Clinical trial NCT03117140
Conditions: Anesthesia, Local
Keywords: Brachial Plexus Block Clonidine Dexamethasone Buprenorphine
Sponsor: Melinda Seering
Start date: 2013-12-01; Completion date: 2017-03-01
Enrollment: 160 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a prospective randomized controlled triple-masked study looking at the duration of nerve block analgesia when using the listed adjuvants (dexamethasone, buprenorphine and clonidine) plus ropivacaine versus plain ropivacaine alone.

Detailed description:
This is a prospective randomized controlled triple-masked study looking at the duration of nerve block analgesia when using the listed adjuvants (dexamethasone, buprenorphine and clonidine) plus ropivacaine versus plain ropivacaine alone. This will be looked on on patients undergoing painful shoulder surgery in the ambulatory surgery center. Patients will be randomized to one of four groups (1. 0.75% plain ropivacaine. The reference comparator 2. A mixture of 0.75% ropivacaine with 300 mcg buprenorphine 3. A mixture of 0.75% ropivacaine with 75 mcg clonidine 4. A mixture of 0.75% ropivacaine with and 8mg dexamethasone) for their regimen in the interscalene block for their surgery. The patients will then be called within 3 days post-operatively to follow-up. Follow-up data collected will be when did the patient experience return of pain to the operative limb (duration of analgesia), when did the patient experience return of motor function of the operative limb (duration of motor block) and when did the patient experience return of sensation of the operative limb (return of sensory block). All three of these adjuvants have been studied previously and shown to have increased analgesic duration with local anesthesia, but have never had a good comparative study. The mechanism of action of the analgesia for these adjuvants pain relief has never been shown although it is likely a indirect effect as there are animal studies looking at their effect on A and C fibers that did not show those results.

Arms: arm 1: Plain Ropivacaine 0.75%, (225 mg) total volume 32 cc for interscalene block given pre-operatively arm 2: A mixture of 0.75% ropivacaine with 300 mcg buprenorphine, total volume 32 cc for interscalene block given pre-operatively arm 3: A mixture of 0.75% ropivacaine with 75 mcg clonidine, total volume 32 cc for interscalene block given pre-operatively arm 4: A mixture of 0.75% ropivacaine with and 8 mg dexamethasone, total volume 32 cc for interscalene block given pre-operatively
Interventions: intervention 1: Ropivacaine 0.75% intervention 2: Ropivacaine 0.75% + 300 mcg Buprenorphine intervention 3: Ropivacaine 0.75% + 75 mcg clonidine intervention 4: Ropivacaine 0.75% + 8 mg dexamethasone
Intervention descriptions: intervention 1: Only ropivacaine 0.75% is administered for this arm of the interscalene block intervention 2: Ropivacaine 0.75% + 300 mcg Buprenorphine is administered for this arm of the interscalene block intervention 3: Ropivacaine 0.75% + 75 mcg Clonidine is administered for this arm of the interscalene block intervention 4: Ropivacaine 0.75% + 8 mg Dexamethasone is administered for this arm of the interscalene block

Protocol documents:
Prot_SAP_000.pdf: 
A Prospective Triple-Masked Randomized Controlled Trial of Analgesia Duration of  
Local Anesthetic Adjuvants in Interscalene Nerve Block 
Page 1 of 13 
A PROSPECTIVE TRIPLE-MASKED RANDOMIZED 
CONTROLLED TRIAL MEASURING ANALGESIA 
DURATION OF DEXAMETHASONE, BUPRENORPHINE, OR 
CLONIDINE WITH ROPIVACAINE FOR INTERSCALENE 
NERVE BLOCK 
 
