Dural Puncture Epidural Versus Epidural Anesthesia for Cesarean Delivery: A Randomized, Double-blind Study
Phase: NA
Conditions: Pain Levels
Sponsor: University of Arkansas

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 1 
 
Study Title: 
Dural Puncture Epidural versus Epidural anesthesia for 
cesarean delivery: A randomized, double-blind study  
 
Principal Investigator:  
Nadir Sharawi, MD 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Telephone: (501) 319-2622 
Email:  NElsharawi@uams.edu 
 
 
Sub-Investigator (s): 
 
                                             Jill Mhyre, MD 
 
University of Arkansas for Medical Sciences 
 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Telephone: (501) 554-4943   
Email:  JMMhyre@uams.edu 
 
Matthew Williams, MD 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Email: MWilliams@uams.edu 
 
Study location: 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 2 
Table of Contents 
 
Table of Contents ............................................................................................................... 2 
Abbreviations ...................................................................................................................... 4 
Background and Rationale ................................................................................................. 5 
Specific Aims ...................................................................................................................... 5 
Primary Outcome .......................................................................................................... 6 
Secondary Outcomes ................................................................................................... 6 
Exploratory Outcome ................................................................................................... 6 
Screening/Baseline Phase ........................................................................................... 7 
Pre-operative Phase ..................................................................................................... 8 
Intra-operative Phase ................................................................................................... 8 
Intra-operative Monitoring ......................................................................................... 10 
Concurrent Medication .............................................................................................. 10 
Assessment of Primary Efficacy Parameters ......................................................... 11 
Epidural Study Solutions .................................................................................................. 11 
Post-operative Phase ................................................................................................. 11 
Inclusion Criteria ........................................................................................................... 11 
Exclusion Criteria .......................................................................................................... 12 
Accrual Goal ................................................................................................................ 12 
Recruitment Plan ........................................................................................................ 12 
Risks and Benefits ...................................................................................................... 12 
Benefits of DPE/ Epidural anesthesia .............................................................................. 12 
Risks of Epidural/DPE anesthesia ................................................................................... 13 
Study Medication Risks ................................................................................................ 13 
Risk Mitigation ............................................................................................................... 14 
Drug Accountability and Subject Compliance.................................................................. 14 
Data Handling and Recordkeeping .................................................................................. 14 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 3 
Data Analysis .................................................................................................................... 14 
Sample Size .................................................................................................................. 15 
Randomization .............................................................................................................. 15 
Withdrawal of Participants ................................................................................................ 15 
Stopping the Study ........................................................................................................... 15 
Ethical Considerations ...................................................................................................... 16 
Dissemination of Data ...................................................................................................... 16 
Appendices ....................................................................................................................... 18 
Appendices……………………………………………………………………………………..19 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 4 
Abbreviations 
ASA  
 
 
  
American Society of Anesthesiologist 
BP 
 
 
 
  
Blood Pressure 
CD 
 
 
 
 
Cesarean delivery 
CSE  
 
 
 
Combined spinal epidural 
CSF  
 
 
  
Cerebro-Spinal Fluid 
DPE  
 
 
 
Dural Puncture Epidural 
ECG  
 
 
  
Electrocardiogram 
HIPAA 
 
 
  
Health Insurance Portability and Accountability Act  
IRB 
 
 
 
 
Institutional Review Board 
LA 
 
 
 
 
Local anesthetic 
L&D  
 
 
  
Labor and Delivery 
Mcg   
 
 
 
Microgram 
Min  
 
 
 
 
Minute 
ml, mls 
 
 
  
Milliliter, Milliliters 
PACU  
 
 
  
Post Anesthesia Care Unit 
SOC  
 
 
 
Standard of care 
T5 
 
 
 
  
Thoracic Dermatome Level 5 
T6 
 
 
 
  
Thoracic Dermatome Level 6 
UAMS  
 
 
  
University of Arkansas for Medical Sciences 
VAS 
 
Visual Analogue Scale 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 5 
Background and Rationale 
Cesarean delivery (CD) is the most commonly performed surgical procedure worldwide. 
Indications for CD include maternal or fetal distress, cervical arrest of dilation and 
elective CD. The rate of CD rose from 20.7% in 1996 to 32.9% in 2009 in US 1. The rate 
of CD nationally currently is 32% of all births 2. CD can be performed under neuraxial 
(epidural, spinal or combined spinal-epidural {CSE}) or general anesthesia. Based on 
expert consensus and clinical evidence, neuraxial anesthesia has been recommended 
over general anesthesia for by the American Society of Anesthesiologists and the 
Society for Obstetric Anesthesia and Perinatology 3. 
 
