An Investigation of Optimal Anesthesia for Morbidly Obese Patients Undergoing Bariatric Surgery: A Randomized Controlled Trial
Phase: PHASE4
Conditions: Obesity, Anesthesia
Sponsor: Taipei Medical University Shuang Ho Hospital

TMU-JIRB Form059/20180201 
Protocol Number: N202002076 
Version：4 
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TMU-JIRB Form059/20180201 
 
 
 
TMU-Joint Institutional Review Board 
 
Protocol Title: An Investigation of Optimal Anesthesia for 
Morbidly Obese Patients Undergoing Bariatric Surgery:  
A randomized controlled trial 
 
Protocol Number: N202002076 
Version/Date：4 / 2020.04.08 
 

 
 
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Page i 
List of abbreviations: 
BIS: bispectral index 
BMI: body mass index  
CPAP: continuous positive airway pressure 
ERAS: Enhanced Recovery After Surgery 
EEG: electroencephalography 
FiO2: fraction of inspired oxygen 
HFNC: high-flow nasal cannula 
IRB: Institutional Review Board 
LSG: laparoscopic sleeve gastrectomy 
NRS: Numeric rating scale 
OSA: obstructive sleep apnea 
PEEP: positive end-expiratory pressure 
PaO2: arterial partial pressure of oxygen 
SpO2: peripheral oxygen saturation 

 
 
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Introduction 
Obese patients have a higher risk of anesthesia compared to the non-obese, including difficult 
intubation, rapid desaturation, difficult vascular access, and delayed recovery from anesthesia. 
This study aims to investigate the optimal anesthesia strategy for morbidly obese patients 
undergoing bariatric surgery in airway management, preoxygenation, arterial cannulation, and 
type of volatile anesthetic with M-Entropy guidance. The investigators will conduct a two-year 
clinical trial using permuted block randomization to evaluate multiple outcomes in patients 
undergoing laparoscopic sleeve gastrectomy (LSG) at Shuang Ho Hospital, Taipei Medical 
University. Particularly, the investigators will explore the role of ultrasound, an easily accessible 
modality for anesthesiologists, in examining upper airway anatomy and guiding arterial 
cannulation. The investigators will also assess the effectiveness of high-flow nasal cannula as a 
preoxygenation tool in preventing desaturation.  
The investigators will conduct a clinical trial using permuted block randomization and 
conforming to the CONSORT Statement to investigate multiple clinical outcomes in obese 
patients undergoing LSG at Shuang Ho Hospital, Taipei Medical University, New Taipei City, 
Taiwan. Three randomizations will be conducted, including radial artery catheterization using 
ultrasound guidance or blind palpitation, preoxygenation using high-flow nasal cannula (HFNC) 
or conventional facemask, and volatile anesthesia with desflurane or sevoflurane with or without 
M-Entropy guidance.  
 
Background 
Obesity is one of the major epidemics of the twenty-first century.1 The worldwide prevalence 
of overweight and obesity has doubled since 1980, and almost a third of the global population is 
now classified as overweight or obese.1 In Taiwan, the prevalence of mild-to-moderate obesity 
(body mass index (BMI) range, 27 – 35 kg/m2) has increased nearly twofold from 1993 to 2014 
and over threefold for morbid obesity (BMI range, > 35 kg/m2).2 Nowadays, morbid obesity has 
affected more than 5 million people on the island.2 In addition to cardiovascular and metabolic 
disorders, obese patients have an increased risk for various types of diseases, including liver and 
gallbladder diseases, gastroenterological cancers, endometrial cancers, and osteoarthritis, which 
also increases the number of obese patients for surgical procedures and anesthesia.3,4  
Bariatric surgery is recommended at a BMI > 40 kg/m2 or BMI > 30 kg/m2 when obesity-
related comorbidities (e.g. hypertension, diabetes, and dyslipidemia) are expected to improve 
with weight loss after surgical intervention.5 In clinical trials, long-term mortality risk is 
significantly lowered in surgically treated groups compared to medically managed patients, 
particularly in deaths from diabetes, heart disease, and cancer.6 Besides, compared to medication 
therapy alone, bariatric surgery plus intensive medical therapy is more effective in decreasing 
hyperglycemia among diabetic and obese patients.7 Due to the health benefit of bariatric surgery 
and the advance in laparoscopic techniques, bariatric surgery has had almost tenfold growth 
worldwide in the past two decades, increasing from 40,000 bariatric procedures in 1997 to nearly 
400,000 in 2016.8,9  
 