STUDY PROTOCOL 
 
1) Protocol Title:  A prospective triple-masked randomized controlled trial measuring 
duration of buprenorphine, dexamethasone, clonidine with ropivacaine for 
interscalene block 
2) Protocol Version:  2.0 
3) Protocol Initiated:  June 18th, 2012 
4) Protocol Revision Date:   
5) Protocol Completed Date:  pending 
6) Principal Investigator: Mindy Seering, MD 
7) Research Team: Michael Todd, MD; John Laur, MD, MS; Julie Weeks, MPT; 
Pamela Jacobs, RN; Emine Bayman, Ph.D.; All research team members must be IRB 
certified. 
8) Study Design:  This is a prospective randomized controlled triple-masked study 
looking at the duration of nerve block analgesia when using the listed adjuvants plus 
ropivacaine versus plain ropivacaine alone. 
9) Questions:   
a) When providing a interscalene nerve block (ISB) for painful shoulder surgery 
using the following four regimens: 
i)  0.75% plain ropivacaine. The reference comparator. 
ii) 
A mixture of 0.75% ropivacaine with 300 mcg buprenorphine 
iii) 
A mixture of 0.75% ropivacaine with 0.1 mcg/kg clonidine  
iv) 
A mixture of 0.75% ropivacaine with and 8mg dexamethasone  
b) Compared to 0.75% plain ropivacaine, will the adjuvant mixture: 
i)  Increase block analgesic duration? 
(Defined as elapsed times from block-needle withdrawal until patient-reported time that they were 
first aware of painful sensation in the operated region of the limb.) 
  
10) Hypothesis: 


A Prospective Triple-Masked Randomized Controlled Trial of Analgesia Duration of  
Local Anesthetic Adjuvants in Interscalene Nerve Block 
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a) Null Hypothesis: Compared to plain ropivacaine, the adjuvant mixture:  
i) Will not increase the nerve block analgesic duration time by 25% or more. 
b) Alternate Hypothesis: Compared to plain ropivacaine, the adjuvant mixture: 
i) Will increase the nerve block analgesic duration time by 25% or more. 
11) Primary Outcome:   
a) Our primary outcome is the time from nerve block-needle withdrawal to return of:  
 
i) 
Painful perception in the operated upon area of the limb. 
 
b) Block Quality: Achieving an inability to sense cold ice-water in the cutaneous 
distribution of the brachial plexus trunk distal to the block within 30 minutes will 
be considered a successful nerve block preoperatively.  If the patient has an 
inability to sense cold ice-water in the cutaneous distribution of the brachial 
plexus trunk distal to the block within 30 minutes will be considered a successful 
nerve block postoperatively. Anything less will be considered a failed nerve 
block. 
 
12) Secondary Outcomes:   
i) 
Return of sensory function in the blocked area of the limb. 
ii) 
Return of motor function in the blocked area of the limb. 
iii) 
Post-op Nausea and vomiting before discharge 
iv) 
Nausea and Vomiting after discharge 
v) 
Changes in Blood Pressure (BP) in the PACU defined as any blood 
pressure +/- 20% of patient’s baseline (either BP on admission if no clinic 
BP is documented, or most recent clinic BP as documented if that exists) 
vi) 
Changes in Blood Pressure in Second Stage defined as any blood pressure 
+/- 20% of patient’s baseline (either BP on admission if no clinic BP is 
documented, or most recent clinic BP as documented if that exists) 
 
 
Motor Block Scale Table 
 
Scale 
 
Muscle function level 
 
Grade 
 
Percent of normal 
No evidence of contractility 
0 
0 % 
Slight contractility, no 
movement 
1 
10 % 
Full range of motion with 
gravity eliminated 
2 
25 % 
Full range of motion against 
gravity 
3 
50 % 
Full range of motion against 
gravity, some resistance 
4 
75 % 
Full range of motion against 5 
100 % 


A Prospective Triple-Masked Randomized Controlled Trial of Analgesia Duration of  
Local Anesthetic Adjuvants in Interscalene Nerve Block 
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gravity, full resistance 
 
Definitions: 
a) Duration of Analgesic Block 
i) 
Time from nerve block-needle withdrawal until the time reported by the 
patient that they first had awareness of painful sensation returning 
anywhere in the surgically operated upon area of the limb. 
ii) 
Patient will be given a form to write time down as it occurs. 
iii) 
They are expected to write down the date and time (hour and minute) they 
first perceive pain in the arm anywhere in the surgical area. (even if they 
wake up from sleep and first notice pain there).   
iv) 
They will be telephoned within three days from the block to gather the 
data from the patient.  
v) 
If they cannot find the form or did not write the date and time down, we 
will then use the date and time the patient recalls from memory.  
 
