Clinical trial NCT02909439
Conditions: Incomplete Reversal of Neuromuscular Block
Sponsor: Stony Brook University
Start date: 2016-11-01; Completion date: 2018-02-01
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will compare patient recovery measures after reversal of neuromuscular blockade with neostigmine or sugammadex after surgery. Measures include pulmonary function, muscle strength, time to extubation and quality of recovery in the post anesthesia care unit.

Detailed description:
Sugammadex has been shown to have a faster onset and more reliable reversal of neuromuscular blockade when compared to neostigmine as measured by return of Train-of-four (TOF) ratio to \>0.9. (Breuckmann, 2015) The investigator's hypothesis is that sugammadex will be associated with improved deep breathing as measured by incentive spirometry in the PACU. The investigators also hypothesize that patients reversed with sugammadex will have shorter times to extubation and better recovery profiles in the PACU as measured by strength, PACU discharge readiness and quality of recovery scores.

Residual neuromuscular blockade after surgery can result in airway compromise, pulmonary complications, and possible need for reintubation and can be a negative experience for patients. Reintubation after surgery is currently a quality measure in NSQIP (National Surgery Quality Improvement Program) A TOF ratio of \<0.9 has been identified as a marker of residual neuromuscular blockade in the PACU. (Farhan 2013) Several clinical trials have shown that reversal of neuromuscular blockade with sugammadex results in a faster and more reliable return to TOF ratio of \>0.9 when compared to neostigmine. However most of these studies primarily report on TOF ratios. There are scant data on clinical outcomes after reversal with neostigmine versus sugammadex. Incentive spirometry is a clinically meaningful measurement of postoperative pulmonary function, i.e the ability to breath deeply, which minimizes atelectasis and risk of postoperative pneumonia.

The investigators will compare recovery profiles of patients who have received sugammadex or neostigmine for reversal of neuromuscular blockade after surgery. The primary outcome will be incentive spirometry volumes after surgery as a measure of pulmonary function. The secondary measures include hand grip measured using a dynamometer, time to extubation, time to PACU discharge, time to sit independently, and quality of recovery 15 survey scores.

This will be a single-center, prospective, randomized, assessor blinded, controlled trial. Patients will be randomized to either receive sugammadex or neostigmine for the reversal of neuromuscular blockade. The anesthesiologist will be unblinded to the study drug however the assessor in the PACU will be blinded.

Arms: arm 1: Patients in this arm will receive neostigmine for reversal of neuromuscular blockade. Neostigmine is historically the medication that has been used for this purpose. arm 2: Patients in this arm will receive sugammadex for reversal of neuromuscular blockade. Sugammadex is a newer, FDA approved, medication for this purpose.
Interventions: intervention 1: Sugammadex intervention 2: Neostigmine
Intervention descriptions: intervention 1: Sugammadex will be given for reversal of neuromuscular blockade. intervention 2: Neostigmine will be given for reversal of neuromuscular blockade.

Protocol documents:
Prot_SAP_000.pdf: 
Version 5, September 25, 2017 
ID 917402-3 
Quality of Recovery after Reversal with Neostigmine or Sugammadex 
NCT 02909439 
9.25.17 
 


Version 5, September 25, 2017 
Title:  
Pulmonary function, muscle strength, time to extubation and quality of recovery in the post 
anesthesia care unit after reversal of neuromuscular blockade with neostigmine or sugammadex.  
 
Investigators:  
Ramon Abola, MD – PI 
Elliot Bennett-Guerrero, MD – Co-I 
Ruchir Gupta, MD – Co-I 
Jamie Romeiser, MPH – Statistician 
 
A. Background & Significance 
 
Residual neuromuscular blockade after surgery can result in airway compromise, pulmonary 
complications, and possible need for reintubation and can be a negative experience for patients. 
Reintubation after surgery is currently a quality measure in NSQIP (National Surgery Quality 
Improvement Program) A Train of Four (TOF) monitor ratio of <0.9 has been identified as a 
marker of residual neuromuscular blockade in the PACU. Several clinical trials have shown that 
reversal of neuromuscular blockade with sugammadex results in a faster and more reliable return 
to TOF ratio of >0.9 when compared to neostigmine. However most of these studies primarily 
report on TOF ratios. There are scant data on clinical outcomes after reversal with neostigmine 
versus sugammadex. Incentive spirometry is a clinically meaningful measurement of postoperative 
pulmonary function, i.e. the ability to breathe deeply, which minimizes atelectasis and risk of 
postoperative pneumonia.  
 
