Clinical trial NCT02724111
Conditions: Neuromuscular Blockade Surgery Anesthesia Spinal Diseases
Keywords: Neuromuscular blockade Surgical rating scale Rocuronium Sugammadex Spinal surgery General anesthesia
Sponsor: Korea University Guro Hospital
Start date: 2016-05-15; Completion date: 2017-02-16
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators aim to investigate operating conditions, postoperative recovery and overall satisfaction of surgeons between deep neuromuscular blockade (NMB) group and restricted NMB group during spinal surgery under general anesthesia. The investigators hypothesize that this study can present good surgical conditions, postoperative recovery outcomes and overall satisfaction of surgeons in deep NMB group, thereby proving the advantages of deep NMB as well as flaws of restricted NMB in spine surgeries.

Detailed description:
* Group treatment (Arms): group treated with restricted neuromuscular blockade (NMB) (Group RB); group treated with deep NMB (Group DB) → randomized allocation (subjects: motor-evoked potential \[MEP\] not monitored surgeries)
* Inclusion criteria: American Society of Anesthesiologists (ASA) physical status I-II adults, aged 18-75 years, scheduled for elective spinal surgery (cervical or lumbar surgeries which have lesions no more than 3 spinal levels and not monitored by MEP) of duration \>1 hour and prone position under total intravenous anesthesia (TIVA).
* Exclusion criteria: Pregnancy, the receipt of medication known to interfere with neuromuscular blockade, diseases affecting neuromuscular transmission, and the history of hypersensitivity on rocuronium or sugammadex. The patients who will have hemodynamic instability, mean blood pressure increase or fall of \> 30% from baseline (lasting for more than 5min), and blood loss \> 1 L during surgery, and MEP monitored surgeries.
* Outcome Measures

  * Primary outcome: Mean value of peak inspiratory pressure recorded every 15 minutes.
  * Secondary outcomes:

    1. The number of body movements (including cough or any diaphragm movement).
    2. The degree of bleeding of each patient scaled by surgeons (Intraoperative scale for assessment of operating condition of surgical field: 0 - No bleeding, 1 - Slight bleeding - no suctioning of blood required, 2 - Slight bleeding - occasional suctioning required but not threatened the operative field, 3 - Slight-bleeding - frequent suctioning of blood was required that threatens the operative field a few seconds after suctioning, 4 - Moderate bleeding - frequent suctioning of blood was required which threatens the operative field directly after suctioning, 5 - Sever bleeding - continuous suctioning of blood was required which severely threatened the operative field make the surgery not possible).
    3. The muscle tone of each patient scaled by surgeons (1: muscle tone is good, suitable for surgery; 2: muscle tone is moderate, but do not affect the operation; 3: muscle tone is hard, making the operation difficult.).

       * Three time-points of assessment of the muscle tone: ① At the placement of back muscle retractor for opening the operating site after the skin and subcutaneous incision, ② At the screw insertion through the pedicle of spine during surgery, ③ At the other period (overall muscle tone).
    4. Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes): measured by the pressure probe placed between the retractor and the back muscle.
    5. Overall satisfaction of surgeons for the surgical condition will be assessed by the surgeons who perform surgery using numerical rating scale (NRS; 1-10) after surgery.
    6. Recovery profiles including eye opening time, extubation time and sedation score (the Observer's Assessment of Alertness/ Sedation (OAA/S) score; awake, 5 to unresponsive, 1) every 10 min for 1 hour at postanesthesia care unit (PACU).
    7. Postoperative adverse events

Arms: arm 1: This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade \[NMB\] (train-of-four \[TOF\] count 0, post-tetanic count \[PTC\] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. arm 2: This arm will not be given sufficient dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade \[NMB\] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change \[a prone position\]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded.
Interventions: intervention 1: sufficient dose of rocuronium intervention 2: sugammadex 10 min after position change
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
ICF_002.pdf: 
KOREA UNIVERSITY MEDICAL CENTER 
INSTITUTIONAL REVIEW BOARD 
Standard Informed Consent Form (for Adult) 
[KUMC II. 01-04] 
 
