Efficacy of Subcutaneous Infiltration With Local Anesthetic During Elective Cesarean Delivery for Postoperative Pain Control: a Randomized Controlled Trial
Phase: PHASE2
Conditions: Pain, Referred
Sponsor: Montefiore Medical Center

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IRB# 2017-8094
Title: Efficacy of subcutaneous infiltration with local anesthetic during elective 
cesarean delivery for postoperative pain control: a randomized controlled trial 
Study Contact Information
Principal investigator:
Jeffrey Bernstein, MD
Professor of Anesthesia
1825 Eastchester Road
Bronx, NY 10461
Telephone: 718-904-2872
Co-investigators:
Catherine M. Igel, MD
Maternal Fetal Medicine Fellow
Department of Obstetrics & Gynecology 
Montefiore Medical Center
Jack D. Weiler Hospital
1825 Eastchester Road
Bronx, NY 10461 USA
Telephone: 925-786-0704
Email: cigel@montefiore.org 
Peter Bernstein, MD, MPH
Professor of Clinical Obstetrics & Gynecology and Women’s Health
Montefiore Medical Center
Jack D. Weiler Hospital
1825 Eastchester Road
Bronx, NY 10461 USA
Telephone: 718-904-2767
Email: pbernste@montefiore.org
Background/Significance
Cesarean delivery is the most common operation performed throughout the world with 
estimates in the United States at 30% of all deliveries being performed via cesarean section. 
Spinal anesthesia is the standard of care for elective cesarean births given its maternal and 
neonatal safety profile. Typical post-cesarean pain relief varies by institution and provider 
preference but typically consists of an oral narcotic with or without an oral non-steroidal anti-
inflammatory inhibitor. Post-cesarean analgesia studies, especially considering the growing 
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opioid abuse epidemic, are of suboptimal quality. In fact, a 2015 Cochrane review noted that 
due to limited data available no conclusions could be drawn on the safest and most effective 
oral analgesics for post-cesarean pain relief.1 
Given its success in showing improved postoperative pain in other surgical procedures, there 
are multiple studies showing the benefit of a Transversus Abdominis Plane (TAP) block at the 
time of cesarean delivery.2–5 However, TAP blocks are long procedures requiring specialized 
training and an ultrasound for guidance. One study by Tawfik et al.4 showed no difference in 
pain scores, opiod consumption or maternal satisfaction scores with TAP vs local infiltration. 
Studies have also been performed assessing placement of pain management systems into the 
incision to release local anesthetics or analgesics over time, however these results have also 
been mixed.6
Multiple studies have been performed in the past assessing local infiltration of multiple 
different kinds of anesthetic and pain medications either before cesarean delivery begins or at 
the end of the procedure for pain control.7,8,17–19,9–16 These studies have had conflicting results 
on the utility of local anesthetics for postoperative pain control. A Cochrane review from 2009 
noted that local infiltration was likely beneficial in reducing postoperative opiod consumption 
but not visual analog pain scales.20 A metanalysis published in 2017 also noted that local 
infiltration was likely beneficial in reducing postoperative opiod consumption but its utility 
when used in combination with intrathecal opiods in spinal regimens (as is now the standard of 
care in obstetrical anesthesia) required more data.21  
 