Our hypothesis is that sugammadex (2 mg/kg for intermediate blockade and 4 mg/kg for deep 
blockade per manufacturer’s package insert) will be associated with and a better recovery profile 
in the PACU when compared to a standard practice dose of neostigmine (70 mcg/kg). Our primary 
outcome is incentive spirometry in the PACU, which is a validated measure of postoperative 
pulmonary function. We also hypothesize that sugammadex will also be associated with a shorter 
time to extubation. Recent publications by Masursky (2013) have defined prolonged times to 
extubation as 15 minutes from the end of surgery. A prolonged time to extubation negatively 
affects OR workflow.   
 
Regarding dose selection, the dose finding study by Groudine (2007) found that there was 
significant variability in recovery times to TOF ratio of >0.9 when patients were reversed from 
profound neuromuscular blockade with Sugammadex 2 mg/kg. A study by Breuckmann (2015) 
used Sugammadex (2 or 4 mg/kg) and in comparison with neostigmine found elimination of 
residual neuromuscular blockade in the PACU (TOF ratio >0.9), and shorter times from study drug 
to extubation and OR discharge.  
 
We have designed this study to reflect routine anesthesia practice. Providers will be instructed to 
aim for a level of neuromuscular blockade (using rocuronium) of 1-2 twitches on TOF during the 
intraoperative period, and data reflecting dosing and the depth of NMB will be recorded in the case 
report form.  The administration of opiates and benzodiazepines will be standardized.  
 


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Previous studies have not measured pulmonary function or objective measures of strength in the 
PACU. Bastin (1997) reported the use of incentive spirometry as a simple means of assessing lung 
function in postoperative lobectomy patients showing good correlation with vital capacity and 
inspiratory reserve volume. A recent study by Bennett-Guerrero (2011) also had used incentive 
spirometry as the primary outcome for pulmonary function in a randomized clinical trial of sternal 
closure devices after cardiac surgery.  
 
Hand Grasp will be measured using a Jamar Dynamometer. This will be measured preoperatively 
and postoperatively in the PACU. This mode of assessing hand grasp has been used in a previous 
Sugammadex study by Baumuller (2015) to assess muscle strength in post anesthesia patients. 
 
Quality of recovery will be assessed using the QOR 15 described by Stark (2013). This is a 
validated, extensive and efficient tool to assess a patient’s quality of recovery.  
 
B. Objectives & Hypotheses 
 
Primary outcome:  
Strength to breathe deeply (inspiratory reserve capacity) using incentive spirometry in PACU – 
30 min, 60 min and 120 min after reversal of neuromuscular blockade.  
 
Secondary outcomes: 
1. Grip strength in PACU – 30 min, 60 min, and 120 min after reversal 
2. Able to sit up unaided in PACU – 30 min, 60 min and 120 min after reversal 
3. Time to extubation (Percentage of prolonged extubation) 
4. Time to readiness for PACU discharge (Aldrete score) 
5. Reintubation in PACU 
6. Adverse Events 
7. TOF Ratio upon PACU admission 
8. QOR 15 Survey 
 
Clinical Hypotheses 
Sugammadex has been shown to have a faster onset and more reliable reversal of neuromuscular 
blockade when compared to neostigmine as measured by return of TOF ratio to >0.9. Our 
hypothesis is that sugammadex will be associated with improved deep breathing as measured by 
incentive spirometry in the PACU.  
 
Patients who are reversed with sugammadex have a lower incidence of residual postoperative 
residual neuromuscular blockade when compared to neostigmine. We hypothesize that patients 
reversed with sugammadex will have better recovery profiles in the PACU as measured by strength 
and PACU discharge readiness. Additionally, we hypothesize that sugammadex will be associated 
with shorter time to extubation compared to neostigmine.  
 
C. Study Design 
 
This will be a single-center, prospective, randomized, assessor blinded, controlled trial.   
 


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Patients will be randomized to either receive sugammadex or neostigmine for the reversal of 
neuromuscular blockade. The anesthesiologist will be unblinded to the study drug however the 
assessor in the PACU will be blinded.  
 
Inclusion Criteria 
The participant must fulfill all the criteria 
listed below for entry.  
1. Each participant must be willing and able 
to provide written informed consent for 
the study 
2. Each participant must be greater than or 
equal to 18 years of age 
3. Each participant must be ASA class I, II or 
III 
4. Planned used of neuromuscular blocking 
drugs 
5. Planned use of endotracheal intubation 
6. Planned for extubation to occur in the OR 
 
 
Exclusion Criteria 
1. ASA Class IV 
2. Age <18 years old 
3. Inability to give oral or written consent 
4. Known or suspected neuromuscular 
disorder impairing neuromuscular function 
5. True allergy to muscle relaxants 
6. A (family) history of malignant 
hyperthermia 
7. A contraindication for neostigmine or 
sugammadex administration 
8. Serum creatinine level of greater than 2.0 
mg/dL 
9. Surgery where the patient’s arm is not 
available for neuromuscular monitoring 
10. A plan to extubate under deep anesthesia 
 