KOREA UNIVERSITY MEDICAL CENTER INSTITUTIONAL REVIEW BOARD 
[KUMC II. 01-04] Standard Informed Consent Form (for Adult) 
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Informed Consent Form 
 
 
 
Official Title : Comparison of Operating Conditions, Postoperative Recovery and Overall Satisfaction 
Between Deep and Restricted Neuromuscular Blockade for Spinal Surgery Under 
General Anesthesia   
 
Identifiers : NCT02724111 
 
Date of Document : 9th June 2016 
 
 


KOREA UNIVERSITY MEDICAL CENTER 
INSTITUTIONAL REVIEW BOARD 
Standard Informed Consent Form (for Adult) 
[KUMC II. 01-04] 
 
KOREA UNIVERSITY MEDICAL CENTER INSTITUTIONAL REVIEW BOARD 
[KUMC II. 01-04] Standard Informed Consent Form (for Adult) 
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[KUMC II. 01-04] Standard Informed Consent Form (for Adult) 
 
Guideline for Research Subjects’ Consent 
Research Title  
Effect of Neuromuscular Blockade on Operating Conditions and Overall Satisfaction During Spinal Surgery 
 
Principal Investigator 
Byung Gun Lim 
 
The purpose of this guideline is to help you gain understanding of this research, and it contains details about the research. 
Please read carefully before deciding whether or not you will participate in this research. 
 
A goal of a research is to explore and investigate undiscovered areas. It is important that you are given sufficient 
information regarding the research and understand such information as the objective, process, subject candidates, potential 
risk/benefit, discomfort, etc. before you decide to participate. 
 
You can talk this over with your family or others before you decide. If you decide to take part in the research, please fill out 
and sign the consent form. 
 
If you decide to participate in the research, you will be asked to voluntarily fill out the informed consent form before 
participation. You may decide not to participate. Even if you decided not to, you will not experience any losses nor 
disadvantages in your treatment. 
 
1. Background and Objective of Human Research 
 
Neuromuscular blockade (NMB; muscle relaxation) during abdominal or laparoscopic surgery under general anesthesia is 
known to be effective for facilitating the surgical procedure by improving the surgical condition. However, there was no report 
about the effectiveness in spine surgeries yet. Therefore, we aim to investigate operating conditions, postoperative recovery and 
overall satisfaction of surgeons between the different degrees of NMB (deep NMB group and restricted [shallow] NMB) for 
spine surgery under general anesthesia.  
 
2. Number of Subjects and Research Venue 
 
This research will be conducted with 90 subjects in Korea University Guro Hospital.  
We plan to recruit 90 subjects in our hospital, and the research will be conducted for 12 months. 
If you decide to proceed with the trial, please be noted that the trial will last 12 months, during this period, you are slated to visit 
total of 2 times, and each visit will take 1 hour in average. 
 
3. Method and Process of Clinical Research  
 
The research process for participants is as follows.  
If you decide to participate with this research, you will be asked to fill out the "Informed Consent Form”. If you have any questions 
regarding the research, you may talk to any research staff. After you sign the consent form, the investigator will take your medical 


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history to check if you meet the criteria for registration. 
 
(Randomization)  
When you are determined to be appropriate by the screening process, you will be randomly assigned to either one of two groups. 
1:1 randomized assignment (which has equivalent possibility of coin flipping) will be used for assignment to either group 
treated with deep NMB (Group DB) or group treated with restricted (shallow) NMB (Group RB). 
 
The methodology of the research is: [questionnaires, application of anesthetic method including muscle relaxant, grading scale, 
etc.] In the questionnaire, you will be asked of expected outcome, satisfaction, etc. in both groups. Filling out the questionnaire 
will take about 60~90 minutes. 
 
