Conditions: Obstructive Sleep Apnea
Keywords: Recovery time reversal of neuromuscular blockers (NMB) obstructive sleep apnea morbid obesity bariatric surgery
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 120
Healthy volunteers: no

Brief summary:
Sugammadex or neostigmine are given at the end of the surgery to reverse neuro muscular blocking drugs (NMBD). This study will evaluate whether reversal of NMBD with sugammadex is associated with faster recovery than neostigmine resulting in faster discharge from the operating room (OR) in obese patients with OSA undergoing bariatric surgery. Half of the patients in the study will receive sugammadex and the other half of the patients will receive neostigmine.

Detailed description:
Sugammadex and neostigmine are NMBD reversal agents. Neostigmine - an anticholinesterase is given to reverse NMBD; however reversal of NMBD with neostigmine may be associated with residual neuromuscular blockade in up to 64% patients postoperatively in the post anesthesia care unit. Even mild degrees of residual neuromuscular blockade can have serious clinical consequences in the postoperative period. The severity of OSA often worsens after surgery and patients with OSA are at increased risk for early respiratory complications after extubating and in the PACU. Morbid obesity is associated with critical respiratory complications in patients with OSA.

Sugammadex is a newer NMBD reversal agent that rapidly and completely reverses rocuronium. It is a modified gamma cyclodextrin that forms a complex with the neuromuscular blocking agent rocuronium. It reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the neuromuscular junction. It has been shown to more rapidly reverse residual neuromuscular blockade than neostigmine in obese patients without obstructive sleep apnea (OSA).

This study will evaluate whether reversal of NMBD with sugammadex is associated with faster recovery than neostigmine resulting in faster discharge from the operating room (OR) in obese patients with OSA undergoing bariatric surgery. Half of the patients in the study will receive sugammadex and other half of the patients will receive neostigmine

Arms:
arm 1: Interventional Arm will receive sugammadex sodium 2 mg/kg actual body weight, At the end of surgery Sugammadex will be administered when the TOF reveals at least 2 responses arm 2: standard drug Arm will receive neostigmine 2.5 mg and glycopyrrolate 0.4 mg, At the end of surgery neostigmine and glycopyrrolate will be administered when the TOF reveals at least 2 responses

Interventions: intervention 1: Sugammadex Sodium intervention 2: Neostigmine
Intervention descriptions: intervention 1: Sugammadex is a FDA approved newer NMBD reversal agent. But does not use in standard of care in most of institutions This study is designed to compare the impact of reversal of neuromuscular blockade with sugammadex vs. neostigmine on discharge time from the operating room in obese patients with OSA undergoing bariatric surgery intervention 2: neostigmine is a FDA approved NMBD reversal drug, uses as standard care drug in most of the institutions. neostigmine use as active comparator to compare with investigational drug Sugammadex in the study.

Protocol document:
Prot_SAP_000.pdf: 
March 1, 2019 
1 
Title: Impact of Sugammadex vs. Neostigmine Reversal on Post-Operative Recovery 
And Postoperative Complications In Patients With Obstructive Sleep Apnea 
Undergoing Bariatric Surgery: A Double-Blind, Randomized Controlled Trial 
 
 
Principle Investigator:   
Dr. Jean Wong  
Associate Professor, Department of Anesthesia, Toronto Western Hospital, 
University Health Network 
 
Co-Principle Investigator:   
Dr. Frances Chung  
Professor, Department of Anesthesia, Toronto Western Hospital, University 
Health Network 
 
Co-Investigators: 
 
Dr. David Wong  
Professor, Department of Anesthesia, Toronto Western Hospital, University 
Health Network 
 
Dr. Ahtsham Niazi 
Associate Professor, Department of Anesthesia, Toronto Western Hospital, 
University Health Network 
 
Dr. Anahi Perlas 
Associate Professor, Department of Anesthesia, Toronto Western Hospital, 
University Health Network 
 
Dr. Timothy Jackson    Assistant Professor, Department of Bariatric Surgery, Toronto Western Hospital, 
University Health Network   
 
 
 Dr. Gincy Lukachan Fellow, Department of Anesthesia, Toronto Western Hospital, University Health 
Network 
 
Dr. Wesley Rajajeelan Fellow, Department of Anesthesia, Toronto Western Hospital, University Health 
Network 
 
Dr.Yuvaraj Kotteeswaran Fellow, Department of Anesthesia, Toronto Western Hospital, University 
                                            Health Network            
 
 
Objectives 
 
Primary Objective: 
To compare the impact of reversal of neuromuscular blockade with sugammadex vs. neostigmine on 
discharge time from the operating room in obese patients with OSA undergoing bariatric surgery. 
 
