Clinical trial NCT04368364
Conditions: Pain, Postoperative
Keywords: post c section pain pain control after baby nerve block for post delivery pain
Sponsor: The University of Texas Health Science Center, Houston
Start date: 2020-05-22; Completion date: 2020-06-29
Enrollment: 3 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
the purpose of this study is to compare opioid consumption in morphine equivalents between the groups that received postoperative analgesia with intrathecal morphine versus US guided QL blocks versus US guided QL catheters

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Intrathecal morphine sulfate (ITM) intervention 2: Bupivacaine hydrochloride intervention 3: ropivacaine hydrochloride
Intervention descriptions: intervention 1: Spinal anesthesia with ITM + US guided QLB single shot sham block + QLB catheters with no continuous infusion intervention 2: Spinal anesthesia without ITM + US guided QLB single shot with bupivacaine hydrochloride + QLB catheters with no continuous infusion intervention 3: Spinal anesthesia without ITM + US guided QLB single shot with bupivacaine hydrochloride + QLB catheters continuously infusing 0.2% ropivacaine hydrochloride

Protocol documents:
Prot_SAP_000.pdf: 
IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
 
 
 
 
 
 
 
A prospective randomized control trial comparing analgesic benefits of ultrasound-guided 
single vs continuous quadratus lumborum blocks vs intrathecal morphine for post cesarean 
section pain 
 
 
NCT04368364 
 
Version Date: 05/04/2020 
 
 
 
 
 
 
 
 
 
 
 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
A prospective randomized control trial comparing analgesic benefits of ultrasound-guided 
single vs continuous quadratus lumborum blocks vs intrathecal morphine for post cesarean 
section pain 
 
I. 
Principal investigator and research team 
Principal investigator- Sudipta Sen 
Co investigators- Nadia Hernandez, Johanna De Haan, Yangdong Jiang 
 
II. 
Contact information 
PI information- Sudipta Sen, 
 
 
Statistician- Xu Zhang, 
  
 
 
III. 
Study site 
Memorial Hermann Hospital at Texas medical center, 6411 Fannin Street, Houston, 
Texas 77030 
 
IV. 
Study Title 
Full title-: A randomized control trial comparing analgesic benefits of ultrasound-guided 
single vs continuous quadratus lumborum blocks vs intrathecal morphine for post 
cesarean section pain 
Running title-: RCT comparing QL blocks, QL catheters vs intrathecal morphine post 
Csection 
 
V. 
Study Duration 
12 months 
 
VI. 
Participant patient study duration 
Patients will be enrolled from time of admission for cesarean section until post-operative 
day 3. Total duration of participant enrollment will be for 72 hours. 
VII. 
Trial registration information
XXX 
 
VIII. 
Clinical Phase 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
Phase 4 
 
IX. 
Study significance and background 
The rate of Cesarean section (CS) is increasing constantly in the United States (US) and 
is currently at 31.9 % per the center of disease control and prevention (CDC).(“Martin 
JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: Final Data for 2016.  
National Vital Statistics Reports; Vol 67 No 1. Hyattsville, MD: National Center for 
Health Statistics. 2018.” 2018) Post-partum (PP) pain and fatigue is commonly 
experienced by the women who have delivered via a CS. Severe untreated post-operative 
CS pain results in increase consumption of opioids, decreased mobility, increased 
postpartum depression and persistent pain.(Landau, Bollag, and Ortner 2013; 
Lavand’homme 2013; Kainu et al. 2010) 
Single-shot intrathecal morphine sulfate (ITM) injected while performing a spinal 
anesthetic for CS has been considered the gold standard for post CS pain. ITM provides 
analgesia for about 14-36 hours. Variable doses of ITM ranging between 50 – 250 
micrograms (µcg) have been used. Lower doses of ITM results in fewer side effects 
however present a tradeoff of shorter duration of analgesia.(Sutton and Carvalho 2017a) 
Side effects of ITM can be treated with effective prophylaxis and treatment medications. 
Nalbuphine and naloxone are given to treat pruritus. Nausea and vomiting are treated 
with ondansetron, metoclopramide, promethazine, and propofol. Respiratory depression 
is seen with higher doses of ITM (≥ 150 µcg). Patients, who are obese, have obstructive 
sleep apnea and are on chronic pain medications or patients with opioid tolerance have a 
higher incidence of respirator depression. Respiratory depression is treated with naloxone 
bolus followed low dose naloxone infusion. This can antagonize opioid effect and result 
in pain. Patients with pre-eclampsia receive magnesium, which is sedating and can 
further cause respiratory depression.(Sutton and Carvalho 2017a) The bimodal 
respiratory depression associated with ITM requires intense monitoring of respiratory 
status for the first 24 hours and special training for providers caring for these patients.  
Eighty-one percent of all women in the US initiate breast-feeding (BF) postpartum. Early 
BF improves maternal-neonatal bonding. Effective pain control promotes successful BF.  
A relative infant dose (RID) expressed as a percentage and is weight adjusted for the 
neonate (Table 1). It quantifies the amount of neonatal drug exposure relative to the 
mother’s dose. A value of greater than 10% is considered high. (Sutton and Carvalho 
2017b) Highly protein bound drugs like non-steroidal anti-inflammatory drugs 
(NSAID’s) and local anesthetics (LA) have limited transfer to the neonate.  
Acetaminophen provides effective analgesia PP with minimal side effects as a part of the 
multimodal analgesia plan (MPP). It has an opioid sparing effect of approximately 20%.  


