8.7 kPa, n (%) 13 (23) 1 (2) <0.001
Oxygen reserve index
Baseline 0.00 (0.00e0.00) 0.00 (0.00e0.00) >0.999
At the end of surgery 0.35 (0.23e0.50) 0.37 (0.29e0.46) 0.516
Lowest oxygen reserve index 0.18 (0.00e0.33) 0.20 (0.02e0.28) 0.763
End-tidal CO2 at the end of surgery (kPa) 6.8 (5.6e8.8) 4.9 (4.8e5.2) <0.001
Rescue intervention, n (%) 13 (23) 2 (3) 0.001
Duration of surgery (min) 15 (10e25) 20 (15e30) 0.090
Duration of anaesthesia (min) 35 (25e45) 45 (35e51) 0.001
Duration of apnoea (min) 20 (15e30) NA NA
PACU stay (min) 40 (38e42) 40 (38e41) 0.550
Postoperative hospital stay (days) 3 (2e3) 2 (2e3) 0.080

(98e100)% vs 100 (100e100)%, with a mean difference of e1.4% Discussion

(95% CI: e2.4% and e0.3%). For secondary outcome variables,
Oxygenation using HFNC was not non-inferior to tracheal
the peak transcutaneous CO2 (7.8 [6.7e8.6] vs 6.1 [5.7e6.4]
intubation with regard to maintaining oxygen saturation
kPa), the incidence of hypercarbia (23% vs 2%), and end-tidal
during laryngeal microsurgery under general anaesthesia and
CO2 at the end of the surgery (6.8 [5.6e8.8] vs 4.9 (4.8e5.2)
neuromuscular block in this randomised non-inferiority
kPa) were greater in the HFNC group than in the tracheal
study. Patients who received HFNC oxygenation had signifi-
intubation group (all P<0.001; Table 2). The incidences of
cantly higher incidences of desaturation and hypercarbia, and
desaturation, defined as SpO2 <95%, (11% vs 2%) and rescue
required more frequent rescue intervention during the first 30
intervention (23% vs 3%) were also higher in the HFNC group
min of surgery.
(P¼0.037 and 0.001, respectively). However, the incidence of
HFNC was first described as a supplemental oxygen mo-
unacceptable desaturation (SpO2 <90%) was not different
dality in preterm neonates.8 Beyond oxygenation, it washes
between the groups (5% vs 0%; P¼0.104; Table 2). In subjects
out CO2 in anatomical dead spaces, provides unmeasured
who received HFNC, those who required rescue intervention
positive airway pressure, and maintains relatively constant
had longer duration of surgery and anaesthesia than those
FiO2.9,10 During endoscopic laryngeal surgeries, an unob-
who did not receive rescue intervention (Supplementary
structed surgical field and intermittent apnoeic periods are
Table S1).
required. Repeated extubation and reintubation of tracheal
Changes in SpO2, transcutaneous CO2, and oxygen reserve
tubes to obtain the tubeless field increase the risk of baro-
index are shown in Figure 2. For repeated measures variables,
trauma, desaturation, and potential for airway injury. HFNC
the interactions between time and group were significant for
may provide the benefit of safe apnoeic periods during airway
SpO2, transcutaneous CO2, and oxygen reserve index
surgeries.5,11
(P¼0.017, <0.001, and 0.014, respectively; mixed model).
In the present study, the main driving factor for rescue
During surgery, SpO2 and oxygen reserve index did not differ
intervention was accumulation of CO2 or desaturation.
between the groups at any measurement time point (Fig. 2a
Amongst 15 patients receiving rescue intervention, the inter-
and c). However, transcutaneous CO2 levels were signifi-
vention was initiated because of hypercarbia in seven patients
cantly higher in the HFNC group compared with the tracheal
(six in the HFNC group and one in the tracheal intubation
intubation group after 5 min of surgery (Fig. 2b). The rate of
group) and desaturation in eight patients (seven in the HFNC
increase in transcutaneous CO2 was 0.12 kPa min1 during
group and one in the tracheal intubation group). Similarly, the
HFNC oxygenation.
PaCO2 and end-tidal CO2 were significantly higher and the pH
Durations of PACU and postoperative hospital stays were
was lower during HFNC compared with mechanical ventila-
similar in the two groups (Table 2). No significant arrhythmia
tion during laryngeal surgery in another previous small
or ST-segment changes were observed in any patient during
study.12
the study period. The best cut-off limit to ensure safe apnoeic
During high-flow continuous insufflation, CO2 can be
period using HFNC oxygenation was 28 min with a specificity
eliminated by gaseous mixing through flow-dependent flush-
of 88% and a specificity of 46% (AUC 0.732; 95% CI: 0.577e0.886;
ing of the dead space.2 However, unrecognised hypercarbia
P¼0.013) in ROC curve analysis (Supplementary Fig. S1).