a) Duration of Sensory Block 
i) 
Time from nerve block-needle withdrawal until the time reported by the 
patient that they first had awareness of tactile (light touch) sensation 
returning anywhere in the blocked area. Patients will be given a form to 
write time down as it occurs. They are expected to write down the date 
and time (hour and minute) they first felt sensation return to the blocked 
area (even if they wake up from sleep and first notice sensation returned).  
ii) 
They will be telephoned within three days from the block to gather the 
data from the patient.  
iii) 
If they cannot find the form or did not write the date and time down, we 
will then use the date and time the patient recalls from memory.  
 
a) Approximate Duration of Motor Block 
i) 
Time from nerve block-needle withdrawal until the time reported by the 
patient that, with the arm of the blocked extremity, they are able to flex 
their bicep.  Patient will be given a form with a diagram and instruct them 
prior to sedation and placing the block. They will write the time down 
when they are able to achieve this outcome. They are to write down the 
date and time (hour and minute) they were first able to flex their bicep on 
the blocked limb.   
ii) 
They will be telephoned within three days to gather the time from the 
form. 
iii) 
If they cannot find the form or did not write the data down, we will then 
use the time the patient recalls from memory.  
 
a) Patient Satisfaction with the block 
i) 
Patients will be asked the question: “Would you want a nerve block again 
if you needed a similar surgery in the future?”    Yes  /  No 
 


A Prospective Triple-Masked Randomized Controlled Trial of Analgesia Duration of  
Local Anesthetic Adjuvants in Interscalene Nerve Block 
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Secondary Outcomes Table 
 
Did patient have nausea before discharge 
Yes 
No 
 
Did patient have vomiting before discharge 
Yes 
No 
 
Did patient have nausea after discharge (72 hours) 
Yes 
No 
 
Did patient have vomiting after discharge (72 hours) 
Yes 
No 
 
Did the patient have +/- 20% deviation of baseline Blood 
pressure in PACU from admission 
Yes 
No 
 
Did the patient have +/- 20% deviation of baseline Blood 
pressure in Second Stage Recovery from admission 
Yes 
No 
 
2) Study Background Information:   
Regional anesthesia in the ambulatory surgery center venue has been shown to decrease 
unwanted side effects of anesthesia and improve patient satisfaction with their operative 
care.  Clinicians often seek ways to increase the duration of peripheral nerve blocks(1, 2) 
for outpatient surgery.  This may enhance patient satisfaction and make for fewer 
unwanted post-operative side effects from anesthesia such as nausea and vomiting.  One 
way to prolong regional anesthesia for patients is to send them home with a peripheral 
nerve catheter. (3-6) However, there can be multiple interventions associated with these.  
Catheter adverse conditions include infection, local anesthetic toxicity, catheter failure or 
dislodgement, infusion leakage, difficulty for the patient to remove their own catheter, 
and inadequate access to medical resources(7-9). 
 
Adding adjuvants to local anesthetics has been a principle for some time.  
Anesthesiologists have been adding epinephrine to spinal Marcaine to extend the spinal 
duration for years.  Candido and Franco both added buprenorphine to upper extremity 
blocks and received triple the pain relief duration from their nerve blocks(10, 11).  In 
addition Candido also added buprenorphine to a sciatic nerve block and received and 
additional 6 hours of pain relief(12).  Cummings (13)of the Cleveland Clinic studied 
dexamethasone added to interscalene blocks and showed it added twice as much 
analgesic duration to the nerve block(14-16).  Kim and Movafegh also studied adding 
decadron to local anesthetics and showed prolongation of sensory and motor block (16-
17).  Casati’s research showed that adding Clonidine to Ropivacaine extended his sciatic 
femoral nerve block extended his pain relief for 3 hours(17-19).  Although neither three 
adjuvant is FDA approved for perineural applications, they have been used in many 
studies without any detriment to patients(20).  Dr. Brian Williams, of the University of 


