Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment
Phase: PHASE2
Conditions: Neuromuscular Blockade, Renal Impairment
Sponsor: University of Texas Southwestern Medical Center

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Reversal of Neuromuscular Blockade in Patients with Severe Renal Impairment  
 
Principal Investigator:  Tiffany Sun Moon, MD 
 
 
 
 
Version 1.5 7/17/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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The University of Texas Southwestern Medical Center 
Institutional Review Board 
 
PROJECT SUMMARY 
 
 
Introduction and Purpose: 
Inadequate reversal of neuromuscular blockade is a common problem and contributes to 
postoperative respiratory complications including hypoventilation, hypoxia, reintubation, and a 
prolonged hospital stay [1-5].  Neostigmine has been the mainstay for reversal of neuromuscular 
blockade, but has a multitude of side effects such as bronchospasm, nausea/vomiting, hypotension, 
and bradycardia [6].  Sugammadex is a novel agent for reversal of neuromuscular paralysis induced 
by steroidal neuromuscular blocking drugs and belongs to a new category of drugs known as 
‘selective relaxant binding agents.’  Sugammadex selectively binds rocuronium in a 1:1 fashion and 
can reverse any depth of neuromuscular blockade and has been used in patients with severe renal 
impairment [7][8-11].   
 
Use of sugammadex has been proven to be safe in patients with a history of severe renal impairment 
[8-11].  The current standard of care for these patients is to use cisatracurium, which undergoes 
Hofmann elimination, which is independent of renal function.  Antagonism of neuromuscular blockade 
is then subsequently achieved with neostigmine.  Currently, there are no specific studies in patients 
with severe renal impairment evaluating the return of neuromuscular function after reversal of 
cisatracurium with neostigmine versus reversal of rocuronium with sugammadex.  Patients with 
severe renal impairment often have other comorbidities and are at high risk for postoperative cardiac 
and pulmonary complications.  Additionally, the simultaneous evaluation of clinical outcomes and 
quality of postoperative recovery has not been undertaken. 
 
The duration of rocuronium in patients with severe renal impairment is prolonged and can be 
unpredictable.  Therefore, cisatracurium is the preferred agent for neuromuscular blockade in patients 
with severe renal impairment since it undergoes Hofmann elimination, which is independent of renal 
function.  Neuromuscular blockade has also been achieved with rocuronium and successful reversed 
with sugammadex, even in patients with severe renal impairment.  Dialysis through a high-flux filter 
effectively removes sugammadex and the sugammadex-rocuronium compound from the circulation 
[26]. 
 
There has been anecdotal evidence that patients treated with sugammadex have better subjective 
measures of recovery compared to patients treated with neostigmine.  However, very few studies 
have systematically evaluated this.  Some authors have shown that patients treated with 
sugammadex have less postoperative nausea and vomiting or pain compared to patients treated with 
cholinesterase inhibitors [27, 28].  Amorim et al. showed that in an observational study of 101 
patients, those treated with sugammadex had improved psychological and nociceptive postoperative 
recovery and higher overall satisfaction compared to those treated with neostigmine [29].  As patient-
reported outcomes have become increasingly important for hospitals, treatments that have the 
potential to increase patient satisfaction are being studied closely [30].  The postoperative quality 
recovery scale (PQRS) is a tool that assesses recovery in terms of different domains over time and 
compares them to baseline values [31].  Some of the advantages of the PQRS are that it is validated, 
takes less than 5 minutes to administer, has a low patient refusal rate, and is acceptable to patients 
across a wide range of ages [34].  
 
This will be a prospective, randomized, double-blinded study of surgical patients with severe 
renal impairment that seeks to address the following: 
 
Specific Aim 1: 
To determine whether rocuronium-induced moderate neuromuscular blockade and reversal with 
sugammadex achieves recovery of neuromuscular function (TOF ≥ 0.9) faster than reversal of 

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cisatracurium-induced moderate neuromuscular blockade and reversal with neostigmine in patients 
with severe renal impairment. 
 
Primary Hypothesis:  
Patients with severe renal impairment who are reversed with sugammadex after rocuronium will 
achieve a TOF ≥0.9 within a time frame that is one-third of the time it takes for reversal with 
neostigmine after cisatracurium.   
 
Specific Aim 2:   
To determine if reversal with sugammadex versus neostigmine results in improved postoperative 
recovery, as measured by the postoperative quality recovery scale (PQRS) and QoR score. 
  
Secondary Hypothesis:   
Patients reversed with sugammadex (versus neostigmine) will have a higher quality of recovery in the 
postoperative period. 
 
Background: 
The incidence of residual postoperative neuromuscular blockade has been reported to be 30-60%, as 
defined by a train of four ratio (TOFR) <0.9 [1, 22-25].  Critical respiratory events (e.g., severe 
hypoxemia, upper airway obstruction, reintubation, aspiration) are significantly increased with TOFR 
<0.9 on admission to the PACU [1, 25].  Patients with severe renal impairment often have major 
comorbidities with little tolerance for postoperative residual neuromuscular blockade.  Neostigmine 
takes much longer to achieve full reversal from neuromuscular paralysis than sugammadex [7, 12-15].   
 
Sugammadex is a modified gamma cyclodextrin that forms a complex with the steroidal 
neuromuscular blocking agents rocuronium and vecuronium.  This complex is then renally excreted, 
which reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic 
receptors in the neuromuscular junction. Therefore, the administration of sugammadex results in the 
rapid reversal of neuromuscular blockade induced by rocuronium and vecuronium.  Neostigmine has 
been the mainstay for reversal of neuromuscular blockade but is associated with adverse side effects 
such as nausea/vomiting, abdominal pain, and increased secretions.  Neostigmine also takes much 
longer to achieve full reversal from neuromuscular paralysis than sugammadex [7-11].  Furthermore, 
unwarranted administration of neostigmine can actually result in worsening of neuromuscular 
paralysis [24-29].   
 
Concise Summary of Project: 
This study is intended to be a single-site, prospective, randomized, double-blinded study that intends 
to enroll a total of 60 patients with severe renal impairment undergoing surgery with general 
endotracheal anesthesia at Parkland Hospital. Patients will be randomized to receive either 
neostigmine (for reversal of cisatracurium) or sugammadex (for reversal of rocuronium). A 
standardized anesthetic protocol that is usual and customary for the type of operation the patient is 
having will be provided to the anesthesia teams of enrolled subjects.  The remainder of the anesthetic 
care of the subject will not deviate from the standard of care.  All patients will be monitored with 
continuous pulse oximetry postoperatively for 24 hours. 
 