For both groups, you are just required to answer several questions in the recovery room and to record any adverse event during 
the postoperative 24 hours. During the anesthesia and surgery, the investigator will observe and record the required data. 
 
Some tests or procedures in the research are provided regardless of participation of the research, as they are included in standard 
treatment process. Tests or procedures additionally provided by the research are as follow. 
 
1) A train-of-four (TOF, frequency 2 Hz, current 50 mA, interval 15 sec) monitoring using an accelerator device (TOF-Watch 
SX; Organon Ltd, Ireland) for assessment of NMB degree. 
2) Pressure monitoring of the back muscle retractor using the probe and device for intracranial pressure measurement 
 
4. Expected Benefit of Participating in Human Research 
 
Sugammadex, the powerful reversal agent of NMB will be given to the participants for free during the surgery. 
Additional inspection about sedation, satisfaction, and adverse events including nausea or vomiting, pain will be checked by the 
investigator during the postoperative period of the clinical trial.  
In addition, it is a great help to improve the surgical condition in patients undergoing spine surgery under general anesthesia and 
similar groups alike. 
 
5. Possible Risks, Side Effects and Discomfort from participating in the research 
` 
Over the course of your participation, inconvenience might occur as you are expected to make 2 visits to the hospital for 
screening and interviews. No additional discomfort, inconvenience, risk associated with additional monitoring devices is 
expected. The participation in the research does not affect your standard treatment process including anesthetics, muscle 
relaxant, reversal agents such as sugammadex, pyridostigmine or analgesics, and therefore standard treatment will be provided 
even if you decide not to participate. 
 
6. Expenditure in Research Participation 
 
Much of the tests or procedures you will be receiving are included in standard treatment processes regardless of your 
participation, and therefore the additional cost of such tests or procedures will not be charged to you. Rather, sugammadex, the 
powerful and expensive reversal agent of NMB will be given to the participants for free. 
 
Still, other tests or procedures including TOF or retractor pressure monitoring for research purpose that are not included in 
standard treatment processes, will not be charged to you, as they will be paid for by the investigator (or the sponsor MSD 
pharmaceutical company). Please note that the research is funded by MSD pharmaceutical company. 


KOREA UNIVERSITY MEDICAL CENTER 
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7. Compensation for Research Participation 
 
No compensation will be provided when you participate in clinical research 
 
8. Compensation and/or Treatments in Case of Damage or harm 
 
The process of the research does not deviate from the standard treatment process which you will experience even if you decide 
not to participate. Therefore, usual safety protection measures will be applied to your treatment process, and information about 
the research objective and methods will be adequately provided prior to the initiation of the research. If, over the course of your 
participation, any expected or unexpected adverse events occur due to procedures or interventions outside the standard 
treatment process, you will be provided with the best treatment possible. 
 
 
9. Participant’s Obligation 
 
Over the course of your participation, you are expected to follow below instructions: 
As you participate in the research, you are expected to follow schedules provided by the investigator, and make total of 2 
hospital visits. Over the course of the research, please notify the investigator if you experience any discomfort. If you have any 
questions regarding above matters, please contact the investigator and you will be provided with necessary information. 
 
 
10. Withdrawal from Clinical Research 
 
Participants will be withdrawn by the investigator for the reasons described below. 
a. Whenever participant wants to be withdrawn from the research. 
b. When participant cannot follow the schedules and protocols of the research. 
 
Participants will continue to be provided with the proper NMB treatment during the surgery even after they drop out of the research; 
the investigator will perform postoperative visit and follow-up to protect participants’ safety.  
Participants’ personal information collected before dropping out will be used for the research, but no additional personal 
information will be collected thereafter.   
 
11. Privacy Policy for Collecting, Using Personal (sensitive) Information and Providing it to The Third-party 
The investigator requires additional consent from participants in case of collecting sensitive data such as health and gene 
information, and in case of providing data to the third-Party.  
 
