Clinical trial NCT03039543
Conditions: Neuromuscular Blockade
Sponsor: Seoul National University Bundang Hospital
Start date: 2017-06-01; Completion date: 2017-11-10
Enrollment: 108 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Transurethral resection of the bladder tumor (TURB) for bladder tumor excision is the mainstream treatment. However, the beneficial effects of sugammadex after general anesthesia for TURB have not been thoroughly evaluated. Investigators hypothesized that deep NMB and the use of sugammadex as a reversal agent may be associated with better endoscopic surgical condition and recovery profile compared with moderate NMB during TURB.

This study was designed to compare patients with deep neuromuscular blockade (NMB) with moderate NMB during transurethral resection of the bladder tumor (TURB) in terms of surgical condition and postoperative recovery.

Detailed description:
Transurethral resection of the bladder tumor (TURB) is the mainstream treatment of bladder cancer. TURB may be performed under regional anesthesia or general anesthesia. During regional anesthesia for TURB, obturator nerve block should be performed to prevent adductor contraction and possible inadvertent bladder perforation. Additionally, some patients prefer not to be conscious during the surgery and patients with spinal deformity or previous spinal fusion surgery are prone to fail regional anesthesia. Therefore, general anesthesia with neuromuscular blockade (NMB) is frequently conducted for patients with TURB.

During general anesthesia for TURB, NMB is needed for intubation and optimal endoscopic surgical condition via obturator nerve block. TURB is a relatively short procedure but patients with NMB usually need sufficient time to be reversed with the conventional NMB reversal agents (anticholinesterases). Additionally, inadequate reversal from NMB may result in respiratory complication during recovery. Sugammadex, a newer reversal agent, is a selective relaxant-binding agent that allows for rapid reversal of rocuronium-induced NMB. With the introduction of sugammadex, immediate reversal of deep NMB has become possible without residual NMB.

Several previous studies evaluated the effect of NMB on surgical condition for relative short surgeries such as laparoscopic cholecystectomy or laryngeal micro-surgery. They suggested that deep NMB and reversal with sugammadex improved surgical condition without postop respiratory complications. TURB is a urological endoscopic procedure performed in a narrow bladder space but the beneficial effects of deep NMB with sugammadex reversal for TURB have not been thoroughly evaluated. We hypothesized that deep NMB and the use of sugammadex as a reversal agent may be associated with better endoscopic surgical condition compared with moderate NMB during TURB. Therefore, this study was designed to compare deep NMB with moderate NMB during TURB in terms of surgical condition and recovery profiles in patients with general anesthesia.

Arms: arm 1: During operation, intravenous rocuronium was used to maintain moderate (TOF count of 1 or 2). Patients in moderate neuromuscular blockade are reversed with 2 mg/kg sugammadex at a TOF count of 1 or 2. arm 2: During operation, intravenous rocuronium was used to maintain deep (TOF count of 0 with post-tetanic count of 2) neuromuscular blockade. Patients in the deep neuromuscular blockade are reversed with 4 mg/kg sugammadex at post-tetanic count of 2.
Interventions: intervention 1: Rocuronium intervention 2: Sugammadex
Intervention descriptions: intervention 1: Intravenous rocuronium was used to maintain moderate (TOF count of 1 or 2) neuromuscular blockade for patients with moderate neuromuscular blockade whereas intravenous rocuronium was used to maintain deep (TOF count of 0 with post-tetanic count of 2) neuromuscular blockade for patients with deep neuromuscular blockade. intervention 2: Patients in moderate neuromuscular blockade are reversed with 2 mg/kg sugammadex at a TOF count of 1 or 2 and patients in the deep neuromuscular blockade are reversed with 4 mg/kg sugammadex at post-tetanic count of 2.

Protocol documents:
Prot_001.pdf: 
Study 
This study is a single center, randomized, controlled, and double-blinded trial. The protocol 
of this study was approved by the Institutional Review Board of Seoul National University 
Bundang Hospital (No B-1701-1378-006) and registered at www.clinicaltrials.gov 
(NCT#03039543). Informed consents were obtained from all patients before the conduction 
of the study.  
 
Patients 
Patients aged more than 19 years who are American Society of Anesthesiologists (ASA) 
physical status I and II and scheduled to undergo elective TURB were included for this trial. 
Exclusion criteria are a history of neuromuscular, renal, or hepatic disease, a body mass index 
(BMI) of < 18.5 or > 30.0 kg/m2, and treatment with drugs known to interfere with 
neuromuscular function. 
 