Study Procedures: 
Screening and Informed Consent 
A member of the research team will use a screening form to look for surgical patients that meet all of 
the inclusion and exclusion criteria. Patients will be informed that they will receive no compensation 
for participating in the study and there will be no adverse consequences if they choose not to 
participate. If the subjects agree to participate, informed written consent will be obtained prior to any 
study procedures and this document will be sent to pmhresearchparticipants@phhs.org, for inclusion 
in the patient’s medical record, per Parkland regulations. The study duration is approximately 30 days, 
from the start of anesthesia until POD 30. 

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Baseline Subjective Measures 
In the preoperative area, patients will be asked to complete the baseline assessment for the 
postoperative quality recovery scale (Appendix 1) and demographic information will be gathered. 
 
Anesthesia Protocol (Appendix 2) 
The anesthesia team that will be caring for the patient during surgery will be given the protocol for the 
study, which standardizes the general anesthetic technique.  Patients in the rocuronium/sugammadex 
group will receive 0.6 mg/kg of rocuronium for neuromuscular paralysis during induction.  Additional 
rocuronium will be given in 0.15 mg/kg increments to keep the patient at a neuromuscular depth of 1 
twitch throughout the surgery until the last 30 minutes, during which the patient will be kept at 2 
twitches.  Patients in the cisatracurium/neostigmine group will receive 0.2 mg/kg of cisatracurium for 
neuromuscular paralysis during induction.  Additional cisatracurium will be given in 0.03 mg/kg 
increments to keep the patient at a neuromuscular depth of 1 twitch throughout the surgery until the 
last 30 minutes, during which the patient will be kept at 2 twitches.  All patients will have the depth of 
neuromuscular block monitored at the adductor pollicis with a TwitchView electromyography-based 
device (Blink, Seattle, WA) that provides real time feedback of the strength of contraction and 
graphically displays the relevant ratios.  All assessments of depth of neuromuscular blockade will be 
recorded into the patient’s electronic medical record.  
 
Maintenance of anesthesia will be with sevoflurane in 50% oxygen, titrated to keep the bispectral 
index (BIS) between 40-60.  All patients will have a forced air warming device (e.g., Bair Hugger, 3M, 
Maplewood, MN) used to maintain normothermia throughout the surgery.  Subjects will be 
randomized to receive all blinded study drugs: either neostigmine for reversal of cisatracurium or 
sugammadex for reversal of rocuronium.  The reversal agent will be administered intravenously at the 
beginning of skin closure when the patient has moderate neuromuscular blockade (i.e., TOF = 2 
twitches).  The anesthesia team will be completely blinded and the postoperative assessments will 
also be completed by a separate blinded member of the research team.  The induction neuromuscular 
blocking agent syringe will be drawn up by pharmacy and contain either cisatracurium 0.2 mg/kg or 
rocuronium 0.6 mg/kg and filled with normal saline to make identical 10mL syringes. If the patient is ≥ 
100 kg, a 20mL syringe will be used (instead of 10mL).  The maintenance neuromuscular blocking 
agent syringe will be drawn up by pharmacy and contain 5 or 10mL of either rocuronium (10 mg/mL) 
or cisatracurium (2 mg/mL) [both in their original, undiluted concentrations].  The reversal agent will 
also be drawn up by pharmacy and will contain neostigmine 50 mcg/kg mixed (maximum 5mg) with 
glycopyrrolate 10 mcg/kg (maximum 1mg) or sugammadex 2 mg/kg.  The blinded study drug 
(“reversal agent”) will be prepared into a 10 mL syringe by a pharmacist in Investigational Drug 
Service (IDS) Pharmacy and labeled as “sugammadex or neostigmine/glycopyrrolate.”  Any volume of 
blinded study drug that is less than 10 mL will be supplemented with 0.9% normal saline solution so 
that all syringes contain a volume of 10 mL and appear identical in order to preserve blinding. The 
remaining aspects of the anesthetic will be standardized and not differ from the standard of care for all 
patients.   
 
Randomization & Dosing: 
Patients will be randomized to one of two groups for neuromuscular blockade and reversal of 
neuromuscular paralysis: 
1. Group 1- cisatracurium + neostigmine (NEO group) 
a. Induction neuromuscular blockade with 0.2 mg/kg cisatracurium 
b. Maintenance neuromuscular blockade with boluses of 0.03 mg/kg cisatracurium to 
keep TOF 1-2 twitches 
c. Reversal: neostigmine 50 mcg/kg, maximum 5 mg mixed with glycopyrrolate, 10 
mcg/kg, maximum 1 mg 
 
2. Group 2- rocuronium + sugammadex (SUG group) 
a. Induction neuromuscular blockade with 0.6 mg/kg rocuronium 
b. Maintenance neuromuscular blockade with boluses of 0.15 mg/kg rocuronium to keep 

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TOF 1-2 twitches 
c. Reversal: Sugammadex 2 mg/kg 
 
The statistician will make randomization envelopes by using a random number generator.  These 
envelopes will be provided to Investigational Drug Services (IDS) Pharmacy before any subjects are 
screened and later only as needed to replenish supply. The words ‘cisatracurium + 
neostigmine/glycopyrrolate’ or ‘rocuronium + sugammadex’ will be printed on a piece of paper and 
placed in an opaque manila envelope that bears a unique subject number.  Upon receiving the 
physician order for the subject, the IDS Pharmacist will randomize the subject to a treatment group by 
opening the randomization envelope bearing the subject number corresponding to the subject number 
written on the physician order.  
 
The Investigator or Co-Investigator will write the patient’s weight on the order form so that the 
pharmacist can perform necessary dose calculations and draw up the appropriate intravenous dose of 
the blinded study drugs. After the blinded study drug syringes are prepared, a pharmacist or 
pharmacy technician will deliver the syringe to the operating room to the anesthesia provider, who will 
sign for receipt of study drug syringe. 
 
