Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study

Abstract

Background:

Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate.

Objective:

To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy.

Design:

Prospective, randomized, and controlled study.

Methods:

Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1–6, respectively.

Results:

The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1–6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43–55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate.

Conclusion:

An HFNC flow rate of 50–60 L/min is recommended to prevent desaturation during sedation for bronchoscopy.

Registration:

NCT05298319 at ClinicalTrials.gov.

Plain language summary

High-flow nasal cannula oxygenation during bronchoscopy

Many patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that’s causing trouble to find out what’s wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there’s a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren’t sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levels—like slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.

Keywords

bronchoscopy effective flow high-flow nasal cannula hypoxemia

Introduction

A high-flow nasal cannula (HFNC) is a noninvasive strategy to deliver warm and humidified oxygen at an adjustable flow rate of 10–60 L/min and to generate a positive end-expiratory pressure, prevent airway collapse, avoid loss of end-expiratory lung volume, and improve gas exchange, thus preventing desaturation.^1–4

Respiratory drive and mechanics are altered during flexible bronchoscopy due to the administration of sedative agents and insertion of the bronchoscope, which can worsen hypoxemia.^5,6 Moreover, hypoxemia can be exacerbated in patients with substantial lung lesions or poor oxygen reserve. In addition, the anesthesiologist and pulmonologist have to share the airway for procedures, such as negative pressure suction and alveolar lavage, which can dramatically decrease oxygen saturation, resulting in severe hypoxemia.

As compared to conventional therapy, HFNC can reduce the incidence of hypoxemia during sedation for bronchoscopy.^2,7–11 However, there is currently no consensus on an optimal flow rate. We hypothesized that increasing the oxygen flow rate can prevent desaturation during bronchoscopy. Therefore, this study aimed to determine the optimal flow rate for HFNC to prevent desaturation in 95% (EF₉₅) of patients during sedation for bronchoscopy.

Materials and methods

Study approval and registration

The protocol of this prospective, randomized, controlled study was approved by the Ethics Committee of Zhejiang Cancer Hospital (approval no. IRB-2022-133) and conducted in accordance with the ethical principles for medical research involving human subjects described in the Declaration of Helsinki. Prior to inclusion in this study, written informed consent was obtained from all subjects. This study is registered at ClinicalTrials.gov (NCT05298319) in accordance with the Consolidated Standards of Reporting Trials guidelines.¹²

Participants

The inclusion criteria were (1) age 18–70 years, (2) American Society of Anesthesiologists physical status score of 1–3, (3) willingness to undergo bronchoscopy, and (4) provision of written informed consent. The exclusion criteria were (1) severe heart disease, including severe aortic stenosis, severe mitral stenosis, severe arrhythmia leading to hemodynamic disorders, acute myocardial infarction in the last 6 months, or cardiac surgery in the last 6 months, (2) baseline oxygen saturation (SpO₂) <90%, (3) infection of the upper respiratory tract or lung, and (4) refusal to participate in the study.

Randomization and blinding

Patients were randomly assigned to one of six groups using a computer-generated randomization program by a research assistant (KX) who was not involved in the study to receive HFNC with propofol sedation [fraction of inspired oxygen (FiO₂), 100%] at 10, 20, 30, 40, 50, or 60 L/min, designated as groups 1–6, respectively. A non-blinded member of the study team (YS) was responsible for controlling the flow rate during the procedure, while the anesthesiologists (WZ, XY, and JW), pulmonologists, and patients were all blinded.

Study protocol

Demographic information (age, sex, weight, past medical history, and concomitant medication) was collected in addition to physical characteristics (mouth opening, thyromental distance, and modified Mallampati score) and data from the STOP-Bang questionnaire [snoring, tiredness, observed apnea, high blood pressure, body mass index (BMI), age, neck circumference, and male sex].