Spinal anesthesia is limited by complications like toxicity of local anesthetic agents, 
transient neurologic back pain, post-dural puncture headache, nerve injury, caudal 
equina syndrome and spinal hematoma 4. While epidural anesthesia is limited by slow 
onset of sensory block and difficulty with achieving bilateral analgesia that may require 
repeated adjustment of the epidural catheter 5. Dural puncture epidural (DPE) is a 
newer technique increasingly used for labor analgesia to overcome these limitations. It 
involves the creation of a single dural perforation with a spinal needle, introduced 
through an epidural needle (similar to a CSE), but without the administration of 
medications through the spinal needle. This technique was developed to address the 
limitations of both epidural and spinal anesthesia when performed for the purpose of 
providing pain relief to laboring women. 
 
When compared to an epidural technique, DPE has been shown to decrease 
manipulation of the epidural catheter, provide a better and earlier onset of labor 
analgesia 6,7,8 , a lower incidence of failure 9, improved bilateral block and a lower 
incidence of intra-op local anesthetic bolus requirement 10. To date most of the studies 
have utilized DPE for the purposes of labor analgesia. Only one study has evaluated the 
use of DPE for surgical anesthesia for lower abdominal surgery 11. The aim of this 
randomized double-blind study is to compare DPE with epidural anesthesia in the 
setting of elective CD. 
Specific Aims 
The aim of this study is to compare the onset time of anesthesia between standard 
epidural and DPE in elective cesarean delivery.  We hypothesize that a DPE technique 
with a 25-gauge spinal needle will have a faster onset and improved quality of surgical 
anesthesia when compared to a standard epidural. 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 6 
Primary Outcome 
The primary outcome will be the onset time of surgical anesthesia. This will be 
measured from the induction of anesthesia (as defined by the beginning of injection of 
the “Induction 1 syringe”) to the point at which sharp sensation is lost bilaterally at the 
T5 dermatomal level (as measured by a blunt plastic neurotip® (Owen Mumford, USA) 
device). 
 
Secondary Outcomes 
1) "Inadequate Neuraxial Anesthesia":   
This composite outcome (any or none) will defined as the failure to achieve at least a 
T10 bilateral sensory level pre-operatively (after 3 ml 1.5% lidocaine with 1:200,000 
epinephrine 45 mg lidocaine and up to 20 ml of 0.0625% bupivacaine), the 
requirement for intraoperative analgesia supplementation, conversion to general 
anesthesia or repeat neuraxial procedure, or failure to achieve the primary outcome 
within 15 minutes between the two groups.  
 
2) We will compare the intraoperative supplementation rate between the two 
groups.  This is defined as the percentage of women who require any additional 
medications to control pain during the elective CD in each arm of the trial.  
 
Exploratory Outcome 
The following will be abstracted from the medical records or reported by the patient in 
the perioperative period: 
• Maximum pain Visual Analogue Scale (VAS) during surgery (as reported by patient, 
scored from 0-10 in the PACU). 
• Incidence of side effects:  
o Nausea (self-reported by patient, yes or no). 
o Vomiting (observed yes or no). 
o Itching (self-reported by patient, yes or no). 
• Use and dose of vasopressors (phenylephrine and ephedrine) 
• Overall patient satisfaction score (asked and scored from 0-10). 
• Neonatal Apgar scores (from medical records). 
• Umbilical cord blood gases taken after delivery (arterial and or venous – from 
medical records). 
• Opioid consumption over 24 hours postoperatively (from medical records) 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 7 
Flow Chart 
 
 
Study Design and Procedure 
 
Screening/Baseline Phase 
The anesthesiologists performing the pre-operative evaluation (standard of care; SOC) 
will alert a member of the study team if the patient meets the inclusion criteria for the 
study.  Following informed consent, we will obtain demographic and clinical information 
including, but not limited to, height, weight, age, current medications, medical 
diagnoses, and history of anesthesia complications (all SOC). Standard non-invasive 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 8 
vital signs (heart rate, blood pressure, respiratory rate, and temperature) will be 
obtained from the pre-operative work up. 
 