※ This applies when the information is used for secondary purpose, outside the pertaining research. 
By signing this consent form, your personal (sensitive) information will be collected and used by the investigator, and can be 
provided to third-party. 
 
※ For more information, please read below. 
1) Purpose of collecting and using personal information  
Report of significant adverse events 


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2) List of personal (sensitive) information 
Participant’s name, gender, age and hospital registration number  
Health-related information such as medical records and documents in the process of clinical research  
 
3) Period of retaining and using personal information  
Your personal (sensitive) information is to be stored and used while participating in clinical research. After the termination of the 
research, the personal information will then either immediately be terminated or kept as a record for five additional years from the 
date of the termination. 
 
4) Right to refuse and disadvantages due to refusal 
Participants have the right to decide freely in clinical research whether they provide personal (sensitive) information or not during 
any phase of the clinical research process. If participants do not allow to be provided their personal information, he or she will not 
experience any losses or disadvantages.   
 
5) Provision of Personal Information to Third-Party 
Collected personal (sensitive) information from following research will not be allowed to use for other purposes except the report of 
significant adverse events. In case of providing participants’ personal information, the identifiable personal information will be not 
included. If participants wish to give his or her consent to providing their personal information, please fill out the "Consent 
Agreement Form." 
 
12. Privacy Policy of Personal Information and Record  
Collected personal information while participating in clinical research will be protected with complete confidentiality and if the 
research results are reported, published or announced, participant’s identity will not be revealed.  
 
Monitor/Auditor, IRB(Institutional Review Board), Relevant Government Agencies (ex: Ministry of Food and Drug Safety, 
Ministry of Health and Welfare Affairs, and etc.) are able to access your medical records to inspect the procedures and reliability, to 
the extent that does not violate your privacy, as per relevant policy.  
 
13. Right to Participate or Withdraw 
 
You have a right to withdraw from the research at any time. In this case, participation will be terminated by the investigator, and 
the investigator will not collect additional information afterwards. If you do not want the investigator to use collected 
information in clinical research, please inform the investigator. 
 
Your decision will not influence treatment you receive. If you decide not to participate or withdraw from the research, you will 
not experience any losses nor disadvantages. If you do not want to participate, please inform the investigator. 
  
If the investigator collects new information, which influence the determining of participating in clinical research, the investigator 
should provide it at the right time to participants or representatives.  
If the investigator collects new information which is deemed significant in your decision making, the investigator will inform you 
or your representative of the information at appropriate time. 
 
14. Contact Information 
All the question about the clinical research will and can be answered by the investigator or staffs.  Please feel free to contact us by 
phone, e-mail, or fax if you or your representatives have any questions during anytime you desire. 


KOREA UNIVERSITY MEDICAL CENTER 
INSTITUTIONAL REVIEW BOARD 
Standard Informed Consent Form (for Adult) 
[KUMC II. 01-04] 
 
KOREA UNIVERSITY MEDICAL CENTER INSTITUTIONAL REVIEW BOARD 
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Name of Principal Investigator: Byung Gun Lim 
 
Address: 148, Gurodong-ro, Guro-gu, Seoul 08308, Korea 
 
Office ☎: 02-2626-3231 
Emergency Contact ☎: 010-3828-9205 
E-mail: bglim9205@korea.ac.kr 
 
Name of Clinical Research Coordinator (CRC): Seok Kyeong Oh 
 
Address: 148, Gurodong-ro, Guro-gu, Seoul 08308, Korea 
 
Office ☎: 02-2626-1437 
Emergency Contact ☎: 010-4180-1703 
E-mail: nanprayboy@naver.com 
 
If you’d like to know more about your rights, contact the research staff or below numbers. The research was reviewed and approved 
by Korea University Guro Hospital Institutional Review Board.  
 