Anesthesia: Induction and maintenance of anesthesia will be at the discretion of the providing 
anesthesiologist. Midazolam (max 2 mg) can be administered prior to induction of GA.  Fentanyl 
(1-3 mcg/kg) will be administered around the time of induction and intubation, and can be 
administered as needed (1-2 mcg/kg/hour). Additional fentanyl, or other opiates, can be 
administered if determined to be appropriate by the anesthesiologist. For patients who receive 
dilaudid, a conversion of dilaudid 1.5 mg to fentanyl 100 mcg will be used to calculate total opiate 
received during data analysis.  Rocuronium will be the only nondepolarizing neuromuscular 
blocking agent utilized in all study patients. Succinylcholine may be given for induction per the 
anesthesiologist discretion. Anesthesiologists will be asked to aim for a depth of neuromuscular 
blockade of 1-2 twitches on train of four (TOF) nerve stimulation. Train of four monitoring via 
peripheral nerve stimulator at the ulnar nerve will be used.  
 
Patients will be assigned a randomization group prior to surgery, however the anesthesiologist will 
only be notified of study arm assignment 15 minutes prior to expected end of surgery to avoid 
bias/confounding due to possible differences in patient management earlier in the case if 
assignment was known earlier.  
 
Group 1: Sugammadex: 2 mg/kg for moderate to shallow block (2-4 twitches on TOF), 4 mg/kg 
for profound block (1-2 post tetanic twitches only) 
Group 2: Neostigmine: 70 mcg/kg with Glycopyrrolate 10 mcg/kg. 
 
Patients will receive reversal of neuromuscular blockade immediately after closure of the surgical 
wound, as defined as the last staple or the last suture. This is consistent with routine anesthesia 
practice.  
 


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Before extubation, the patient should be awake and hemodynamically stable. The patient should 
have regained full muscle strength (5 second head lift or sustained tetanus without fade), follow 
simple verbal commands (e.g. lift head), and breathe spontaneously with acceptable oxygenation 
and ventilation (At least 8 breaths per minute, and a tidal volume of greater than 5 mL/kg). 
 
Additional neuromuscular blockade reversal can be administered at the discretion of the primary 
anesthesiologist. This additional reversal can be given if the patient demonstrates residual 
neuromuscular blockade that is preventing extubation 15 minutes after administration of the initial 
dose of reversal. After extubation, if the patient demonstrates respiratory distress secondary to 
residual neuromuscular blockade, additional neuromuscular reversal can be given. There is no time 
restriction for additional neuromuscular reversal after extubation. Either neostigmine or 
sugammadex may be given for this additional reversal at the discretion of the anesthesiologist. 
Need for additional reversal agent and drug crossovers will be collected as an outcome between 
groups.  
 
Data Collection: Preoperative information will be collected for each patient including age, BMI, 
medical comorbidities, sex, ASA class, race/ethnicity. In the pre-operative holding area, baseline 
measurements of hand grip and incentive spirometry will be measured.  
 
Intraoperative data will be collected by an unblinded research coordinator or team member. 
Intraoperative data will include total dose of rocuronium, time of last rocuronium dose, TOF prior 
to administration of reversal, time of reversal agent, time of extubation, time of OR discharge, 
surgical procedure, duration of surgery (surgery start to surgery stop) and duration of anesthesia 
(anesthesia start to anesthesia stop). TOF ratio will be measured with TOF-watch SX 
acceleromyograph. The unblinded research coordinator will accompany the patient from the OR 
to PACU and measure TOF ratio upon PACU admission. 
 
The patient will be assessed in the PACU by a research coordinator/assistant blinded to the 
patient’s randomization. The research coordinator/assistant will not be directly involved in the 
patient’s care. Incentive spirometry (measured with an incentive spirometer), hand grip strength 
(measured with a Jamar dynamometer), and ability to sit independently will be assessed at 30, 60 
and 120 minutes from reversal of neuromuscular blockade. Level of sedation will be measured at 
30, 60 and 120 minutes using the RASS sedation scale. Time to PACU readiness will also be 
assessed using the Aldrete score.  
 
The 120-minute measurement will be completed even if the patient has been discharged from the 
PACU prior to this time. If a patient is ready for discharge home prior to 120 minutes, they will 
remain longer in the holding area to complete the 120-minute assessment. The patient consent will 
allow for this provision.  
 