Pre-operative Phase 
Patients who have been enrolled into the study will be randomized to receive either 
DPE or standard epidural. As is standard practice, the informed consent process will be 
undertaken before any mood alerting medications are administered. This procedure will 
be performed in the patient’s room upon admission to the Labor & Delivery Suite (L&D) 
shortly before (usually 1 hour) their scheduled time for cesarean section. Epidural/ DPE 
will be performed by an un-blinded anesthesiologist. The un-blinded anesthesiologist 
will have no other role in the patient’s care other than performing the procedure. After 
insertion of the epidural or DPE, a low dose local anesthetic infusion will be infused into 
the epidural catheter up until the time of surgery (bupivacaine 0.0625% with 2 mcg/ml 
fentanyl; SOC). We have previously performed a similar study (IRB # 207313) with 
great success. Participant would then move on to the next phase of the study (see 
below). Patients who are not enrolled in the study would normally receive either an 
epidural or DPE in the same manner. The choice of anesthetic technique for the non-
study patients is dependent on the preference of the anesthesiologist and clinical 
context. 
 
Epidural or DPE study group 
Participants will be blinded to which group they are being assigned. Participants are 
unable to see the procedure (due to placement in the lower back). Both procedures are 
almost identical except for a minor variation in technique. As such the time taken and 
“feel” of the procedure are identical. The unblinded anesthesiologist will insert the 
epidural or DPE based on randomization. They will have no further role in the study 
after the procedure. Insertion of the epidural or DPE will follow the standard practices in 
which all epidurals/DPE are inserted.  
 
Intra-operative Phase 
The patient will be transferred from her room to the operating room at the time of 
scheduled surgery. The epidural pump will be discontinued, and anesthesia care will be 
conducted in the same manner as all cesarean deliveries under epidural extension 
anesthesia (this refers to the process of providing anesthesia using a pre-existing 
epidural/DPE).  Anesthesia will be induced in the standard manner. Motor and sensory 
block will be tested at the end of the epidural loading dose. Loss of sharp sensation will 
be measured using a blunt plastic neurotip® (Owen Mumford, USA) until the sensation 
of “sharpness” at the T5 dermatomal level has been reached. The neurotip is a 
noninvasive medical device that we use routinely to assess the level of anesthesia for 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 9 
CD. The T6 level measured at the xiphoid process (which is an easily palatable bony 
landmark) will be marked bilaterally with a washable marker pen to guide assessment of 
the primary end point. Sensory testing will be performed from caudad to cephald (i.e. 
from blocked to unblocked dermatomes) to identify the first unblocked dermatome. 
To identify the level where the sensation of sharp is first appreciated, the investigator 
will ask the question: “Tell me when you feel the sensation of something sharp touching 
your skin.” Both the motor and sensory block evaluations are part of the standard 
clinical care of patients receiving neuraxial anesthesia. The main difference for 
participants enrolled in the study is that the frequency of sensory assessments will be 
increased so that the onset of surgical anesthesia can be accurately documented 
(approximately every minute and then more frequently as the sensory block approaches 
the primary end point).  
The local anesthetic solution will be given in three phases (SOC for epidural/DPE 
extension anesthesia): 
1. Test dose – to check for correct placement of epidural 
2. Induction dose 1 – to induce anesthesia 
3. Induction dose 2 – further dose of local anesthesia if required (as per instructions 
below) 
A second anesthesiologist, blind to the type of block will manage the clinical care of the 
patient from the beginning of the study (after epidural catheter placement) and will 
administer the induction drug (prepared by that anesthesiologist as per SOC). There will 
be no difference in this clinician’s care of the subject than if she were not enrolled in the 
study. They will assess the onset of anesthesia and manage all aspects of the subject’s 
clinical care including the documentation of the local anesthetic (LA) solution 
administration timing and its clinical effects. The speed of onset will be assessed from 
the end of epidural test dose.  This will be defined as time zero and the start of 
anesthesia.  The primary outcome will be the time taken to lose sharp sensation from a 
neurotip/pen device at the thoracic dermatome level 6 (T6). See below for a description 
of this assessment.  
The primary outcome will be documented on a separate data collection tool (which the 
un-blinded anesthesiologist will not have access to). If required, intra-operative 
analgesia will be offered in the form of further epidural top-up, intravenous fentanyl, 
ketamine, nitrous oxide or replacement of neuraxial anesthesia/conversion into general 
anesthesia at the Standard of care (SOC).  These are all commonly used medications 
that provide pain relief during cesarean sections in the event of breakthrough pain.  The 
choice of which drug to use is at the discretion of the anesthesiologist. This information 
will be abstracted from medical records. In the event of an emergency situation blinding 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 10 
would be broken and the treating anesthesiologist would be informed to what group the 
patient belongs. 
 