Blinding/Un-blinding: 
The patient, all medical providers (surgeons, anesthesia faculty, anesthesia residents, certified 
registered nurse anesthetists, nurses), and the postoperative evaluator will be blinded as to what 
neuromuscular blocking drug and reversal agent the patient receives.  A member of the research 
team that is not involved in the direct care or assessment of the patient will provide the randomization 
envelopes to IDS Pharmacy. IDS Pharmacy staff will be the only un-blinded personnel.  
 
In emergency scenarios when un-blinding becomes necessary (e.g., anaphylaxis), the principal 
investigator or co-investigators may call the IDS Pharmacy to ascertain which specific medication(s) 
was dispensed.  A detailed log of patient enrollments, randomization assignments and drug 
accountability will be kept in Investigational Drug Service (IDS) Pharmacy, which has controlled 
security access.  
 
Calculation of Key Times 
The time that the reversal agent (sugammadex versus neostigmine) is given will be marked as 
‘Reversal Time’, and times to last stitch, extubation, and out of OR will be ascertained from the 
electronic medical record (EMR) (i.e., Epic Systems, Verona, WI).  Once the patient arrives in the 
PACU, a trained research assistant will assess the degree of neuromuscular function the patient has 
using the TwitchView set to 30mA.  Adequate reversal will be defined as a train of four ratio (TOFR)  
0.9.  Anything less than 0.9 will be defined as residual paralysis or inadequate reversal.  
 
PACU Assessment 
A blinded, trained research assistant will observe and record all parameters from the time the patient 
arrives in the PACU until they are discharged from the PACU.  All episodes of hypoxia and any use of 
supplemental oxygen will be recorded.  All vital signs will be extracted from the EMR.  Any drugs 
given in the PACU will be recorded.  At 15 minutes (T15), 40 minutes (T40), and 80 minutes (T80) after 
arrival to the PACU, the patient will be assessed using the postoperative quality recovery scale 
(PQRS) in 3 domains (Appendix 1). 
 
Postoperative Day (POD) 1 Assessments 
All patients will be admitted to the hospital for continuous SpO2 monitoring for 24 hours.  Patients who 
are on dialysis will resume their normal dialysis schedule, which will be recorded.  On POD 1 the 
patient will be assessed using the postoperative quality of recovery scale (PQRS) in 5 domains 
(Appendix 3).  Patients who are still in the hospital on POD 2 will be assessed using the PQRS as 
well.  Patients who are discharged home will be called on the telephone and the PQRS will be 
assessed in 4 domains (no physiological assessments).  All patients will be followed for their total 
hospital length of stay and assessed for any major adverse events (reintubation, pneumonia, 

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myocardial infarction, stroke, unplanned hospital admission, or readmission within 30 days of hospital 
discharge).   
 
 
Data Sources 
Protected health information including name, medical record number, and date of birth will be 
recorded and stored securely in an IRB approved, secured REDCap database. 
  
Parameters: 
1. Protected health information (PHI):  name, medical record number, date of birth, phone number 
2. Demographic information (age, weight, height, BMI), medical and surgical history, ASA status  
3. Preoperative PQRS assessment 
4. Intraoperative parameters  
• 
Frequency and dose of all neuromuscular blocking and reversal agents 
• 
Intraoperative vitals (systolic, diastolic, and mean blood pressures, temperature, heart rate) at 
least every 3 minutes 
• 
ECG rhythm 
• 
Fluids administered 
• 
End-tidal concentration of anesthetic (e.g., sevoflurane) 
• 
Total intraoperative opioids 
• 
Length of surgery 
• 
The time from last neuromuscular blocking agent given to reversal agent (min) 
• 
The time from neuromuscular reversal to last stitch (min) 
• 
The time from neuromuscular reversal to extubation (min) 
• 
The time from neuromuscular reversal to discharge from the OR (min) 
• 
The time from surgery completed (bandage on) to discharge from the OR (min) 
• 
Depth of neuromuscular blockade throughout the surgery at 15-minute intervals 
• 
Presence of hemodynamic changes, rash, erythema, or flushing after reversal agent given 
5. PACU parameters 
• 
Evaluation of residual paralysis with train of four (TOF) stimulation using the TwitchView within 
5 minutes of PACU arrival and every 5 minutes until a TOF  0.9 is reached 
• 
Time it takes to achieve TOFR  0.9 
• 
Vitals during PACU stay (BP, temperature, HR, SpO2) every 10 minutes 
• 
Number of hypoxic episodes (SpO2<95%) 
• 
Lowest observed SpO2 during any episode of airway obstruction 
• 
Need for supplemental oxygen  
• 
Any episodes of airway obstruction and treatment (e.g., jaw thrust, insertion of 
nasopharyngeal, oropharyngeal or laryngeal mask airway or reintubation). 
• 
The time when PACU discharge criteria are met 
• 
Total PACU time (PACU arrival to actual discharge from PACU) 
• 
PQRS in 3 domains (Appendix 1) at 15 minutes, 40 minutes and 80 minutes 
6. Postoperative day 1-2 evaluation  
• 
PQRS in 4-5 domains (Appendix 3) 
8.  Adverse event monitoring (until POD 30) 
• 
Reintubation 
• 
Recurarization  
• 
Critical respiratory adverse event including bronchospasm, atelectasis, pulmonary edema 
• 
Cardiovascular adverse events such as tachycardia, bradycardia, cardiac arrhythmias, 
hypotension, and hypertension 
• 
Major adverse postoperative events (pneumonia, reintubation, myocardial infarction, stroke) 
• 
Unplanned hospital admission 
 
Criteria for Inclusion of Subjects: 

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• 
18-80 years old 
• 
Severe renal impairment (CrCl < 30 mL/min) 
• 
Undergoing non-emergent surgery that requires neuromuscular blockade 
• 
Planned extubation in the operating room immediately after surgery 
• 
ASA physical status classification 3 to 4 
• 
Willing and able to consent in English or Spanish 
• 
No personal history of neuromuscular disease 
 