24 hours after surgery, patients will complete a QOR15 survey either in person (if still hospitalized) 
or via telephone from a research coordinator/assistant blinded to the patient’s study arm 
assignment.  


Version 5, September 25, 2017 
 
 
D. Study Procedures 
 
Patients who are scheduled for surgery at Stony Brook Hospital will be identified based on 
inclusion/exclusion criteria. Explanation of the research protocol and consent will be obtained 
during the preoperative period allowing patients sufficient time to decide if they wish to participate 
in this study. Once patients have consented to participate, they will be assigned a unique 
identification number.  
 
Patients will be randomized (1:1) to either the neostigmine or sugammadex group. When enrolling 
patients, we will divide patients into short (expected < 2 hours) or long (expected > 2 hours) 
surgical groups and have separate randomization lists for these two durations of surgery. This will 
allow us to ensure balance of this important confounding variable between study groups.  
 
Patients will be evaluated in the preoperative area to obtain their medical history, demographic 
information, and type of surgery. Preoperatively, we will obtain hand grasp, and incentive 
spirometry measures. For each incentive spirometry measurement, patients will use the device 
three times. Each volume will be recorded and the largest volume will be used for analysis. To 
avoid confounding factors of patient position, we will standardize our measurements: patients will 
be sitting at a 45-degree angle in a stretcher, unless there are medical contraindications to this 
positioning. 
 
Patient Enrollment: 60 
Randomization 
Sugammadex (n=30) 
2 mg/kg moderate block 
4 mg/kg profound block 
Neostigmine (n=30) 
70 mcg/kg (max 5mg) 
Time to extubation 
Time to discharge from OR 
TOF Ratio upon PACU 
Grip strength in PACU – 30 min, 60 min, and 120 min after reversal 
Able to sit up unaided in PACU – 30 min, 60 min and 120 min after reversal 
Time to readiness for PACU discharge (Aldrete score) 
Adverse Events 
QOR 15 Survey 
QoR Quality of Recovery patient survey 
(blinded 
assessor) 
(blinded assessor) 
In PACU 
24 hours post-op 
Intra-operative 
(unblinded assessor) 


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The patients will undergo anesthesia and surgery and receive either neostigmine or sugammadex 
based on their group assignment. Intraoperative information will be collected regarding the 
duration of surgery, time to extubation, and information about use and depth of neuromuscular 
blockade. In the PACU, patients will be assessed by a blinded assessor for hand grip strength, 
incentive spirometer measures, and ability to sit independently. Time to PACU discharge readiness 
will be assessed using the Aldrete score. The patients will be surveyed 24 hours after surgery using 
the QOR 15 to assess their quality of recovery.  
 
This will then complete their participation in the study.  
 
E. Statistical Analysis and Sample Size Justification 
 
Statistical procedures/analysis will be performed by the trial’s biostatistician.  
 
Randomization: Randomization will be performed using a sealed envelope technique.  Envelopes 
will not be reused in any case.  Two computer generated randomization schema, in permuted 
blocks, will be provided by the trial’s statistician, one for short cases and one for long cases. 
 
Unblinding Process: The investigator and the PACU assessor will remain blinded to patient 
allocation during this study. The primary anesthesiologist conducting the anesthesia for these 
patients will not be blinded to their allocation, for purposes of appropriate and safe reversal of 
neuromuscular blockade. An unblinded member of the study team will record intraoperative 
information for each patient to which the primary investigator will blinded to until final analysis. 
After all patients have completed the study and all data has been collected, the clinical database 
will be locked and unblinded for statistical analysis. 
 
Variables/Time Points of Interest: All variables will be collected on the day of surgery with the 
exception of the QOR 15 which will be collected on postoperative day one.  
 
Preoperative variables collected include:  
1. Age 
2. ASA Classification 
3. Ethnicity 
4. BMI 
5. Surgery 
6. Surgical Division (Ortho, General, GYN, Urology, ENT, Neuro, Plastics) 
7. Hand Grip Strength 
8. Incentive Spirometry Measure 
9. Ability to sit independently 
 
Intraoperative variables collected include:  
1. Duration of surgery (surgery start to surgery stop) 
2. Time to extubation (surgery stop to extubation time) 
3. Time to OR discharge (surgery stop to time out of OR) 
4. Total dose of rocuronium 
5. Time of last dose rocuronium 


Version 5, September 25, 2017 
6. Time of reversal of neuromuscular blockade 
7. # of twitches of TOF prior to reversal 
 
Postoperative variables collected include:  
1. Incentive spirometry at 30, 60 and 120 min after reversal 
1. TOF ratio measured by TOF watch on PACU admission 
2. Hand Grip at 30, 60 and 120 min after reversal 
3. Independent sitting ability at 30, 60 and 120 min after reversal 
4. Time to PACU discharge readiness (PACU admit to Aldrete score of 10) 
5. QOR 15 Survey after surgery 
6. RASS sedation score at 30, 60 and 120 min 
 
These variables will be analyzed after all patients have completed this study and all medical data 
has been collected. Preoperative data and intraoperative data (duration of surgery, amount of 
rocuronium) will be used to compare that both study groups have similar characteristics. Incentive 
spirometry measures in the PACU will be our primary outcome. Secondary outcomes will look at 
time to extubation and measures of PACU recovery with relation to agent used for reversal of 
neuromuscular blockade.  
 
