Comparison of Operating Conditions, Postoperative Recovery and Overall Satisfaction Between Deep and Restricted Neuromuscular Blockade for Spinal Surgery Under General Anesthesia
Phase: PHASE4
Conditions: Neuromuscular Blockade, Surgery, Anesthesia, Spinal Diseases
Sponsor: Korea University Guro Hospital

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 
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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.  
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Intraoperative monitoring of tibialis anterior muscle motor evoked responses to 
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