All patients were nebulized for 20 min with 10 mL of 2% lidocaine. During the procedure, three-lead electrocardiography, pulse oximetry, and noninvasive monitoring of blood pressure were conducted. Real-time heart rate, oxygen saturation, and blood pressure were recorded every 5 min throughout the procedure. All patients were instructed to breathe deeply for initial pre-oxygenation with HFNC (AIRVO 2; Fisher & Paykel Healthcare Corporation Limited, Auckland, New Zealand) at a flow rate of 10 L/min at 100% oxygen for 1 min. Sufentanil was administered as a single-push injection. Propofol was titrated slowly to achieve sedation, with an initial bolus dose of 20 mg followed by additional doses of 10–20 mg as clinically indicated throughout the procedure with an interval of ⩾20 s between each dose.¹³

Sedation was assessed using the Observer Assessment of Alertness/Sedation (OAA/S) scale. The patients were administered the allocated flow rate once the OAA/S score decreased to <4. Bronchoscopy was performed when the OAA/S score reached <2 and 3 mL of 2% lidocaine was sprayed locally over the vocal cords and trachea. An OAA/S score of <2 was maintained throughout the procedure. Additional propofol was administered at 10–20 mg during the procedure if the patient exhibited premature arousal, agitation, persistent cough, or oppositional behavior to manipulation.

After the procedure, stable patients were transferred to the post-anesthesia care unit (PACU). All patients received oxygen at 3 L/min via a nasal cannula in the PACU. After at least 30 min of observation in the PACU and evaluation by the anesthesia team, the patients were allowed to leave the clinic.

Outcomes and airway interventions

The primary outcome of this study was the incidence of desaturation (SpO₂ < 90%)^14–16 and the secondary outcome was airway intervention required to rectify desaturation.

A jaw thrust maneuver was administered if SpO₂ dropped below 95%. If SpO₂ dropped below 90%, the flow rate was increased to 60 L/min in addition to the jaw thrust maneuver. If severe desaturation (SpO₂ <75% for any duration or 75% ⩽SpO₂ <90% lasting >60 s) occurred,^14–16 bag-mask ventilation was administered. Endotracheal intubation was performed if SpO₂ worsened after bag-mask ventilation.

Statistical analysis

A pilot study was conducted to determine the sample size, which was calculated with the Cochran–Armitage trend test using PASS^® software (version 15.0; NCSS, LLC, Kaysville, UT, USA). The preliminary data showed that 30%, 15%, 10%, 10%, 5%, and 5% of patient groups 1–6, respectively, experienced hypoxemia. The results showed that a sample size of 36 subjects per group would provide 90% power with an alpha error of 0.05 to detect a linear trend among groups in the proportion of subjects with hypoxemia using a two-sided Z-test with continuity correction. To compensate for possible dropouts, the sample size was increased to 40 subjects per group.

Analyses were performed using IBM SPSS Statistics for Windows version 26.0 (IBM Corporation, Armonk, NY, USA) and Prism software version 8.0 (GraphPad Software, Inc., San Diego, CA, USA). A probability (p) value <0.05 was considered statistically significant. Categorical data were analyzed with the Cochran–Armitage χ² test for trend or χ² test and are presented as numbers and percentages. Continuous data were tested for normality using the Kolmogorov–Smirnov method. Normally distributed data were analyzed using one-way analysis of variance with trend analysis and are presented as the mean ± standard deviation. Non-normally distributed data were analyzed using the Kruskal–Wallis test and are presented as the median and interquartile range. The EF₉₅ values of HFNC to prevent hypoxemia were determined by probit regression.

Results

Of 343 patients assessed for eligibility from April 2022 to August 2022, only 240 met the inclusion criteria and were included for analysis (Figure 1). There were no significant differences in the general characteristics of the patients among the six groups (Table 1).

Figure 1.

CONSORT flowchart of patient recruitment.

Table 1.

Basic characteristics of patients between different groups during bronchoscopy.

