Comparison of Obturator Nerve Blockade and Neuromuscular Blockade for the Prevention of Adductor Spasm in Patients Undergoing Transurethral Resection of Bladder Tumors.
Phase: PHASE4
Conditions: Cancer of Bladder
Sponsor: University of Florida

Protocol 
Page 1 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
Title: Comparison of obturator nerve blockade and neuromuscular blockade for the 
prevention of adductor spasm in patients undergoing transurethral resection of bladder 
tumors. 
NCT: NCT03063255 
Date:  October 25, 2016

Protocol 
Page 2 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
Protocol 
 
1. Project Title: 
 
Comparison of obturator nerve blockade and neuromuscular blockade for the 
prevention of adductor spasm in patients undergoing transurethral resection of bladder 
tumors. 
 
2. Investigator(s): 
 
Principal investigator:   
José R. Soberón, Jr., MD 
 
 
 
 
NF/SG Veterans Health System 
 
 
 
 
Malcom Randall VA Medical Center 
 
 
 
 
Department of Anesthesiology 
 
 
 
 
1601 Archer Road 
 
 
 
 
Gainesville, Florida 32608 
 
 
 
 
Work:  (352) 548-6000, Extension 3581 
 
 
 
 
Pager:  (352) 413-2317 
 
 
 
 
Cellular:  (786) 247-2749 
 
 
 
 
Email:  jose.soberon@va.gov 
 
Sub-Investigator(s):  
Benjamin K. Canales, MD, MPH 
 
 
 
 
UF Health Shands & Malcom Randall VA Medical Center 
 
 
 
 
Department of Urology 
 
3. Abstract: 
 
Transurethral resection of bladder tumor(s) (TURBT) is a commonly performed 
procedure to diagnose and treat bladder cancer.  The obturator nerve is located lateral 
to the bladder wall in the pelvis prior to innervating the adductor muscles of the thigh.  
The adductor muscles include the adductor longus, adductor brevis, adductor magnus, 
and the pectineus muscle.  These muscles are innervated by the obturator nerve and 
the adductor magnus muscle receives additional innervation from the tibial nerve [1].  In 
addition to hip adduction, these muscles contribute to flexion/extension as well as 
internal and external rotation of the hip [1].   
 
Depending on the location of the tumor(s), electrocautery or surgical stimulation may 
result in stimulation of the obturator nerve, resulting in adduction of the leg, which is 
called the adductor reflex or spasm.  This may occur violently and unexpectedly, and 
result in bladder perforation, bleeding, or cancer dissemination [2].   
 
Ultrasound-guided obturator nerve blockade has been advocated as a technique to 
minimize or ablate the obturator reflex [2-4] in patients receiving spinal or general 
anesthesia for TURBT.  Quadriceps weakness secondary to peripheral nerve blocks 
has been associated with an increased risk of falls in the orthopedic population [5-8].  
Although obturator nerve blockade (ONB) results in adductor weakness [9, 10], it is not 

Protocol 
Page 3 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
known if this results in an increased fall risk.  Much of the anesthesiology literature on 
ONB is focused on patients undergoing knee surgery and, to our knowledge, no 
literature exist regarding the incidence of falls in patients receiving an ONB for TURBT.   
 
To date, there are no prospective studies comparing the incidence of adductor spasm in 
patients undergoing general anesthesia with neuromuscular blocking agents versus 
obturator block.  No major complications—including falls—have been reported with 
obturator nerve blocks.  This may be a reflection of underutilization, lack of reporting, or 
simply a reflection of their use primarily in an orthopedic patient population whose 
mobility status is limited and closely observed.   
 
4. Background: 
 
Much of the available data on obturator blocks is taken from the orthopedic anesthesia 
literature on patients undergoing knee surgery.  To date, there are no complications 
(including falls) related to obturator blocks reported in the literature.  ONB is performed 
in patients undergoing TURBT to minimize or ablate the obturator reflex [2-4]. 
 
Ultrasound guided regional anesthetic techniques have a long record of safety and 
efficacy, and are commonly performed for patients undergoing surgery in both the 
outpatient and inpatient setting.   
 
Neuromuscular blocking medications are commonly used to prevent patient movement 
under general anesthesia.  Use of neuromuscular agents may result in postoperative 
weakness, which may lead to hypoxemia and airway obstruction, complaints of muscle 
weakness or fatigue, longer postanesthesia care unit stays, delays in tracheal 
extubation, increased risk of pulmonary aspiration, and atelectasis [11].  Additionally, 
adductor spasm has been reported despite the use of these medications [12, 13].   
 
