Clinical trial NCT03007966
Conditions: Nerve Block Herniorrhaphy Regional Anesthesia
Sponsor: Wake Forest University Health Sciences
Start date: 2017-01-30; Completion date: 2018-02-17
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Open inguinal herniorrhaphy is a common outpatient surgical procedure. Post-operative pain can be a significant hindrance to discharge from the post anesthesia care unit. Pain can be treated with opioid therapy, but the literature supports that these agents are known to create or exacerbate adverse effects and complications, including post-operative nausea and vomiting, hypoxia, and urinary retention. In contrast, analgesia provided by regional anesthesia results in a decreased risk of the aforementioned complications.1 Because of this, various regional anesthetic techniques have been developed to provide analgesia following open herniorrhaphy. One technique is a combined ilioinguinal and iliohypogastric nerve block (IINB), which has been shown to decrease the initial pain after inguinal herniorrhaphy.2 The quadratus lumborum block (QLB) is a newer regional anesthetic technique that we think could be as effective as IINB at providing pain control following open herniorrhaphy. Additionally, because local anesthetic injected during a QLB has the potential to spread cranially into the thoracic paravertebral space following its lumbar deposition it could lead to alleviation of both somatic and visceral pain.3 This might therefore improve the quality and or duration of analgesia as compared to the IINB. To the best of the author's knowledge there has been no investigation comparing the efficacy, with regards to post-operative pain management, between IINB and QLB.

Detailed description:
This study will be a double-blinded prospective randomized controlled equivalency trial comparing QLB to IINB. Patients presenting for unilateral open inguinal herniorrhaphy who agree to participate in the study and do not meet exclusion criteria will be randomized to either receiving an IINB or a QLB for post-operative analgesia. After performing a timeout, applying monitors (ECG, capnography, Sp02, non-invasive blood pressure), and confirming all paperwork per the usual pre-procedural check list the study participants will be administered procedural sedation (fentanyl and midazolam) to comfort as well as supplemental oxygen. The anatomy of both block sites will be identified by palpation of landmarks, labeling of structures with a skin marking pen, and visualization under ultrasound guidance. Both sites will be administered a small skin wheal of lidocaine 1% at the site the block needle would be introduced into the skin. Our intent with regards to administering a local anesthetic skin wheal is to increase our success in blinding the patient to which block was actually performed. A regional anesthetic block will only be performed at the randomized block site (IINB vs. QLB). After 15-30 minutes post block or post operatively the block will be assessed for success. Loss of cold sensation in the area of the surgical site would be indicative of block success. The patient will then proceed to the operating room and receive a general anesthetic with the final details of that anesthetic to be determined by the anesthesiologist responsible for the patient in the operating room. We will ask the operating room anesthesiologist and surgeon to avoid administration of medications that would confound our results. Specifically, no additional local anesthetic is to be injected at the incision site, no long acting opioids (hydromorphone, morphine, methadone etc…), dexamethasone or ketamine. After completion of the procedure the patient will recover in the post anesthesia care unit (PACU) where the participant will recover as per the usual process. The patient's discharge disposition will be at the discretion of the surgeon and anesthesiologist responsible for the participant's PACU care. The patient will be provided a diary that the participant will complete at 8hrs and 24hrs post block that will help the participant compile the data pertinent to the investigators primary and secondary outcomes. This diary should take no more than a minute or two for each sampling time. Participants will receive two phone calls at home to obtain this data at 8hrs and 24hrs.