Randomization and intervention 
Randomization is conducted by a person who was not involved in the study using a 
computer - generated randomization code (Random Allocation Software, version 2.0). The 
result of randomization was sealed in an opaque envelope, which was delivered to the 
anesthesiologist who is in charge of the patient. Patients, surgeons and outcome assessors for 
recovery profiles were blinded to the group assignment. However, the anesthesiologist 
responsible for the patients during surgery was not blinded to the assigned group. From a 
table of random numbers, a total of 108 patients undergoing elective TURB are randomized 
into either moderate NMB group (n = 54) or deep NMB group (n = 54).  


Moderate NMB group: During maintenance of anesthesia, added bolus doses of intravenous 
rocuronium (5–10 mg) were used to maintain moderate NMB (TOF count of 1 or 2) if needed. 
After the surgery, patients were reversed with 2 mg/kg sugammadex at a TOF count of 1 or 2. 
Deep NMB group: During maintenance of anesthesia, added bolus doses of intravenous 
rocuronium (5–10 mg) were used to maintain deep NMB (TOF count of 0 with PTC of 2) if 
needed. After the surgery, patients were reversed with 4 mg/kg sugammadex at PTC of 2. 
 
Anesthesia 
Premedication was administered with intravenous midazolam (0.02 mg/kg) as a 
premedication at the reception area of operating theater and then transferred to the operating 
room. In the operating room, standard monitoring, including electrocardiography, 
noninvasive arterial pressure measurements, and pulse oximetry was placed. The level of 
NMB was monitored using acceleromyography (TOF-Watch® SX, Organon Ireland Ltd., a 
subsidiary of Merck & Co., Inc., Swords, Co. Dublin, Ireland) at the adductor pollicis muscle. 
The TOF ratio was recorded for each patient every 5 min during the operation. The TOF-
watch was calibrated in each patient before performing the measurements. The stimulation 
current was set to 30 mA and the TOF-watch SX was calibrated in the calibration 1 mode. 
During induction of anesthesia, patients received propofol (2 mg/kg) and alfentanil and the I-
gel™ (Intersurgical Ltd, Wokingham, UK) was inserted after the administration of 0.6 mg/kg 
rocuronium in both groups. Anesthesia was maintained with desflurane while monitoring the 
bispectral index (A-2000 BISTM monitor; Aspect Medical Systems, Inc., Natick, MA, USA) 
between 40-60. A bolus dose of intravenous rocuronium (5–10 mg) was used to maintain 
moderate (moderate NMB group, TOF count of 1 or 2) or deep (deep NMB group, TOF 
count of 0 with PTC of 2) NMB if needed. At the end of the operation, the surgeon rated the 
endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = 


acceptable, 4 = good, 5= optimal, Table 1) [9]. Patients in moderate NMB group are reversed 
with 2 mg/kg sugammadex at a TOF count of 1 or 2 (group A) and patients in the deep NMB 
group are reversed with 4 mg/kg sugammadex at PTC of 2 (group B). Patients were extubated 
when spontaneous ventilation of the patient was adequate. After the surgery, patients were 
transferred to the post-anesthesia care unit (PACU)  
Postoperative residual curarization (PORC, TOF ratio < 0.9) is recorded if it occurred. 
Patients were evaluated every 15 min using the modified Aldrete scoring system until ready 
for discharge from the PACU and the criterion used for patient discharge was the 
achievement of a modified Aldrete score of 9 [10]. Respiratory complication such as 
desaturation (SpO2 < 90%) or respiratory depression (RR < 8) and other adverse events 
including postoperative nausea and/or vomiting (PONV) were recorded during PACU stay.  
 
Outcome measurement 
Primary outcome was the endoscopic surgical condition that was evaluated right after the 
operation by the surgeon (Table 1), who was blinded to the group assignment. Secondary 
outcomes were recovery profiles including the postoperative residual curarization (PORC, 
TOF ratio < 0.9), respiratory complications, recovery time (PACU discharge, a modified 
Aldrete score of 9) and other postoperative adverse events. 
 
Sample size 
The sample size was calculated based on the preliminary data using G*Power 3.1.2 
(Heinrich-Heine University, Düsseldorf, Germany). The proportion of optimal endoscopic 
surgical condition (score 5) during TURB was 30 % after the use of moderate NMB (n = 10) 
and 30% increase of optimal endoscopic surgical condition by deep NMB was considered to 


be clinically significant. Fifty four (54) patients per group was calculated with α = 0.05 and β 
= 0.2, allowing for a 10 % drop-out rate. 
 