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Figure 1: Obese Patient as an Anesthesia Challenge  
 
Obesity Patient as a Challenge in Anesthetic Management 
Obese patients represent an evident challenge in anesthetic management due to their higher 
risks of difficult intubation and ventilation, impaired pulmonary functions, difficult vascular 
access, and delayed recovery from anesthesia.10 (Figure 1) Study has showed the risk of difficult 
tracheal intubation is higher in obese patients with a three times higher risk compared to the 
nonobese.11 Besides, obese patients have multiple respiratory abnormalities, including reduced 
vital capacity, inspiratory capacity, expiratory reserve volume, functional residual capacity, and 
lower lung compliance.12 Obesity is also the greatest risk factor for obstructive sleep apnea 
(OSA)13, which predisposes obese patients to higher risks of difficult ventilation and rapid 
oxygen desaturation during induction of general anesthesia.14 Study has showed the nonhypoxic 
apnea time of peripheral oxygen saturation (SpO2) decreasing to 90% after facemask 
preoxygenation is less than 3 minutes in obese patients compared to 6 minutes in patients having 
a normal BMI.15 In addition to respiratory complications in anesthesia, morbidly obese patients 
are prone to have a difficult arterial puncture because of their excessive subcutaneous tissue and 
higher risk of vascular complication after arterial puncture.16  
Morbidly obese patients are susceptible to low emergence from anesthesia due to delayed 
release of volatile agent from excessive adipose tissue.17 They have an increased risk of lingering 
respiratory depression effects of anesthetic drugs. However, the current Enhanced Recovery 
After Surgery (ERAS) protocol does not recommend specific anesthetic agents for bariatric 
surgery due to mixed results of available studies.18 Some studies showed desflurane has 

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consistent and rapid recovery profile compared to sevoflurane and propofol.19-21 Conversely, 
other studies reported that the difference in immediate recovery between desflurane and 
sevoflurane is clinically non-significant.22 Moreover, although electroencephalography (EEG)-
based monitoring of anesthesia depth is widely used and effective in maintaining the optimal 
range of anesthesia depth in total intravenous anesthesia, there is spare evidence regarding the 
role of EEG-based monitoring in volatile general anesthesia for obese patients.23  
 
Difficult Laryngoscopy Intubation 
Obese patients have a high risk of difficult laryngoscopy due to their short, thick neck, large 
tongue, and significant redundant pharyngeal soft tissue.11 However, till now there is no 
established predictor for difficult intubation in obese patients. One study reported a correlation 
between oropharyngeal Mallampati score and BMI as predictors of difficult laryngoscopy.24 
However, another study showed BMI was not associated with difficult intubation in obese 
patients.25 Although Mallampati score may predict potential intubation difficulties, intubation by 
direct laryngoscopy was successful in 99% patients.25 Other investigators demonstrated that 
Mallampati score had low specificity (62%) and low positive predictive values (29%) for 
difficult intubation.26 Interestingly, an abundance of pretracheal soft tissue measured 
ultrasonically and neck circumferences may predict difficult laryngoscopy.27,28  
 
Difficult Arterial Cannulation 
The common cardiovascular comorbidities present in obese patients frequently necessitate 
continuous arterial pressure monitoring in surgery.29 However, it is more difficult for clinicians 
to perform an arterial catheterization in obese patients due to their excessive subcutaneous tissue. 
Besides, obese patients tend to have a higher risk of vascular complication after arterial 
catheterizations.16 Therefore, strategy to increase the success rate of arterial cannulation and 
reduce potential vascular complications becomes an important issue for obese surgical patients.  
Ultrasound guidance has emerged as a useful tool for central vein catheterization with the 
advantages of higher success rate, patient safety, and cost-effectiveness.30 For radial artery 
catheterization, ultrasound guidance is also an effective and safe technique, especially in 
pediatric population.31-33 For resident physicians, ultrasound achieved significantly faster 
placement of the arterial lines, fewer attempts, and fewer catheters used.34 However, the 
effectiveness and safety of ultrasound-guided arterial catheterization have not been investigated 
in obese patients. Besides, ultrasound offers the most accurate measurement for thickness of 
subcutaneous adipose tissue layers.35 The distance from skin surface to commonly-catheterized 
arteries (e.g. radial artery, brachial artery, and femoral artery) has not been explored in obese 
patients. 
 