Statistical Methods 
 
Primary Outcome: Spirometry readings at baseline, PACU 30, 60 and 120 minutes after reversal 
of neuromuscular blockade 
A “change from baseline” spirometry score will be calculated for the PACU 30, 60 and 120 time 
points for each patient. A repeated measures (mixed) ANOVA will be performed comparing the 
mean spirometry change scores at 30, 60 and 120 time points, by treatment group. This ANOVA 
design will allow us to test 3 things: 1 – is there a difference in mean spirometry change score by 
treatment group; 2- does spirometry measurement change over time; and 3 – is there a group/time 
interaction, specifically, does the sugammadex group spirometry measurement change differently 
over time compared to the neostigmine group? Alpha will be set at 0.05.  
Secondary outcomes: There will be six secondary outcomes:  
1. Grip strength in PACU – 30 min, 60 min and 120 min 
2. Able to sit up unaided in PACU – 30 min, 60 min and 120 in 
3. Time to extubation (Percentage of prolonged extubation) 
4. Time to readiness for PACU discharge (Aldrete score) 
5. TOF ratio upon PACU admission 
6. QoR 15 


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We will use a Bonferroni correction for multiplicity, thus, each secondary outcome will be tested 
at the alpha of 0.008 (0.05/6 = 0.008) level for significance. We plan to test the 6 secondary 
outcomes even if the primary outcome does not show a difference.  All continuous outcomes will 
be first tested for normality using a Shapiro-Wilk test, and appropriate analytical methods will be 
used. A repeated measures ANOVA (or Friedmen’s test) will be used to test for group differences 
in grip strength over time. T-tests or Wilcoxon rank sum tests will be used to test for differences 
in treatment groups for Aldrete score and QOR15 score. Chi-Square and Fisher exact tests will be 
used to examine for group differences in proportion of first sit time, prolonged extubation and TOF 
ratio upon PACU admission.  
1. Grip strength in PACU – 30 min, 60 min and 120 min – A repeated measures ANOVA will 
be used to test for group differences in grip strength over time.  
2. Able to sit unaided in PACU – 30 min, 60 min, and 120 min – A chi square/fisher’s exact test 
will be used to see if there is a difference between the 2 groups’ ability to sit independently.  
3. Time to extubation (Percentage of prolonged extubation) – Prolonged extubation is defined 
as 15 minutes after end of surgery. Time to extubation will be dichotomized into either YES- 
prolonged, or NO- normal. Chi Square or Fisher’s exact tests will be performed to test for 
significant differences in proportion between groups.  
4. Time to readiness for PACU discharge (Aldrete score) – Either t-tests or Wilcoxon rank sum 
tests will be performed to assess the difference in mean/rank Aldrete score.  
5. TOF Ratio upon PACU admission – Chi-square or Fisher’s exact tests will be performed to 
test for significant differences in proportion between groups.  
6. QoR 15 – Either t-tests or Wilcoxon rank sum tests will be performed to assess the 
differences in mean/rank QoR15 score.  
Reintubation in PACU: Because we anticipate reintubation rates to be 0% for both groups, this 
variable will not be a secondary outcome, but rather an adverse event worth reporting.  
Drug crossover: We will collect and analyze the incidence of drug crossovers for each group. This 
is defined as patients who received the initial neuromuscular reversal, but then were given the 
other neuromuscular reversal agent due to residual paralysis. 
 
Analysis Population: Our primary population for data analysis will be a “modified intention to 
treat” grouping. Any patient who received a neuromuscular blockade reversal agent (neostigmine 
or sugammadex) will be included in this population. Patients who received neither reversal agent 
(i.e. patients who remain intubated after surgery) will be excluded from this primary population 
analysis. Our secondary population for analysis will be “actual medication received.” Patients 
will be included in the group of which reversal agent they actually received, in the event that the 
wrong reversal agent is given. Patients who receive both reversal agents (drug crossover) will be 
excluded from this secondary population analysis. Drug crossovers will be collected as a separate 
outcome measure.  
 