Local anesthetic solution for anesthesia 
Below is the description of the SOC preparation & administration of local anesthetic and 
conduct within the operating room for epidural extension anesthesia in parturients that 
require CD. 20 ml of 3% chloroprocaine which will be drawn up into a 20 ml syringe  
At the start of epidural extension anesthesia, a 5 ml test dose will be administered 
through the epidural (as previously described above).  After three minutes, if there are 
no signs of accidental spinal block or intravascular administration then the remaining 15 
ml of the Local Anesthetic solution will be administered.  
 
A further 5 ml of chloroprocaine will be administered if Induction dose 1 is not effective 
in providing sufficient anesthesia (reaching primary end point) after 10 minutes. This is 
referred to as Induction dose 2.  If the primary end point is not reached at the 15-minute 
mark (total elapsed time after giving Induction dose 1) then a final 5 ml of 
chloroprocaine can be given. If the primary end point is not reached within 20 minutes 
the subject will be withdrawn from the study and the anesthesiologist can induce 
anesthesia in whichever way they think is best.  At this point the anesthesiologist will 
break blinding.  Therefore, the total volume of local anesthesia that can be given to the 
patient at this stage is 30 ml (20 ml from Induction dose 1 and up to 10 ml from 
Induction dose 2 if necessary). 
 
This above is our usual practice except for the following: 
• We are being very precise in regard to documentation of timing (primary end 
point of study) 
• Monitoring the sensory block more frequently 
• Blinding and randomization as part of a clinical trial 
 
Intra-operative Monitoring  
As with all cesarean sections, full monitoring in the operating room will be applied and 
will be the same whether the participant is in the study or not. 
 
Concurrent Medication 
Subjects enrolled in the study will be treated as per normal practice for elective 
cesarean section. If a general anesthetic must be instituted, the subject’s participation in 
the study will be stopped.   
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 11 
Assessment of Primary Efficacy Parameters 
Assessment will be made of the sensory level after the epidural induction dose. This will 
give an indication of the suitability of surgical anesthesia before proceeding with 
cesarean section. This will be assessed by the blinded clinical anesthesiologist with a 
NeurotipTM device, 2 minutes after the completion of the epidural top-up and then 
continuously if possible or at intervals of approximately 1 minute until a T6 level to sharp 
sensation is achieved. Motor function will be assessed using the Modified Bromage 
Score.  
Epidural Study Solutions 
The solutions and their administration procedures are identical to those used outside 
this research and are almost exclusively used for epidural extension anesthesia for non-
scheduled cesarean delivery. All patients enrolled will receive the same study solution 
exactly prescribed as above which is our routine practice. 
 
Post-operative Phase 
Participants will be admitted to the PACU after completion of the operation. Care will be 
as per the SOC for all elective cesarean deliveries.  Pain scores and cumulative opioid 
usage over the first 24 hours postoperatively, will be abstracted from the medical 
records of these subjects after discharge.  
Before discharge from the PACU, the un-blinded anesthesiologist would access the 
patient’s medical record and replace the charted “study group” with the either standard 
Epidural or DPE administered before closing the anesthetic record. 
 