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
Scheduling acetaminophen for 2-3 days post CS has been recommended.(Bollag et al., 
n.d.)  
Ibuprofen has a short half-life. RID is 0.6% in colostrum and <0.38% in mature milk. 
This is equivalent to 0.2% of the pediatric dose. Scheduled ibuprofen for 2-3 days has 
also been recommended in addition to scheduled acetaminophen. (Bollag et al., n.d.) 
Table 1: Relative infant dose for different medications 
Drug 
Relative infant dose 
Acetaminophen 
1.3-6.4 
Ibuprofen 
0.1-0.7 
Ketorolac 
0.2-0.4 
Celecoxib 
0.3 
Gabapentin 
1.3-6.5 
Hydrocodone 
1.6-3.7 
Oxycodone 
1.5-8 
Tramadol 
2.4-2.9 
Fentanyl 
0.9-3 
Morphine 
5.8-10.7 
The quadratus lumborum block (QLB) was initially described by R. Blanco.(Blanco, 
Ansari, and Girgis 2015) This block covers not only the somatic innervation of the body 
wall, but also provides relief of visceral pain. Given its versatility, the quadratus 
lumborum block has successfully been used in a wide range of procedures including 
gastrectomies, colectomies, prostatectomies, nephrectomies, cystectomies, cesarean 
sections and hysterectomies.  
There are three types of quadratus lumborum blocks: quadratus lumborum type 1 
(QLB1), quadratus lumborum type 2 (QLB2) and trans-muscular quadratus lumborum 
block (TQLB). For all three blocks, the needle enters the lateral abdomen near the 
posterior axillary line, below the costal margin and above the iliac crest. In QLB1, the 
anesthetic agent is injected into the potential space medial to the abdominal wall muscles 
and lateral to the quadratus lumborum muscle (QL). This block covers the dermatomal 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
area from T10 to L1, and is typically used for abdominal surgeries being conducted 
below the umbilicus. In QLB2, the anesthetic agent is injected just posterior to the QL 
muscle and covers T4 to L1. The QLB2 block effectively blocks the anterior and lateral 
cutaneous branches of the nerves. It is typically used for abdominal surgery either above 
or below the umbilicus (any type of operation that requires intrabdominal visceral pain 
coverage and abdominal wall incisions as high as T6). In TQLB, the anesthetic agent is 
injected anterior to the QL muscle, between the QL and the psoas major muscles. This 
block has analogous coverage to the QLB2 block and thus has the same clinical 
indications as the QLB2 block. However, this block is more difficult to perform than the 
QLB2 block, and can result in quadriceps weakness due to spread to the lumbar plexus on 
the anterior surface of the psoas major muscle. (Ueshima, Otake, and Lin 2017) 
Early oral intake, mobilization, removal of urinary catheter are all important components 
of the enhanced recovery after surgery protocol (ERAS). We hypothesize that by 
performing QL blocks post CS the amount of pain, narcotic consumption will be reduced 
significantly. Early ambulation will help prevent deep vein thrombosis. Performing QL 
blocks will also minimize side effects secondary to ITM and will facilitate ERAS and 
better patient satisfaction scores.  
A recent study conducted by Salama et al concluded that QLB (without ITM) provided 
lower numeric rating scores at rest and during movement when compared to the group 
that received ITM (without QLB). Time to first morphine dose was also longer in the 
QLB. This study concluded that a longer duration of analgesia and reduced postoperative 
morphine consumption was achieved with QLB when compared to ITM.(Salama 2019)  
 