Power/Sample Size 
We believe that a 20% difference in incentive spirometry volumes is clinically relevant. We 
anticipate that patients will have a preoperative incentive spirometry volume of 2200mL and a 
postoperative incentive spirometry of 1540 mL with regular care. A 20% difference with 
sugammadex would translate to 300 mL increase in inspiratory reserve capacity (1840 mL vs 1540 
mL):  


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300 mL difference in volume (assuming a standard deviation of +/- 400 mL):  
Group 1: 1540 mL +/- 400 mL 
Group 2: 1840 mL 
Enrollment Ratio 1:1, alpha 0.05 and power 80%  Total sample size required is 60 patients. 
The study expects to enroll about 80 subjects to end with 60 “randomizable” subjects after 
accounting for screen failures, withdrawals or surgery cancelations.  
 
F. Adverse Experience Reporting 
 
Safety evaluation: For this Phase 4 (post marketing) study serious adverse events (SAEs) that may 
occur during the study will be recorded in the case report form. The AE record in the case report 
form includes the nature of the event (with onset date and time, end date and time) severity, 
treatment, outcome, and the relationship to the treatment given. All serious AEs that require 
reporting will be reported to the medical ethics committee and authorities as required by GCP/GRP 
guidelines.  
 
References 
 
Masursky D, Dexter F, Kwakye MO, Smallman B. Measure to quantify the influence of time from 
end of surgery to tracheal extubation on operating room workflow. Anesthesia and analgesia. 
2012;115(2):402-6. 
 
Groudine SB, Soto R, Lien C, Drover D, Roberts K. A randomized, dose-finding, phase II study 
of the selective relaxant binding drug, Sugammadex, capable of safely reversing profound 
rocuronium-induced neuromuscular block. Anesthesia and analgesia. 2007;104(3):555-62. 
 
Brueckmann B, Sasaki N, Grobara P, Li MK, Woo T, de Bie J, et al. Effects of sugammadex on 
incidence of postoperative residual neuromuscular blockade: a randomized, controlled study. 
British journal of anaesthesia. 2015;115(5):743-51. 
 
Bastin R, Moraine J-J, Bardocky G, Kahn R-J, Melot C. Incentive Spirometry Performance, A 
reliable Indicator of Pulmonary Function in the Early Postoperative Period after Lobectomy? 
Chest. 1997;111:559-63. 
 
Bennett-Guerrero E, Phillips-Bute B, Waweru PM, Gaca JG, Spann JC, Milano CA. Pilot Study 
of Sternal Plating for Primary Closure of the Sternum in Cardiac Surgery Patients. Innovations. 
2011;6:382-8. 
 
Baumuller E, Schaller SJ, Chiquito Lama Y, Frick CG, Bauhofer T, Eikermann M, et al. 
Postoperative impairment of motor function at train-of-four ratio >/=0.9 cannot be improved by 
sugammadex (1 mg kg-1). British journal of anaesthesia. 2015;114(5):785-93. 
 
Stark PA, Myles PS, Burke JA. Development and Psychometric Evaluation of a Postoperative 
Quality of Recovery Score. Anesthesiology. 2013;118(6):1332-40. 

ICF_001.pdf: 
 
ID 917402-3 
Quality of Recovery after Reversal with Neostigmine or Sugammadex 
NCT 02909439 
5.26.17 
 


 
 
RESEARCH CONSENT FORM 
 
 
Project Title:  Pulmonary function, muscle strength, time to extubation, and quality of recovery 
in the post anesthesia care unit after reversal of neuromuscular blockade with neostigmine or 
sugammadex 
 
Principal Investigator: Ramon Abola, MD  
Co-Investigators: Elliott Bennett-Guerrero, MD 
       TJ Gan, MD 
       Jamie Romeiser, MPH 
 
Department:  Anesthesiology 
You are being asked to be a volunteer in a research study.  
You are encouraged to take your time in making your decision. You may want to discuss this 
study with your friends and family. 
PURPOSE  
The purpose of this study is to determine how recovery after anesthesia is different in patients 
who receive neostigmine or sugammadex. Neostigmine and sugammadex are both FDA-
approved medications to reverse the effect of neuromuscular blockade (paralysis) at the end of 
surgery. We will be assessing breathing function, hand grip strength, ability to sit independently, 
and time spent in the post anesthesia care unit before discharge.  
 
Neuromuscular blockade is a routine component of general anesthesia that allows for 
placement of a breathing tube and optimizing operating conditions.  Neostigmine and 
sugammadex are both FDA-approved medications that reverse neuromuscular blockade at the 
end of surgery. Residual muscle weakness after anesthesia can result in breathing difficulties, 
patient discomfort, and poor recovery after surgery.  
 