Study Population 
All subjects scheduled for elective cesarean delivery will be screened for recruitment 
when admitted to UAMS labor and delivery unit. A member of the research team will 
approach the subject after completion of the anesthetic pre-assessment which is a 
standard of care.  
 
Inclusion Criteria 
Any patient requiring an elective cesarean section at UAMS labor and delivery unit who 
is: 
● ≥ 18 years of age for the mother 
● Singleton pregnancy 
● Gestation > 36 weeks 
● ASA class II and III 
● Provides written consent 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 12 
● Infant of mother 
● Elective or non-urgent cesarean delivery 
 
Exclusion Criteria 
• Patient refusal 
• Urgent/emergent cesarean sections 
• ASA class IV or above 
• Unable to understand English 
• Significant back surgery or scoliosis 
• Lethal fetal abnormality or likely to affect APGAR scores 
• Weight > 120 kg 
• Height < 150 cm 
• Allergy to study solutions  
Accrual Goal 
A total of 140 mother-infant dyads (a total of 280 subjects) requiring an elective 
cesarean section at UAMS labor and delivery unit will be enrolled into the study. 
 
Recruitment Plan 
Potential subjects will be offered participation in the study after admission into the Labor 
and Delivery unit.  All potential subjects will be informed of the study by a member of the 
study team after the anesthetic pre-operative consultation.  The informed consent 
/HIPAA discussion will take place prior to any pre-operative medications being 
administered and the potential subject will be allowed as much time as necessary to 
consider participating in the study. 
 
Risks and Benefits 
The benefits and risks to the study participants overall will be the same as all patients 
presenting to L&D for elective cesarean delivery. That is, whether a patient decides to 
participate or not in the study, the normal standard of care is neuraxial anesthesia for 
CD as opposed to general anesthesia. The spinal, epidural and DPE are all commonly 
used in our unit to provide anesthesia for CD. The choice of anesthetic technique 
depends on the anesthesiologist’s discretion. 
 
Benefits of DPE/ Epidural anesthesia 
These techniques will be considered together as they are similar. The main advantage 
of epidural/DPE anesthesia is the ability to extend anesthesia for as long as required. 
This also allows the administration of further local anesthetic solution through the 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 13 
epidural if surgery is prolonged or to treat any episodes of intraoperative pain without 
having to convert to general anesthesia. 
 
Risks of Epidural/DPE anesthesia 
Risks to participants in this study due to epidural/DPE anesthesia is: Inadvertent 
intravascular injection or high epidural. This risk can be minimized by aspirating blood 
through the epidural catheter and administering a ‘test dose’ to rule out intravascular 
injection or accidental spinal administration that may lead to a high block. The above 
interventions are usually enough to minimize the risk of any hazards of intravascular 
injection or inadvertent spinal that may lead to a high block.  
 
Disadvantages of participating in the study  
Research related risk to study participants include the potential for loss of 
confidentiality.  Measures to protect the confidentiality of study participants will be 
implemented as described in the Data Handling and Recordkeeping section below.  
There will be no direct benefits to the study participants; however, knowledge gained 
from the study could potentially benefit patients in the future. 
 
Study Medication Risks 
 
 
Severe allergic reactions (rare) 
• 
Swelling of the face, lips, tongue or throat. This may make it difficult to swallow 
and breath. 
• 
Severe itching of the skin (with raised lumps). 
• 
Nerve damage that may cause changes in sensation or muscle weakness 
(neuropathy). 
• 
Slowed or stopped breathing or stopped heartbeat. 
• 
Total spinal block  
• 
Uneven heart beat (arrhythmias). 
 
Common 
• 
Low blood pressure (causing dizziness or light-headedness). 
• 
Feeling sick (nausea) or being sick (vomiting). 
• 
Pins and needles. 
 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 14 
Uncommon  
• 
Ringing in the ears (tinnitus) or being sensitive to sound. 
• 
Numbness of the tongue or around the mouth. 
• 
Feeling sleepy. 
• 
Shivering. 
 