X. 
Sample size 
25 in each group 
Total number of enrolled patients: 75 
 
XI. 
Study population 
Inclusion criteria 
1. Age greater than 18 years 
2. Elective C section via Pfannenstiel incision 
3. Living singleton pregnancy 
4. Gestation week at least 37 weeks 
5. ASA status 1, 2 and 3 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
6. Primary and secondary C sections 
Exclusion criteria 
1. Chronic pain 
2. Opioid tolerant patients 
3. Allergy to drugs used in the study.  
4. Cognitive dysfunction 
5. BMI > 40 
6. Coagulation disorder 
7. Local infection 
8. Inability to tolerate oral medication 
9. Previous intra-abdominal surgery 
10. Patients who will receive a combined spinal epidural for their C section 
11. Local anesthetics injected at any other fascial plane except the QLB plane (for  
e.g.- local wound infiltration by surgeon) 
12. Patients who received sedation or general anesthesia during their CS (midazolam, 
ketamine, fentanyl, propofol, hydromorphone) 
Voluntary patient withdrawal from the study- patient has right to withdraw at any point 
during the study period 
Withdrawal in case of unexpected events- This will be determined by the investigators. 
 
XII. 
Primary objective 
Primary objective of the study is to compare opioid consumption in morphine equivalents 
between the groups that received postoperative analgesia with intrathecal morphine 
versus US guided QL blocks versus US guided QL catheters 
Our working hypothesis is- 
1. Single shot QL block is equivalent to intrathecal morphine with less side effects in 
providing post-operative pain control for the first 24 hours. 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
2. Continuous QL catheter is more beneficial than single shot QL block or intrathecal 
morphine after 24 hours in providing post-operative pain control. 
3. Our exploratory hypothesis is that after 48 hours a QL catheter would continue to 
reduce morphine consumption until 72 hours. 
Primary outcome measure 
Total narcotic consumption in morphine equivalents (in milligrams) for the first 72 hours 
after surgery will be calculated. Total narcotic used in the spinal anesthetic will be 
excluded. 
 
XIII. 
Secondary objectives 
1. Total narcotic usage at 24 and 48 hours will be assessed in morphine equivalents. 
Intraoperative consumption of opioids will be excluded. 
2. Time to first analgesic request 
3. Numeric pain score (NPS)- static and dynamic at 6, 12, 24, 48 and 72 hours 
4. Pruritus at 24, 48 and 72 hours 
5. Nausea at 24, 48 and 72 hours 
6. Vomiting at 24, 48 and 72 hours 
7. Sedation at 24, 48 and 72 hours 
8. Patient satisfaction- quality of sleep, ability to ambulate, and ability to breast feed 
and take care of newborn at 24, 48 and 72 hours 
Secondary outcome measures-  
1. Total narcotic consumption in morphine equivalents (in milligrams) at 12, 24 and 
48 hours will be measured. 
Time after CS 
Total morphine equivalents (mg) 
At 4 hours 
 
At 6 hours 
 
At 12 hours 
 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
At 24 hours 
 
At 72 hours 
 
2. Time to first analgesic request will be reviewed from the chart 
3. Our research personnel will use NPS.  This will be assessed at 6, 12, 24, 48 and 
72 hours. NPS is a 11-point scale as shown below. The study patient will verbally 
select a numerical value that best corresponds with the pain the patient is 
experiencing at that point. This data will be statistically analyzed. Static and 
dynamic pain scores will be assessed. Dynamic pain scores will be assessed by 
asking the patient to sit up in bed from supine to sitting at 6 hours. This will be 
repeated at 12, 24,48 and 72 hours however if patient is ambulating, dynamic pain 
score during ambulation will be assessed.  
 