 
Office of IRB: 02-2626-1632, 1639, 1659 
Office of Quality Assurance: 02-2626-1863


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Participant’s Consent Form 
Research Title: Effect of Neuromuscular Blockade on Operating Conditions and Overall Satisfaction During Spinal Surgery 
 
▶ please check “V” in the box if you consent to below items. 
(Check) I have read this statement and fully understand the objective, method, expected outcomes, possible risks, other 
treatment options, and management of health information, of this research  
(Check) All my questions were answered. 
(Check) I understand that I can withdraw from this research anytime I desire even after my consent, and that I will receive 
appropriate treatment after my withdrawal. 
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• Do you agree to allow your personal information to be used for purpose of other researches? 
□ N/A     □ Yes     □ No (If “yes”, please check the question as described below)  
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□ N/A     □ Yes     □ No 
(Check) I have received a copy of the guideline and written and filled out consent form. 
(Check) You agree to participate in this clinical research voluntarily with full consideration. 
I consent to participate in this research on my own free will, after full consideration with sufficient time. 
▶ Check items that apply to your consent  
Person received 
statement 
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□ Participant himself or herself 
 
 
 
□ Representative 
 
 
 
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□ Witness(if necessary) 
 
 
 
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statement 
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Prot_000.pdf: 
Study Protocol 
 
 
 
Official Title : Comparison of Operating Conditions, Postoperative Recovery 
and Overall Satisfaction Between Deep and Restricted 
Neuromuscular Blockade for Spinal Surgery Under General 
Anesthesia   
 
Identifiers : NCT02724111 
 
Date of Document : 4th February 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol of the Research 
1.1 Objectives & 
Hypotheses  
* Objectives 
Primary Outcome Measure(s): 
1.   Mean Value of Peak Inspiratory Pressure [Time Frame: Every 15 minutes 
during anesthesia] 
 
Secondary Outcome Measure(s): 
2.   Mean Value of Pressure of Back Muscle Retractor [Time Frame: Every 15 
minutes during the placement of the retractor] 
3.   Overall Satisfaction of Surgeons for the Surgical Condition [Time Frame: 
After surgery] 
4.   The Muscle Tone [Time Frame: at the screw insertion through the pedicle 
of spine during surgery] 
5.   The Number of Body Movements [Time Frame: Throughout the surgery] 
6.   The Degree of Bleeding [Time Frame: Throughout the surgery] 
7.   Recovery Time (Time to Reach Sedation Score 5 at Post-anesthesia Care 
Unit (PACU). [Time Frame: every 10 min for 1 hour at PACU.] 
8.   Adverse Events [Time Frame: during the postoperative 24 hours] 
 
* Clinical hypotheses 
(1) Mean value of peak inspiratory pressure (PIP) is lower in deep NMB group 
than in restricted NMB group. The higher PIP in restricted NMB group is related 
to the more surgical bleeding compared to deep NMB group. 
(2) Operating conditions including the number of body movement, degree of 
bleeding and muscle tone in deep NMB group are superior to restricted NMB 
group. 
(3) Overall satisfaction of surgeons in deep NMB group is superior to restricted 
NMB group. 
1.2 Background 
& Rationale, 
Significance of 
Selected Topic  
Current standard of anesthesia in Motor Evoked Potential (MEP) monitored 
neurospinal surgeries is TIVA (total intravenous anesthesia) without muscle 
relaxant or with shallow NMB because deep NMB prevents monitoring of MEPs 
during surgery.  
However, there are several disadvantages associated with surgical and anesthetic 
conditions in MEP monitored surgeries.  
We aim to investigate operating conditions, postoperative recovery and overall 
satisfaction of surgeons between deep NMB group and restricted NMB for MEP 
not monitoring spinal surgery under general anesthesia. We expect that this study 
can present good surgical conditions, postoperative recovery outcomes and 
overall satisfaction of surgeons in deep NMB group, thereby proving the 
advantages of deep NMB as well as flaws of restricted NMB in spine surgeries.  
In this study, channeling bias is not likely to be problematic, as the establishment 
of group and the indications or criteria of MEP monitoring in spine surgeries are 
mainly associated with the patient’s clinical signs and pre-existing motor deficits 