Criteria for Exclusion of Subjects: 
• 
Age less than 18 or older than 80 
• 
Patient does not speak English or Spanish 
• 
Morbidly obese (BMI> 40-49.9 kg/m2) 
• 
Planned postoperative intubation/ventilation 
• 
Allergy to sugammadex, neostigmine, glycopyrrolate, cisatracurium, or rocuronium 
• 
Family or personal history of malignant hyperthermia 
• 
Patient refusal 
• 
“Stat” (emergent) cases 
• 
Patients undergoing thoracic operations (e.g., video assisted thoracoscopic surgery, 
thoracotomy) 
• 
Pre-existing muscle weakness of any etiology 
• 
Patients with moderate to severe COPD 
• 
Patients with sleep apnea  
• 
Patients on toremifene (a selective estrogen receptor modulator) 
• 
Women of childbearing age who: 
a. Have a positive pregnancy test 
b. Are on oral contraceptives and not willing to use a non-hormonal method of contraception 
for 7 days after surgery  
            c. Nursing women 
 
 
Sources of Research Material: 
• 
Identifying patient information including name, medical record number, and birth date 
• 
Medical history  
• 
Surgical history 
• 
Weight and height 
• 
Medication list 
• 
Laboratory studies 
• 
Vital signs 
• 
ECGs and radiologic studies 
• 
Intraoperative anesthetic record 
• 
Postoperative notes and discharge summary 
 
Recruitment Methods and Consenting Process: 
Subjects who meet all inclusion and exclusion criteria will be approached by a member of the 
research team either in the pre-anesthesia evaluation clinic or in the preoperative area of day surgery 
in a private room or in their private room on the floor if they are an inpatient.  All study procedures will 
be explained to the patient in layman’s terms.  If the subject agrees to participate, he or she (or their 
legal representative) will sign the consent form and HIPAA Authorization Form prior to any study 
procedures.  
 
Potential Risks: 
The additional risks posed by participation in this study are not different than the usual risks 
associated with surgery and general anesthesia.  There is a potential for a direct benefit to the patient 

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if they receive sugammadex, based on available literature, which reports that sugammadex is superior 
to neostigmine for reversal of neuromuscular blockade [7-17].  The anesthetic management of 
subjects will not differ from the standard care.  Patients will be randomized to receive either 
neostigmine or sugammadex for reversal of neuromuscular paralysis.  
 
Risk of Sugammadex: 
The most common adverse reactions after administration of sugammadex are nausea/vomiting, pain, 
hypotension, dizziness, itching, and headache. There is a 0.3% chance of an allergic reaction to 
sugammadex.  
 
Neuromuscular blockade recurrence could theoretically occur after the administration of sugammadex 
due to displacement of rocuronium from sugammadex by other drugs.This has not been reported in 
the literature.  The association rate of rocuronium with sugammadex is very high and the dissociation 
rate is very low, due to the intermolecular (van Der Waals’) forces and hydrophobic interactions.  It is 
estimated that for every 25 million sugammadex-rocuronium compounds, only 1 dissociates (Nag 
2013).    
 
The sugmmadex label has a warning for the use of the drug in patients with severe renal impairment. 
Sugammadex is “not recommended” for use in patients with severe renal impairment, including those 
requiring dialysis. The label states that sugammadex is known to be substantially excreted by the 
kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal 
function and the elderly because elderly patients are more likely to have decreased renal function. 
The half-life of sugammadex in patients with mild, moderate and severe renal impairment is 4, 6, and 
19 hours, respectively. 
 
Marked bradycardia can be seen, some of which have resulted in cardiac arrest, have been observed 
within minutes after the administration of sugammadex. This is not different for patients with vs 
without renal impairment. 
 
The sugammadex label states that it may bind to progesterone thereby decreasing exposure. 
Therefore, the administration of a bolus dose of sugammadex is considered to be equivalent to 
missing dose(s) of oral contraceptives containing an estrogen or progesterone. If an oral 
contraceptive is taken on the same day that sugammadex is administered, the patient must use an 
additional, non-hormonal contraceptive method or back-up method of contraception (such as 
condoms and spermicides) for the next 7 days.  Female subjects who are using oral contraceptives 
will be informed during the consenting process that they will need to use a non-hormonal method of 
contraception for 7 days if they participate in the study.  Women who do not wish to do this will not be 
enrolled in the study.  Women who do choose to participate will be provided a letter (in English or 
Spanish) with this information and phone number of the PI if they have any additional questions.   
 
Risks of Rocuronium  
The most common adverse reactions after administration of rocuronium are nausea, vomiting, light 
headedness, and minor changes in blood pressure. 
 
Risks of Cisatracurium  
The most common adverse reactions after administration of cisatracurium are nausea, vomiting, light 
headedness, and minor changes in blood pressure. 
 
Risks of Neostigmine 
The most common adverse reactions after administration of neostigmine are nausea, vomiting, and 
low heart rate, but another drug called glycopyrrolate is always given along with neostigmine to 
counteract the potential drop in heart rate. 
 
Risks of Glycopyrrolate 

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The most common adverse reactions after administration of glycopyrrolate are tachycardia, dry 
mouth, nausea/vomiting, and headache. A rare but serious complication of glycopyrrolate is a severe 
rise in body temperature and abnormal heart rhythm. 
 
Psychological Stress 
There is minimal risk for psychological stress to the patient as a result of participation in this study.  
Subjects may refuse to answer any of the questions or take a break or stop participation in the study 
at any time. 
 
Subject Safety and Data Monitoring: 
Study oversight will include a Data Safety and Monitoring Board (DSMB).  The DSMB will be chaired 
by a faculty member that is not the PI and will include specialists from different specialties including 
anesthesiology, critical care medicine, and nephrology.  The DSMB will meet quarterly as needed to 
review all patient enrollments.  If necessary, the DSMB will meet more often to review specific study 
subjects, unanticipated events, protocol violations, and adverse events.  All study subjects will be 
reviewed by the DSMB for any study-related adverse outcomes.  A written record of all meetings will 
be kept.  The IRB will be notified in writing of any adverse study-related outcomes. The PI will provide 
to the Parkland Office of Research Administration (ORA) safety progress reports after the first 3 
patients, then again at 10 patients and then with the annual continuing review.   
 
 
Procedures to Maintain Confidentiality: 
A non-identifiable code will be assigned to the data collection sheet so that there is not a direct link to 
specific names.  Patient IDs will be standardized in chronological order as subject 1, subject 2, etc. A 
key to the coding system will be maintained in a locked storage cabinet with limited access until all the 
data is collected and analyzed. Access to study data will be restricted to authorized study personnel 
only. Following the completion of the analysis and the project, the key to the coding system or subject 
identifiers themselves will be destroyed by shredding the documents so that there is no direct or 
indirect link to subject identifiers and information. 
 