The most recently published randomized controlled trial on this topic is from Egypt in 2016 
assessing postoperative pain with local infiltration of lidocaine versus lidocaine with 
epinephrine in women undergoing general anesthesia.22 This study demonstrated safety of 
both regimens and showed improved pain relief for women receiving lidocaine with 
epinephrine. Our study seeks to assess pain relief with incisional infiltration of local anesthetic 
(with and without epinephrine) during cesareans performed under spinal anesthesia also using 
intrathecal opiods. Our study is more relevant given the infrequency of cesareans performed 
under general anesthesia in the United States. We will also be assessing women who receive no 
local infiltration of anesthetic, the current standard of care, as our control group. 
Multiple professional societies and government agencies have recommended a decrease in the 
use of opioids for postoperative analgesia given the opiod misuse epidemic. Our study attempts 
to further assess postoperative oral opioid consumption in patients undergoing spinal 
anesthesia with intrathecal opiods by assessing the addition of local subcutaneous infiltration 
of anesthetic.
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Study Design
Objective: The objective of our study is to assess the addition of subcutaneous bupivacaine 
(Marcaine) with or without epinephrine to the standard intrathecal morphine/fentanyl 
combination given during spinal anesthesia during elective cesarean delivery on postoperative 
pain control as measured by postoperative usage of oral opioids and a postoperative pain 
assessment scale.
Hypothesis: The addition of subcutaneous bupivacaine with epinephrine at the cesarean 
incision site prior to skin closure to the standard spinal anesthesia regimen at the time of 
elective cesarean delivery will reduce postoperative narcotic usage in the first 24 hours 
postoperatively by 25%
Null Hypothesis: There will be no difference in postoperative narcotic usage in the first 24 
hours after cesarean delivery with the addition of subcutaneous bupivacaine with or without 
epinephrine at the cesarean incision site prior to skin closure at the time of elective cesarean 
delivery.
Methods: Trial will be registered on ClinicalTrials.gov and follow CONSORT guidelines

Type of study: 3 arm, blinded, randomized controlled trial involving patients who 
receive spinal anesthesia for elective cesarean delivery
o
Randomization: Subjects will be randomized using the blocking method. To 
achieve comparable groups, we will randomize enrollees to one of three 
treatment arms. Randomization will be done with block sizes of 6 to reduce 
the likelihood of unmasking the randomized assignment.  All potential 
subjects will be randomized prior to study start (patient’s # 001- 276) and the 
group that they are randomly assigned to will be written on cards placed into 
pre-sealed envelopes.
o
Blinding: The envelopes will not be opened, and the subjects’ group not 
known, until immediately prior to the subjects’ cesarean delivery to maintain 
the randomization process. Only the physicians drawing up and supplying the 
medication (the anesthesia physicians- resident and attending) will be aware 
of the patients group.  The physicians administering the medication (i.e. the 
OBGYN attending and resident) will NOT be told the composition of what 
they are injecting. The patient will be blinded to (i.e. will not be told) their 
intervention group. The investigator collecting the data will be blinded to (i.e. 
not know) which intervention group each individual patient was assigned to 
while collecting the data. Therefore, the patient, the physician administering 
the medication, and the personnel collecting the data will all be blinded to 
the patient’s intervention group. The anesthesia team will only record the 
patient’s pre-assigned number into the medical record (EPIC electronic 
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health record) and mention that they received an injection at incision closure 
of “study drug- patient #001-276.” The master list of what each patient 
received (i.e. the key to the randomization) will be kept with the anesthesia 
team and no one else will have access to view the key to maintain blinding. 
o
Groups: Injection will consist of 5 ml of either bupivacaine 0.25%, bupivacaine 
0.25% + epinephrine, or NACL 0.9% infiltrated subcutaneously in 4 
approximately equidistant injections sites in the subcutaneous tissue (2 sites 
in the cephalad portion and 2 sites in the caudad portion) after closure of 
fascia and prior to subcutaneous closure (if performed) and skin closure at 
the cesarean section incision site. Total volume infiltrated will consist of 20 
ml.

Group 1 (intervention 1): standard intrathecal bupivacaine 
(Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 
150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous 
bupivacaine (Marcaine) 0.25% 

Group 2 (intervention 2): standard intrathecal bupivacaine 
(Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 
150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous 
bupivacaine (Marcaine) 0.25% with Epinephrine 

Group 3 (control/standard therapy group): standard intrathecal 
bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine 
(Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml 
subcutaneous NACL 0.9% (placebo)

All groups: post-operative pain control- as assessed per routine 
nursing protocol during the first 24 hours postoperatively

Routine post-cesarean oral analgesics:
o
Ibuprofen 600 mg PO prn mild (1-3); moderate (4-6); 
severe (7-10) pain
o
Percocet prn severe pain (7-10) if unrelieved by 
ibuprofen 

Routine nursing protocol for postoperative pain assessment 
consists of patient assessment (pain scale 1-10) every hour for 
the first 2-4 hours postoperatively while the patient is in the 
PACU and every 1-4 hours for the remainder of their hospital 
stay while the patient is on the postpartum unit. The pain 
scale will be recorded in EPIC at a minimum of every 4 hours 
postoperatively. 