The “reversal” drug sugammadex is widely used in Europe and elsewhere. It was recently 
approved by the FDA so there is less experience with its use in the US. We have been using 
Sugammadex at Stony Brook for several months with good results.  Studies have suggested 
that sugammadex may be a more effective reversal agent compared to our traditional reversal 
agent, neostigmine. The purpose of this study is to assess differences between the two reversal 
agents on the quality of recovery after anesthesia.  
 
Any patient who will receive neuromuscular blocking drugs as a component of their anesthesia 
with reversal of these drugs, at the end of surgery, is eligible for this study. We expect to enroll 
80 patients in this study. 


 
PROCEDURES 
If you decide to be in this study, your part will involve: 
Medical history survey: This survey will ask you questions about your general health during the 
time of the survey, before your surgery. 
Randomization: You will be randomly (by chance) assigned to one of two groups: one group will 
receive neostigmine with glycopyrrolate for reversal from anesthesia and the other group will 
receive sugammadex for reversal from anesthesia.  Pain management standards will remain 
unchanged and drugs to prevent nausea and vomiting will be the same in both groups. 
Anesthesia: Your anesthesiologist will administer general anesthesia on the day of surgery. As 
part of this study, you will receive rocuronium, a neuromuscular blocking drug which is a routine 
medication given during general anesthesia. The anesthesiologist will maintain a specific depth 
of neuromuscular blockade that will also provide optimal operating conditions. This 
neuromuscular blockade will be reversed at the end of surgery. Either neostigmine or 
sugammadex will be given for reversal of neuromuscular blockade depending on which group 
you have been assigned to. The administration of opiate medication (fentanyl) and 
benzodiazepine medication (midazolam) as part of your anesthetic care will be standardized to 
typical amounts.  
Postoperative Assessment: Measurements will be taken at 30, 60 and 120 minutes after 
surgery, in the post anesthesia care unit (PACU), to assess breathing function and hand grip 
strength. Breathing function will be measured using an incentive spirometer. An incentive 
spirometer is a device that measures how deeply you can breathe in. If you are ready for 
discharge from the PACU prior to 2 hours after surgery, you will remain long enough to 
complete the 2-hour assessment. 
Quality of Recovery: We will ask you to take a 15 question survey called Quality of Recovery 
(QOR) 24 hours after surgery. This asks you questions about your well-being, pain, nausea, 
anxiety, sleep and other questions. You will complete a QOR15 survey either in person (if still 
hospitalized) or via telephone with a research coordinator/assistant.  
The duration for participation in this study is 2 days (from the day of your surgery through 
approximately 24 hours after you are discharged from the recovery room). 
RISKS / DISCOMFORTS 
Although this study will not involve many changes to the care that you would already be 
receiving, the following risks/discomforts may occur as a result of being in this study: 
Discomfort from the Intravenous (IV) line: In many surgeries as part of your routine (non-study) 
care, your anesthesiologist will insert a second IV, often after you have been put to sleep for the 
operation.  If a second IV is not inserted as part of your routine care  we will place this second 
as part of the study after you have gone to sleep, since we need a second IV for the study.  
Some potential risks associated with IV lines include: 
 
Bleeding/bruising: There is a risk of bleeding at the skin puncture site. There is also the 
possibility of bruising where the IV is inserted. We will applying pressure directly to the 
puncture site to minimize the risk. 


 
 
Local infection: As with all needle punctures, there is a possibility of local infection. This 
will be reduced by using antiseptics and by using sterile equipment. 
Loss of Confidentiality: Research often poses the risk of loss of confidentiality to subjects who 
participate. Many persons who would not otherwise be privy to identifiable, private information 
about the subject may be involved in the research process.  To minimize this risk, all the study 
data that we get from you will be coded and kept locked up. If any papers and talks are given 
about this research, your name will not be used (see below on confidentiality).  
Discomfort from the Train of Four (TOF) monitor: To assess the level of muscle strength, a 
monitor will be placed on one of your hands during surgery to stimulate the muscles of that 
hand.  This monitor, called a TOF watch, will be used specifically for this research. You may 
have some muscle soreness from the repeated twitches, though this would be a highly unlikely, 
unexpected and rare occurrence with this monitor.  
 
Residual muscle weakness: After the surgery has ended and the breathing tube has been 
removed from your mouth, there is a small chance you may still feel muscle weakness.  This is 
not commonly seen with the drugs we are using for your surgery.  However, to minimize this risk 
further, we will ensure that your muscle strength has fully recovered prior to waking you up, that 
your lungs are properly breathing on their own without the assistance of any mechanical device 
such as a ventilator, and that your vital signs are stable prior to waking you up and removing the 
breathing tube. 
 