Arms: arm 1: Patient's randomized to receive an Ilioinguinal / Iliohypogastric nerve block (IINB) for post operative analgesia following inguinal herniorrhaphy will have said block performed in a supine position in a manner consistent with the technique described by Willschke, but modified to utilize an in-plane technique rather than an out-of-plane technique for needle to ultrasound probe orientation. Either a Sonosite linear HFL38x/13-6 MHz or Sonosite curvilinear C60x/5-2 MHz probe will be utilized to visualize the pertinent ultrasound anatomy. A Pajunk 21g x 100mm Sono Plex Stim Cannula will be utilized to appropriately deposit a single local anesthetic aliquot consisting of 25cc's of bupivacaine 0.25% with epinephrine 5mcg/cc and clonidine 1.66mcg/cc. arm 2: Patient's randomized to receive a Quadratus Lumborum block (QLB) for post operative analgesia following inguinal herniorrhaphy will have said block performed in a lateral position in a manner consistent with the technique described by Børglum. Either a Sonosite linear HFL38x/13-6 MHz or Sonosite curvilinear C60x/5-2 MHz probe will be utilized to visualize the pertinent ultrasound anatomy. A Pajunk 21g x 100mm Sono Plex Stim Cannula will be utilized to appropriately deposit a single local anesthetic aliquot consisting of 25cc's of bupivacaine 0.25% with epinephrine 5mcg/cc and clonidine 1.66mcg/cc.
Interventions: intervention 1: Ilioinguinal / Iliohypogastric Block intervention 2: Quadratus Lumborum Block intervention 3: Bupivacaine 0.25% intervention 4: Epinephrine 1:200k intervention 5: Clonidine 1.66mcg/cc
Intervention descriptions: intervention 1: Patients randomized to this arm will receive 25cc's of Bupivacaine 0.25% + Epinephrine 1:200k + Clonidine 1.66mcg/cc administered via an ultrasound guided ilioinguinal / iliohypogastric block technique. intervention 2: Patients randomized to this arm will receive 25cc's of Bupivacaine 0.25% + Epinephrine 1:200k + Clonidine 1.66mcg/cc administered via an ultrasound guided quadratus lumborum block technique. intervention 3: Administered as part of the local anesthetic mixture intervention 4: Administered as part of the local anesthetic mixture intervention 5: Administered as part of the local anesthetic mixture

Protocol documents:
Prot_SAP_000.pdf: 
Protocol version: 1 
 
1 
 
 
Title:   ILIOINGUINAL/ILIOHYPOGASTRIC VS. QUADRATUS LUMBORUM NERVE 
BLOCKADE FOR ELECTIVE OPEN INGUINAL HERNIORAPHY 
PI:  Christopher Edwards, MD 
NCT:  NCT03007966 
Date of Protocol:  11/18/2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol version: 1 
 
2 
 
 
 
 
Study Title:  Ilioinguinal/Iliohypogastric vs. Quadratus Lumborum Nerve Blockade for Elective 
Open Inguinal Herniorrhaphy 
 
Principal Investigator, Co-investigator(s): Christopher J. Edwards, MD, Daryl S. Henshaw, MD 
 
Sponsor or funding source: Wake Forest Baptist Health, Department of Anesthesiology 
 
Background, Rationale and Context 
Open inguinal herniorrhaphy is a common outpatient surgical procedure.  Post-operative pain can 
be a significant hindrance to discharge from the post anesthesia care unit.  Pain can be treated with opioid 
therapy, but the literature supports that these agents are known to create or exacerbate adverse effects and 
complications, including post-operative nausea and vomiting, hypoxia, and urinary retention.  In contrast, 
analgesia provided by regional anesthesia results in a decreased risk of the aforementioned 
complications.1 Because of this, various regional anesthetic techniques have been developed to provide 
analgesia following open herniorrhaphy.  One technique is a combined ilioinguinal and iliohyogastric 
nerve block (IINB), which has been shown to decrease the initial pain after inguinal herniorrhaphy.2   
 
The quadratus lumborum block (QLB) is a newer regional anesthetic technique that we think 
could be as effective as IINB at providing pain control following open herniorrhaphy.  Additionally, 
because local anesthetic injected during a QLB has the potential to spread cranially into the thoracic 
paravertebral space following its lumbar deposition it could lead to alleviation of both somatic and 
visceral pain.3  This might therefore improve the quality and or duration of analgesia as compared to the 
IINB.  To the best of the author’s knowledge there has been no investigation comparing the efficacy, with 
regards to post-operative pain management, between IINB and QLB.   
 