Primary outcome: postoperative pain medication usage
o
Documented postoperative usage of cumulative opioid pain medication 
(oxycodone in morphine equivalents) in the first 24 hours postoperatively
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
Secondary outcomes: 
o
Documented postoperative usage of pain medication 

cumulative usage of postoperative pain medication- opioid 
(oxycodone) (at 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 
hours postoperatively)
o
Time to first postoperative pain medication
o
Need for additional breakthrough pain medication outside of protocol 
(amount and type of medication will be documented)
o
Subjective patient pain assessment

immediate postoperative pain scale performed in postoperative 
anesthesia care unit (PACU) and throughout the postoperative period 
according to current nursing protocol (see above)

Patient satisfaction with pain management
o
Time to return of bowel function
o
Time to discharge from the recovery room
o
Time to first ambulation
o
Breastfeeding during hospital stay (assessment of both initiation of and 
exclusive breastfeeding)
o
Maternal side effects/outcomes

Intraoperative: hypotension, nausea, vomiting, pruritus, respiratory 
depression, prolonged numbness or immobility, failed neuraxial 
anesthesia requiring intubation, systemic toxicity of local anesthesia 

Postoperative: fever, postoperative wound separation, postoperative 
wound infection, skin site irritation, incisional hematoma/seroma 
formation
o
Other variables to be collected:

Demographic

Maternal: Age, gravidy, parity, number of prior cesarean 
deliveries, number of prior surgeries, maternal co-morbidities 
(chronic hypertension, gestational hypertension, 
preeclampsia, diabetes mellitus -pregestational, gestational- 
diet or medication controlled- autoimmune disease, known 
pain syndromes- i.e. fibromyalgia, etc.), reason for current 
cesarean delivery, history of tobacco use, history of anxiety or 
depression, amniotic membrane status, body mass index, 
ethnicity

Fetal: gestational age, suspected intrauterine growth 
restriction, estimated fetal weight, known or suspected 
congenital or chromosomal anomalies, placenta previa

Intraoperative variables
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
Length of surgery, estimated blood loss, intraoperative 
complications, concurrent bilateral tubal ligation, any other 
analgesia given intraoperatively and amount of other 
anesthetic given 

Postoperative variables

Neonatal outcomes (will be stratified based on fetal 
gestational age as this study includes all gestational ages and 
neonatal outcomes will likely be affected by gestational age; 
we will therefore stratify results by completed weeks of 
gestation: >37 weeks, 34-37 weeks, 30-34 weeks, <30 weeks)
o
APGARS, APGAR <7 at 5 min, fetal arterial blood gas pH 
and base deficit, neonatal intensive care unit 
admission, fetal weight

Study Population: all pregnant female patients who will be undergoing an elective 
cesarean delivery under spinal anesthesia at any gestational age
o
Inclusion criteria: 

Elective cesarean delivery with or without planned bilateral tubal 
ligation

Planned spinal anesthesia 

Planned Pfannenstiel or low transverse skin incision  
o
Exclusion criteria: 

Known maternal allergy to bupivacaine or derivative 

Known maternal allergy to oxycodone, ibuprofen, acetaminophen or 
derivative

Currently have an epidural catheter in place

Planned general anesthesia  

Maternal age <18 years old

Emergent cesarean delivery

Active labor [defined as: >6cm cervical dilation and regular 
contractions noted on tocometer (>2 contractions in a 10 minute 
period for 30 consecutive minutes)]

Chronic antepartum opioid use 

History of substance abuse (alcohol or drug)

Current tobacco use

Chronic steroid use or needing stress dose steroids at the time of 
delivery

Medical contraindication to neuraxial anesthesia such as 
thrombocytopenia (platelet count <80,000/microliter) or space 
occupying lesion of the brain

Category 3 fetal heart rate pattern
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
Maternal fever or suspected chorioamnionitis