Furthermore, there is a study that suggests that use of an obturator nerve block in 
patients undergoing TURBT may prolong time to cancer recurrence in patients with 
superficial bladder tumors [14].  The obturator block results in a decreased incidence of 
adductor spasm, which allows for optimal surgical conditions and improved tumor 
resection [14].  The incidence of adductor spasm during TURBTs is currently unknown.  
While one study has estimated the incidence to be 16.5% [18], three others have 
reported it to be 40-55% [13, 19, 20] in patients with posterolateral bladder tumors. 
 
Given the presence of the adverse events associated with use of neuromuscular 
blocking agents and the current lack of adverse events reported with the obturator 
block, we are interested in conducting an investigation comparing the two approaches in 
a prospective and randomized manner. 
 
5. Specific Aims: 
 

Protocol 
Page 4 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
The primary objective will be to compare the incidence of adductor spasm (also known 
as the obturator reflex) during transurethral resection of posterolateral bladder tumors 
under general anesthesia. 
 
Secondary objectives will include assessments of leg weakness and fall risks, as 
measured using a handheld dynamometer and the timed up and go (TUG) test, 
respectively.  Adverse events related to the anesthetic and surgical techniques will also 
be recorded. 
 
6. Research Plan: 
 
Veterans diagnosed with posterolateral bladder tumors will be invited to participate in 
the study.  After obtaining written informed consent, the veteran will be randomized to 
receive an ultrasound-guided obturator block or a neuromuscular blocking agent after 
the induction of general anesthesia in an attempt to block the obturator reflex during 
surgery.  Both techniques are commonly performed and accepted techniques for the 
prevention of the obturator reflex. 
 
Inclusion criteria  
1. Patients ≥ 18 years of age undergoing TURBT for unilateral or bilateral 
posterolateral bladder tumors 
2. Ability to understand and provide informed consent 
 
Exclusion criteria 
1. Patient refusal or inability to provide informed consent 
2. True allergy, not sensitivity, to any of the following substances:   
a. Local anesthetics 
b. Propofol 
c. General anesthetic agents 
3. Pregnancy 
4. Severe hepatic impairment 
5. Evidence of infection at or near the proposed needle insertion site 
6. Any sensorimotor deficit of the lower extremity, whether acute or chronic, as 
determined by the PI 
7. Inability to walk without assistance 
8. Lower extremity joint replacement surgery in the preceding six months 
 
Methods:   
Research related procedures:  Veterans (n=60) with be randomized to the obturator 
block or neuromuscular block arm upon enrollment, using randomized permutated 
blocks of six (GraphPad Software, Inc).  The TUG test and dynamometer 
measurements will be obtained preoperatively and one hour postoperatively.  Handheld 
dynamometers are commonly used to determine leg muscle strength and have been 
utilized in multiple recent nerve block studies and other clinical settings [7, 8, 15].  The 
TUG test requires the participant to stand from a seated position, walk ten feet, turn 
around, and return to a seated position.  The test is free and available to all health care 

Protocol 
Page 5 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
providers (http://www.cdc.gov/steadi/index.html).  It is a sensitive and specific tool for 
evaluating fall risk with excellent intra- and interrater reliability [16].  It is easily 
performed, does not require specialized equipment or training, and correlates well with 
other balance and gait measures [17].  Times ≥ 13.5 seconds are associated with an 
increased risk of falls [16, 17]. 
 
Once a potential study candidate provides consent to participate in the study, s/he will 
undergo a baseline TUG test and dynamometer measurements.   
 
Planned statistical analyses 
All analyses will be conducted in JMP Pro 12.0 (SAS Institute, Cary, NC). Categorical 
measures (e.g. block success) will be summarized as percentages (%). For continuous 
measures (e.g. TUG, dynamometer), normally distributed measures will be summarized 
as means and standard deviations, and non-normally distributed measures will be 
summarized as median with interquartile range. Differences in block success between 
groups will be examined with χ2 tests. Differences in dynamometer measurements and 
TUG tests will be examined through t-tests, with transformation of outcomes as 
necessary to satisfy assumptions of the statistical test. P < 0.05 will be considered 
statistically significant.  
 
Sample size justification 
The target sample size for the proposed study is n=60 (n=30 per group). Power 
calculations were performed assuming 80% power and alpha=0.05. With n=60, our 
sample can detect a minimum 28% decrease is block success in the neuromuscular 
block group compared to the obturator block group, assuming a 97% success rate in the 
obturator block group. This sample size will also be able to detect a minimum group 
mean difference of 7.4 on the TUG (SD=10.0).  
 