Statistical analysis 
Statistical analysis is performed using SPSS 21 (SPSS Inc., Chicago, IL, USA) and the test 
of normal distribution was assessed with the Shapiro–Wilk test. Chi-square test or Fisher’s 
exact test was used for the analysis of incidence variables (gender, ASA physical class, 
additional rocuronium, surgical condition score, PORC, respiratory complications and other 
adverse events). Student’s t test is used to compare normally distributed continuous variables 
(age, weight, height, BMI, operation time, anesthesia time, propofol, alfentanil, rocuronium, 
and recovery time). All values presented are number of patients (%) or mean (SD). A p 
values < 0.05 were considered to indicate statistical significance.


Table 1. Surgical condition score (Ref 7 by Martini et al.) 
Score 
Surgical condition 
 
1. 
Extremely poor conditions 
 
The surgeon is unable to work because of coughing or 
because of the inability to obtain a endoscopic view 
because of inadequate muscle relaxation. Additional 
neuromuscular blocking agents must be given 
2. 
Poor conditions 
 
There is a endoscopic view but the surgeon is severely 
hampered by inadequate muscle relaxation with 
continuous muscle contractions, movements, or both 
with the hazard of tissue damage. Additional 
neuromuscular blocking agents must be given 
3. 
Acceptable conditions 
 
There is a wide endoscopic view but bladder 
contractions, movements, or both occur regularly 
causing some interference with the surgeon’s work. 
There is the need for additional neuromuscular 
blocking agents to prevent deterioration 
4. 
Good conditions 
 
There is a wide endoscopic working field with 
sporadic muscle contractions, movements, or both. 
There is no immediate need for additional 
neuromuscular blocking agents unless there is the fear 
of deterioration 
5. 
Optimal conditions 
 
There is a wide endoscopic working field without any 
movement or contractions. There is no need for 
additional neuromuscular blocking agents 


Surgical conditions were evaluated right after the surgery by the surgeon, who was blinded to 
the group assignment. 
 

SAP_000.pdf: 
Study 
This study is a single center, randomized, controlled, and double-blinded trial. The protocol 
of this study was approved by the Institutional Review Board of Seoul National University 
Bundang Hospital (No B-1701-1378-006) and registered at www.clinicaltrials.gov 
(NCT#03039543). Informed consents were obtained from all patients before the conduction 
of the study.  
 
Patients 
Patients aged more than 19 years who are American Society of Anesthesiologists (ASA) 
physical status I and II and scheduled to undergo elective TURB were included for this trial. 
Exclusion criteria are a history of neuromuscular, renal, or hepatic disease, a body mass index 
(BMI) of < 18.5 or > 30.0 kg/m2, and treatment with drugs known to interfere with 
neuromuscular function. 
 
Randomization and intervention 
Randomization is conducted by a person who was not involved in the study using a 
computer - generated randomization code (Random Allocation Software, version 2.0). The 
result of randomization was sealed in an opaque envelope, which was delivered to the 
anesthesiologist who is in charge of the patient. Patients, surgeons and outcome assessors for 
recovery profiles were blinded to the group assignment. However, the anesthesiologist 
responsible for the patients during surgery was not blinded to the assigned group. From a 
table of random numbers, a total of 108 patients undergoing elective TURB are randomized 
into either moderate NMB group (n = 54) or deep NMB group (n = 54).  


Moderate NMB group: During maintenance of anesthesia, added bolus doses of intravenous 
rocuronium (5–10 mg) were used to maintain moderate NMB (TOF count of 1 or 2) if needed. 
After the surgery, patients were reversed with 2 mg/kg sugammadex at a TOF count of 1 or 2. 
Deep NMB group: During maintenance of anesthesia, added bolus doses of intravenous 
rocuronium (5–10 mg) were used to maintain deep NMB (TOF count of 0 with PTC of 2) if 
needed. After the surgery, patients were reversed with 4 mg/kg sugammadex at PTC of 2. 
 