A Prospective Triple-Masked Randomized Controlled Trial of Analgesia Duration of  
Local Anesthetic Adjuvants in Interscalene Nerve Block 
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Pittsburg has extensiveky studied these adjuvants on a laboratory level and has not shown 
any neural toxicity with these adjuvant additions(21, 22).  Steroids have also been used in 
epidural injections for years without problems.  Dexamethasone has even been used (23).  
Clonidine has been studied for epidural and intrathecal applications(24-26).  It is FDA 
approved for used in epidural with chronic pain patients.  Currently, we are using 
clonidine at the University of Iowa Hospitals and Clinics in our Acute Pain Service.  We 
have it in our epidural solution for pediatric patients.  Buprenorphine has also been 
studied for use intrathecally without problems(27).  There is a study by an oral surgery 
department showing its safety and efficacy when added to oral nerve blocks(28).   
Study Methods:   
This study will be performed in the Ambulatory Surgery Center at the University of 
Iowa.  All included patients will be undergoing orthopedic surgery on their shoulder for a 
surgery on the shoulder girdle, excluding the scapula.  All regional blocks will be 
performed or directly observed and guided by the listed investigators.  Blocks will be 
done using the interscalene approach to the brachial plexus.  All the injections will be 
placed using simultaneous ultrasound guidance and a nerve stimulator technique with a 
previously published compressed air injection technique to limit injection pressure.(29, 
30)  
 
Per previous protocols involving anesthesia studies at University of Iowa Hospitals and 
Clinics (UIHC), those patients who are eligible will be given information on the day of 
surgery.  A nurse not involved with the study will give the patient a card briefly 
informing the patient that they are eligible for a nerve block study.  If the patient 
indicates their consent to hear more and possibly enroll in the study, a representative 
from the investigating team will then meet with the patient to explain the study and 
obtain informed consent.   
 
An offer of regional anesthesia with or without intravenous sedation or general anesthesia 
will be provided to all patients regardless of their decision to participate or not.  The 
techniques, practices, medications and use of ice-water to test blocks described in this 
protocol are currently used in common practice.  
 
3) Inclusion Criteria:   
Patients who have or are: 
a) Orthopedics service patients having shoulder surgery 
b) ASA class I, II, or III. 
c) Patients at least 18 years old but less than 71 years old. 
d) Patients giving informed consent. 
 
2) Exclusion Criteria:   
Patients who have or are: 
a) An inability to cooperate during the block placement. 
b) Any neuropathy 
c) Diabetes 
d) Documented kidney disease 
e) Documented Hepatic disease 


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f) A lack of or inability to give informed consent. 
g) Currently incarcerated. 
h) Pregnancy 
 
 


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3) Consent:   
a) The study will be explained to the patient’s satisfaction, their questions will be 
answered, and informed consent will be obtained from the patient after 
explanation of the risks, benefits, and alternatives. 
b)  Once the patient has consented to the study, they will be included in the study 
and followed throughout. 
c) Patients with failed blocks will be included in the intention to treat analysis. 
d) If the block is unable to be placed due to infection at the site, poor visualization of 
structures with the ultrasound, inability to obtain study drugs within a reasonable 
time frame, or unexpected operator difficulty in placing the block, the patient will 
not be included in the intention to treat analysis and dropped from the study. 
 
4) Randomization:   
a) A computerized random number generator will be used by a staff of the 
Anesthesia Department not involved with the study. They will create a 
randomized numbered sequence with four groups (A, B, C or D) that will be 
given to the pharmacy team. This will be used to fill study syringes in the 
sequence according to the randomization schema.  
b) The UIHC Pharmacy will compound the study drugs and will fill and label the 
coded study syringes. 
c) Coded study syringes must be created and delivered within 30 minutes of the 
physician’s request. 
d) The Pharmacy will keep a record of which patient received each coded syringe 
and the solution they contained. 
e) They will be given to the practitioner at the time of block placement.   
f) Practitioners will perform the block using the pharmacy coded study drug.  
 