Objectives 
This study will seek to investigate the efficacy of two distinct nerve blocks (QLB vs. IINB) with 
regards to post-operative pain scores with movement following an open inguinal hernia repair.  We 
hypothesize that the QLB will provide equivalent analgesia when compared to the IINB as determined by 
a comparison of verbal reported pain scores.   
 
Methods and Measures 
 
Design 
 
This study will be a double-blinded prospective randomized controlled equivalency trial 
comparing QLB to IINB. 
 
Setting 
 
The setting for the study will be an academic medical center and all patients recruited 
will have surgery at Wake Forest Baptist Medical Center. 
 
Subjects selection criteria 
Patients with a diagnosis of inguinal hernia scheduled for elective unilateral open inguinal hernia 
repair. 
 
Inclusion Criteria 
o All patient’s scheduled for elective unilateral open inguinal hernia repair  
 
Exclusion Criteria 


Protocol version: 1 
 
3 
o The anesthesiologist performing the intraoperative anesthetic deems the patient 
inappropriate for general anesthesia.   
o If the patient uses more than 40mg of Oxycodone equivalents per 24 hours or is 
on extended release opioid formulations.     
o If there is a contraindication to the performance of a regional block 
 
Concomitant anticoagulation use 
 
Allergy to local anesthetic 
 
Infectious or dermatologic conditions in the area of block placement that 
would otherwise increase the risk of peripheral nerve blockade 
o Patient refusal 
o Pregnancy 
o Institutionalized individuals 
o Extremes of age:  Age > 90 or < 18 
o Non English speaking 
 
 
Sample Size 
o The study design will compare X and Y for postoperative pain following Z.  The 
trial will compare these two approaches for postoperative pain control under the 
hypothesis that X will provide equal to Y.  Using an 11-point numerical pain 
scale (0-10), the study will be powered to find that the average numeric pain 
score on the pain scale (8 hours following block placement) following the two 
approaches does not differ by more than 2 points.  The assumption for this study 
is that differences of less than 2 numerical points on the pain scale are not 
clinically significant .4  Preliminary data from 10 II/IH subjects performed at 
WFUBMC indicates average pain scores with movement of 6.40 at 8 hours post-
op (SD=2.41).  Assuming an alpha level of 0.05, we therefore estimated that 26 
patients in each group would provide a power of 80%.  Allowing for potential 
drop out, we plan to enroll 30 patients per group (60 total patients) in this study. 
 
Interventions and Interactions 
 
Patients will be randomized to either receive an IINB or QLB for post-operative 
analgesia 
o Randomization to either QLB or IINB will occur via block randomization using 
sealed sequentially numbered opaque envelopes that will correspond to the order 
with which patients are enrolled.  
 
Patients will be blinded to their randomization by administration of intravenous sedation 
(titrated to patient comfort), examination of both block sites with ultrasonography, 
marking of landmarks for each block, and performance of a skin wheel with 1% lidocaine 
at each block site prior to performance of the randomized block.  
 
The QLB will be performed in a lateral position in a manner consistent with the 
technique described by Børglum.3 
 
The IINB will be performed in a supine position in a manner consistent with the 
technique described by Willschke5, but modified to utilize an in-plane technique rather 
than an out-of-plane technique for needle to ultrasound probe orientation.  
 
For both QLB and IINB either a Sonosite linear HFL38x/13-6 MHz or Sonosite 
curvilinear C60x/5-2 MHz probe will be utilized respectively to visualize the pertinent 
anatomy as outlined in the citations above as well as to visualize the appropriate 
deposition of local anesthetic.  
 