Anesthesia 
Premedication was administered with intravenous midazolam (0.02 mg/kg) as a 
premedication at the reception area of operating theater and then transferred to the operating 
room. In the operating room, standard monitoring, including electrocardiography, 
noninvasive arterial pressure measurements, and pulse oximetry was placed. The level of 
NMB was monitored using acceleromyography (TOF-Watch® SX, Organon Ireland Ltd., a 
subsidiary of Merck & Co., Inc., Swords, Co. Dublin, Ireland) at the adductor pollicis muscle. 
The TOF ratio was recorded for each patient every 5 min during the operation. The TOF-
watch was calibrated in each patient before performing the measurements. The stimulation 
current was set to 30 mA and the TOF-watch SX was calibrated in the calibration 1 mode. 
During induction of anesthesia, patients received propofol (2 mg/kg) and alfentanil and the I-
gel™ (Intersurgical Ltd, Wokingham, UK) was inserted after the administration of 0.6 mg/kg 
rocuronium in both groups. Anesthesia was maintained with desflurane while monitoring the 
bispectral index (A-2000 BISTM monitor; Aspect Medical Systems, Inc., Natick, MA, USA) 
between 40-60. A bolus dose of intravenous rocuronium (5–10 mg) was used to maintain 
moderate (moderate NMB group, TOF count of 1 or 2) or deep (deep NMB group, TOF 
count of 0 with PTC of 2) NMB if needed. At the end of the operation, the surgeon rated the 
endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = 


acceptable, 4 = good, 5= optimal, Table 1) [9]. Patients in moderate NMB group are reversed 
with 2 mg/kg sugammadex at a TOF count of 1 or 2 (group A) and patients in the deep NMB 
group are reversed with 4 mg/kg sugammadex at PTC of 2 (group B). Patients were extubated 
when spontaneous ventilation of the patient was adequate. After the surgery, patients were 
transferred to the post-anesthesia care unit (PACU)  
Postoperative residual curarization (PORC, TOF ratio < 0.9) is recorded if it occurred. 
Patients were evaluated every 15 min using the modified Aldrete scoring system until ready 
for discharge from the PACU and the criterion used for patient discharge was the 
achievement of a modified Aldrete score of 9 [10]. Respiratory complication such as 
desaturation (SpO2 < 90%) or respiratory depression (RR < 8) and other adverse events 
including postoperative nausea and/or vomiting (PONV) were recorded during PACU stay.  
 
Outcome measurement 
Primary outcome was the endoscopic surgical condition that was evaluated right after the 
operation by the surgeon (Table 1), who was blinded to the group assignment. Secondary 
outcomes were recovery profiles including the postoperative residual curarization (PORC, 
TOF ratio < 0.9), respiratory complications, recovery time (PACU discharge, a modified 
Aldrete score of 9) and other postoperative adverse events. 
 
Sample size 
The sample size was calculated based on the preliminary data using G*Power 3.1.2 
(Heinrich-Heine University, Düsseldorf, Germany). The proportion of optimal endoscopic 
surgical condition (score 5) during TURB was 30 % after the use of moderate NMB (n = 10) 
and 30% increase of optimal endoscopic surgical condition by deep NMB was considered to 


be clinically significant. Fifty four (54) patients per group was calculated with α = 0.05 and β 
= 0.2, allowing for a 10 % drop-out rate. 
 
Statistical analysis 
Statistical analysis is performed using SPSS 21 (SPSS Inc., Chicago, IL, USA) and the test 
of normal distribution was assessed with the Shapiro–Wilk test. Chi-square test or Fisher’s 
exact test was used for the analysis of incidence variables (gender, ASA physical class, 
additional rocuronium, surgical condition score, PORC, respiratory complications and other 
adverse events). Student’s t test is used to compare normally distributed continuous variables 
(age, weight, height, BMI, operation time, anesthesia time, propofol, alfentanil, rocuronium, 
and recovery time). All values presented are number of patients (%) or mean (SD). A p 
values < 0.05 were considered to indicate statistical significance.


Table 1. Surgical condition score (Ref 7 by Martini et al.) 
Score 
Surgical condition 
 
1. 
Extremely poor conditions 
 
The surgeon is unable to work because of coughing or 
because of the inability to obtain a endoscopic view 
because of inadequate muscle relaxation. Additional 
neuromuscular blocking agents must be given 
2. 
Poor conditions 
 
There is a endoscopic view but the surgeon is severely 
hampered by inadequate muscle relaxation with 
continuous muscle contractions, movements, or both 
with the hazard of tissue damage. Additional 
neuromuscular blocking agents must be given 
3. 
Acceptable conditions 
 
There is a wide endoscopic view but bladder 
contractions, movements, or both occur regularly 
causing some interference with the surgeon’s work. 
There is the need for additional neuromuscular 
blocking agents to prevent deterioration 
4. 
Good conditions 
 
There is a wide endoscopic working field with 
sporadic muscle contractions, movements, or both. 
There is no immediate need for additional 
neuromuscular blocking agents unless there is the fear 
of deterioration 
5. 
Optimal conditions 
 
There is a wide endoscopic working field without any 
movement or contractions. There is no need for 
additional neuromuscular blocking agents 


Surgical conditions were evaluated right after the surgery by the surgeon, who was blinded to 
the group assignment.