Characteristics	Group 1 (n = 40)	Group 2 (n = 40)	Group 3 (n = 40)	Group 4 (n = 40)	Group 5 (n = 40)	Group 6 (n = 40)	p Value
Age (years)	60.15 ± 7.82	58.63 ± 6.50	59.80 ± 6.01	60.62 ± 8.95	59.48 ± 8.43	60.08 ± 9.30	0.914
Sex, male	27	29	25	28	29	27	0.903
Weight (kg)	65.13 ± 11.15	67.10 ± 10.29	63.03 ± 9.70	65.25 ± 10.28	62.83 ± 11.57	64.51 ± 10.64	0.488
BMI (kg/m)	23.75 ± 3.14	24.39 ± 2.94	23.42 ± 3.18	24.25 ± 3.54	23.34 ± 3.46	23.42 ± 3.10	0.554
ASA physical status^a
1/2	40	39	39	40	39	38	0.234
3	0	1	1	0	1	2
Comorbidities
Hypertension, n (%)	12 (30%)	13 (32.5%)	12 (30%)	7 (17.5%)	15 (37.5%)	14 (35%)	0.651
Asthma, n (%)	1 (2.5%)	1 (2.5%)	2 (5%)	1 (2.5%)	0	0	0.234
COPD, n (%)	1 (2.5%)	0	1 (2.5%)	3 (7.5%)	3 (7.5%)	0	0.528
Obstructive sleep apnea, n (%)	0	0	0	0	0	0	NS
Lung cancer, n (%)	12 (30%)	12 (30%)	6 (15%)	8 (20%)	10 (25%)	10 (25%)	0.537
STOP-Bang score ⩾5, n (%)	3 (7.5%)	3 (7.5%)	2 (5%)	2 (5%)	4 (10%)	1 (2.5%)	0.585
Snoring	18 (45%)	18 (45%)	20 (50%)	17 (42.5%)	15 (37.5%)	18 (45%)	0.648
Modified Mallampati score^b, I/II/III/IV	25/11/4/0	27/9/3/1	30/7/2/1	26/12/2/0	20/20/0/0/	25/14/1/0	0.574
Mouth opening^c, 1/2/3, n	0/0/40	0/0/40	0/0/40	2/0/38	0/0/40	0/0/40	0.074
Thyromental distance^d, I/II/III	34/5/1	37/3/0	36/3/1	34/6/0/	34/6/0	36/4/0	0.841

Data are presented as number (%) or mean ± standard deviation.

ASA physical status: (1) normal healthy patient, (2) patient with mild systemic disease that does not limit physical activity, and (3) patient with severe systemic disease.

Modified Mallampati score: Class I: the entire palatal arch is visible down to the bases of the pillars. Class II: the upper part of the faucial pillars and most of the uvula are visible. Class III: only the soft and hard palates are visible, Class IV: only the hard palate is visible.

Mouth opening: 1, one finger; 2, two fingers; 3, three fingers.

Thyromental distance: I, >6.5 cm; II, 6–6.5 cm; III, <6 cm.

ASA, American Society of Anaesthesiologists; BMI, body mass index; COPD, chronic obstructive pulmonary disease; NS, not significant; STOP-Bang, snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and male sex.

As shown in Table 2, the incidence of desaturation progressively decreased as the oxygen flow rate was increased (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% in groups 1–6, respectively, p < 0.0001). A flow–response curve is provided in Figure 2. After probit regression, the EF₉₀ and EF₉₅ values were 34.40 [95% confidence interval (CI) = 28.96–42.92] and 43.20 (95% CI = 36.43–55.96) L/min, respectively. The requirement for airway intervention, such as the jaw thrust maneuver and increased oxygen flow, decreased as the oxygen flow rate was increased (Table 2 and Figure 3).

Table 2.

Primary outcome and airway interventions during bronchoscopy.

	Group 1 (n = 40)	Group 2 (n = 40)	Group 3 (n = 40)	Group 4 (n = 40)	Group 5 (n = 40)	Group 6 (n = 40)	p Value
Primary outcome							<0.0001
Normal, n (%)	23 (57.5%)	33 (82.5%)	34 (85%)	36 (90.0%)	39 (97.5%)	40 (100.0%)
Desaturation, n (%)	17 (42.5%)	7 (17.5%)	6 (15%)	4 (10.0%)	1 (2.5%)	0
Lowest SpO₂ (%)	93 (84–100)	99 (91–100)	99 (93–100)	99 (96–100)	99 (96–100)	99 (98–100)	0.011
Airway interventions
Jaw thrust maneuver, n (%)	21 (52.5%)	15 (37.5%)	9 (22.5%)	6 (15%)	3 (7.5%)	2 (5%)	<0.0001
Increase the flow of oxygen, n (%)	17 (42.5%)	6 (15%)	4 (10%)	2 (5%)	1 (2.5%)	0	<0.0001
Mask ventilation, n (%)	2 (5%)	2 (5%)	1 (2.5%)	1 (2.5%)	0	0	0.0528
Intubation, n (%)	0	0	0	0	0	0	NS

Data were presented as numbers (%) or medians (interquartile ranges).

NS, not significant; SpO₂, oxygen saturation.

Figure 2.

Flow–response curve of the incidence of desaturation calculated by probit regression.

Figure 3.

Requirement of airway interventions between different groups.