For both QLB and IINB a Pajunk 21g x 100mm Sono Plex Stim Cannula will be utilized 
for placement of local anesthetic.  


Protocol version: 1 
 
4 
 
For both QLB and IINB the following local anesthetic mixture will be administered 
o Bupivacaine 0.25% 
 
Local anesthetic 
o Epinephrine – 5mcg/cc (1:200,000 concentration) 
 
Utilized for vasoconstriction, prolongation of regional block, and as an 
intravascular marker 
o Clonidine – 1.66mcg/cc 
 
Utilized for prolongation of regional block and for improvement in block 
quality.   
o A total of 25cc of the above local anesthetic mixture will be administered in 
performance of both the QLB and IINB 
 
An ultrasound image of the block will be saved for both the QLB and IINB as per our 
normal practice for billing and documentation.  This image should be stored on a secure 
server as per our usual practice with all ultrasound images.   
 
Block success will be assessed either prior to proceeding to the OR if time permits, or in 
the immediate post-operative period.  Loss of cold sensation in the immediate vicinity of 
the incisional site will indicate block success.  
 
Surgeons will be asked to not infiltrate the incision site with additional local anesthetic. 
 
All patients will receive preoperative multimodal analgesic medications, per the typical 
approach at our institution.  These include acetaminophen orally (1000mg), celecoxib 
orally (200mg) and pregabalin orally (150mg) unless contraindicated.   
 
Patients will undergo general anesthesia for the surgical procedure.  
 
Intraoperative management of the patient will be at the discretion of the attending 
anesthesiologist for that particular surgery.  However, the intraoperative analgesics will 
be standardized to minimize the chance of their effect on the primary outcome.  
o Patients will not receive ketamine intravenously.  
o Patients will not receive dexamethasone intravenously.  
o Fentanyl intravenously will be the primary analgesic and patients will not receive 
longer acting intravenous opioids such as hydromorphone or morphine.  
 
Patients will receive a diary to be completed over the next 24hrs at specific time intervals 
to aid in collection of data pertinent to both primary and secondary outcomes.   
 
Postoperative oral pain medications will be ordered as usual by the surgical team without 
restrictions.   
 
Patients will be called at home to collect the data from their diary at 8hrs and 24hrs post 
block.   
 
 
 
 
Outcome Measure(s) 
 
Primary Outcome 
o Post-operative verbal pain score assessed on an 11-point (0-10) numeric analog scale at 8 
hours following block placement during movement.  
 
Secondary outcomes 
o Post-operative verbal pain score at 8 hours at rest 
o Post-operative verbal pain scores at 24 hours both at rest and with activity 
o Time to first oral analgesic 
o Time when post-operative pain first noted 
o Total opioids used in 24 hours 


Protocol version: 1 
 
5 
o Incidence of opioid related side effects (Nausea, Vomiting, and Itching) at both 8 hours 
and 24 hours   
 
Analytical Plan 
The primary analysis will consist of an equivalency comparison between X and Y in terms of their effect 
on pain scores. For each individual, pain scores will be compared post-op at 8 hours following block 
placement with movement. Testing equivalency requires specifying a clinical difference (hereafter labeled 
as d); if the mean difference in pain scores between blocks can be estimated to fall between –d and +d, 
then the two nerve blockades will be deemed equivalent.  Equivalence will be tested using the Two One-
Sided Tests (TOST) procedure6. Preliminary data from 10 II/IH subjects performed at WFUBMC 
indicates average pain scores with movement of 6.40 at 8 hours post-op (SD=2.41). Power for the TOST 
procedure can be estimated as in Julious (see equation 5.17)7, which accounts for the uncertainty 
associated with our estimates of the standard deviation in pain scores. Estimated sample size is based on 
power of 80% and assumes an alpha level of 0.05.    
   