All data from the study will be kept on encrypted computers belonging to the University, which are 
stored in secured areas. All electronic study data will be password protected and passwords will be 
changed on a regular basis. 
 
All data will be de-identified when exported from the REDCap database.  Patient data will be analyzed 
without patient identifiers by assigning study ID subject numbers that are de-linked from patient 
identifiers.  Signed consent forms, HIPAA forms, and study questionnaires will remain in a locked 
cabinet in the PI’s office. 
 
 
Potential Benefits: 
This study is not designed to directly benefit the study subjects who participate in this study, but there 
may be potential for a direct benefit to the patient if they receive sugammadex, based on available 
literature, which reports that sugammadex is superior to neostigmine for reversal of neuromuscular 
blockade [7-17].  This study is intended to evaluate if sugammadex provides superior reversal of 
neuromuscular blockade compared to neostigmine with regard to decreased hypoxia, increased 
operating room efficiency, and improved postoperative recovery quality.  
 
Statistics: 
The principal investigator will be responsible for analyzing the study data with a biostatistician.  For 
the final analysis, the database will not be unblinded until enrollment, medical review, protocol 
violations, and data have been collected. 
 
Specific Aim 1: 

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To determine whether rocuronium-induced moderate neuromuscular blockade and reversal with 
sugammadex achieves recovery of neuromuscular function (TOF ≥ 0.9) faster than reversal of 
cisatracurium-induced moderate neuromuscular blockade and reversal with neostigmine in patients 
with severe renal impairment. 
 
Primary Hypothesis:  
Patients with severe renal impairment who are reversed with sugammadex after rocuronium will 
achieve a TOF ≥0.9 within a time frame that is one-third of the time it takes for reversal with 
neostigmine after cisatracurium.   
 
Sample Size Justification: 
The sample size calculation is based on the assumption that the treatment group (SUG) will have a 10 
min faster time to mean recovery to TOF ≥0.9 compared to the control group (NEO) (assuming 5 
minutes reversal time for SUG group and 15 minutes for NEO group).  With 24 subjects in each 
group, this gives the study a power > 99% to detect a difference of at least 10 min in the mean time to 
recovery, assuming a SD of 1.5 min in the SUG group and a SD of 5.5 min in the NEO group. 
Accounting for dropouts, protocol deviations, or unexpected postoperative ventilation, etc. a maximum 
of 60 patients will be enrolled. 
 
Analysis Plan: 
In the primary analysis, we will compare the mean time to recovery to TOF≥0.9 by the two-sample t 
test, using a Satterthwaite correction to the degrees of freedom to account for an anticipated 
difference in the variances between the treatment arms.  Two key secondary outcomes are the 
numbers of hypoxic episodes in the recovery room and in the first 24 hours postoperatively. We will 
also analyze these data using two-sample t tests with the Satterthwaite correction.  For each type of 
adverse event, we will create a two-way table cross-classifying subjects by treatment arm and 
whether they experienced the adverse event.  We will conduct a Fisher exact test on each such table 
to determine whether there is a significant association between treatment arm and the event.  As 
these are safety analyses, we will not adjust for multiplicity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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References: 
1. 
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(1):130-137. 
2. 
Brull SJ, Murphy GS: Residual neuromuscular block: lessons unlearned. Part II: methods 
to reduce the risk of residual weakness. Anesth Analg 2010, 111(1):129-140. 
3. 
Plaud B, Debaene B, Donati F, Marty J: Residual paralysis after emergence from 
anesthesia. Anesthesiology 2010, 112(4):1013-1022. 
4. 
Thilen SR, Hansen BE, Ramaiah R, Kent CD, Treggiari MM, Bhananker SM: Intraoperative 
neuromuscular monitoring site and residual paralysis. Anesthesiology 2012, 117(5):964-
972. 
5. 
Kumar GV, Nair AP, Murthy HS, Jalaja KR, Ramachandra K, Parameshwara G: Residual 
neuromuscular blockade affects postoperative pulmonary function. Anesthesiology 
2012, 117(6):1234-1244. 
6. 
Pani N, Dongare PA, Mishra RK: Reversal agents in anaesthesia and critical care. Indian J 
Anaesth 2015, 59(10):664-669. 
7. 
Carron M, Zarantonello F, Tellaroli P, Ori C: Efficacy and safety of sugammadex compared 
to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized 
controlled trials. J Clin Anesth 2016, 35:1-12. 
8. 
Staals LM, Snoeck MM, Driessen JJ, Flockton EA, Heeringa M, Hunter JM: Multicentre, 
parallel-group, comparative trial evaluating the efficacy and safety of sugammadex in 
patients with end-stage renal failure or normal renal function. Br J Anaesth 2008, 
101(4):492-497. 
9. 
Staals LM, Snoeck MM, Driessen JJ, van Hamersvelt HW,   EA, van den Heuvel MW, Hunter 
JM: Reduced clearance of rocuronium and sugammadex in patients with severe to end-
stage renal failure: a pharmacokinetic study. Br J Anaesth 2010, 104(1):31-39. 
10. 
de Souza CM, Tardelli MA, Tedesco H, Garcia NN, Caparros MP, Alvarez-Gomez JA, de 
Oliveira Junior IS: Efficacy and safety of sugammadex in the reversal of deep 
neuromuscular blockade induced by rocuronium in patients with end-stage renal 
disease: A comparative prospective clinical trial. Eur J Anaesthesiol 2015, 32(10):681-
686. 
11. 
Panhuizen IF, Gold SJ, Buerkle C, Snoeck MM, Harper NJ, Kaspers MJ, van den Heuvel MW, 
Hollmann MW: Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for 
reversal of deep neuromuscular blockade in patients with severe renal impairment. Br J 
Anaesth 2015, 114(5):777-784. 
12. 
Jones RK, Caldwell JE, Brull SJ, Soto RG: Reversal of profound rocuronium-induced 
blockade with sugammadex: a randomized comparison with neostigmine. 
Anesthesiology 2008, 109(5):816-824. 
13. 
Geldner G, Niskanen M, Laurila P, Mizikov V, Hubler M, Beck G, Rietbergen H, Nicolayenko 
E: A randomised controlled trial comparing sugammadex and neostigmine at different 
depths of neuromuscular blockade in patients undergoing laparoscopic surgery. 
Anaesthesia 2012, 67(9):991-998. 
14. 
Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME: Reversal of 
rocuronium-induced neuromuscular blockade with sugammadex compared with 
neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. 
Eur J Anaesthesiol 2010, 27(10):874-881. 
15. 
Schaller SJ, Fink H: Sugammadex as a reversal agent for neuromuscular block: an 
evidence-based review. Core Evid 2013, 8:57-67. 
16. 
Illman HL, Laurila P, Antila H, Meretoja OA, Alahuhta S, Olkkola KT: The duration of residual 
neuromuscular block after administration of neostigmine or sugammadex at two visible 
twitches during train-of-four monitoring. Anesth Analg 2011, 112(1):63-68. 
17. 
Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H, Alvarez-Gomez 
JA: Sugammadex provides faster reversal of vecuronium-induced neuromuscular 
blockade compared with neostigmine: a multicenter, randomized, controlled trial. 
Anesth Analg 2010, 110(1):64-73. 