Risk Mitigation 
These risks can occur in any patient undergoing the procedure under anesthesia and 
are not study specific. All subjects will be observed in a unit accustomed to treating 
patients recovering from surgery and anesthesia. Customary clinical care will be 
provided by the patient’s treating physician. No standard treatments will be withheld as 
a result of participation in the study.  
Drug Accountability and Subject Compliance 
This study will take place within the UAMS hospital’s labor and delivery unit. There will 
be full drug accountability throughout the study. There will be an accountability log, 
labels for each ampoule marked especially for the study (DPE/Epidural Study). The 
procedure will be performed by an un-blinded anesthesiologist and the assessments 
and conduct of surgery will be performed by another anesthesiologist who remains 
blinded to the patient allocation group. The procedure (DPE or epidural) will be 
documented within the anesthetic record by the unblinded anesthesiologists. 
Compliance will be confirmed by comparing the medical chart to the accountability 
logbook. 
Data Handling and Recordkeeping 
The Principal Investigator will carefully monitor study procedures to protect the safety of 
research subjects, the quality of the data and the integrity of the study.  All study subject 
material will be assigned a unique identifying code or number.  The key to the code will 
be kept in a locked file cabinet and password protected Principal Investigator’s 
computer in the Principal Investigator’s office.  Only Nadir Sharawi, MD will have access 
to the code and information that identifies the subject in this study. At the conclusion of 
the study, the data will be permanently deidentified.  Deidentified study data will be 
maintained and ultimately destroyed per UAMS policy. 
Data Analysis 
The alternative hypothesis is that DPE group will have a faster onset time to achieve 
loss of sharp sensation at the T6 dermatome compared to the epidural group.  

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 15 
For statistical analysis, the Student’s t- test will be used for continuous normally 
distributed variables and the Mann-Whitney test for nonparametric variables. Linear 
regression analysis will be used to assess any relationship between the pre epidural 
extension parameters and the subsequent speed of onset of the block. 
 
Sample Size 
The sample size will be calculated for continuous outcome date for a superiority study. 
We have assumed that an onset time difference of two minutes is the smallest 
difference that is clinically acceptable, so that a difference of more than two minutes 
would matter in clinical practice. Approximately 120 mother-infant dyads are required to 
have a 90% chance of detecting, as significant at the 5% level, an increase in the 
primary outcome measure from 10 minutes in the DPE group to 12 minutes in the 
epidural group, assuming a standard deviation of 3 minutes. Therefore 60 mother – 
infant dyads will be recruited to each arm. Statistical significance will be taken as P < 
0.05. In total, 140 mother – infant dyads will be recruited to account for any withdrawals 
or protocol violations. 
 
 
Randomization 
70 pieces of paper will be printed for each group containing (DPE or epidural groups) for 
a total of 140.  Each of the individual pieces of paper will then be placed in a sealed 
envelope.  All envelopes will be shuffled and then numbered 1 – 140. 
Patients will be assigned a number 1 – 140 as they are enrolled in the study.  The 
envelope will be obtained and opened by an un-blinded anesthesiologist revealing their 
randomization group.  The un-blinded Anesthesiologist will not be involved in the 
patient’s care or data collection. They will insert the epidural or DPE accordingly. They 
will not be aware of primary outcome result as this will be documented on a separate 
data collection form. All members of the patient’s care team are blinded to the 
assignment study drug. The un-blinded anesthesiologist will inform the clinical team 
which procedure was undertaken if determined to be clinically necessary. 
Withdrawal of Participants 
Subjects will have the right to withdraw from the study at any point in time and have the 
right to withdraw any accompanying data. The study has been powered to account for 
approximately a 15% withdrawal / procedure failure rate. 
Stopping the Study 
Subject participation in the study will be stopped if either of the following occurs: 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 16 
• the subject did not achieve sharp sensation lost bilaterally at the T5 dermatomal 
level (as measured by a blunt plastic neurotip® (Owen Mumford, USA) device) 
after 18 minutes from administration of 3 ml test dose; 
• the subject experiences significant pain that is not relieved by the intraoperative 
analgesic supplementation described above; 
• if general anesthesia must be instituted to the subject. 
Ethical Considerations 
This study will be conducted in accordance with all applicable government regulations 
and University of Arkansas for Medical Sciences research policies and 
procedures.  This protocol and any amendments will be submitted and approved by the 
UAMS Institutional Review Board (IRB) to conduct the study.   
The formal consent of each subject, using the IRB-approved consent/HIPAA form, will 
be obtained before that subject is submitted to any study procedure.  All subjects for this 
study will be provided a consent/HIPAA form describing this study and providing 
sufficient information in language suitable for subjects to make an informed decision 
about their participation in this study.  The person obtaining consent will thoroughly 
explain each element of the document and outline the risks and benefits, alternate 
treatment(s), and requirements of the study.  The consent process will take place in a 
quiet and private room, and subjects may take as much time as needed to make a 
decision about their participation.  Participation privacy will be maintained and questions 
regarding participation will be answered.   No coercion or undue influence will be used 
in the consent process.  This consent/HIPAA form must be signed by the subject and 
the individual obtaining the consent.  A copy of the signed consent/HIPAA will be given 
to the participant, and the informed consent process will be documented in each 
subject’s research record.   
Dissemination of Data 
Results of this study may be used for presentations, posters, or publications. The 
publications will not contain any identifiable information that could be linked to a 
participant. 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 17 
References 
 