5) Masking: 
a) Masking will be accomplished by using coded labels on the study mixtures. 
b) At the end of the study enrollment, information given to the statistical analyst will 
be blindly coded as groups A, B, C or D for data analysis.   
c) The Pharmacy will keep the group codes until after data analysis is complete.  
d) The anesthesiologist and nurse assistants will be masked to the study mixtures. 
e) Any assisting anesthesia Staff, Fellows, Residents, CRNAs, SRNAs, or medical 
students will be masked to the study mixtures. 
f) Patients will be masked to the study mixtures. 
g) Any person collecting and/or scribing the data will be masked to the study 
mixtures. 
h) Any person analyzing the data will be masked to the study mixtures. 
i) Once all the data has been collected and analyzed according to group code, the 
blinding on the study mixtures can be broken and the codes for the study mixtures 
made known. 
j) Safety monitors will not be masked to the mixtures.  They can communicate with 
the pharmacy to unmask the mixtures for only themselves.  They will not report 
the mixtures or pharmacy codes to anyone except for patient safety purposes. 


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k) The coded sample syringes will be kept for reanalysis in case there is any question 
of what mixture was given to any patient.  The syringe contents can be tested by 
the pharmacy and a group code for that patient or set of patients will then be given 
to the analyst.  The masking will remain intact. 
 
6)  Study Mixtures 
a) The local anesthetic study mixtures volumes will be the same (32mL) and 
contained in two thirty-milliliter syringes with 16 mL in each. They consist of: 
i) 
0.75% Ropivacaine x 30mL (225 mg max dose) + 2 mL saline for a total 
volume of 32 mL 
ii) 
0.75% Ropivacaine x 30mL (225 mg max dose) with 300 mcg 
buprenorphine (1 mL) + 1 mL sterile saline for a total volume of 32 mL 
iii) 
0.75% Ropivacaine x 30mL (225 mg max dose) with 100 mcg/kg 
clonidine (0.1 mL) + 1.9 mL sterile saline for a total volume of 32 mL 
iv) 
0.75% Ropivacaine x 30mL (225 mg max dose) with 8mg dexamethasone 
(2 mL) + 0 mL sterile saline for a total volume of 32 mL. 
v) 
Note: If drug shortages occur during the study and we are unable to use 
the same concentration of any additive drugs (e.g. dexamethasone 
10mg/mL instead of 4mg/mL), then a substitution will be allowed and the 
total volume in the syringe will be changed so that all syringes will be the 
same volume and final ropivacaine drug mass.   
 
7) Techniques:   
All the blocks will be performed: 
a) Either by, or under the direct supervision and direction of the Primary Investigator 
or regional anesthesia faculty listed on the investigation team. 
b) In the Ambulatory Surgery Center at the University of Iowa Hospitals and Clinics 
using the posterior approach to the brachial plexus at the trunk level.  
c) A timeout will be performed before the block to verify the patient, site of surgery 
and that we are blocking the correct side (already marked). 
d) Using sterile technique, cleaning the skin with tinted chlorhexidine and with the 
operators wearing caps, masks, and sterile gloves.  The ultrasound probe will have 
a sterile sheath over it. Sterile ultrasound gel will be used. 
e) With ultrasound guidance and nerve stimulator from 0.2 mA to 2.0 mA using a 
sterile Arrow 90mm insulated stimulation needle (StimuQuick). 
f) If we are unable to stimulate the brachial plexus at the trunk level with the nerve 
stimulator, we will place local anesthetic in the region where the brachial plexus 
nerves are visualized using ultrasound based on the practitioner’s experience with 
ultrasound-guided interscalene (brachial plexus trunks) nerve blocks.  
g) Block start and end times will be recorded. Start time begins at block needle 
insertion. Stop time is the time of nerve block-needle withdrawal. 
h) All patients will be monitored with blood pressure, pulse oximetry, ECG and have 
2 liters per minute of oxygen administered by nasal cannula. 
i) Emergency resuscitation equipment, intralipid, and emergency medications are 
present and immediately available for patient safety.  


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j) Anesthesiologists will be present and/or immediately available should 
resuscitation efforts be necessary in the unlikely event of drug toxicity, cardiac 
arrest, or other adverse event. 
k) Any adverse outcomes (listed in “stopping rules” #23 below) will be reported to 
the Safety Monitors on the day it happens. 
l) The use of rescue blocks in the PACU will be counted and analyzed. 
 