Preoxygenation Strategy to Prevent Desaturation 
Multiple strategies to prolong nonhypoxic apnea time in the induction of anesthesia have been 
investigated, including use of CPAP during preoxygenation, facemask application of positive 
end-expiratory pressure (PEEP), and mechanical ventilation following induction of anesthesia.36-
38 Application of 10 cm H2O CPAP during preoxygenation achieved a higher arterial partial 
pressure of oxygen (PaO2) after intubation and reduced the amount of atelectasis.36 Similarly, use 
of CPAP 10 cm H2O with post-induction mechanically ventilation with PEEP 10 cm H2O for 5 
min prolonged the nonhypoxic apnea time from 127 seconds to 188 seconds.37 However, 

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preoxygenation of 7.5 cm H2O CPAP for 3 minutes did not increase the nonhypoxic apnea time 
to an SpO2 of 90% for obese patients.38 Preoxygenation using 25 degrees head-up position 
increased the nonhypoxic apnea time to an SpO2 of 92% and also achieved 23% higher oxygen 
tensions.39  
Recently, HFNC is widely used in patients receiving sedative procedures. HFNC is able to 
deliver up to 60 L/min gas flow with a fraction of inspired oxygen (FiO2) 100%.40 It may also 
produce a low level of positive airway pressure and improve patient comfort compared to 
facemask ventilation.41 The effectiveness of HFNC in preventing arterial oxygen desaturation of 
obese patients has been compared with standard nasal cannula or facemask ventilation in various 
settings.42-45 In propofol sedation for colonoscopy, HFNC was not better than standard nasal 
cannula for prevention of arterial oxygen desaturation.42 In induction of general anesthesia, 
HFNC prolonged the nonhypoxic apnea time by 76 seconds (40%) and enhanced minimum SpO2 
in morbidly obese patients.43 Another study recently showed the use of HFNC at the time of 
extubation reduced postoperative hypoxemia in obese patients after bariatric surgery compared 
to receive conventional oxygen therapy.44 However, a randomized trial reported that 
preoxygenation with HFNC offered lower end-tidal oxygen concentration  after intubation and a 
higher risk of desaturation < 95% in obese patients.45 The available evidence is conflicting 
regarding the effectiveness of HFNC for prevention of perioperative desaturation, and the most 
optimal strategy of preoxygenation in general anesthesia has not been clearly clarified for obese 
patients. 
 
Delayed Recovery from Anesthesia 
Recovery from anesthesia might be compromised in obese patients due to delayed release of 
volatile anesthetics from excessive fat tissue.17 However, evidence regarding optimal anesthesia 
strategy to enhance obese patients’ recovery is still insufficient and conflicting.18 Randomized 
trial has showed that anesthetic maintenance using desflurane achieves more rapid postoperative 
immediate and intermediate recoveries than propofol or isoflurane anesthesia.19 Similarly, 
another study reported obese patients receiving bispectral index(BIS)-guided desflurane 
anesthesia had faster immediate recovery, eye opening, extubation, airway maintenance, and 
orientation compared to sevoflurane anesthesia.20 However, other investigators claimed that the 
differences in immediate recovery between desflurane and sevoflurane are not clinically 
significant.22,46  
Meta-analysis has showed that BIS-guided anesthesia may enhance early recovery times in 
patients undergoing surgery under general anesthesia compared to clinical signs.47 However, few 
studies have investigated whether anesthesia with EEG-based monitoring of anesthesia depth 
improves the postoperative recovery in obese patients. Ibraheim and colleagues reported that 
patients receiving BIS-guided sevoflurane anesthesia had significantly faster awakening and 
shorter extubation time, and lower sevoflurane consumption and cost compared to the control 
group.48 However, this study had a small patient sample and did not evaluate other volatile 
anesthetics, such as desflurane anesthesia.48  
Eligible Criteria 
Adult obese patients (BMI ≥ 30 kg/m2) undergoing LSG at Shuang Ho Hospital, Taipei 
Medical University will be included.  Exclusion criteria will be severe cardiopulmonary disease, 
psychiatric disorder, history of head and neck surgery or radiation therapy, cervical spine injury, 

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renal insufficiency (estimated creatinine clearance < 60 ml/min), SpO2 < 90% in room air, 
hemodynamic instability, preexisting arterial catheterization during the same visit within 7 days, 
and patient refusal. 
 