rather than the extent or difficulty of surgery. However, channeling regarding to 
the group treatment according to MEP monitoring can make this study be a non-
randomized trial and certain patient differences would be expected between 
treatment groups. Therefore, we will enroll patients undergoing spinal surgery 
without MEP monitoring to determine the value of deep block on surgical and 
anesthetic condition. 
1.3 Study Design 
Group treatment (Arms): Group RB, group treated restricted NMB; Group 
DB, group treated with deep NMB → randomized allocation (subjects: MEP not 
monitored surgeries) 
Inclusion criteria: Ninety ASA class I–II adults, aged 18-75 years, scheduled 
for elective spinal surgery (lumbar surgeries which have lesions no more than 3 
spinal levels and not monitored by MEP) of duration >1 hour and prone position 
under TIVA  
Exclusion criteria: Pregnancy, the receipt of medication known to interfere 
with neuromuscular blockade, diseases affecting neuromuscular transmission, 
and the history of hypersensitivity on rocuronium or sugammadex. The patients 
who will have hemodynamic instability, mean blood pressure increase or fall of 
> 30% from baseline (lasting for more than 5min), and blood loss > 1 L during 
surgery, and MEP monitored surgeries. 
Monitoring devices: An electrocardiograph, pulse oximetry probe, 
esophageal temperature probe, entropy sensor (Datex Ohmeda) and noninvasive 
blood pressure cuﬀ or invasive arterial and central vein lines will be applied to 
patients before or after anesthesia induction. The neuromuscular blockade will be 
monitored with a train-of-four (TOF, frequency 2 Hz, current 50 mA, interval 15 
s) using an accelerator device (TOF-Watch SX; Organon Ltd, Ireland). The 
stimulation electrodes will be placed on the wrist at the level of the ulnar nerve, 
and the accelerometer will be placed at the distal part of the thumb. The skin 
temperature on the patient’s thenar will be maintained above 32°C throughout 
the study by wrapping the arm in cotton. The TOF ratio (T4/T1) and T1 value 
will be displayed on the screen and recorded. State entropy will be used as a 
guide for anesthetic depth and it will be maintained at 40 to 60 during surgery. 
1.4 Study 
Flowchart 
 
 
Patients 
Enrollment 
(n=90) 
 
 
Group DB (n=45) 
 
* NMB strategy: 
- rocuronium 1 mg/kg for 
induction 
- maintain deep NMB (TOF 
count 0, PTC of 1-2) 
 
 
 
 
 
Group RB (n=45) 
 
* NMB strategy: 
- rocuronium 1 mg/kg for 
induction 
- use of sugammadex to 
reverse the NMB 10 min 
after position change 
(supine → prone) and 
thereafter, maintain the state 
of no more use of additional 
muscle relaxant 
 
 


Operation condition assessment 
1) airway pressure (peak inspiratory pressure) 
2) pressure of back muscle retractor 
3) the number of body movements 
4) the degree of bleeding of each patient scaled by surgeons 
5) the muscle tone of each patient scaled by surgeons 
Reversal of NMB 
Sugammadex 4 mg/kg 
at the end of the surgery 
 