Concern for morbidly adherent placenta

Planned cesarean hysterectomy

Power analysis: 
o
Sample size was determined assuming a power of 80%, p value of 0.05 to 
detect a 25% difference in the primary outcome of cumulative opioid usage 
in the first 24 hours postoperatively 

In a previous unpublished, randomized controlled study conducted by 
Dr. Jeffrey Bernstein, average use of opioids in post-cesarean 
subjects was 47mgSD 35 morphine equivalence in the first 24 hours 
postoperatively 

Therefore, in our protocol, with three groups and keeping the 
hypothesis as one of the groups will consume fewer opioids (SD as 25) 
to demonstrate a minimum 25% difference between any two groups, 
this will require 255 subjects total (85 subjects per group). However, 
to accommodate for missing data and study withdrawal we will 
increase the sample size by 10 % therefore there will be 276 subjects 
total- or 92 patients per group

Exclusion of any population group: 
o
Minors <18 will be excluded

There are regulations for protection of human subjects allow 
consenting adults to accept a higher level of risk than is permitted for 
children
o
Only subjects who have the capacity to consent will be enrolled

Sources of research material:
o
Data and access to the electronic medical records (EPIC, EPF, ASOBGYN) will 
be obtained from individually identifiable living human subjects as part of 
routine clinical care.

Participant recruitment: Study team members (i.e. key personnel) on labor and 
delivery will ask patients who present for elective cesarean delivery if they are 
interested in the study. The key personnel will then approach the intended patients 
to obtain consent for the research study. We are requesting a waiver of informed 
consent and HIPAA authorization to access medical records for recruitment 
purposes. 
o
All patients will be told that the study is voluntary, they do not have to 
participate and whether they participate will not affect their care in any way
o
Maintenance of safety of PHI data/confidentiality

All records will be kept in a secure manner on a secure server. Access 
to the records will only be by the listed protocol key personnel and 
the computer records will be password protected. All patients will be 
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assigned a number and all information will be recorded under this 
number - not patient identifying information - and a separate list will 
be kept in a separate location under password protection listing 
medical records of patients identified to the code and only researcher 
Igel will have access to this list. 

Informed consent
o
The informed consent document adhering to Montefiore’s template is 
uploaded to IRIS.
o
Informed consent will be obtained by listed key personnel when the patients 
present to the labor and delivery unit. These patients will be approached 
based on the inclusion/exclusion criteria noted above and will NOT be 
women in labor as outlined in the exclusion criteria. They are women for 
elective cesarean delivery.
o
There will be no waiver of informed consent and minors will not be included
o
There is no cost or remuneration to the participants 
o
HIPPAA authorization will take place at the same time as the informed 
consent process

Risks/Benefits
o
Anticipated risks (e.g. medical, social, psychological, and/or legal)

The anticipated medical risks involved with the addition of 
bupivacaine include possible allergic reaction, systemic toxicity or 
intravascular injection of the anesthetic. There are no social or legal 
risks.  Psychological risks include discomfort completing 
questionnaires and breach of confidentiality/ loss of privacy. 

Risks of injection process include: pain, redness, infection or allergy to 
medication components 

Adverse reactions of study medications according to FDA:

Oxycodone: abuse, misuse, addiction; (>5%): constipation, 
nausea, somnolence, dizziness, vomiting, pruritus, dry mouth, 
sweating, asthenia; (1-5%) anorexia, nervousness, insomnia, 
fever, confusion, diarrhea, abdominal pain, dyspepsia, rash, 
anxiety, euphoria, dyspnea, postural hypotension, chills, 
twitching, gastritis, abnormal dreams, thought abnormalities, 
hiccups; (<1%): lymphadenopathy, palpitations, tinnitus, 
syndrome of inappropriate antidiuretic hormone secretion, 
abnormal vision, dysphagia, flatulence, ileus, stomatitis, 
increased appetite, eructation, chest pain, edema, facial 
edema, malaise, pain, peripheral edema, thirst, withdrawal 
syndrome (with and without seizures), anaphylactic or 
anaphylactoid reaction, pharyngitis, accidental injury, 
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hyponatremia, increased hepatic enzymes, ST depression, 
dehydration, neck pain, abnormal gait, amnesia, hyperkinesia, 
hypertonia (muscular), hypesthesia, hypotonia, migraine, 
paresthesia, seizures, speech disorder, stupor, syncope, taste 
perversion, tremor, vertigo, agitation, depersonalization, 
depression, emotional lability, hallucination, dysuria, 
hematuria, polyuria, urinary retention, urination impaired, 
amenorrhea, decreased libido, impotence, cough increased, 
voice alteration, dry skin, exfoliative dermatitis, urticarial, 
vasodilation