Obturator block group 
Standard of care:  After the induction of general anesthesia, the block will be performed 
on the side of the posterolateral bladder tumor(s).  If a patient has bilateral 
posterolateral bladder tumors, bilateral blocks will be performed.  A time out procedure 
will be performed confirming the patient’s identity, the proposed surgical procedure, and 
laterality of the tumor(s) and block procedure(s).  The patient’s inguinal region will be 
cleansed with Chlorohexidine prep solution.  A 21ga Pajunk SonoPlex needle will be 
advanced under ultrasound guidance and 20-30mL of 2% mepivacaine will be injected 
using an interfascial approach.  All nerve blocks will be performed by Dr. José Soberón, 
who has expertise in ultrasound-guided regional anesthesia.  Block time will be counted 
as the time from needle insertion until the completion of the injections.  Any 
inadequate/failed blocks will be recorded.  Unless clinically indicated, neuromuscular 
blocking agents will be avoided (with the exception of succinylcholine for tracheal 
intubation). 
 
Neuromuscular block group 
Standard of care:  After the induction of general anesthesia, rocuronium (a 
neuromuscular blocking agent) will be administered intravenously in 5-10mg increments 

Protocol 
Page 6 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
titrated to a goal of 2/4 twitches.  An obturator block will not be performed unless 
adductor spasm persists despite the administration of additional rocuronium.   
 
Research related procedure:  The incidence of block- and procedure-related adverse 
events, including the obturator reflex, will be recorded.  In addition to clinical 
observation, a Nerve Integrity Monitor (Medtronic) will be used to detect adductor 
spasm using continuous electromyography.  Adhesive skin (non-needle) electrodes will 
be placed on the thigh to objectively detect and record instances of adductor spasm. 
 
Standard of care:  Unless contraindicated, all patients will be extubated and transported 
to the post anesthesia care unit (PACU).  The patients will then be discharged home or 
to a hospital room (per the surgical service).   
 
Research related procedure:  One hour after arrival to PACU or when discharge criteria 
are met (whichever comes first), repeat dynamometer measurements and TUG tests 
will be performed.  Patients will be called 24-48 hours post procedure to inquire about 
falls or evidence of nerve injury, as well as patient satisfaction.   
 
7. Possible Discomforts and Risks: 
 
In addition to the risks of general anesthesia, veterans in the obturator block group may 
experience the following:  nerve damage, intravascular injection of local anesthetic, 
cardiac arrest, seizure, bleeding/hematoma, infection, ineffective or failed block, pain at 
the injection site, or numbness or tingling (paresthesia).  These events are rare and, to 
date, none of these complications have been reported in patients receiving an obturator 
block.   
 
Because the obturator block will be performed after the induction of general anesthesia, 
the enrolees should not experience any discomfort during the block procedure. 
 
8. Possible Benefits: 
 
Because adductor spasm may interfere with tumor resection, performance of an 
obturator block or use of neuromuscular relaxing agents may block or ameliorate the 
reflex and allow for safer operating conditions and improved cancer removal.  The 
efficacy and safety of one approach versus the other is not known.  The results of this 
study may be used to guide clinical decisions for future patients undergoing TURBT or 
to conduct larger prospective studies. 
 
9. Conflict of Interest: 
 
None of the investigators have any relevant financial disclosures. 
 
10.  References: 
 

Protocol 
Page 7 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
1. Patricios J. Adductor muscle and tendon injury. UpToDate. 
http://www.uptodate.com/contents/adductor-muscle-and-tendon-
injury?source=machineLearning&search=adductor+injury&selectedTitle=1%7
E74&sectionRank=4&anchor=H49279219#H49279219. Updated August 18, 
2015. Accessed September 22, 2016. 
 
2. Mihara T, Itoh H, Hashimoto K, Goto T. Trans-resectoscope stimulation 
predicts the need to block adductor response during bladder tumor resection. 
Anesth Analg. 2013 Sep;117(3):740-4. doi: 
10.1213/ANE.0b013e3182a07063. 
 
3. Hızlı F, Argun G, Güney I, Güven O, Arık AI, Başay S, Günaydın H, Başar H, 
Köşüş A. Obturator nerve block transurethral surgery for bladder cancer: 
comparison of inguinal and intravesical approaches: prospective randomized 
trial. Ir J Med Sci. 
 
4. Ishiyama T, Kotoda M, Asano N, Ikemoto K, Masamune T, Matsukawa T. 
Ultrasound-guided out-of-plane obturator nerve block. Anaesthesia. 2013 
Oct;68(10):1074-5. doi: 10.1111/anae.12432. 
 