8) Statistics  
a) For our primary outcome, we will use ANOVA or Kruskall-Wallis test, after 
checking the normality of the data, to compare the duration of the analgesic block.  
If we find a difference among all 4 groups, we will use 2-sample t-test or Mann-
Whitney U-test to explore differences between the individual groups.  
b) For our continuously distributed secondary outcomes, given that outcomes will 
be observed on every patient, we will use ANOVA or Kruskall-Wallis test. For 
outcomes with categories (nausea and vomiting and blood pressure), we will use 
the chi-square test.  Similarly, we will explore the different group or groups using 
chi-square test or Fisher’s Exact test.  
c) We based our estimates upon Cumming’s, Candido’s and Casati’s previous 
studies and our clinical experience.  We have estimated the expected additional 
analgesic time between the three groups.  
d) Using the above parameters, a sample size is 40 per group with 4 total groups 
calculates to a sum of 160 subjects while using 90% power and 0.05 type I error 
rate.  
 
9) Safety Monitoring:  
a) An Anesthesiology Faculty member who is not involved in the study will act as 
safety monitor and will review the data and any complications when half of the 
patients (n = 80) have been completed.  
 
10) Stopping Rules:   
a) Any incidence of patient complications that occur with an incidence higher than 
published data for the following complications for peripheral nerve blocks will be 
enough cause for the Safety Monitors to stop the study(31, 32). Numbers in 
parentheses below are the highest incidence reported in the referenced article for 
peripheral nerve block complications.  The highest incidence of complications 
was reported to be from the supraclavicular block, which we will not be 
performing.  We are relying on results reported from our own regional anesthesia 
follow-up clinic.  This is a clinic developed here to see patients with troublesome 
complications of peripheral nerve blocks.  The complication rates have been 
reviewed and studied since the clinic inception over 4 years ago(33). We are 
erring on the side of caution by using higher complication rates of the 
supraclavicular adverse event reports. 
 
b)  Published Peripheral Nerve Block Complication rates: 
i) 
Seizure (26.3/10,000)  
ii) 
Cardiac arrest (Code Blue)  (15.9/10,000) 


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iii) 
Respiratory Failure  (15.9/10,000) 
iv) 
Peripheral neuropathy  (32/10,000) 
v) 
Patient death  (15.9/10,000) 
 
 


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References: 
 