Acetaminophen: (>3%) nausea, vomiting, headache, insomnia, 
pyrexia; (>1%): anemia, fatigue, infusion site pain, peripheral 
edema, aspartate aminotransferase increased, breath sounds 
abnormal, hypokalemia, muscle spasms, trismus, anxiety, 
dyspnea, hypertension, hypotension

Ibuprofen: (>1% but <3%) Nausea, stomach pain, heartburn, 
vomiting, constipation, abdominal cramps, bloating, gas, 
dizziness, headache, nervousness, rash, itching, ringing in ears, 
decreased appetite, swelling, fluid retention; (<1%): ulcer, 
bleeding ulcer, black stools, abnormal liver function tests, 
inflammation of liver/ pancreas/ stomach, depression, 
difficulty sleeping, confusion, sleepiness, hives, thinning of 
hair, Stevens Johnson syndrome, hearing loss, blurred vision 
or changes in vision, neutropenia, aplastic anemia, 
thrombocytopenia, eosinophila, decrease in blood count, 
elevated blood pressure, bronchospasm, acute kidney failure, 
blood in urine, kidney injury, increase urination, inflammation 
of bladder, dry eyes and mouth, gum ulcer, inflammation of 
nose

Bupivicaine Hydrochloride: (toxicity most commonly dose 
related from overdosage, rapid absorption from injection site, 
diminished tolerance, or from unintentional intravascular 
injection of local anesthetic) -excitation and/or depression, 
restlessness, anxiety, dizziness, tinnitus, blurred vision, 
tremors, convulsions, drowsiness, unconsciousness, 
respiratory arrest, depression of the myocardium, decreased 
cardiac output, heartblock, hypotension, bradycardia, 
ventricular arrhythmias, cardiac arrest, paralysis of legs, loss of 
consciousness, respiratory paralysis, urinary retention, fecal 
and urinary incontinence, loss of perineal sensation and sexual 
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function, persistent anesthesia, paresthesia, weakness, 
paralysis of lower extremities, loss of sphincter control, 
headache, backache, septic meningitis, meningismus, cranial 
nerve palsies; nausea, vomiting, chills, constriction of the 
pupils; allergic type reactions, 

Bupivicaine Hydrochloride and Epinephrine: see “Bupivicaine 
Hydrochloride” above; allergic-type reactions to sulfites in 
epinephrine-containing solutions 

Fentanyl citrate injection: respiratory depression, apnea, 
rigidity, bradycardia, respiratory arrest, circulatory depression 
or cardiac arrest, hypertension, hypotension, dizziness, 
blurred vision, nausea, emesis, diaphoresis, pruritus, urticarial, 
laryngospasm, anaphylaxis 

Morphine sulfate injection (Duramorph): pruritus, nausea, 
vomiting, constipation, urinary retention, headache, dizziness, 
euphoria, anxiety, hypotension, confusion, reduced male 
potency, decreased libido in men and women, menstrual 
irregularities including amenorrhea, depression of cough 
reflex, interference with thermal regulation, oliguria, 
urticarial, wheals, local tissue irritation, respiratory depression 
and/or respiratory arrest, tolerance, myoclonus, convulsions, 
dysphoric reactions, toxic psychoses, drug abuse and 
dependence; overdosage: respiratory depression with or 
without concomitant CNS depression, apnea, circulatory 
collapse, cardiac arrest 
o
Describe how anticipated risks will be minimized:

The patients will be monitored extensively during anesthesia 
administration and afterwards according to anesthesia protocols and 
will be attached to a continuous monitor and have blood pressure 
and pulse taken according to operating room protocol for regional 
anesthesia. The subjects will be monitored for local anesthetic toxicity 
according to routine anesthesia protocols (monitoring patients for 
symptoms and vital signs). During injection extreme care and caution 
will be used to ensure that the injection in not intravascular by 
aspiration prior to injection. Appropriate interventions for any 
perceived risk will take place. This will be performed in the operating 
room where all resuscitative equipment and personnel (including 
anesthesia physicians) are present. 
o
Document how potential benefits to participants or others justify potential 
risks
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
Benefits of potential decreased postoperative pain above current 
baseline postoperative pain justifies potential risks
o
Describe the plan for data storage and for maintenance of subjects' 
confidentiality

All records will be kept in a secure manner on a secure server 
(Box.com). Access to the records will only be by the listed protocol 
investigators and key personnel and the computer records will be 
password protected. All patients will be assigned a number and all 
information will be recorded under this number - not patient 
identifying information - and a separate list will be kept in a separate 
location under password protection listing medical records of patients 
identified to the code and only researcher Igel will have access to this 
list

Subjects will not be video or audio taped

Data Analysis
o
Appropriate statistical methods will to be used to evaluate study objectives

Hypothesis: The addition of incisional subcutaneous bupivacaine with 
epinephrine to standard spinal anesthesia regimen at the time of 
elective cesarean delivery will decrease postoperative narcotic usage 
by at least 25% in the first 24 hours 

A statement regarding specifically what data are to be used to test 
the hypothesis (or to generate the hypotheses)

Our hypothesis will be tested by assessing cumulative 
postoperative opioid usage in the first 24 hours 
postoperatively 

The statistical method(s) to be used to test the hypothesis with that 
data

Depending on the distribution of the data appropriate 
statistical analysis including one way ANOVA or non-
parametric Kruskal Wallis test will be used to analyze the data. 
Categorical variables such as adverse events, we will be 
analyzed using Chi-Square analysis. Additionally, we will be 
using a linear mixed effects regression analysis to model the 
difference in mean pain scores during the hospital stay. 

A power analysis to determine the sample size 

See above for sample size calculation in Methods section) for 
power analysis
o
Describe methods for interim analyses or early stopping, if applicable

Data Safety Monitoring Board (DSMB) will review interim findings at 
the midpoint of the study. The study will be terminated early if 
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evidence of effect is established, if the intervention appears futile, or 
if harm is established. Specifically, if the p-value of the intervention-
by-time effects based on data accumulated by the midpoint of the 
study is smaller than 0.005 (O’Brien-Fleming boundary), we will 
declare the superiority of the intervention. On the other hand, if the 
upper bound of the 95% confidence interval for the difference 
between the groups is less than 5%, we will declare futility of the 
intervention. The DSMB will also be authorized to recommend early 
termination for other reasons related to patient safety. We will have 
a planned interim analysis halfway through patient recruitment to 
stop the study if there is a significant impact 
o
Describe how possible confounding and/or effect modification will be 
addressed

All patients will be randomized and blinded to their intervention 
groups. Baseline demographic variables will be collected to assess for 
differences among the groups. Patients with a history of chronic pain 
syndromes or chronic opioid use will be excluded from the study.
o
Describe how loss to follow up will be addressed

We will increase the power calculated sample size by 10% to account 
for loss to follow up
Data safety monitoring plan: Patient outcomes will be monitored in real time for side effects 
and patient safety. In order to maintain additional patient safety, a DSMP will be in place for 
the study. The data will be reviewed by two clinicians familiar with spinal anesthesia, cesarean 
birth and perioperative and postoperative management and complications, namely Dr. Yelena 
Spitzer (Obstetric Anesthesia attending) and Dr. Diana Wolfe (Maternal Fetal Medicine 
attending). In addition, clinical researcher Dr. Singh Nair, will review the data. The Data safety 
monitoring committee will meet every 6 months. Minutes of the meetings including 
attendance, a summary of discussion and any relevant findings will be recorded. Data will be 
reviewed for adverse events throughout the study duration. The results of findings and 
recommendations of the team will be reported to the Albert Einstein College of Medicine 
institutional review board for review and action. 
Data quality control and database management.