No pain 
 Distressing pain 
Worst pain 
 
No pain (0)         Mild pain (1,2,3)         Moderate pain (4,5,6)      Severe pain (7,8,9,10) 
Time interval after CS 
NPS (static) 
NPS (dynamic) 
At 6 hours 
 
 
At 12 hours 
 
 
At 24 hours 
 
 
At 48 hours 
 
 
At 72 hours 
 
 
4. Numeric scale to rate side effects (SE) of pruritus, nausea, vomiting and sedation 
at 24, 48 and 72 hours; 0- no side effects 10- extremely severe side effect 
possible. This numeric scale is a 11-point scale as shown below. The study patient 
will verbally select a numerical value that best corresponds with the side effects 
the patient is experiencing at that point. This data will be statistically analyzed. 
 
No SE 
               Distressing SE 
                                       Worst SE 
 
No SE (0)               Mild SE (1,2,3)          Moderate SE (4,5,6)           Severe SE (7,8,9,10) 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
Side effects 
Scale at 24 hours 
Scale at 48 hours 
Scale at 72 
hours 
Pruritus 
 
 
 
Nausea 
 
 
 
Vomiting 
 
 
 
Sedation 
 
 
 
5. Patient satisfaction will be measured on a Likert scale (5 points) at 48 and 72 
hours. How satisfied were you with the following? 
 
Extremely 
satisfied 
Very  
satisfied 
Moderately 
satisfied 
Slightly 
satisfied 
Not 
satisfied 
Quality of 
sleep 
 
 
 
 
 
Ability to 
ambulate 
 
 
 
 
 
Ability to 
breast feed/  
formula  
feed 
 
 
 
 
 
Ability to 
take care of 
new born 
 
 
 
 
 
 
XIV. 
Study drugs 
1. Preservative free morphine 
2. Normal saline 
3. Bupivacaine hydrochloride 0.25 % 
4. Ropivacaine hydrochloride 0.1 % XV. 
Study schedule 
Expected start date for enrolling patients 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
Expected end date for enrolling patients 
Enrollment period for each patient- 72 hours, earlier if discharged. 
 