 212 - Min et al.
causes progressive respiratory acidosis and disturbing
myocardial contraction and conduction, and can lead to a
predisposition for fatal arrhythmia and even death.4 The up-
per limit of 95% CI of occurrence of death attributable to
acidosis was pH 6.9 during diffusion respiration.13
In most studies, the median apnoea time using HFNC was
15e20 min.2,6,14,15 After this period, transcutaneous CO2
increased significantly, mostly without profound desatura-
tion.2,14 When discontinuation criteria were applied to termi-
nate the apnoeic oxygenation at a serial arterial partial
pressure of CO2 (PaCO2) of 12 kPa or pH 7.15, that for apnoea
time was 25 (20e30) min in patients with BMI <30 kg m2 using
HFNC during laryngeal surgery.16 Similarly, we demonstrated
the best cut-off for a safe apnoeic period of 28 min using HFNC
in patients who were not obese. Beyond this period, significant
respiratory acidosis may occur, prohibiting the use of HFNC for
longer duration of procedure.
In most previous studies, only pulse oxygen saturation was
monitored, whereas end-tidal CO2 could be checked only at
the end of the surgery.6 In another study, apnoea time was
limited by significant CO2 accumulation and concomitant
respiratory acidosis within 30 min during apnoeic oxygenation
with HFNC.17 Although oxygenation is sufficient (mean PaO2
48.6 kPa), significant acidosis occurs during apnoea with HFNC
(pH 7.15 in a median of 25 min).16
However, assessment of hypercarbia by arterial blood gas
analysis and obtaining PaCO2 is not always feasible in clinical
practice. As an alternative, transcutaneous CO2 monitoring
enables continuous and noninvasive measurement of CO2
accumulation, providing acceptable agreement with the
measure of PaCO2.11,18 Moreover, transcutaneous CO2 moni-
toring does not induce patient discomfort, arterial injury or
infection, or time delay to determine the CO2 accumulation.
The strength of this study is that it was conducted as a
randomised, non-inferiority clinical trial with sample size
calculation and acceptable statistical power. Previously, the
usefulness of HFNC for airway surgery has been reported
mostly as case series or retrospective reviews with small
numbers of patients.5,6,15,19,20 In one clinical trial, only 30 pa-
tients were randomised and compared with mechanical
ventilation; the results revealed no differences in lung volume
changes between the groups.12
This study had several limitations. First, the predefined
margin of non-inferiority (2%) was too small in this study. As
we assumed the lowest SpO2 during laryngeal surgery to be
97%, the assessment of non-inferiority might be a comparison
of hyperoxia and hyperoxia, which was not clinically mean-
ingful. However, we presented the incidence of unacceptably
low SpO2 (<90%), which was similar between the groups.
Second, we did not obtain blood gas analysis. However,
continuous monitoring of transcutaneous CO2 was used as an
alternative to end-tidal CO2 or PaCO2.18 Thereby, we could
detect hypercarbia and have avoided excessive respiratory
acidosis. For short durations of minor surgery, noninvasive
monitoring of transcutaneous CO2 may be useful for ensuring
patient safety and quality of anaesthetic management for
apnoeic oxygenation. Third, our cohort included a very small
proportion of patients with obesity, with only 4% (5/118) of
patients showing BMI >30 kg m2 (maximum 34.1 kg m2).
Previously, several reports demonstrate that patients with
morbid obesity experienced desaturation during HFNC
oxygenation.5,6 However, in our study, amongst 15 patients
who required rescue intervention, only three had BMI >30 kg
m2. Therefore, our results cannot represent oxygenation or
ventilatory profiles of patients with morbid obesity under
HFNC treatment, and further investigations are required.
Fourth, we did not include patients treated using a CO2 laser,
mainly because of limited experience and evidence for the
safety of the use of HFNC combined with CO2 laser. Although
there have been case reports, in which HFNC was successfully
used during CO2 laser treatment,21 and it is known that laser
can be used in the absence of fuel sources, such as tracheal
tubes, further studies are required. Fifth, the duration of pre-
oxygenation was relatively short (3 min) in both groups.
Whether extended periods of preoxygenation would allow
maintenance of adequate oxygen saturation during HFNC
comparable with tracheal intubation is remained to be
explored. Lastly, we assessed the oxygenation and ventilation
only during the first 30 min mainly because of the short
duration of the included surgery. However, clinicians may
need to understand what happens during prolonged proced-
ure, and this remains to be investigated in further studies.
Conclusion
HFNC oxygenation was not non-inferior compared with
tracheal intubation during general anaesthesia and neuro-
muscular block for laryngeal microsurgery. Incidences of
desaturation, hypercarbia, and requirement for rescue inter-
vention were more frequent during HFNC oxygenation
compared with tracheal intubation even during the short
duration of surgery. Leaving aside the benefits over tracheal
intubation, apnoeic HFNC oxygenation should be used with
cautious monitoring during laryngeal microsurgery.
Authors’ contributions
Full access to all of the data in the study: S-HM, YJC
Responsibility for the integrity of the data and the accuracy of
the data analysis: S-HM, HY, GH, YJC
Concept and design: S-HM, SKK, J-HS, YJC
Drafting of paper: S-HM, HY, YJC
Critical revision of paper: GH, SKK, J-HS
All authors agreed to be accountable for all aspects of this
work, and ensure the accuracy and integrity of any part of this
work.
Acknowledgements
The authors thank the Medical Research Collaborating Centre
for their advice concerning the statistical analyses.
Declarations of interest
The authors declare that they have no conflicts of interest.
Funding
Department of Anaesthesiology and Pain Medicine, Seoul
National University Hospital.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.bja.2021.09.016.
 High-flow nasal cannula in laryngeal microsurgery
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Handling editor: Takashi Asai