Describe methods for data entry and data management 
o
All data will be gathered by key personnel member Igel and entered into a 
password protected excel spreadsheet located on a secure Montefiore server 
(Box.com)

Describe the mechanism for checking and editing the data.
o
Data will be checked monthly by randomly selecting patients to check all data 
input by a different key personnel member than originally entered the data

Describe computer data security and subject confidentiality
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o
All records will be kept in a secure manner on a secure server (Box.com) on a 
secure excel spreadsheet with password protection; access to the records will 
only be by the listed protocol investigators and the computer records will be 
password protected; all patients will be assigned a number and all information 
will be recorded under this number - not patient identifying information - and a 
separate list will be kept in a separate location under password protection listing 
medical records of patients identified to the code and only researcher Igel will 
have access to this list

Data given to researchers for future research projects:
o
The de-identified database may be used for future quality improvement and 
research projects. If the database is used for future research projects, it will only 
be available to internal researchers within the Albert Einstein institution. 
Researcher Igel will maintain possession of the database. 
References
1. 
Mkontwana N, Novikova N. Oral analgesia for relieving post-caesarean pain. In: 
Mkontwana N, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John 
Wiley & Sons, Ltd; 2015:CD010450. doi:10.1002/14651858.CD010450.pub2.
2. 
Trabelsi B, Charfi R, Bennasr L, et al. Pharmacokinetics of bupivacaine after bilateral 
ultrasound-guided transversus abdominis plane block following cesarean delivery under 
spinal anesthesia. Int J Obstet Anesth. 2017;32:17-20. doi:10.1016/j.ijoa.2017.04.007.
3. 
Sahmeddini MA, Azemati S, Motlagh EM. Local Infiltration of Tramadol versus 
Bupivacaine for Post Cesarean Section Pain Control: A Double-Blind Randomized Study. 
Iran J Med Sci. 2017;42(3):235-241. http://www.ncbi.nlm.nih.gov/pubmed/28533571. 
Accessed December 18, 2017.
4. 
Tawfik MM, Mohamed YM, Elbadrawi RE, Abdelkhalek M, Mogahed MM, Ezz HM. 
Transversus Abdominis Plane Block Versus Wound Infiltration for Analgesia After 
Cesarean Delivery. Anesth Analg. 2017;124(4):1291-1297. 
doi:10.1213/ANE.0000000000001724.
5. 
Krohg A, Ullensvang K, Rosseland LA, Langesæter E, Sauter AR. The Analgesic Effect 
of Ultrasound-Guided Quadratus Lumborum Block After Cesarean Delivery. Anesth 
Analg. November 2017:1. doi:10.1213/ANE.0000000000002648.
6. 
Kranke P, Jokinen J, Pace NL, et al. Continuous intravenous perioperative lidocaine 
infusion for postoperative pain and recovery. In: Kranke P, ed. Cochrane Database of 
Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2015:CD009642. 
doi:10.1002/14651858.CD009642.pub2.
7. 
Bensghir M, Elwali A, Miller C, et al. [Effects of skin infiltration with ropivacaine 0,75% 
on postoperative pain after caesarean section]. Gynecol Obstet Fertil. 2008;36(5):516-520. 
doi:10.1016/j.gyobfe.2008.03.007.
8. 
Carvalho B, Clark DJ, Yeomans DC, Angst MS. Continuous Subcutaneous Instillation of 
Bupivacaine Compared to Saline Reduces Interleukin 10 and Increases Substance P in 
Surgical Wounds After Cesarean Delivery. Anesth Analg. 2010;111(6):1452-1459. 
IRB NUMBER: 2017-8094
IRB APPROVAL DATE: 07/11/2018