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18. 
Lemmens HJ, El-Orbany MI, Berry J, Morte JB, Jr., Martin G: Reversal of profound 
vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex 
versus neostigmine. BMC Anesthesiol 2010, 10:15. 
19. 
Della Rocca G, Pompei L, Pagan DEPC, Tesoro S, Mendola C, Boninsegni P, Tempia A, 
Manstretta S, Zamidei L, Gratarola A et al: Reversal of rocuronium induced neuromuscular 
block with sugammadex or neostigmine: a large observational study. Acta Anaesthesiol 
Scand 2013, 57(9):1138-1145. 
20. 
Woo T, Kim KS, Shim YH, Kim MK, Yoon SM, Lim YJ, Yang HS, Phiri P, Chon JY: 
Sugammadex versus neostigmine reversal of moderate rocuronium-induced 
neuromuscular blockade in Korean patients. Korean J Anesthesiol 2013, 65(6):501-507. 
21. 
Wu X, Oerding H, Liu J, Vanacker B, Yao S, Dahl V, Xiong L, Claudius C, Yue Y, Huang Y et 
al: Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized 
study in Chinese and Caucasian subjects. BMC Anesthesiol 2014, 14:53. 
22. 
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(1):120-128. 
23. 
Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Vender JS, Parikh KN, Patel 
SS, Patel A: Residual Neuromuscular Block in the Elderly: Incidence and Clinical 
Implications. Anesthesiology 2015, 123(6):1322-1336. 
24. 
Baillard C, Clec'h C, Catineau J, Salhi F, Gehan G, Cupa M, Samama CM: Postoperative 
residual neuromuscular block: a survey of management. Br J Anaesth 2005, 95(5):622-
626. 
25. 
Martinez-Ubieto J, Ortega-Lucea S, Pascual-Bellosta A, Arazo-Iglesias I, Gil-Bona J, Jimenez-
Bernardo T, Munoz-Rodriguez L: Prospective study of residual neuromuscular block and 
postoperative respiratory complications in patients reversed with neostigmine versus 
sugammadex. Minerva Anestesiol 2016, 82(7):735-742. 
26. 
Cammu G, Van Vlem B, van den Heuvel M, Stet L, el Galta R, Eloot S, Demeyer I: 
Dialysability of sugammadex and its complex with rocuronium in intensive care 
patients with severe renal impairment. Br J Anaesth 2012, 109(3):382-390. 
27. 
Lee OH, Choi GJ, Kang H, Baek CW, Jung YH, Woo YC, Oh J, Park YH: Effects of 
sugammadex vs. pyridostigmine-glycopyrrolate on post-operative nausea and 
vomiting: propensity score matching. Acta Anaesthesiol Scand 2017, 61(1):39-45. 
28. 
Castro DS, Jr., Leao P, Borges S, Gomes L, Pacheco M, Figueiredo P: Sugammadex 
reduces postoperative pain after laparoscopic bariatric surgery: a randomized trial. 
Surg Laparosc Endosc Percutan Tech 2014, 24(5):420-423. 
29. 
Amorim P, Lagarto F, Gomes B, Esteves S, Bismarck J, Rodrigues N, Nogueira M: 
Neostigmine vs. sugammadex: observational cohort study comparing the quality of 
recovery using the Postoperative Quality Recovery Scale. Acta Anaesthesiol Scand 2014, 
58(9):1101-1110. 
30. 
Bluemel S, Menne D, Milos G, Goetze O, Fried M, Schwizer W, Fox M, Steingoetter A: 
Relationship of body weight with gastrointestinal motor and sensory function: studies 
in anorexia nervosa and obesity. BMC Gastroenterol 2017, 17(1):4. 
31. 
Royse CF, Newman S, Chung F, Stygall J, McKay RE, Boldt J, Servin FS, Hurtado I, 
Hannallah R, Yu B et al: Development and feasibility of a scale to assess postoperative 
recovery: the post-operative quality recovery scale. Anesthesiology 2010, 113(4):892-905. 
32. 
Fong TG, Fearing MA, Jones RN, Shi P, Marcantonio ER, Rudolph JL, Yang FM, Kiely DK, 
Inouye SK: Telephone interview for cognitive status: Creating a crosswalk with the Mini-
Mental State Examination. Alzheimers Dement 2009, 5(6):492-497. 
33. 
Gursoy C, Ok G, Aydin D, Eser E, Erbuyun K, Tekin I, Baytur Y, Uyar Y: Effect of 
Anaesthesia Methods for Regaining Daily Life Activities in Cesarean Patients. Turk J 
Anaesthesiol Reanim 2014, 42(2):71-79. 
34. 
Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie JB, Allard M, Turan A, Windle 
P, Odom-Forren J et al: Who is at risk for postdischarge nausea and vomiting after 
ambulatory surgery? Anesthesiology 2012, 117(3):475-486. 