 
Objectives of Study 
The main objective of this study is to investigate the optimal anesthesia strategy in the airway 
evaluation, preoxygenation, arterial cannulation, and choice of volatile anesthetics in obese 
patients undergoing bariatric surgery, as the followed: 
1. To explore potential predictors for difficult intubation using ultrasound evaluation of upper 
airway anatomy and tongue base 
2. To evaluate the safety and effectiveness of ultrasound-guided radial artery catheterization 
compared to traditional blind-palpation method 
3. To compare the effectiveness of high-flow nasal cannula and facemask in the preoxygenation 
of general anesthesia 
4. To compare the effect of different volatile anesthetics and M-Entropy guidance on the 
postoperative recovery in obese patients. 
 
Study Protocol 
The investigators will conduct a clinical trial using permuted block randomization and 
conforming to the CONSORT Statement49,50 to investigate multiple clinical outcomes in obese 
patients undergoing LSG at Shuang Ho Hospital, Taipei Medical University, New Taipei City, 
Taiwan. Three randomizations will be conducted, including radial artery catheterization using 
ultrasound guidance or blind palpitation, preoxygenation using HFNC or conventional facemask, 
and volatile anesthesia with desflurane or sevoflurane with or without M-Entropy guidance. A 
computer-generated list of randomizations (Research Randomizer, www.randomizer.org) will be 
used for these group allocations. 
The flow diagram for research conduction is shown in Figure 2. Before surgery, every 
participant will undergo echocardiography to rule out severe cardiopulmonary disease (LVEF < 
40% or moderate-to-severe pulmonary hypertension or confirmed diagnosis of coronary artery 
disease) 
 
Substudy 1. Exploring potential risk factors of difficult intubation using ultrasound: A 
prospective single-blind cohort study 
Before surgery, all enrolled patients will be examined for appearance features regarding 
difficult airway, including interincisor distance (< 3 cm or not)51, mentohyoid distance, 
thyromental distance (< 6.5 cm or not)52, neck movement (< 80 degrees or not)53, neck 
circumference measured at the thyroid cartilage (> 43 cm or not)28, modified Mallampati score54, 
upper lip bite test55, and mandibular prognathism test56. Besides, ultrasound will be used to 
assess upper airway anatomy, including pretracheal soft tissue depth27 and height and width of 
tongue base57. Regarding pretracheal soft tissue depth, the distance from the skin to the anterior 
aspect of the trachea will be measured at three levels: vocal cords, thyroid isthmus, and 
suprasternal notch.27 The amount of soft tissue at each zone is calculated by averaging the 
amounts of soft tissue in millimeters obtained in the central axis of the neck and 15 millimeters 
to the left and right of the central axis.  

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Figure 2: Flow diagram for research conduction 

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Moreover, the increased tongue volume and deposition of fat at the base of tongue in obese 
people has been shown to be highly associated with risk of obstructive sleep apnea.58 To measure 
the anatomy of tongue base, with the patient in a seated position, the convex transducer in the 
frequencies 1.5 to 5.0 MHz (GE C1-5-RS, GE Healthcare, Chicago, IL, USA) of a portable 
ultrasound device (LOGIQTM, GE Healthcare, Chicago, IL, USA) will be introduced to the skin 
of the neck in the submental region coronally, immediately cephalad to the body of the hyoid 
bone, and then in the area between the hyoid bone and the symphysis of the mandible. The 
patients will be instructed to avoid tongue movements, swallowing, or talking.57 Maximal width 
of tongue base, tongue base height, and maximal height of mid-tongue will be measured. 
The same anesthesiologist will perform all ultrasound measurements before surgery. Upon 
arrival at operating room, patients will be initially placed in a ramped position and then moved 
into a reverse Trendelenburg position to achieve a 30-degree incline of the thorax before 
preoxygenation. After induction of anesthesia, another anesthesiologist, blinded to all 
preoperative evaluation, will perform all laryngoscopies in this study. The laryngoscopy 
intubation will be performed using a size‐3 or -4 Macintosh (Rüsch Inc., Duluth, GA, USA) 
blade and a styleted endotracheal tube. The laryngoscopic view will be graded according to 
Cormack and Lehane's classification with external laryngeal pressure applied.59 Laryngoscopy 
views graded as III or IV are defined as difficult. In case of failed direct laryngoscopy despite 
external laryngeal manipulation in the first attempt, video-assisted laryngoscope GlideScope® 
(Verathon Medical, Bothell, WA, USA) will be used as an intubation rescue technique. The 
video-assisted laryngoscope will be kept on standby at the operating room before induction. The 
correct placement of the endotracheal tube will be confirmed by capnography. Primary outcome 
is occurrence of difficult laryngoscopy. Secondary outcomes are first-attempt success rate and 
time to successful intubation.  
 