1. 
Brummett CM, Williams BA. Additives to local anesthetics for peripheral 
nerve blockade. International anesthesiology clinics. 2011;49(4):104-16. Epub 
2011/10/01. 
2. 
Yilmaz-Rastoder E, Gold MS, Hough KA, Gebhart GF, Williams BA. Effect 
of adjuvant drugs on the action of local anesthetics in isolated rat sciatic nerves. 
Regional anesthesia and pain medicine. 2012;37(4):403-9. Epub 2012/03/21. 
3. 
Ilfeld BM, Morey TE, Enneking FK. Continuous infraclavicular brachial 
plexus block for postoperative pain control at home: a randomized, double-blinded, 
placebo-controlled study. Anesthesiology. 2002;96(6):1297-304. Epub 2002/08/10. 
4. 
Ilfeld BM, Morey TE, Thannikary LJ, Wright TW, Enneking FK. Clonidine 
added to a continuous interscalene ropivacaine perineural infusion to improve 
postoperative analgesia: a randomized, double-blind, controlled study. Anesthesia 
and analgesia. 2005;100(4):1172-8. Epub 2005/03/23. 
5. 
Ilfeld BM, Morey TE, Wang RD, Enneking FK. Continuous popliteal sciatic 
nerve block for postoperative pain control at home: a randomized, double-blinded, 
placebo-controlled study. Anesthesiology. 2002;97(4):959-65. Epub 2002/10/03. 
6. 
Ilfeld BM, Vandenborne K, Duncan PW, Sessler DI, Enneking FK, Shuster 
JJ, et al. Ambulatory continuous interscalene nerve blocks decrease the time to 
discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, 
placebo-controlled study. Anesthesiology. 2006;105(5):999-1007. Epub 2006/10/27. 
7. 
White PF, Issioui T, Skrivanek GD, Early JS, Wakefield C. The use of a 
continuous popliteal sciatic nerve block after surgery involving the foot and ankle: 
does it improve the quality of recovery? Anesthesia and analgesia. 2003;97(5):1303-
9. Epub 2003/10/23. 
8. 
Capdevila X, Pirat P, Bringuier S, Gaertner E, Singelyn F, Bernard N, et al. 
Continuous peripheral nerve blocks in hospital wards after orthopedic surgery: a 
multicenter prospective analysis of the quality of postoperative analgesia and 
complications in 1,416 patients. Anesthesiology. 2005;103(5):1035-45. Epub 
2005/10/27. 
9. 
Saporito A, Sturini E, Petri J, Borgeat A, Aguirre JA. Case report: Unusual 
complication during outpatient continuous regional popliteal analgesia. Canadian 
journal of anaesthesia = Journal canadien d'anesthesie. 2012;59(10):958-62. Epub 
2012/07/26. Etude de cas: Complication inhabituelle pendant un bloc regional 
poplite continu chez un patient ambulatoire. 
10. 
Candido KD, Franco CD, Khan MA, Winnie AP, Raja DS. Buprenorphine 
added to the local anesthetic for brachial plexus block to provide postoperative 
analgesia in outpatients. Regional anesthesia and pain medicine. 2001;26(4):352-6. 
Epub 2001/07/21. 
11. 
Candido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD. 
Buprenorphine added to the local anesthetic for axillary brachial plexus block 
prolongs postoperative analgesia. Regional anesthesia and pain medicine. 
2002;27(2):162-7. Epub 2002/03/27. 
12. 
Candido KD, Hennes J, Gonzalez S, Mikat-Stevens M, Pinzur M, Vasic V, et 
al. Buprenorphine enhances and prolongs the postoperative analgesic effect of 


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bupivacaine in patients receiving infragluteal sciatic nerve block. Anesthesiology. 
2010;113(6):1419-26. 
13. 
Cummings KC, 3rd, Napierkowski DE, Parra-Sanchez I, Kurz A, Dalton JE, 
Brems JJ, et al. Effect of dexamethasone on the duration of interscalene nerve 
blocks with ropivacaine or bupivacaine. British journal of anaesthesia. 
2011;107(3):446-53. Epub 2011/06/17. 
14. 
Vieira PA, Pulai I, Tsao GC, Manikantan P, Keller B, Connelly NR. 
Dexamethasone with bupivacaine increases duration of analgesia in ultrasound-
guided interscalene brachial plexus blockade. European journal of anaesthesiology. 
2010;27(3):285-8. Epub 2009/12/17. 
15. 
Kim YJ, Lee GY, Kim DY, Kim CH, Baik HJ, Heo S. Dexamathasone added 
to levobupivacaine improves postoperative analgesia in ultrasound guided 
interscalene brachial plexus blockade for arthroscopic shoulder surgery. Korean 
journal of anesthesiology. 2012;62(2):130-4. Epub 2012/03/02. 
16. 
Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A. Dexamethasone 
added to lidocaine prolongs axillary brachial plexus blockade. Anesthesia and 
analgesia. 2006;102(1):263-7. Epub 2005/12/22. 
17. 
Casati A, Magistris L, Fanelli G, Beccaria P, Cappelleri G, Aldegheri G, et 
al. Small-dose clonidine prolongs postoperative analgesia after sciatic-femoral nerve 
block with 0.75% ropivacaine for foot surgery. Anesthesia and analgesia. 
2000;91(2):388-92. Epub 2000/07/27. 
18. 
Couture DJ, Cuniff HM, Maye JP, Pellegrini J. The addition of clonidine to 
bupivacaine in combined femoral-sciatic nerve block for anterior cruciate ligament 
reconstruction. AANA journal. 2004;72(4):273-8. Epub 2004/09/10. 
19. 
Duma A, Urbanek B, Sitzwohl C, Kreiger A, Zimpfer M, Kapral S. Clonidine 
as an adjuvant to local anaesthetic axillary brachial plexus block: a randomized, 
controlled study. British journal of anaesthesia. 2005;94(1):112-6. Epub 2004/11/02. 
20. 
Sripada R, Bowens C, Jr. Regional anesthesia procedures for shoulder and 
upper arm surgery upper extremity update--2005 to present. International 
anesthesiology clinics. 2012;50(1):26-46. Epub 2012/01/10. 
21. 
Williams BA. Forecast for perineural analgesia procedures for ambulatory 
surgery of the knee, foot, and ankle: applying patient-centered paradigm shifts. 
International anesthesiology clinics. 2012;50(1):126-42. Epub 2012/01/10. 
22. 
Williams BA, Hough KA, Tsui BY, Ibinson JW, Gold MS, Gebhart GF. 
Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in 
comparison with ropivacaine. Regional anesthesia and pain medicine. 
2011;36(3):225-30. Epub 2011/04/27. 
23. 
Ahadian FM, McGreevy K, Schulteis G. Lumbar transforaminal epidural 
dexamethasone: a prospective, randomized, double-blind, dose-response trial. 
Regional anesthesia and pain medicine. 2011;36(6):572-8. Epub 2011/10/19. 
24. 
Bonhomme V, Doll A, Dewandre PY, Brichant JF, Ghassempour K, Hans P. 
Epidural administration of low-dose morphine combined with clonidine for 
postoperative analgesia after lumbar disc surgery. Journal of neurosurgical 
anesthesiology. 2002;14(1):1-6. Epub 2002/01/05. 