Secondary Objectives: 
To compare the effect of reversal of neuromuscular blockade with sugammadex vs. neostigmine on 
time: the patient open eyes to command, extubation, moves independently from the OR table to the 
bed, TOF at extubation, and the readiness for discharge from PACU of obese patients with OSA 
undergoing bariatric surgery. 
 
Exploratory Objectives: 
To compare the impact effect of reversal of neuromuscular blockade with sugammadex vs. 
neostigmine on perioperative complications in obese patients with OSA undergoing bariatric surgery. 
 
2.1.1 Hypotheses  


March 1, 2019 
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1. Reversal of NMBD with sugammadex is associated with faster recovery than neostigmine resulting in 
faster discharge from the operating room (OR) in obese patients with OSA undergoing bariatric 
surgery. 
2. Reversal of NMBD with sugammadex is associated with faster time for the patient to: open eyes to 
command, extubation, move independently from the OR table to the bed, higher TOF at extubation, 
and the readiness for discharge from PACU than neostigmine in obese patients with OSA undergoing 
bariatric surgery. 
 
 
Neuromuscular blocking drugs (NMBD) are administered intra-operatively to facilitate intubation and to 
achieve muscle relaxation for surgical procedures such as laparoscopic bariatric surgery. Traditionally, at the 
end of surgery, neostigmine - an anticholinesterase is given to reverse NMBD; however reversal of NMBD 
with neostigmine may be associated with residual neuromuscular blockade in up to 64% patients in the post-
anesthesia care unit (PACU).1,2 Even mild degrees of residual neuromuscular blockade can have serious 
clinical consequences in the postoperative period.3,4 
  
 
Obstructive sleep apnea (OSA) is a common form of sleep disordered breathing. The prevalence of OSA is 
estimated to be 71-86% in patients undergoing bariatric surgery.5,6 The severity of OSA often worsens after 
surgery7 and patients with OSA are at increased risk for early respiratory complications after extubation and 
in the PACU.8 Morbid obesity is associated with critical respiratory complications in patients with OSA.7 The 
increase in early respiratory complications including hypoxemia,10 emergent re-intubation, and mechanical or 
non-invasive ventilation11,12 in patients with OSA may be due to residual neuromuscular blockade. Morbidly 
obese patients with OSA have anatomical risk factors that increase vulnerability to airway collapse and 
obstruction of the upper airway placing them at greater risk for postoperative complications from residual 
neuromuscular blockade, opioids, and anesthetics. 
 
Our systematic review showed that patients with OSA who received NMBD were at higher risk for residual 
neuromuscular blockade, respiratory failure, and hypoxemia than patients without OSA13-15 (manuscript under 
review). The previous studies did not control the amount of opioids administered during the surgery, making it 
difficult to assess the differential effect of opioids vs. residual neuromuscular blockade on early postoperative 
respiratory complications. Minimizing the amount of opioids, using short-acting anesthetics, and complete 
reversal of NMBD in these vulnerable patients may reduce risks for early respiratory complications. Providing 
a moderate level of muscle relaxation as defined by a TOF count of 1-2 during laparoscopic bariatric surgery 
optimizes surgical conditions. However, in obese patients with OSA, anesthesiologists often give minimal 
NMBD in the latter half of the surgical procedure due to concerns about the inability of neostigmine to 
completely reverse NMBD leading to subsequent respiratory complications after extubation. This practice 
may reduce the risk for postoperative respiratory complications but can lead to sub-optimal surgical 
conditions. The usual standard of care is to administer neostigmine to reverse residual neuromuscular 
relaxant at the end of surgery. For bariatric surgery, in order to minimize risks for postoperative 
complications, short acting anesthetics and minimal opioids are administered. 
 