XVI. 
Study design 
This is a prospective double-blinded randomized control trial performed at a single 
institution. 
Screened patients meeting inclusion criteria will be randomized into three groups: 
Group 1- Spinal anesthesia with ITM + US guided QLB single shot sham block + QLB 
catheters with no continuous infusion 
Group 2- Spinal anesthesia without ITM + US guided QLB single shot with bupivacaine 
hydrochloride + QLB catheters with no continuous infusion 
Group 3- Spinal anesthesia without ITM + US guided QLB single shot with bupivacaine 
hydrochloride + QLB catheters continuously infusing 0.2% ropivacaine hydrochloride 
Placement of spinal anesthesia- This will be performed by the attending anesthesiologist 
or anesthesiology resident who are providing anesthesia for the patient in the operating 
room. The anesthesia technique will be standardized. A spinal anesthetic will be 
performed in the sitting position at the lumbar vertebra level (L) either at L3-L4 or L4-L5 
level. All women will receive a spinal anesthetic using 0.75% hyperbaric bupivacaine 
912 mg plus fentanyl 20 micrograms plus epinephrine 1:100,000 100 micrograms 
administered intrathecally. The anesthesiologist caring for the patient will not be blinded. 
The anesthesiologist caring for the patient will open an opaque envelope handed to 
him/her by the research personnel. The envelope will clearly state the group the patient is 
assigned to and if ITM 200 micrograms should be added or excluded from the spinal 
medication. Spinal block efficacy will be considered successful if a sensory block to 
pinprick is achieved at a level of thoracic (T) 6 or higher. Anesthesia and surgery will be 
performed in the usual manner.  
Placement of QL blocks- Immediately after wound closure, bilateral QL blocks will be 
placed by one of the investigators under direct ultrasound guidance (Sonosite X-Porte, 
Sonosite, Bothell, WA). For the purpose of our study we will be utilizing the QL 2 
technique by Blanco to achieve blockade from T7-L1 dermatomes.(Blanco et al. 2016; 
Blanco, Ansari, and Girgis 2015) The anesthesiologist caring for the patient will open the 
opaque envelope and prepare the study drug. The study drug will either be a sham 20 ml 
empty syringe or 0.25% bupivacaine hydrochloride 20 ml each side. The patients will be 
in the supine position with a small roll of blanket placed under the ipsilateral flank. The 
abdomen will be cleaned with 2 % chlorhexidine gluconate and 70 % isopropyl alcohol 
solution (ChloraPrep® One-Step). If the patient has an allergy to any of the contents of 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
the cleaning solution, 10% Povidone-Iodine solution will be used. The ipsilateral 
abdomen will be draped with sterile towels. A transverse linear array probe (HFL50 6-15 
MHz) placed in a sterile probe cover with an imaging depth of 4-6 cm will be placed at 
the level of the anterior superior iliac spine and moved cranially until the three abdominal 
muscles are identified; external oblique (EO), internal oblique (IO), transverse abdominis 
(TA). The EO muscle will be followed posterior and laterally until its posterior border is 
visualized. The IO muscle should come into view overlying the QL muscle. The probe 
will be tilted to identify a bright hyperechoic line that corresponds to the middle layer of 
the thoraco-lumbar fascia. An 18 G echogenic peripheral nerve block needle (Contiplex® 
Ultra 360™ continuous nerve block set, B Braun, Bethlehem, PA, USA) will be inserted 
in plane from anterolateral to posteromedial direction. The optimal point of injection for 
the QL will be determined by hydro dissection with normal saline. Primary block will be 
performed depending on the group allocation of the patient. The patient will receive 
either no drug (Group 1) or bupivacaine hydrochloride (Group 2 and Group 3). QL 
catheters will be placed as described below. A QL2 block will be performed on the 
contralateral side in a similar fashion. 
Placement of QL catheters- A 20 G peripheral nerve polyamide catheter (Contiplex® 
Ultra 360™ continuous nerve block set, B Braun, Bethlehem, PA, USA) will be inserted 
through the 18 G echogenic needle under direct ultrasound visualization. The catheter 
will be secured using the standard technique employed at our institution. Correct 
placement of QL catheters will be confirmed by injecting saline under ultrasound 
guidance. QL catheter will be placed on both sides in a similar fashion. A member of the 
research team who performed the initial QLB in the operating room will attach a 
peripheral nerve pump (CADD® Solis ambulatory infusion pump, Minneapolis, MN, 
USA) to the QL catheter once the patient reaches the post anesthesia care unit (PACU).  
No infusion will be initiated if the patient is assigned to group 1 (Spinal anesthesia with 
ITM + US guided QLB single shot sham block + QLB catheters with no continuous 
infusion) and group 2 (Spinal anesthesia without ITM + US guided QLB single shot with 
bupivacaine hydrochloride + QLB catheters with no continuous infusion). Infusion of 0.2 
% ropivacaine at 10 ml/hour on each side will be initiated if the patient is randomized to 
group 3 (Spinal anesthesia without ITM + US guided QLB single shot with bupivacaine 
hydrochloride + QLB catheters infusing 0.2% ropivacaine hydrochloride). A member of 
our research team who is blinded to the group allocation will manage all peripheral nerve 
catheters. No extra bolus medication will be given through any of the catheters. We are 
not initiating any infusion through the peripheral nerve catheters in group 1 and 2 to 
avoid the possibility of pain due to stretching of muscles and facial planes by normal 
saline. 
All patients will be started on a multimodal pain regimen. They will receive scheduled 
acetaminophen 1000 mg orally and ibuprofen 600 mg every 6 hours. Oxycodone 2.5 mg- 
5 mg oral every 4 hours as needed will be added for breakthrough pain. Patients will be 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
evaluated by the anesthesia pain service for adding a PCA with intravenous 
hydromorphone if pain not adequately controlled on their regimen.   
Our research personnel who will be blinded, will follow up patients for the first 48 hours 
to collect data listed under primary and secondary objectives. We are not assessing 
dermatomal levels to determine the spread of local anesthetic as it could possibly result in 
patients and study personnel knowing which group they fall under and potentially 
unblinding the study. 
XVII. 
Conduct 
 