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35. 
Niraj G, Kelkar A, Kaushik V, Tang Y, Fleet D, Tait F, McMillan T, Rathinam S: Audit of 
postoperative pain management after open thoracotomy and the incidence of chronic 
postthoracotomy pain in more than 500 patients at a tertiary center. J Clin Anesth 2017, 
36:174-177. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 1: Postoperative Quality Recovery Scale evaluation at baseline, T15, T40, T80 
 
Demographic and Preoperative Dataa 
Age  
yrs 
Gender 
Male or Female 
ASA Status 
1     2     3     4 
Weight 
kg 
Height 
in 
BMI 
kg/m2 
Education 
Highest level finished: 
Alcohol consumption 
units/wk 
Smoking status 
Never, used to but quit, current smoker 
Employment 
Unemployed  
Employed and plan to return 
Employed but plan not to return 
Occupation:  
Approximate hrs/wk: 
Inpatient 
Yes or No 
Surgical procedure 
 
Physiological Factorsa,d 
P1 Blood Pressure 
Please record the patient’s blood 
pressure 
 
 
3= SBP 90-140; 2= SBP 70-89 or 141-180;  
1= SBP <70 or >180 
P2 Heart Rate 
Please record the patient’s heart rate 
 
 
3= 45-100; 2= 35-44 or 101-139; 1= <35 or 
>140 
P3 Temperature 
Please record the patient’s 
temperature 
Method 1. Sublingual 2. Tympanic 3. 
Esophageal 
 
3= 36-37.6; 2= 35-35.9 or 37.7-38.9; 1= <35 
or >39 
P4 Respiration 
Please record the patient’s respiratory 
rate 
                        
 /breaths per minute 
P5 Oxygen use to maintain SpO2 
Please record oxygen requirement 
3= Oxygen administered by protocol or not 
required 
2= Any SpO2 <95% requiring oxygen as an 
intervention 
1= Any SpO2 <90% requiring oxygen as an 
intervention 
P6 Airway 
Please record the number 
corresponding to the assessment 
3= Self-maintenance of airway 
2= Maintenance of airway with support 
(describe) 
1= Device in situ 
P7 Agitation 
Please record the number 
corresponding to the assessment 
3= Shows no signs of agitation 
2= Patient shows occasional agitation 
1= Patient shows severe agitation 
 
 
P8 Alertness 
Please record the number 
corresponding to the actual 
 
 
5= Awake, following commands 
4= Responds to name spoken in normal tone 
3= Responds only after name is spoken 
/

STU2018-0411, Moon, Form A3, Mod_7, 08-05-19 
 
 
 
Page 15 of 21 
assessment 
loudly and repeatedly or both 
2= Responds only after mild prodding or 
shaking 
1= Does not respond to mild prodding or 
shaking 
P9 What is the level of your strength now? 
Please record the number 
corresponding to the actual 
assessment 
 
3= No weakness 
2= A little weak 
1= Very weak 
Nociceptive Factorsa,b,c 
N1 I am going to show you a series of faces 
and I would like you to indicate which face, 
number or description most accurately 
describes your level of pain at the moment.  
 
N2 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description most accurately 
describes your level of feeling nauseous or 
vomiting at the moment.  
 
Emotional Factorsa,b 
E1 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description accurately describes 
to what extent you feel sad, low, or 
depressed at the moment.  
 
E2 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description accurately describes 
to what extent you feel anxious or nervous at 
the moment.  
 
a. Patient questionnaire adapted from Royse et al. 2010 and Amorim et al. 2014 
b. Pain, depression, and anxiety scales are modified from Wong and Baker 1988 
c. Nausea scale is modified from Baxter et al. 2011 
d. Alertness scale adapted from Doufas et al. 2001 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Page 16 of 21 
 
 
Appendix 2: Anesthesia Protocol for Reversal of Neuromuscular Blockade in Patients with 
Severe Renal Impairment 
 
 
1. Monitoring 
a. Standard ASA monitors + BIS monitor 
b. All patients will be monitored with a TwitchView accelerometer device at 15-minute 
intervals.  This device records real time feedback of the strength of contraction and 
graphically displays the relevant ratios. 
2. Induction 
a. Propofol 1.5 – 2.0 mg/kg 
b. Fentanyl 1 – 1.5 mcg/kg 
c. Lidocaine 0.5 – 1.0 mg/kg 
d. NMBD Syringe (will contain either cisatracurium 0.2 mg/kg OR rocuronium 0.6 mg/kg)-  
3. Maintenance Anesthesia:   
a. FiO2 50% (No Nitrous Oxide) 
b. Fentanyl ~ 0.5-1 mcg/kg/hr in divided doses as appropriate  
c. Sevoflurane inhalational anesthesia to maintain BIS 40-60 
d. Maintenance NMBD at 0.015 mL/kg (equal to rocuronium in 0.15 mg/kg increments or 
Cisatracurium in 0.03 mg/kg increments) 
e. Keep TOF at 1 until 30 minutes prior to anticipated conclusion of surgery (allow TOF to 
reach 2 twitches before reversal!) 
f. 
Bair Hugger to maintain normothermia 
g. Ventilatory parameters to maintain normocapnia 
4. Prophylaxis  
a. Ondansetron 4 mg 
b. Dexamethasone 4 mg 
5. Reversal 
a. The patient will be randomized to receive sugammadex vs. neostigmine/glycopyrrolate.  
A research assistant will bring a 10mL syringe labeled ‘reversal agent’ to the OR.  You 
will not be told what reversal agent the patient has been randomized to receive, as this 
is a double-blinded study.  The syringe will contain either sugammadex 2mg/kg or 
neostigmine 50 mcg/kg mixed with glycopyrrolate 10 mcg/kg. 
b. Please administer the reversal agent at the START of skin closure and mark this time 
in EPIC with a Quick Note.  
6. Extubation 
a. Patients will be extubated when all extubation criteria are met  
b. Patients will be transported to the PACU with 8L/min O2 by face mask 
7. Post-anesthesia Care Unit (PACU) 
a. T0 will be the time the patient arrives to the PACU. 
b. All vital signs will be recorded every 10 minutes while the patient is in the PACU. 
c. The first postoperative PQRS assessment will occur 15 minutes after arrival to the 
PACU (T15), the second PQRS assessment will occur 40 minutes after arrival to the 
PACU (T40), and the third PQRS assessment will occur 80 minutes after arrival to the 
PACU (T80). 
d. Patients will be weaned from supplemental oxygen to keep SpO2 ≥ 94%.   
e. The time at which the patient meets all criteria for discharge from the PACU will be 
recorded, as well as the actual PACU duration. 
 