Sugammadex is a newer NMBD reversal agent that rapidly and completely reverses rocuronium. It is a 
modified gamma cyclodextrin that forms a complex with the neuromuscular blocking agent rocuronium. It 
reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the 
neuromuscular junction. It has been shown to more rapidly reverse residual neuromuscular blockade than 
neostigmine in obese patients without obstructive sleep apnea (OSA). Two systematic reviews showed that 
reversal of NMBD with sugammadex is associated with a lower incidence of residual neuromuscular blockade 


March 1, 2019 
3 
compared to neostigmine,16 and fewer composite adverse events.17 However, the OSA status was not 
reported in these reviews, limiting the ability to evaluate a differential effect in this sub-population. We have 
conducted a systematic review (as part of the Society of Anesthesia and Sleep Medicine’s guidelines on 
intraoperative management of OSA patients) showing there are only a few low-quality studies18,19 that have 
compared sugammadex with neostigmine in patients with OSA (guidelines manuscript in press, systematic 
review under review). We identified a knowledge gap and unmet needs in the area of reversal of NMBD for 
surgical patients with OSA. It is unclear from previous studies whether sugammadex may improve discharge 
times of patients with OSA from the OR. 
 
 
Rationale and Significance 
The prevalence of OSA has increased over the last two decades, and is likely to continue to increase in 
association with the rise of the obesity epidemic. There is currently a lack of high-quality evidence 
(randomized double-blinded trials) to determine whether sugammadex has any advantages over neostigmine 
in obese patients with OSA. In this study, we will provide a moderate level of muscle relaxation during 
surgery to optimize surgical conditions, use short-acting anesthetics and minimize intraoperative opioids 
allowing us to assess the impact of sugammadex vs. neostigmine on postoperative recovery, patient care 
efficiency, and postoperative complications in patients with OSA. Our study is designed to simulate usual 
clinical practice, increasing generalizability of our results. Our study will provide evidence for whether 
sugammadex has any advantages over neostigmine in obese patients with OSA undergoing bariatric surgery. 
Ensuring that an obese patient with OSA has optimal muscle relaxation and surgical conditions, but is 
completely reversed after surgery may ensure patient safety, reduce the risks for postoperative respiratory 
complications in this vulnerable patient population, while at the same time, improving workflow in the 
operating room (OR), justifying the higher cost of sugammadex.  
 
 
 


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Study Design 
 
This study is a prospective, double-blinded randomized controlled superiority trial with two parallel 
groups. Randomization will be performed with a 1:1 allocation into reversal of NMBD with sugammadex 
or neostigmine. This study will be conducted at Toronto Western Hospital, University Health Network – a 
Bariatric Centre of Excellence located in Toronto, Ontario, Canada. A total of 120 patients will be 
included in this study. This study will be registered with clinicaltrials.gov prior to enrolment of participants. 
 
Participants:  
 
Inclusion Criteria: Adult (≥18 yrs.) patients with OSA diagnosed by polysomnography for elective bariatric 
surgery under general anesthesia.   
 
Exclusion Criteria: Allergy to rocuronium, sugammadex or neostigmine, malignant hyperthermia, hepatic 
or renal insufficiency, neuromuscular diseases, pregnancy, inability to give consent.  
 
Study Procedures 
 
Screening: Research Ethics Board approval will be obtained from the institution, and informed consent 
will be obtained from all subjects for participation in this study. A research coordinator will screen 
patients in the preoperative clinic or bariatric clinic for eligibility criteria and obtain informed consent from 
participants. 
 
Randomization: 
 
Treatment/Intervention: Patients will be randomized to receive: 1) sugammadex 2 mg/kg actual body 
weight or 2) neostigmine 2.5 mg and glycopyrrolate 0.4 mg at the end of surgery (defined as “at skin 
closure”), and the train of four (TOF) stimulation reveals at least 2 responses.  
 
A research analyst who is not involved in the study will create a computer generated randomization list. 
The patient assignments will be placed in serially numbered, opaque-sealed envelopes corresponding 
with the randomization schedule. An anesthesiologist who is not involved in administering the anesthetic 
will open the envelope and prepare the study medication. The study medications will be identical in 
volume and appearance. The sugammadex will be mixed with saline to produce a volume equivalent to 
the neostigmine/glycopyrrolate dose. The dose of neostigmine - 2.5 mg will be used In order to simulate 
real clinical practice since this dose is the standard dose used to reverse NMBD when the TOF shows at 
least 2 responses at most institutions including ours.  
 
All study investigators, research coordinators, patients, surgeons, anesthesiologists, health care 
personnel will be blinded to the treatment arm allocation. 
 