 
Reversal of NMB 
No reversal agent; 
but if TOF ratio<0.9 
pyridostigmine 10 mg 
Postoperative assessment 
   - recovery time 
- occurrence of adverse events 
   - overall satisfaction of surgeons 
1.5 Study 
Procedures 
* Blinding and measure of outcomes 
∙A double blinded approach will be used in this trial: randomization for group 
allocation and allocation concealment will be kept in this study. In the operating 
room, induction and maintenance (including the operation of TOF-Watch) of 
anesthesia will be performed by independent anesthesiologists not involved in 
the study and they are not blinded to the group allocation of patients. However, 
all surgeons will be blinded and so the evaluation of muscle tone of each patient 
scaled by surgeons will be blinded. Also, after the end of surgery, a blinded, 
independent investigator will assess the patients during the emergence and 
recovery phases. Postoperative outcomes including recovery time and surgeon 
satisfaction will be measured by the investigator blinded to the group 
assignment. 
 If the patients show any body movement during surgery or if surgeons 
express any complaint about muscle tone (the muscle tone: grade 3), 
rescue rocuronium 5 mg will be administered and the number of body 
movements and rescue rocuronium administration (dose) will be recorded.  
 The extubation criteria are as follows: TOF ratio > 0.9, BIS > 70, regular 
respiratory pattern, tidal volume of at least 5 ml/kg and SpO2 > 95% when 
the patient breathes spontaneously. 
 
* Drug treatment  
∙ Premedication: midazolam 2 mg, i.m (in all patients) 
∙ Induction: In all patients, after lidocaine 40 mg, i.v, effect-site concentration 
(CE) of propofol will be increased stepwise from the initial CE of 2.0 μg/mL 
until loss of the eyelash reflex (or arrival of state entropy less than 60), and then 
the TOF-Watch will be calibrated using the automatic calibrating procedure as 
soon as the patient is asleep. The ﬁrst response in the TOF sequence (T1) will be 
deﬁned as the baseline value to which all subsequent responses are compared. 
Effect-site concentration of remifentanil will be then fixed to 1.5 ng/mL and 
rocuronium 1 mg/kg will be injected and the patients will be tracheally intubated 
at arrival of minimum T1 height.  


∙ Ventilator settings: Tidal volume 8 mL/kg, respiratory rate initially 10 to 12 
breaths/min, positive end-expiratory pressure (PEEP) 4 cmH2O and inspiratory-
to-expiratory time ratio 1:2. Mechanical ventilation (respiratory rate) will be 
adjusted to maintain an end-tidal partial pressure of carbon dioxide at between 30 
and 35 mmHg during surgery. 
∙ Maintenance: The patients will be allocated to one of the 2 groups receiving 
either DEEP NMB (group DB) or RESTRICTED NMB (group RB) according to 
the assignment using a computer random number generator. 
∙ NMB: In the group DB, rocuronium will be administered to maintain deep 
NMB (TOF count 0, PTC of 1-2 twitches) until the end of surgery and the 
reversal of NMB will be performed by sugammadex 4 mg/kg. 
 In the group RB, sugammadex will be administered according to the prescribing 
indications (4 mg/kg for deep NMB state or 2 mg/kg for moderate NMB or less) 
to reverse the NMB 10 min after position change (10 min after placing the 
patient prone). Thereafter, muscle relaxants will not be injected any more 
throughout the surgery except the following situations: If the patients show any 
body movement during surgery or if surgeons express any complaint about 
muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be 
administered and the number of body movements and rescue rocuronium 
administration (dose) will be recorded. 
 