Substudy 2. Radial artery catheterization using ultrasound guidance or blind palpation: An 
open-label randomized controlled trial 
Before surgery, the investigators will use a portable ultrasound device (LOGIQTM, GE 
Healthcare, Chicago, IL, USA) to measure the skin-to-artery distance of common sites of arterial 
cannulation of all enrolled patients, including radial artery, brachial artery, and dorsalis pedis 
artery. Patients will be randomized in a ratio of 1:1 into ultrasound group (N=40) or palpation 
group (N=40). Radial artery cannulation will be performed using a radial artery catheterization 
kit (Arrow International Inc, Reading, PA, USA). For all patients, the wrist will be extended and 
taped to a board to maintain wrist extension, and the skin near the puncture site will be cleaned 
with chlorhexidine according to standard protocol. Allen test will be used to assess the vascular 
patency of the hand before cannulation of the radial artery.60 All patients will receive local skin 
anesthesia at the anticipated puncture site. All radial artery catheterizations will be performed by 
trained year 1 or 2 anesthesiology residents with similar levels of experience in both blind-
palpation and ultrasound-guided radial arterial catheterization. All residents have performed at 
least 5 blind-palpation and 5 ultrasound-guided radial arterial catheterizations prior to the study.  
In the ultrasound group, a linear vascular probe in the frequencies 5 to 13 MHz (GE 12L-RS, 
GE Healthcare, Chicago, IL, USA) of portable ultrasound device (LOGIQTM, GE Healthcare, 
Chicago, IL, USA) will be applied to the skin to localize the radial artery and a 20-gauge catheter 
will be inserted distal to the transducer and directed according to the ultrasound image. Start time 
is defined as the time when the ultrasound probe is placed on the wrist. In the palpation group, 

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the radial artery will be identified by palpation, and the cannula will be directed by continuous or 
intermittent palpation of arterial pulsation. The attending anesthesiologist will supervise the 
resident and act as the second operator if needed. An attempt is defined as a new penetration of 
the skin with the needle, followed by an unlimited number of subcutaneous needle redirections. 
Clinical judgment by the supervising anesthesiologist is used to determine the time allowed for 
an attempt, number of attempts allowed, and changes to a new site. The attending 
anesthesiologist will take over arterial cannulation if residents perform for more than 3 times or 
> 15 minutes. The start time is defined when the operator’s finger is initially placed on the 
patient’s wrist. The end point for both methods is when the arterial catheter is successful placed. 
Primary outcome is first-attempt success rate, and secondary outcomes comprise time to 
successful arterial catheterization, number of attempts, sites and catheters used. Complications 
related to arterial cannulation will also be recorded, including pain, hematoma formation, and 
arterial vasospasm or occlusion. 
 
Substudy 3. Comparing the effectiveness of preoxygenation between HFNC and facemask: 
A single-blind randomized controlled trial 
 Patients will be randomized in an allocation ratio of 1:1 into HFNC group (N=40) or 
facemask group (N=40). Preoxygenation will be performed according to the randomization 
group for a 5-minute duration. In the HFNC group, preoxygenation will be performed using 
HFNC (Optiflow™, Fisher & Paykel Healthcare, Auckland, NZ), nasal prongs set at 30 L/min 
flow of heated and humidified 100% oxygen. In the facemask group, patients will breath 
spontaneously with an anesthetic facemask and 100% oxygen 15 L/min.61 Gas flow for HFNC or 
facemask can be adjusted depending on patients’ tolerance. After preoxygenation, general 
anesthesia will be induced with propofol 1.5 – 2.0 mg/kg ideal body weight, alfentanil 8 – 10 
μg/kg total body weight, and rocuronium 0.8 – 1.0 mg/kg ideal body weight. Rapid sequence 
intubation will be performed in all patients. During laryngoscopy intubation, HFNC will be left 
in place with the nasal flow escalated to 50 L/min of 100% oxygen in order to achieve apneic 
oxygenation. In the facemask group, the facemask will be removed when apnea occurs. After 
tracheal intubation, correct placement of the endotracheal tube will be confirmed by 
capnography and the nasal prongs of the HFNC group will be removed. If desaturation (SpO2 < 
92%) occurs, patients will be then administered 100% O2, and the recruitment maneuver (peak 
airway pressure 40 cm H2O for 10 seconds) will be applied until SpO2 restores to baseline values. 
Primary outcome is PaO2 after preoxygenation. Secondary outcomes are SpO2 before 
preoxygenation, after preoxygenation, and after intubation, desaturation event (SpO2 < 92%), the 
lowest SpO2 during intubation, PaO2 before preoxygenation, and PaCO2 before and after 
preoxygenation, alveolar-arterial oxygen gradient (A-a gradient)62, and patient comfort levels. 
All the outcomes will be measured by a nursing anesthetist, blinded to group allocation. Arterial 
line will be placed before induction. Arterial blood gas will be measured twice: first, before the 
preoxygenation in room air and, second, just after the 5-minute preoxygenation. Comfort levels 
of the HFNC and standard facemask will be assessed using a 10-point Likert scale, and patients 
will be asked which of the two devices they preferred regarding comfort before referral to ward.  
 