Since this is a research study, not all risks may be known at this time; there may be unforeseen 
risks associated with study participation. 
BENEFITS  
There is no direct benefit expected as a result of you being in this study  
PAYMENT TO THE INSTITUTION    
This project is funded, in part, by a grant or contract from Merck Investigator’s Program (MISP) 
to the Research Foundation of Stony Brook University, in support of the Investigators' work on 
this study  
CONFIDENTIALITY   
We will take steps to help make sure that all the information we get about you is kept 
confidential. Your name will not be used wherever possible. We will use a code instead. All the 
study data that we get from you will be kept locked up. The code will be locked up too. If any 
papers and talks are given about this research, your name will not be used.  
We want to make sure that this study is being done correctly and that your rights and welfare 
are being protected. For this reason, we will share the data we get from you in this study with 
the study team, Stony Brook University's Committee on Research Involving Human Subjects, 
applicable Institutional officials, and certain federal offices, including the Office for Human 
Research Protections (OHRP), and, where applicable, the Food and Drug Administration (FDA).  


 
Merck, who is providing the grant for this study, will be provided a final study report with 
descriptive data, tables, data listings and adverse experiences. Any subject level data shared 
with Merck will be coded with a number and no other personal identifiers such as birth date or 
study subject initials.  
However, if you tell us you are going to hurt yourself, hurt someone else, or if we believe the 
safety of a child is at risk, we will have to report this.  
In a lawsuit, a judge can make us give him the information we collected about you.  
While you are in this study we will get data about your health from your medical record. We will 
also get health data from the results of the tests you will have done in this study. You have a 
right to privacy but the data we get about your health in this study can be shared with the people 
referenced above (the study team, Stony Brook University's Committee on Research Involving 
Human Subjects, applicable institutional officials, and federal offices such as OHRP, FDA) as 
well as your medical doctor. 
Your health data are shared to make sure the study is being done correctly, costs are charged 
correctly, and to make sure your rights and safety are protected. Not all of these people are 
required by law to protect your health data. They might share it with others without your 
permission.  
You have the right to stop allowing us to use or give out your health data. You can do this at any 
time by writing to Ramon Abola. If you do this, we will stop collecting any new health data from 
you, except if we need to keep an eye on a bad side effect you were having in the study. We will 
use any data we collected before you wrote your letter. When you sign the consent form at the 
end, it means:  
 
That you have read this section.  
 
That you will allow the use and reporting of your health data as described above.  
 
You have received a form from the University Hospital. It is called the Notice of Privacy 
Practices form.  
Clinical Trial Registry 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time”. 
COSTS TO YOU   
There are no foreseeable costs to you.   
ALTERNATIVES  
Your alternative to being in this study is to simply not participate. 
IN CASE OF INJURY  


 
If you are injured as a result of being in this study, please contact the study’s principal 
investigator, Dr. Ramon Abola at telephone # 631-624-7045. The services of Stony Brook 
University Hospital will be open to you in case of such injury. However, you and/or your 
insurance company will be responsible for payment of any resulting treatment and/or hospital 
stay. 
YOUR RIGHTS AS A RESEARCH SUBJECT   
 
Your participation in this study is voluntary. You do not have to be in this study if you 
don't want to be. 
 
You have the right to change your mind and leave the study at any time without giving 
any reason, and without penalty. 
 
Any new information that may make you change your mind about being in this study will 
be given to you. 
 
You will get a signed and dated copy of this consent form to keep. 
 
You do not lose any of your legal rights by signing this consent form. 
QUESTIONS ABOUT THE STUDY OR YOUR RIGHTS AS A RESEARCH SUBJECT    
 
If you have any questions, concerns, or complaints about the study, you may contact Dr. 
Ramon Abola, at telephone # 631-624-7045. 
 
If you have any questions about your rights as a research subject or if you would like to 
obtain information or offer input, you may contact Ms. Judy Matuk, Committee on 
Research Involving Human Subjects, (631) 632-9036, OR by e-mail, 
judy.matuk@stonybrook.edu.  
 
Visit Stony Brook University’s Community Outreach page, 
http://www.stonybrook.edu/research/orc/community.shtml for more information about 
participating in research, frequently asked questions, and an opportunity to provide 
feedback, comments, or ask questions related to your experience as a research subject. 
If you sign below, it means that you have read (or have had read to you) the information given in 
this consent form, and you would like to be a volunteer in this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Name (print) 
 
 
  
Subject Signature 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Person Obtaining Consent (print) 
Signature of Person Obtaining Consent Date