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Version 3: 6/1/18                                                  2017-8094 
doi:10.1213/ANE.0b013e3181f579de.
9. 
Corsini T, Cuvillon P, Forgeot A, Chapelle C, Seffert P, Chauleur C. [Single-dose 
intraincisional levobupivacaine infiltration in caesarean postoperative analgesia: a 
placebo-controlled double-blind randomized trial]. Ann Fr Anesth Reanim. 2013;32(1):25-
30. doi:10.1016/j.annfar.2012.10.035.
10. 
Demiraran Y, Albayrak M, Yorulmaz IS, Ozdemir I. Tramadol and levobupivacaine 
wound infiltration at Cesarean delivery for postoperative analgesia. J Anesth. 
2013;27(2):175-179. doi:10.1007/s00540-012-1510-7.
11. 
Eldaba AA, Amr YM, Sobhy RA. Effect of wound infiltration with bupivacaine or lower 
dose bupivacaine/magnesium versus placebo for postoperative analgesia after cesarean 
section. Anesth essays Res. 2013;7(3):336-340. doi:10.4103/0259-1162.123227.
12. 
Ducarme G, Sillou S, Wernet A, et al. [Single-shot ropivacaine wound infiltration during 
cesarean section for postoperative pain relief]. Gynecol Obstet Fertil. 2012;40(1):10-13. 
doi:10.1016/j.gyobfe.2011.07.035.
13. 
Fredman B, Shapiro A, Zohar E, et al. The Analgesic Efficacy of Patient-Controlled 
Ropivacaine Instillation After Cesarean Delivery. Anesth Analg. 2000;91(6):1436-1440. 
doi:10.1097/00000539-200012000-00025.
14. 
Givens VA, Lipscomb GH, Meyer NL. A randomized trial of postoperative wound 
irrigation with local anesthetic for pain after cesarean delivery. Am J Obstet Gynecol. 
2002;186(6):1188-1191. doi:10.1067/mob.2002.122984.
15. 
Jolly C, Jathières F, Keïta H, Jaouen E, Guyot B, Torre A. Cesarean analgesia using 
levobupivacaine continuous wound infiltration: a randomized trial. Eur J Obstet Gynecol 
Reprod Biol. 2015;194:125-130. doi:10.1016/j.ejogrb.2015.08.023.
16. 
Jabalameli M, Safavi M, Honarmand A, Saryazdi H, Moradi D, Kashefi P. The 
comparison of intraincisional injection tramadol, pethidine and bupivacaine on 
postcesarean section pain relief under spinal anesthesia. Adv Biomed Res. 2012;1:53. 
doi:10.4103/2277-9175.100165.
17. 
Kainu JP, Sarvela J, Halonen P, et al. Continuous wound infusion with ropivacaine fails to 
provide adequate analgesia after caesarean section. Int J Obstet Anesth. 2012;21(2):119-
124. doi:10.1016/j.ijoa.2011.12.009.
18. 
Kessous R, Wiznitzer A, Polachek H, et al. Preoperative analgesia with local lidocaine 
infiltration for post cesarean delivery pain management. J Matern Neonatal Med. 
2012;25(7):1131-1134. doi:10.3109/14767058.2011.624222.
19. 
LARSEN KR, KRISTENSEN BB, RASMUSSEN MA, et al. Effect of high-volume 
systematic local infiltration analgesia in Caesarean section: a randomised, placebo-
controlled trial. Acta Anaesthesiol Scand. 2015;59(5):632-639. doi:10.1111/aas.12509.
20. 
Bamigboye AA, Hofmeyr GJ. Local anaesthetic wound infiltration and abdominal nerves 
block during caesarean section for postoperative pain relief. Cochrane Database Syst Rev. 
2009;(3):CD006954. doi:10.1002/14651858.CD006954.pub2.
21. 
Adesope O, Ituk U, Habib AS. Local anaesthetic wound infiltration for postcaesarean 
section analgesia. Eur J Anaesthesiol. 2016;33(10):731-742. 
doi:10.1097/EJA.0000000000000462.
IRB NUMBER: 2017-8094
IRB APPROVAL DATE: 07/11/2018

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22. 
Tharwat AA, Yehia AH, Wahba KA, G. Ali A-E. Efficacy and safety of post-cesarean 
section incisional infiltration with lidocaine and epinephrine versus lidocaine alone in 
reducing postoperative pain: A randomized controlled double-blinded clinical trial. J 
Turkish Ger Gynecol Assoc. 2016;17(1):1-5. doi:10.5152/jtgga.2015.0185.
IRB NUMBER: 2017-8094
IRB APPROVAL DATE: 07/11/2018