Perioperative Management: 
 
The perioperative management of patients in both groups will be identical except for the administration of 
NMBD reversal agent. There will be no change in the usual surgical or postoperative management of 
patients. The intraoperative abdominal pressures will be recorded at 10-minute intervals.  
 
Anesthetic management will be standardized. Routine monitors including electrocardiography, pulse 
oximetry, noninvasive blood pressure, and capnography will be applied. The depth of anesthesia will be 
monitored using entropy – an electroencephalography based method for determining hypnotic levels. 
Neuromuscular function will be assessed using the GE Healthcare NeuroMuscular Transmission (NMT) 
module. The  ElecroSensor will be used with the electrodes placed over the ulnar nerve. The TOF count 
will be assessed by delivering a train of four impulses 500 milliseconds apart (2 Hz) at 80 mA with a 
pulse width of 200 microseconds. 
 


March 1, 2019 
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After 3-5 minutes of preoxygenation with 100% oxygen by face mask with the patient on a TROOP 
elevation pillow, general anesthesia will be induced using propofol (2.5-3 mg/kg) based on the lean 
scaled weight (LSW), , fentanyl (1-2 mcg/kg), rocuronium (0.6 mg/kg) – LSW, ± 30-50 mcg remifentanil. 
The LSW will be determined using the following formulas; for men: LSW = 11,432 x total body 
weight/(6,680 + 216 x body mass index); for women: LSW = 14, 148 x total body weight/(8,780 + 244 x 
body mass index).20,21 
 
General anesthesia will be maintained with desflurane – an inhalational volatile anesthetic that has a low 
blood gas partition coefficient allowing rapid recovery and emergence from general anesthesia. 
Desflurane will be adjusted to maintain the age-adjusted minimum alveolar concentration (MAC) 
between 0.9 – 1.2. The inspired oxygen concentration will be 50-60% with an air mixture to maintain an 
oxygen saturation >96%. Additional doses of fentanyl 25-50 mcg may be administered intraoperatively at 
the discretion of the anesthesiologist Up to 1mg of hydromorphone may be administered intraoperatively. 
As per standard practice, local infiltration with bupivacaine – a long acting local anesthetic will be 
administered at the beginning of surgery to reduce postoperative pain and the amount of opioids 
required. Additional doses of 10 mg rocuronium will be given as needed to maintain a moderate level of 
muscle relaxation (TOF count of 1-2) or as requested by the surgeon. Prophylactic antiemetic 
medications will be given as per usual practice. The total doses of all medications administered 
intraoperatively will be recorded. 
 
Five minutes before the end of surgery, desflurane will be titrated to an age-adjusted MAC of 0.7-0.8. As 
per usual clinical practice, at the end of surgery, defined as at skin closure, the NMBD reversal agent will 
be administered when the TOF reveals at least 2 responses. Desflurane will be discontinued, and the 
fresh gas flow will be increased to 15L/min. The TOF ratio will be recorded prior to administration of 
NMBD reversal agent, and at 15-second intervals until prior to extubation. The anesthesiologist will be 
aware of the TOF prior to administration of NMBD reversal agent. 
 
In order to simulate typical clinical practice, the anesthesiologist will not be aware of the TOF ratio when 
considering extubation but the patient will be extubated based on the clinical judgment of the attending 
anesthesiologist based on whether the patient is awake, opens eyes to command, has good hand grip 
strength, sustained head lift for >5 seconds, is stable hemodynamically, is breathing spontaneously with 
an expired tidal volume between 5 and 8 ml/kg, respiratory rate between 12 and 25 breaths/min, and 
maintaining oxygen saturation ≥97%. The TOF ratio will be recorded prior to and at the time of 
extubation. As per usual clinical practice for bariatric patients at this institution, the patient will be asked 
to move independently from the OR table to the bed. The patient will be discharged from the OR to 
PACU when they are awake, responding to commands, has stable vital signs, is breathing 
spontaneously and maintaining oxygen saturation ≥97% with supplemental oxygen via a face mask. 
Episodes of upper airway obstruction, hypoxemia and need for interventions after extubation will be 
recorded. If incomplete NMBD reversal is suspected after extubation, the anesthesiologist will be 
informed of the TOF ratio. 
 
The vital signs including heart rate, oxygen saturation, respiratory rate, blood pressure, pain scores, 
nausea/vomiting and level of sedation (Ramsey Scale)22 will be recorded in the PACU. All complications 
including episodes of upper airway obstruction, hypoxemia, respiratory failure will be recorded. 
 