1. Screening 
Our research team will assess patients for eligibility based on the inclusion 
criteria. We will obtain informed written consent from all eligible patients. Any 
member of our research team at any point will obtain this consent during the 
preoperative period (anesthesia clinic, surgery clinic, preoperative holding area). 
Patients will be given adequate time to consult with family members and use the 
internet for additional information. All questions and concerns by the patient will 
be addressed at this point. 
Once a written informed consent is obtained the patient will be educated about the 
study protocol, NPS assessment, other assessment tools and the use of MMP 
medications. Baseline pain score will be recorded at this point. A complete 
preoperative evaluation, physical examination and preoperative testing will be 
conducted per usual protocol by the anesthesiologist caring for the patient. 
Three copies will be made of the written informed consent. Patient will be given a 
copy of the signed written informed consent. A copy of the consent will be placed 
in the patient’s chart. Our research team will keep one copy of the consent. 
 
2. Enrollment 
Patient will be enrolled if all inclusion, exclusion criteria are met and the patient 
has provided an informed written consent. Our research coordinator will then 
randomly assign the patient into one of the groups based on the random allocation 
software. 
 
3. Randomization and allocation concealment 
Anesthesiologist in the operating room will not be blinded to the patient’s 
randomization, as they must prepare the spinal with or without intrathecal 
morphine and the prescribed solution for block placement. Anesthesiologist 
performing the regional nerve block not be blinded as they will have to perform a 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
sham QLB or a QLB with the study drug.  All other research personnel collecting 
data or seeing the patient postoperatively will not know what the contents of the 
spinal medication were, whether or not the QLB contained no drug or 
bupivacaine, or whether the QLB catheter infusions contain no drug or 
ropivacaine.   
Patient’s assigned group will be communicated to the anesthesiologist caring for 
the patient in an opaque envelope so that no other research personnel are wise to 
the assignment.  
Research personnel responsible for randomizing and assigning group will not be 
the same personnel as those evaluating the patient or collecting data.  
 
4. Preoperative assessment 
A complete pre-operative assessment will be done by the anesthesiologist or 
resident physician caring for the patient. Our research personnel will only 
evaluate patient to verify if they meet our inclusion criteria. 
 
5. Follow up 
Our research personnel who will be blinded to the study drugs used, will follow 
up patients. 
Following data will be collected from the patient at the following time intervals. 
At 6 hours 
NPS 
 
 
At 12 hours 
NPS 
 
 
At 24 hours 
NPS 
NRS for SE 
 
At 48 hours 
NPS 
NRS for SE 
Likert scale for 
patient satisfaction 
 
6. Termination of enrollment 
Enrollment will be terminated if the following criteria are met- 
i. 
At the end of the 48-hour period 
ii. 
Intraoperative complication resulting in post-operative prolonged 
ventilation 
iii. 
Failure of neuraxial spinal anesthesia or conversion to general 
endotracheal anesthesia during the C section 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
iv. 
Pfannenstiel incision converted to any other type of incision during 
surgery 
v. 
Patient death within 48 hours vi. Termination of study 
 
7. Termination of study 
After data collection, analysis and publication of results. 
XVIII. 
Adverse event reporting 
All patients will be monitored for adverse events. Adverse events if any will be duly 
documented in the research file as well as in the patient’s medico legal record. All 
adverse events will be reported to the data safety monitoring board (DSMB). The patient 
will be informed of all adverse events such as local anesthetic systemic toxicity, local 
infection, bleeding.  
 