A Prospective Triple-Masked Randomized Controlled Trial of Analgesia Duration of  
Local Anesthetic Adjuvants in Interscalene Nerve Block 
Page 13 of 13 
25. 
Vukovic J, Ramakrishnan P, Milan Z. Does epidural clonidine improve 
postoperative analgesia in major vascular surgery? Med Glas (Zenica). 
2012;9(1):49-55. Epub 2012/05/29. 
26. 
Walker SM, Yaksh TL. Neuraxial analgesia in neonates and infants: a review 
of clinical and preclinical strategies for the development of safety and efficacy data. 
Anesthesia and analgesia. 2012;115(3):638-62. Epub 2012/07/17. 
27. 
Kawamoto S, Tatsumi K, Kataoka T, Kamikawa T, Yanagida T, Mandai R. 
[Comparison of intrathecal morphine and buprenorphine for postoperative 
analgesia in cesarean delivery]. Masui The Japanese journal of anesthesiology. 
2011;60(8):892-6. Epub 2011/08/25. 
28. 
Modi M, Rastogi S, Kumar A. Buprenorphine with bupivacaine for intraoral 
nerve blocks to provide postoperative analgesia in outpatients after minor oral 
surgery. Journal of oral and maxillofacial surgery : official journal of the American 
Association of Oral and Maxillofacial Surgeons. 2009;67(12):2571-6. Epub 
2009/11/21. 
29. 
Ip VH, Tsui BC. Practical concepts in the monitoring of injection pressures 
during peripheral nerve blocks. International anesthesiology clinics. 2011;49(4):67-
80. Epub 2011/10/01. 
30. 
Tsui BC, Li LX, Pillay JJ. Compressed air injection technique to standardize 
block injection pressures. Canadian journal of anaesthesia = Journal canadien 
d'anesthesie. 2006;53(11):1098-102. Epub 2006/11/03. 
31. 
Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier FJ, et al. 
Major complications of regional anesthesia in France: The SOS Regional Anesthesia 
Hotline Service. Anesthesiology. 2002;97(5):1274-80. Epub 2002/11/02. 
32. 
Neal JM, Bernards CM, Hadzic A, Hebl JR, Hogan QH, Horlocker TT, et al. 
ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia and 
Pain Medicine. Regional anesthesia and pain medicine. 2008;33(5):404-15. Epub 
2008/09/09. 
33. 
Laur JJ, Chehade JM, Merrill DG. Managing neural dysfunction after 
regional anesthesia: experience in a walk-in follow-up clinic. International 
anesthesiology clinics. 2011;49(3):44-55. Epub 2011/06/24.