The time from administration of NMBD reversal agent to the time the patient is extubated, moves from 
the OR table to the bed, is discharged from the OR, and is ready for discharge from PACU will be 
recorded. The time from first incision to extubation, time from first incision to OR discharge, total time in 
the operating room, time to readiness for discharge from PACU (achieving a modified Aldrete score ≥ 
9),23 actual length of stay in PACU, and duration of hospital stay will be recorded. Postoperative 
abdominal and shoulder tip pain scores and opioid consumption while in hospital will be recorded.  
 
Postoperatively, patients will be monitored with continuous pulse oximetry on the ward as per usual care 
for bariatric patients. All in-hospital complications including length of stay will be recorded. 
 
Outcomes: 


March 1, 2019 
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The primary outcome will be the time from administration of NMBD reversal agent to discharge from the 
OR.  
 
The secondary outcomes will include the time from administration of NMBD reversal agent to the time: 
the patient open eyes to command, extubation, moves independently from the OR table to the bed, TOF 
prior to and at the time of extubation, and the readiness for discharge from PACU. Other evaluated 
outcomes will include all in-hospital complications including cardiovascular complications (tachycardia, 
bradycardia, hypertension, hypotension, myocardial ischemia or infarction, etc.), and respiratory 
complications (hypoxemia, airway obstruction, aspiration, need for re-intubation, etc.), and length of stay.  
 
Study Duration 
 
The recruitment of the participants will occur over a period of 15 months beginning on January 14, 2019 
and continue until April 15, 2020. The follow-up for all patients will be completed by May 15, 2020. The 
study data will be analyzed by a statistician who is blinded to the treatment allocation. Unless a serious 
adverse event occurs that is deemed by the PI to be possibly related to the study drug – necessitating 
unblinding, blinding will be maintained until the study statistician cleans the data. The data cleaning, 
analysis, and preparation of the manuscript will require 4 months. 
 
 
Statistical Methods 
 
The primary outcome – time from administration of NMBD reversal agent to discharge from the OR will 
be compared and the difference will be assessed with student t-test (parametric data) or Wilcoxon-Mann-
Whitney test (non-parametric data) as appropriate. An intention-to-treat analysis will be conducted to 
compare the two groups. Statistical significance will be assessed using two-sided tests with P values < 
0.05 considered significant for all comparisons. 
 
The secondary outcomes for this study include the time from administration of NMBD reversal agent to 
the time: the patient opens his/her eyes to verbal command, extubation, the patient moves from the OR 
table to the bed, TOF prior to and at extubation, readiness for discharge from PACU will be assessed 
using student t-test (parametric data) or Wilcoxon-Mann-Whitney test (non-parametric data) as 
appropriate.  
 
The study is not powered to detect a difference in complications since complications are rare, however, 
other outcomes including: signs of residual neuromuscular blockade, and all in-hospital complications 
will be summarized (numbers and rates of events) and the comparison of differences in frequency of 
each outcome in both groups will be assessed by using Chi-Square test.  
 
Demographic data, vital signs, intra-abdominal pressures, pain, all medications administered to patients 
in both groups will be summarized using summary statistics for continuous variables. 
 
The time from first incision to extubation, time from first incision to OR discharge, total time in the 
operating room, time to readiness for discharge from PACU, actual length of stay in PACU, and duration 
of hospital stay will be described using summary statistics. To compare the mean time for the above 
events between the two groups of reversal agents, a student t-test (parametric data) or Wilcoxon-Mann-
Whitney test (non-parametric data) will be used as appropriate.  
 
Sample Size 
The estimation of sample size is based on the primary outcome of time from administration of the 
reversal agent until discharge from the OR. There are no previous studies comparing sugammadex to 
neostigmine for obese patients with OSA undergoing bariatric surgery. However, a previous study 
comparing sugammadex vs. neostigmine for discharge readiness from the OR to PACU reported 
discharge times for sugammadex vs. neostigmine of 9.15 ± 4.23 vs. 13.87 ± 11.47 minutes.24 Using a 
minimal clinically acceptable difference of 5 minutes, assuming a power of 0.90, and a two-sided level of 


March 1, 2019 
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significance of alpha =0.05, a total sample size of 120 patients (60 in each group) is required. Given the 
short duration of follow up, no adjustment is made for potential dropouts.  
 