XIX. 
Sample size and statistical analysis 
Size consideration: 
Based on preliminary data collected on 12 patients receiving intrathecal morphine at our 
institution, the mean consumption in morphine equivalents are 27 (SD=25), 29 (SD=23) 
and 11 (SD=10) for 24 hours, 24-48 hours and 48-72 hours, respectively. Significance 
level 0.05 and two-sample t test are used for all size calculations. Working hypothesis 1: 
One patient receiving single shot QL block did not consume morphine within 24 hours. 
We conservatively use 10 as the mean for single shot QL block. Using a one-sided t-test, 
single shot QL block would be considered as non-inferior to intrathecal morphine if 
µSµI<δ, where δ is the non-inferiority margin. Given SD=25, for δ=5, 23 patients per 
group provides the power of 90% for confirming non-inferiority. Working hypothesis 2: 
Based on preliminary data of morphine consumption in 24-48 hours, one patient 
receiving continuous QL catheter consumed 20 and one patient receiving single shot QL 
block consumed 49. We use 20 and 49 as mean consumptions of these two arms with SD 
23. Based on a two-sided t-test, the size of 15 per group provides the power of 91.5% for 
detecting significant lower amount of consumption for continuous QL catheter. Final size 
and power: We aim at confirming both hypotheses 1 and 2 with type I error 5%. The 
overall power is probability of confirming both hypotheses given the aforementioned 
means (as well as SD’s) for these three arms. We set the target enrollment to be 23 per 
group. The overall power for this size is estimated to be 89.4% based on simulation of 
10000 replicates, assuming independence between tests of hypotheses 1 and 2. We 
compensate the drop-out by inflating the size to 25 per group. 
Statistical analysis plan: 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
The data will be analyzed within one month after completion of data collection for all 
enrolled patients. The deidentified data will be uploaded to PI’s UTH-Share account and 
shared with the statistician. We will conduct Kolmogorov–Smirnov test to test normal 
distribution. Continuous variables will be summarized as mean and standard deviation for 
each group. Comparisons between any two groups will be evaluated by two-sample t test. 
If a variable has skewed distribution, we will report median and inter-quartile range and 
use Wilcoxon rank sum test for two-sample comparison. Incidences of side effects and 
patient satisfaction scales will be summarized as frequency and percentage for each 
group. Their association with intervention arm will be evaluated by Fisher’s exact test. P 
values less than 0.05 will be considered as significant. Test and confidence interval are 
equivalent methods. SD is needed in calculating a confidence interval. The test is 
equivalent to obtaining a 90% confidence interval and comparing the upper limit of 
confidence interval to δ. All statistical analyses will be performed by using the SAS 
software (version 9.4, the SAS Institute, Cary, NC). 
 
XX. 
Ethics 
1. Informed consent- An informed, voluntary consent will be obtained 
systematically. Once the patient meets inclusion criteria, a member of our 
research team will speak with the patient about the study. Information will be 
provided regarding all study drugs, intervention and post-operative care. Standard 
treatment options will also be provided. Adequate time will be provided so that 
the patient can consult with family members, friends or look up more information 
using the internet. 
2. Privacy and confidentiality- The patient will be linked with a study number. Only 
specific computers will be used by our research team to store patient information. 
All data will be restricted to team members, institutional review board (IRB) and 
FDA. Health insurance portability and accountability act (HIPPA) will be strictly 
followed.  
3. Risk vs benefits- Major risks involved with this study are unintentional disclosure 
of patient information and adverse effect due to the local anesthetic leading to 
LAST. There is no monetary benefit involved with this study. Patient will benefit 
from adequate pain control with this intervention. 
 
XXI. 
Study timeline 
Recruitment of sample size- 9 months 
Data collection and analysis- 3 months 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
No long-term follow up is needed with this study. 
Results will be published at the end of data analysis. 
XXII. 
Data safety monitoring 
All drugs are FDA approved for the indication being used for.  
XXIII. 
Conflict of interest 
No conflicts of interest 
XXIV. 
Publication 
Study results will be submitted as a poster at an international conference and will be 
published in a peer-reviewed journal. 
XXV. 
Funding 
I have applied for funding through the Clinical Research Grant through the UTHealth 
Department of Anesthesiology.  
XXVI. 
Abbreviations 
QL- Quadratus lumborum block 
CS- Cesarean section 
ITM- Intrathecal morphine 
µcg- Micrograms  
ASA- American Society of Anesthesiologist 
MMP- Multimodal analgesia plan 
NPS- Numeric pain scale 
NRS- Numeric rating scale 
VAS- Visual analogue scale 
PCA- Patient controlled analgesia 
PP- Post partum 
BF- Breast-feeding 


IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
US- United States 
NSAID’s- Non-steroidal anti-inflammatory drugs 
LA- Local anesthetics 
LAST- Local anesthetic systemic toxicity 
DSMB- Data safety monitoring board 
FDA- United states food and drug administration 
IRB- Institutional review board 
HIPPA- Health insurance portability and accountability act 
XXVII. 
References 
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IRB NUMBER: HSC-MS-20-0143 
IRB APPROVAL DATE: 
05/04/2020 
Salama, Eman Ramadan. 2019. “Ultrasound Guided Bilateral Quadratus Lumborum Block vs. 
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