There were no significant differences in the doses of propofol and sufentanil or the duration of the bronchoscopy among the six groups (Table 3). Hemodynamics before bronchoscopy, after bronchoscopy, and in the PACU are shown in Table 3.

Table 3.

Procedural sedation medications, duration, and hemodynamics during bronchoscopy.

	Group 1(n = 40)	Group 2(n = 40)	Group 3(n = 40)	Group 4(n = 40)	Group 5(n = 40)	Group 6(n = 40)	p Value
Propofol initial (mg)	120.50 ± 21.60	124.75 ± 18.11	119.19 ± 15.52	124.50 ± 16.94	117.30 ± 16.77	122.50 ± 18.50	0.389
Propofol initial (mg kg⁻¹)	1.87 ± 0.26	1.87 ± 0.20	1.86 ± 0.21	1.93 ± 0.23	1.85 ± 0.19	1.92 ± 0.24	0.575
Propofol total (mg)	151.50 ± 41.23	148.75 ± 37.29	144.25 ± 30.37	153.75 ± 29.93	138.42 ± 31.58	139.71 ± 24.91	0.232
Propofol total (mg kg⁻¹)	2.32 ± 0.40	2.21 ± 0.36	2.32 ± 0.46	2.36 ± 0.35	2.20 ± 0.36	2.16 ± 0.30	0.109
Sufentanil dose (µg kg⁻¹)	0.07 ± 0.01	0.07 ± 0.01	0.07 ± 0.01	0.07 ± 0.01	0.07 ± 0.01	0.07 ± 0.01	0.167
Duration of bronchoscopy(s)^a	355.00 (245.00–479.50)	272.50 (180.00–381.75)	313.50 (237.50–479.25)	393.50 (240.00–480.00)	296.50 (209.75–400.75)	285.00 (221.25–367.50)	0.065
Procedures
Inspection only, no. (%)	34 (85%)	35 (87.5%)	36 (90%)	33 (82.5%)	31 (77.5%)	32 (80%)	0.668
Biopsy, no. (%)	6 (15%)	5 (12.5%)	4 (10%)	6 (15%)	9 (22.5%)	8 (20%)
BAL, no. (%)	0	0	0	1 (2.5%)	0	0
Before bronchoscopy
SpO₂ (%)	99 (98–100)	99 (98–100)	99 (98–99.75)	99 (97.25–100)	99 (99–100)	99 (97–100)	0.568
Mean BP (mmHg)	107.73 ± 15.09	104.64 ± 12.02	116.33 ± 57.30	102.11 ± 11.91	102.39 ± 13.15	104.01 ± 13.05	0.144

Heart rate (bpm)	79.60 ± 13.93	74.43 ± 12.16	79.10 ± 14.88	80.90 ± 15.53	75.03 ± 12.32	76.83 ± 12.56	0.196
After bronchoscopy
Mean BP (mmHg)	91.51 ± 15.61	93.94 ± 15.94	95.84 ± 21.96	86.84 ± 11.08	90.58 ± 12.87	94.61 ± 17.14	0.146
Heart rate (bpm)	86.90 ± 11.05	82.43 ± 13.20	85.30 ± 12.66	83.48 ± 12.76	78.25 ± 13.87	84.90 ± 10.46	0.040
In PACU
Mean BP (mmHg)	88.53 ± 13.03	87.21 ± 10.53	91.46 ± 14.24	83.44 ± 10.43	86.68 ± 12.32	93.35 ± 14.04	0.008
Heart rate (bpm)	79.48 ± 9.94	77.65 ± 11.55	80.53 ± 12.44	77.88 ± 12.14	71.85 ± 12.65	78.10 ± 9.67	0.019

Data are presented as means ± standard deviations, medians (interquartile ranges), or numbers (%).

The duration of bronchoscopy was the duration between the insertion of the bronchoscope to the removal of the bronchoscope.

BAL, bronchoalveolar lavage; BP, blood pressure; PACU, post-anesthesia care unit.

Discussion

The results of this study demonstrated that the incidence of desaturation and requirements for airway maneuvers decreased as the oxygen flow rate increased. An oxygen flow rate of 50–60 L/min is recommended to prevent desaturation during sedation for bronchoscopy.