Drug Handling 
 
Open-label supplies of sugammadex for 60 patients will be provided from Merck. Clinical supplies will be 
received by the PI at the study site, handled and stored safely and properly, and kept in a secured 
location to which only the study investigators and designated research coordinators have access. Clinical 
supplies will be dispensed in accordance with the protocol. The PI and co-investigators will be 
responsible for keeping accurate records of the clinical supplies, the amount dispensed to and returned 
by the patients, and the disposition at the end of the study. The study medication will be handled and 
stored safely and properly according to ICH/GCP Guidelines and the institutional policies. At the end of 
the study, the PI will be responsible for the destruction of the supplies at the study center pursuant to the 
ICH/GCP Guidelines, local regulations and the PI’s institutional policies. 
 
Potential Risks 
 
There are no anticipated risks expected with this study as the administration of reversal agents is 
consistent with standard practice. Sugammadex is approved by Health Canada for reversal of NMBD, 
but is not used routinely due to the higher cost compared to neostigmine. Sugammadex may reduce the 
effectiveness of birth control pills or non-oral hormonal contraception for up to 7 days. Female patients 
with child-bearing potential using birth control pills or non-oral hormonal contraception should use an 
additional, non-hormonal contraceptive for the next 7 days after their surgery.  
 
 
Adverse Experience Reporting 
 
All adverse events will be recorded and serious adverse events will be reported to the institutional REB. 
 
Direct Access to Source Data/Documents 
 
Health information will only be shared with members of the research team. Original study forms and 
research charts will be kept on file at the participating study site.  
 
Data Handling and Record Keeping 
 
All paper based documents and data will be stored in a locked cabinet in a locked research office. 
Electronic data will be stored in a password-protected electronic database that will be stored on the 
departmental network drive and only be accessible via password-protected departmental computers. A 
study code ID will be used to identify all participants, instead of names. The participants’ personal 
identifying information and names will be stored separately from the study data. Only the principal 
investigator, co-investigators, research assistants, and research statistician will have access to the final 
trial dataset. 
 
Financing and Insurance 
 
This study will be supported by a research grant from Merck Canada. 
 
Publication Policy 
 
Research study results will be presented for publication in peer reviewed journals and research study 
meetings. Participants will be asked whether they would like to receive a copy of the research 
publication. 


March 1, 2019 
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References 
 
1. 
Fortier L-P, McKeen D, Turner K, de Medicis E, Warriner B, Jones PM, Chaput A, Pouliot J-
F, Galarneau A. The RECITE study: a Canadian prospective, multicenter study of the 
incidence and severity of residual neuromuscular blockade. Anesth Analg 2015; 121:366-72. 
 
2. 
Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, 
incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg 
2010;111:120-8. 
3. 
Fuchs-Buder T, Nemes R, Schmartz D. Residual neuromuscular blockade: management 
and impact on postoperative pulmonary outcome. Curr Opin Anesthesiol 2016; 29:662-7. 
4. 
Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual 
neuromuscular blockade and critical respiratory events in the postanesthesia care unit. 
Anesth Analg 2008;107:130-7. 
 