5. Wasserstein D, Farlinger C, Brull R, Mahomed N, Gandhi R. Advanced age, 
obesity and continuous femoral nerve blockade are independent risk factors 
for inpatient falls after primary total knee arthroplasty. J Arthroplasty. 2013 
Aug;28(7):1121-4. doi: 10.1016/j.arth.2012.08.018 
 
6. Ilfeld BM, Duke KB, Donohue MC. The association between lower extremity 
continuous peripheral nerve blocks and patient falls after knee and hip 
arthroplasty. Anesth Analg. 2010 Dec;111(6):1552-4. doi: 
10.1213/ANE.0b013e3181fb9507. 
 
7. Kwofie MK, Shastri UD, Gadsden JC, Sinha SK, Abrams JH, Xu D, Salviz EA. 
The effects of ultrasound-guided adductor canal block versus femoral nerve 
block on quadriceps strength and fall risk: a blinded, randomized trial of 
volunteers. Reg Anesth Pain Med. 2013 Jul-Aug;38(4):321-5. doi: 
10.1097/AAP.0b013e318295df80. 
 
8. Jaeger P, Nielsen ZJ, Henningsen MH, Hilsted KL, Mathiesen O, Dahl JB. 
Adductor canal block versus femoral nerve block and quadriceps strength: a 
randomized, double-blind, placebo-controlled, crossover study in healthy 
volunteers. Anesthesiology. 2013 Feb;118(2):409-15. doi: 
10.1097/ALN.0b013e318279fa0b 
 
9. Akkaya T, Ozturk E, Comert A, Ates Y, Gumus H, Ozturk H, Tekdemir I, 
Elhan A. Ultrasound-guided obturator nerve block: a sonoanatomic study of a 
new methodologic approach. Anesth Analg. 2009 Mar;108(3):1037-41. doi: 
10.1213/ane.0b013e3181966f03. 

Protocol 
Page 8 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
 
10. Helayel PE, da Conceição DB, Pavei P, Knaesel JA, de Oliveira Filho GR. 
Ultrasound-guided obturator nerve block: a preliminary report of a case 
series. Reg Anesth Pain Med. 2007 May-Jun;32(3):221-6. 
 
11. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part 
I: definitions, incidence, and adverse physiologic effects of residual 
neuromuscular block. Anesth Analg. 2010 Jul;111(1):120-8. doi: 
10.1213/ANE.0b013e3181da832d. Epub 2010 May 4. Review. 
 
12. So PC. Two case reports of obturator nerve block for transurethral resection 
of bladder tumour. Hong Kong Med J. 2004 Feb;10(1):57-9 
 
13. Tatlisen A, Sofikerim M. Obturator nerve block and transurethral surgery for 
bladder cancer. Minerva Urol Nefrol. 2007 Jun;59(2):137-41. PubMed PMID: 
17571049. 
 
14. Tekgül ZT, Divrik RT, Turan M, Konyalioğlu E, Şimşek E, Gönüllü M. Impact 
of obturator nerve block on the short-term recurrence of superficial bladder 
tumors on the lateral wall. Urol J. 2014 Mar 3;11(1):1248-52. 
 
15. Jæger P, Zaric D, Fomsgaard JS, Hilsted KL, Bjerregaard J, Gyrn J, 
Mathiesen O, Larsen TK, Dahl JB. Adductor canal block versus femoral nerve 
block for analgesia after total knee arthroplasty: a randomized, double-blind 
study. Reg Anesth Pain Med. 2013 Nov-Dec;38(6):526-32. doi: 
10.1097/AAP.0000000000000015. 
 
16. Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional 
mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. 
 
17. Shumway-Cook A, Brauer S, Woollacott M. Predicting the probability for falls 
in community-dwelling older adults using the Timed Up & Go Test. Phys Ther. 
2000 Sep;80(9):896-903. 
 
18. Khorrami MH, Javid A, Saryazdi H, Javid M. Transvesical blockade of the 
obturator nerve to prevent adductor contraction in transurethral bladder 
surgery. J Endourol. 2010 Oct;24(10):1651-4. doi: 10.1089/end.2009.0659. 
 
19. Bolat D, Aydogdu O, Tekgul ZT, Polat S, Yonguc T, Bozkurt IH, Sen V, Okur 
O. Impact of nerve stimulator-guided obturator nerve block on the short-term 
outcomes and complications of transurethral resection of bladder tumour: A 
prospective randomized controlled study. Can Urol Assoc J. 2015 
Nov-Dec;9(11-12):E780-4. doi: 10.5489/cuaj.3149. 
 

Protocol 
Page 9 of 9 
IRB version 03.09.04 
PI version 9/14/2020 9:43 AM 
20. Mihara T, Itoh H, Hashimoto K, Goto T. Trans-resectoscope stimulation 
predicts the need to block adductor response during bladder tumor resection. 
Anesth Analg.2013 Sep;117(3):740-4. doi: 10.1213/ANE.0b013e3182a07063.