Beyond oxygenation, HFNC washes out CO₂ from anatomical dead spaces¹⁷ and improves gas exchange,^18,19 generates a positive end-expiratory pressure of 3–7 cmH₂O, prevents alveolar collapse, avoids loss of end-expiratory lung volume,²⁰ and prevents atelectasis. In addition, HFNC can reduce upper respiratory resistance and work. In this study, titrated propofol was used to maintain sedation during bronchoscopy, which resulted in upper airway obstruction. Although effective in relieving an obstruction, the jaw thrust maneuver was not effective for patients with respiratory depression. Hence, HFNC therapy should be selected in such cases to provide apneic oxygenation and reduce the incidence of desaturation during bronchoscopy.

To the best of our knowledge, this is the first report of the optimal oxygen flow rate for HFNC to prevent desaturation during bronchoscopy. Although several studies have reported that HFNC can reduce the incidence of desaturation during bronchoscopy,^2,7–11 none reported an ideal oxygen flow rate.

A low oxygen flow rate generates a lower FiO₂, which is associated with the occurrence of desaturation. Several studies have demonstrated that increasing the oxygen flow rate during HFNC can increase the FiO₂ and airway pressure.^21,22 To ensure stable FiO₂ delivery to the alveoli, the oxygen flow rate must exceed the inspiratory flow rate (~30 L/min) to minimize room air entrainment.^21,23 There was a near linear response between mean upper airway pressure and increased delivered gas flow rates. Notably, at 50 L/min, the mean upper airway pressure reached 7.1 cmH₂O.²⁴ Besides, a low oxygen flow rate cannot generate sufficient positive end-expiratory pressure to prevent airway collapse and is associated with atelectasis, more anatomic dead space, and a lower tidal volume.^2,25,26

A higher oxygen flow rate can yield a higher FiO₂ and airway pressure to prevent atelectasis and improve oxygenation. However, a flow rate of 60 L/min is uncomfortable for conscious patients and could cause nasal dryness, epistaxis,²⁷ sore throat, headache, and even stomach distension with prolonged use. Therefore, this study aimed to determine the optimal oxygen flow rate for bronchoscopy. The EF₉₅ value for HFNC to prevent desaturation during sedation for bronchoscopy was 43.20 L/min. The physiological benefits of a high flow rate were confirmed. Thus, an oxygen flow rate of 50–60 L/min is recommended. However, the patient cohort included only a very small proportion of obese patients (BMI >30 kg/m²) and none diagnosed with obstructive sleep apnea. HFNC may be more appropriate for patients at high risk for desaturation in consideration of the cost-effectiveness and short duration of bronchoscopic procedures.

Some limitations of this study should be addressed. First, an inspiratory oxygen fraction of 100% was selected, which would blind the physiological effects of lung derecruitment prevention of HFNC. At FiO₂ of 0.36–0.40, HFNC is not superior to the standard nasal cannula for the prevention of desaturation in morbidly obese patients undergoing colonoscopy. However, further studies are needed to determine the optimal flow rate for HFNC with lower FiO₂ to effectively prevent desaturation during bronchoscopy. Second, most of the patients only had inspection during bronchoscopy and the duration of the procedure was relatively short. Thus, the efficacy of HFNC during longer procedures remains unclear. Third, arterial blood gas was not analyzed in this study. Thus, it was not possible to compare pH, PaO₂, and PaCO₂ among the six groups. Fourth, a pulmonary function test was not performed prior to the study, thus whether pulmonary function affects the incidence of hypoxemia remains unknown. Finally, although the anesthesiologist was blinded to patient allocation, an oxygen flow at 60 L/min might produce a louder sound than at 10 L/min, which may have introduced bias.

Conclusion

The incidence of desaturation during sedation for bronchoscopy decreased as the oxygen flow rate was increased, which also reduced the requirement for airway intervention, such as the jaw thrust maneuver and increased oxygen flow. A flow rate of 50–60 L/min is recommended during sedation for bronchoscopy.

Supplemental Material

sj-docx-1-tar-10.1177_17534666241246637 – Supplemental material for Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study

Supplemental material, sj-docx-1-tar-10.1177_17534666241246637 for Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study by Wen Zhang, Xiaohong Yuan, Yajian Shen, Jiangling Wang, Kangjie Xie and Xinzhong Chen in Therapeutic Advances in Respiratory Disease

Footnotes

Acknowledgements

The authors thank the staff of the Department of Anesthesiology and the Department of Endoscopy, Zhejiang Cancer Hospital, China, for their help and cooperation in this study.

Declarations

ORCID iD

Wen Zhang

Supplemental material

Supplemental material for this article is available online.

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