5. 
Ravesloot MJ, van Maanen JP, Hilgevoord AA, van Wagensveld BA, de VN. Obstructive 
sleep apnea is underrecognized and underdiagnosed in patients undergoing bariatric 
surgery. Eur Arch Otorhinolaryngol 2012;269:1865-1871. 
6. 
Sharkey KM, Machan JT, Tosi C, Roye GD, Harrington D, Millman RP. Predicting 
obstructive sleep apnea among women candidates for bariatric surgery. J. Womens Health 
(Larchmt.) 2010;19:1833-1841. 
7. 
Chung F, Liao P, Elsaid H, Shapiro CM, Kang W. Factors associated with postoperative 
exacerbation of sleep-disordered breathing. Anesthesiology 2014; 120:299-311.  
8. 
Opperer M, Cozowicz C, Bugada D, Mokhlesi B, Kaw R, Auckley D, Chung F, Memtsoudis 
SG. Does Obstructive Sleep Apnea Influence Perioperative Outcome? A Qualitative 
Systematic Review for the Society of Anesthesia and Sleep Medicine Task Force on 
Preoperative Preparation of Patients with Sleep-Disordered Breathing. Anesth Analg 
2016;122:1321-34. 
9. 
Subramani Y, Nagappa M, Wong J, Patra J, Chung F. Death or near-death in patients with 
obstructive sleep apnoea: a compendium of case reports of critical complications. Br J 
Anaesth 2017; 1-15. 
10. 
Kaw R, Chung F, Pasupuleti V, Mehta J, Gay PC, Hernandez AV. Meta-analysis of the 
association between obstructive sleep apnoea and postoperative outcome. Br J Anaesth 
2012;109:897-906. 
11. 
Mokhlesi B, Hovda MD, Vekhter B, Arora VM, Chung F, Meltzer DO. Sleep-disordered 
breathing and postoperative outcomes after bariatric surgery: Analysis of the nationwide 
inpatient sample. Obes Surg 2013; 23:1842-51. 
12. 
Memtsoudis SG, Stundner O, Rasul R et al. The impact of sleep apnea on postoperative 
utilization of resources and adverse outcomes. Anesth Analg 2014; 118:407-18. 
13. 
Ahmed S, Nagle A, McCarthy R, Fitzgerald PC, Sullivan JT, Prystowsky J. Postoperative 
hypoxemia in morbidly obese patients with and without obstructive sleep apnea undergoing 
laparoscopic bariatric surgery. Anesth Analg 2008; 107:138-43. 
14. 
Pereira H, Xara D, Mendonca J, Santos A, Abelha FJ. Patients with a high risk for 
obstructive sleep apnea syndrome: Postoperative respiratory complications. Rev Port 
Pneumol 2013; 19:144-151.  
15. 
Sudré ECM, De Batista PR, Castiglia YMM. Longer immediate recovery time after 
anesthesia increases risk of respiratory complications after laparotomy for bariatric surgery: 
A Randomized Clinical Trial and a Cohort Study. Obes Surg 2015; 25:2205-12. 
16. 
Abad-Gurumeta A, Ripolles-Melchor J, Casans-Frances R, Espinosa A, Martinez-Hurtado E, 
Fernandez-Perez C, Ramirez JM, Lopez-Timoneda F, Calvo-Vecino JM. A systematic 
review of sugammadex vs neostigmine for reversal of neuromuscular blockade. Anaesthesia 
2015;70:1441-52. 


March 1, 2019 
10
17. 
Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus 
neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev 
2017;8:Cd012763. 
18. 
Unal DY, Baran I, Mutlu M, Ural G, Akkaya T, Ozlu O. Comparison of sugammadex versus 
neostigmine costs and respiratory complications in patients with obstructive sleep apnoea. 
Turk J Anaesth Reanim 2015; 43:387-95. 
19. 
Llaurado S, Sabate A, Ferreres E, Camprubi I, Cabrera A. Postoperative respiratory 
outcomes in laparoscopic bariatric surgery: Comparison of a prospective group of patients 
whose neuromuscular blockade was reverted with sugammadex and a historical one 
reverted with neostigmine. Rev Esp Anestesiol Reanim 2014; 61:565-70. 
20. 
Friesen JHP. Lean-scaled weight: a proposed weight scalar to calculate drug doses for 
obese patients. Can J Anaesth. 2013 Feb;60(2):214–5. 
21. 
Friesen JHP. Lean Body Weight Is Not a Weight Scalar for Estimating Drug Doses in Morbid 
Obesity. Obes Surg. 2015;25(8):1496–7.  
22. 
Ramsay MAE, Savege TM, Simpson BRJ & Goodwin R. Controlled sedation with 
alpaxalone-alphadolone. BMJ 1974; 2: 656-659.  
23. 
Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth 1995; 7:89-91. 
24. 
Putz L, Dransart C, Jamart J, Marotta ML, Delnooz G, Dubois PE. Operating room discharge 
after deep neuromuscular block reversed with sugammadex compared with shallow block 
reversed with neostigmine: a randomized controlled trial. Journal of Clinical Anesthesia 
2016;35: 107–113. 
 
 
 
 
 


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Study Flowchart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Elective bariatric surgical 
patients (Age ≥ 18yrs.)  
Obstructive sleep apnea 
 
Neostigmine 2.5 mg 
Glycopyrrolate 0.4 mg  
Time from administration of reversal agent to: 
Discharge from OR 
Opens eyes 
Extubation 
Moves from OR table to bed 
Readiness for discharge from PACU 
 
Sugammadex 2 
mg/kg IV  
Randomize 
All in-hospital complications  
Postoperative pain scores/Opioid consumption 
Nausea/vomiting 
Length of stay