Substudy 4. The effect of type of volatile anesthetics and M-Entropy guidance of anesthesia 
depth on postoperative recovery: A double-blind randomized controlled trial 

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Patients will be randomized by a computer-generated list into one of the four groups, 
desflurane with usual care (N=20), desflurane with M-Entropy guidance (N=20), sevoflurane 
with usual care (N=20), and sevoflurane with M-Entropy guidance (N=20). At the operating 
room, a M-Entropy™ sensor and S/5™ module (GE Healthcare, Helsinki, Finland) will be 
applied to all patients’ forehead before induction of anesthesia according to the manufacturer’s 
recommendations. This will be connected to a M-Entropy Monitor that will be concealed from 
the patients and operators.  
In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the 
Response and State Entropy value between 40 and 60 from the start of anesthesia to the end of 
surgery. In the usual care group, dosage of volatile anesthetics will be titrated according to 
clinical judgment. This will be to maintain arterial pressure within 20% range of the baseline and 
the heart rate within the range 50 to 100 beats/min. In case of signs of inadequate anesthesia (e.g. 
movement, cough and swallowing), anesthetic dose will be increased. M-Entropy monitoring 
will be continued in the usual care group, but the Entropy number and EEG waveform will be 
concealed from the anesthetist in charge. Entropy values, hemodynamic, and expiratory gas data 
will be recorded in 5-min intervals. In all patients, cessation of general anesthesia will be timed 
to facilitate early awakening after wound closure. All patients will be decurarized from 
rocuronium-induced neuromuscular blockade with sugammadex dosed at 2 mg/kg ideal body 
weight + 40%.63 Primary outcome is time to spontaneous eye opening. Secondary outcomes 
include time to tracheal extubation, time to orientation in time and place, and time to leave 
operating room, event of emergence agitation. The Richmond Agitation-Sedation Scale (RASS) 
will be used to evaluate the level of agitation and sedation promptly after extubation.64 For 
patients who are transferred to the intensive care unit for postoperative mechanical ventilation, 
the investigators will record the time to extubation. 
 
Statistical Analysis Plan  
The distributions of baseline patient characteristics and outcome variables will be compared 
between two groups using chi-square tests or Fisher’s exact test for categorical variables and 
either t tests or Wilcoxon rank sum tests for continuous variables, as appropriate. For four-group 
comparisons, either ANOVA tests or Kruskal-Wallis tests will be used for continuous variables, 
as appropriate. A Bonferroni correction to the significance criterion for multiple comparisons is 
applied where appropriate. For time to event data, Kaplan-Meier method and log-rank test will 
be applied for group comparisons. Multivariable logistic regression, simple linear regression, or 
Cox proportional hazards regression analyses will be used to identify potential influential factors 
of outcomes of interest. A two-sided significance level of 0.05 was used to define statistically 
significant difference. All the statistical analyses will be conducted using Statistics Analysis 
System (SAS), Version 9.4 (SAS Institute Inc., Cary, NC, USA). 
According to prior study37, at least 37 patients in each group of HFNC or facemask 
preoxygenation are needed to detect a difference of 30 seconds of nonhypoxic apnea time 
between the HFNC and facemask group, accepting a type I error of 5% and type II error of 20% 
with anticipated nonhypoxic apnea time of mean 188 ± SD 46 seconds in the facemask group.65 
Nevertheless, in order to allocate 20 patients into each group of volatile anesthesia with 
desflurane or sevoflurane with or without M-Entropy guidance, a total of 80 patients will be 
enrolled in this study.  

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There are about 120 patients undergoing LSG at our hospital per year. Considering the patient 
selection criteria and possible patient refusal, a total of 50 patients per year will be enrolled in 
this study. Therefore, it will take about 2 years for patient recruitment. Besides, the investigators 
will select all randomized subjects for analysis. 

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