* Anesthesia & management of hemodynamics 
 After induction, the infusion paradigm of propofol and remifentanil for both the 
groups is as follows: remifentanil will be infused with a constant rate of CE 1.5 
ng/mL, and the CE of propofol at loss of the eyelash reflex will be maintained. 
The most preferred BIS value of each patient was around 50, the CE of propofol 
will be titrated upwards or downwards 0.5 to 1.0 μg/mL each time if the BIS 
keeps increasing or decreasing. The BIS level of both the groups will be kept at 
40 to 60 during surgery, which was regarded as the proper sedative depth. The 
infusion will be stopped at the time of skin suture. Ephedrine 4 mg or nicardipine 
0.5 mg will be injected intravenously if the mean arterial pressure falls or 
increases by > 30% relative to baseline. Glycopyrrolate 0.2 mg will be given if 
the heart rate falls below 50 beats per minute. At the end of surgery, the TOF 
count or ratio will be recorded, and after patients are turned supine, in the group 
DB, sugammadex 4 mg/kg will be administered for the reversal of NMB. In the 
group RB, pyridostigmine 10 mg and glycopyrrolate 0.4 mg will be administered 
only if TOF ratio is < 0.9. 
1.6 References 
Chen N, Zhou SJ, Yan HC, Xie Z. Influence of neuromuscular blockade on 
motor evoked potential of forearm muscles. Zhonghua Yi Xue Za Zhi 2009 
24;89(7):445-8.  
Edmonds HL Jr, Paloheimo MP, Backman MH, Johnson JR, Holt RT, Shields 
CB. Transcranial magnetic motor evoked potentials (tcMMEP) for functional 
monitoring of motor pathways during scoliosis surgery. Spine (Phila Pa 1976) 
1989;14(7):683-6. 
Hashimoto Y, Gotanda Y, Ito T, Ushijima K. Recovery from rocuronium by 
sugammadex does not affect motor evoked potentials. Masui 2011;60(8):968-71.  
Kalkman CJ, Drummond JC, Kennelly NA, Patel PM, Partridge BL. 
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SAP_001.pdf: 
Statistical Analysis Plan 
 
 
 
Official Title : Comparison of Operating Conditions, Postoperative Recovery 
and Overall Satisfaction Between Deep and Restricted 
Neuromuscular Blockade for Spinal Surgery Under General 
Anesthesia   
 
Identifiers : NCT02724111 
 
Date of Document : 4th February 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan 
1.Statistical 
Analysis Plan 
and Sample Size 
Justification  
* Statistical Analysis Plan 
Statistical analyses will be performed using SPSS software (SPSS version 20.0, 
IBM, Chicago, IL, USA).  
Student’s t-test or Mann–Whitney U-test will be used to compare continuous 
data including the mean values of the peak inspiratory pressure, the pressure of 
back muscle retractor and recovery time between the groups. Though 
measurement timepoints of peak inspiratory pressure and pressure of back 
muscle retractor are multiple, the mean value of each timepoint will be 
calculated and the mean value of each group will be analysed by Student’s t-test. 
The normal distribution of the continuous data will be first evaluated using the 
Shapiro-Wilk test (P > 0.05). The normally distributed data will be analysed 
using the Student’s t-test, and the abnormally distributed data will be analysed 
using the Mann–Whitney U-test.  
Ordinal variables including, the degree of bleeding of each patient scaled by 
surgeons, assessed using a 6-point scale and overall satisfaction of surgeons, 
assessed using numerical rating scale (NRS; 1-10) will be compared using the 
Mann–Whitney U-test. Categorical variables such as the muscle tone of each 
patient scaled by surgeons, assessed using a 3-point scale, the number of body 
movements during the surgery and the incidence of adverse events between the 
groups will be compared using a chi-squared test (or Fisher’s exact test).  
The data will be expressed as the mean ± standard deviation, median (25; 75 
quartiles), or number of patients (%). P-values will be reported as two-tailed 
values and a P-value < 0.05 will be considered statistically significant. 
 
* Sample size calculation 
Primary endpoint in this study is mean value of peak inspiratory pressure during 
the surgery. The sample size calculation was based on the results of a pilot study 
with 10 cases in each group. In the pilot study, peak inspiratory pressure (mean ± 
standard deviation) was 18.8 ± 2.9 cmH2O in Group DB and 20.7 ± 3.0 cmH2O 
in Group RB, respectively. Therefore, the effect size of 2-groups was 0.64. On 
the assumption that the allocation ratio of 2-groups was 1, a sample size of 39 
patients was selected for each group, calculated by Student’s t-test, two-sided 
test, a level of significance of 0.05 and a power of 0.8. We estimated a 15% 
drop-out, resulting in the final enrolment of 45 patients in each group (total, 90 
patients).