 
 

STU2018-0411, Moon, Form A3, Mod_7, 08-05-19 
 
 
 
Page 17 of 21 
Appendix 3: Postoperative Quality Recovery Scale evaluation at POD1 and POD2** 
 
Physiological Factorsa,d 
P1 Blood Pressure 
Please record the patient’s blood 
pressure 
 
 
3= SBP 90-140; 2= SBP 70-89 or 141-180;  
1= SBP <70 or >180 
P2 Heart Rate 
Please record the patient’s heart rate 
 
 
3= 45-100; 2= 35-44 or 101-139;  
1= <35 or >140 
P3 Temperature 
Please record the patient’s 
temperature 
Method 1. Sublingual 2. Tympanic 3. 
Esophageal 
 
3= 36-37.6; 2= 35-35.9 or 37.7-38.9; 1= <35 
or >39 
P4 Respiration 
Please record the patient’s respiratory 
rate 
                       
  /breaths per minute 
P5 Oxygen use to maintain SpO2 
Please record oxygen requirement 
3= Oxygen administered by protocol or not 
required 
2= Any SpO2 <95% requiring oxygen as an 
intervention 
1= Any SpO2 <90% requiring oxygen as an 
intervention 
P6 Airway 
Please record the number 
corresponding to the assessment 
3= Self-maintenance of airway 
2= Maintenance of airway with support 
(describe) 
1= Device in situ 
P7 Agitation 
Please record the number 
corresponding to the assessment 
3= Shows no signs of agitation 
2= Patient shows occasional agitation 
1= Patient shows severe agitation 
P8 Alertness 
Please record the number 
corresponding to the actual 
assessment 
5= Awake, following commands 
4= Responds to name spoken in normal 
tone 
3= Responds only after name is spoken 
loudly and repeatedly or both 
2= Responds only after mild prodding or 
shaking 
1= Does not respond to mild prodding or 
shaking 
P9 What is the level of your strength now? 
Please record the number 
corresponding to the actual 
assessment 
 
3= No weakness 
2= A little weak 
1= Very weak 
 
 
 
 
 
 
 
 
 
/

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Page 18 of 21 
 
 
Nociceptive Factorsa,b,c 
N1 I am going to show you a series of faces 
and I would like you to indicate which face, 
number or description most accurately 
describes your level of pain at the moment.  
 
N2 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description most accurately 
describes your level of feeling nauseous or 
vomiting at the moment.  
 
Emotional Factorsa,b 
E1 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description accurately describes 
to what extent you feel sad, low, or 
depressed at the moment.  
 
E2 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description accurately describes 
to what extent you feel anxious or nervous at 
the moment.  
 
Activities of Daily Livinga  
A1 Able to breathe easily  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A2 Been able to enjoy food 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A3 Feeling rested 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A4 Have had a good sleep  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A5 Able to look after personal toilet and hygiene   
      unaided  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A6 Able to communicate with family or friends 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A7 Getting support from hospital doctors and 
nurses 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A8 Able to return to work or usual home 
activities 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A9 Feeling comfortable and in control  
Please record the number corresponding to the 
0 to 10,  
where 0=none of the time [poor] and 10=all 

STU2018-0411, Moon, Form A3, Mod_7, 08-05-19 
 
 
 
Page 19 of 21 
actual assessment 
of the time [excellent] 
A10 Having a feeling of general well-being  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
Overall Patient Satisfactiona 
O1 Patient Satisfaction 
Please record the number corresponding 
to the actual assessment 
5= Very satisfied 
4= Satisfied 
3= Moderately satisfied 
2= Unsatisfied 
1= Very Unsatisfied 
Nociceptive Factorsa,b,c 
N1 I am going to show you a series of faces 
and I would like you to indicate which face, 
number or description most accurately 
describes your level of pain at the moment.  
 
N2 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description most accurately 
describes your level of feeling nauseous or 
vomiting at the moment.  
 
Emotional Factorsa,b 
E1 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description accurately describes 
to what extent you feel sad, low, or 
depressed at the moment.  
 
E2 I am going to show you a series of faces 
and I would like you to indicate which face, 
number, or description accurately describes 
to what extent you feel anxious or nervous at 
the moment.  
 
Activities of Daily Livinga  
A1 Able to breathe easily  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A2 Been able to enjoy food 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A3 Feeling rested 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A4 Have had a good sleep  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A5 Able to look after personal toilet and hygiene   
      unaided  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A6 Able to communicate with family or friends 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A7 Getting support from hospital doctors and 
nurses 
0 to 10,  
where 0=none of the time [poor] and 10=all 

STU2018-0411, Moon, Form A3, Mod_7, 08-05-19 
 
 
 
Page 20 of 21 
Please record the number corresponding to the 
actual assessment 
of the time [excellent] 
A8 Able to return to work or usual home 
activities 
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A9 Feeling comfortable and in control  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
A10 Having a feeling of general well-being  
Please record the number corresponding to the 
actual assessment 
0 to 10,  
where 0=none of the time [poor] and 10=all 
of the time [excellent] 
Overall Patient Satisfactiona 
O1 Patient Satisfaction 
Please record the number corresponding 
to the actual assessment 
5= Very satisfied 
4= Satisfied 
3= Moderately satisfied 
2= Unsatisfied 
1= Very Unsatisfied 
** Patients who are discharged home by POD 2 will not be assessed in the physiological domain 
a. Patient questionnaire adapted from Royse et al. 2010 and Amorim et al. 2014 
b. Pain, depression, and anxiety scales are modified from Wong and Baker 1988 
c. Nausea scale is modified from Baxter et al. 2011 
d. Alertness scale adapted from Doufas et al. 2001 
 
 
 
 
 
 
 
 
 
 

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Appendix 4: Study Flowchart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study cohort of patients 
Randomization 
CIS/NEO 
ROC/SUG 
PACU 
T15 
PACU 
ParametersP
T40 
POD 1 
POD 2-30 
PQRS 
PQRS & adverse 
event monitoring 
Pre-operative 
PQRS 
PQRS 
Pre-
Operative
Intra-
Operative
Post-
Operative
PQRS 
Intraoperative 
ParametersP
arameters
T80 
PQRS