Analytic part: 
We will compare the characteristics of patients randomized to the X and Y using t-tests for continuous 
variables and Chi-Square tests for categorical variable. Equivalence (in terms of the impact of each block 
on pain) will be tested using the Two One-Sided Tests (TOST) procedure.6  If we let 
denote the 
average change in pain using the quadratus lumborum block, and 
using the 
ilioinguinal/iliohypogastric block, the TOST procedure requires rejecting both of the null hypotheses 
 and 
 in order to declare equivalence 
 
Human Subjects Protection 
 
Subject Recruitment Methods 
Potential study participants will be identified by review of the daily operative schedule, and all patients 
undergoing open inguinal hernia repair will be identified.  Preliminary review of the patient’s chart will 
be performed to identify any exclusion criteria as noted above.  Should no exclusion criteria be noted, the 
patient will be identified as a possible study candidate.  The patient will be brought to the Regional 
Anesthesia work area, where the details of the study will be fully disclosed to the patient and consent to 
participate will be sought. 
 
Informed Consent 
Signed informed consent will be obtained from each subject.  Consent will be obtained by the 
investigators or study coordinator.  The consent process for the study will be carried out in the 
Regional Anesthesia work area. 
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify 
subjects, and maintaining all study information in a secure manner.  To help ensure subject privacy 
and confidentiality, only a unique study identifier will appear on the data collection form.  Any 
collected patient identifying information corresponding to the unique study identifier will be 
maintained on a linkage file, store separately from the data.  The linkage file will be kept secure, with 
access limited to designated study personnel.  Following data collection subject identifying 
information will be destroyed (three years after closure of the study via secured document 
destruction), consistent with data validation and study design, producing an anonymous analytical 
data set.  Data access will be limited to study staff.  Data and records will be kept locked and secured, 


Protocol version: 1 
 
6 
with any computer data password protected.  No reference to any individual participant will appear in 
reports, presentations, or publications that may arise from the study. 
 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of 
study participants.  The principal investigator will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes 
will be promptly reported by the principal investigator or designated member of the research team to 
the IRB and sponsor or appropriate government agency if appropriate. 
 
References 
1. Williams BA, Kentor ML, Vogt MT, Vogt WB, Coley KC, Williams JP, Roberts MS, Chelly JE, 
Harner CD, Fu FH. Economics of Nerve Block Pain Management after Anterior Cruciate 
Ligament Reconstruction.  Anesthesiology 2004;  100(3): 697-706 
 
2. Toivonen J, Permi J, Rosenberg PH. Analgesia and discharge following preincisional ilioinguinal 
and iliohypogastric nerve block combined with general or spinal anaesthesia for inguinal 
herniorrhaphy.  Acta Anaesthesiol Scand 2004; 48: 480-85 
3.  Børglum J, Moriggl B, Jensen K, Lӧnnqvist PA, Christensen AF, Sauter A, Bendtsen TF. 
Ultrasound-guided transmuscular quadratus lumborum blockadge. Br J Anaesth 25 March 2013 
4. Farrar JT, Berlin JA, Strom BL. Clinically important changes in acute pain outcome measures: a 
validation study. J Pain Symptom Manage 2003; 25:406–11 
5. Willschke H, Marhofer P, Bӧsenberg A, Johnston S, Wanzel O, Cox SG, Sitzwohl C, Kapral S. 
Ultrasonography for ilioinguinal/iliohypogastric nerve blocks in children. Br J Anaesth 2005; 
95(2): 226-30 
6. Schuirmann DJ. A Comparison of the Two One-Sided Tests Procedure and the Power Approach 
for Assessing the Equivalence of Average Bioavailability. J of Pharamcokinetics and 
Biopharmaceutics 1987; 15(6): 657-680. 
7. Julious SA. Sample Sizes for Clinical Trials. Chapman and Hall/CRC, Boca Raton, FL, 2010. 
 
 
Appendix 
1. Data collection form 
2. Patient diary 
3. Consent form  
4. Other Appendix items as appropriate