1. 
Martin, J.A., et al., Births: final data for 2012. Natl Vital Stat Rep, 2013. 62(9): p. 
1-68. 
2. 
Martin, J.A., B.E. Hamilton, and M.J. Osterman, Births in the United States, 2015. 
NCHS Data Brief, 2016(258): p. 1-8. 
3. 
Practice Guidelines for Obstetric Anesthesia: An Updated Report by the 
American Society of Anesthesiologists Task Force on Obstetric Anesthesia and 
the Society for Obstetric Anesthesia and Perinatology. Anesthesiology, 2016. 
124(2): p. 270-300. 
4. 
Liu, S.S. and S.B. McDonald, Current issues in spinal anesthesia. 
Anesthesiology, 2001. 94(5): p. 888-906. 
5. 
Bauer, M., et al., Recent advances in epidural analgesia. Anesthesiol Res Pract, 
2012. 2012: p. 309219. 
6. 
Wilson, S.H., et al., Labor Analgesia Onset With Dural Puncture Epidural Versus 
Traditional Epidural Using a 26-Gauge Whitacre Needle and 0.125% 
Bupivacaine Bolus: A Randomized Clinical Trial. Anesth Analg, 2018. 126(2): p. 
545-551. 
7. 
Yadav, P., et al., Comparison of Dural Puncture Epidural Technique versus 
Conventional Epidural Technique for Labor Analgesia in Primigravida. Journal of 
Obstetric Anaesthesia and Critical Care, 2018. 8(1): p. 24-28. 
8. 
Cappiello, E., et al., A randomized trial of dural puncture epidural technique 
compared with the standard epidural technique for labor analgesia. Anesth 
Analg, 2008. 107(5): p. 1646-51. 
9. 
Gupta, D., A. Srirajakalidindi, and V. Soskin, Dural puncture epidural analgesia is 
not superior to continuous labor epidural analgesia. Middle East J Anaesthesiol, 
2013. 22(3): p. 309-16. 
10. 
Chau, A., et al., Dural Puncture Epidural Technique Improves Labor Analgesia 
Quality With Fewer Side Effects Compared With Epidural and Combined Spinal 
Epidural Techniques: A Randomized Clinical Trial. Anesth Analg, 2017. 124(2): 
p. 560-569. 
11. 
Suzuki, N., et al., Dural puncture with a 26-gauge spinal needle affects spread of 
epidural anesthesia. Anesth Analg, 1996. 82(5): p. 1040-2. 
 
 
 

Title:  
Dural Puncture Epidural versus Epidural anesthesia for cesarean delivery: A randomized, double-
blind study 
PI: 
Nadir Sharawi, MD 
Site: 
University of Arkansas for Medical Sciences 
 
Version #: 6 
 
IRB # 228768 
Date: 08/24/2022 
Page 18 
Appendices 
1. Bromage Score  
2. Neonatal Apgar Score 
3. Pain Visual Analogue Scale (VAS)