Clinical trial NCT01170702
Conditions: Postoperative Pain Pregnancy Obesity
Keywords: Cesarean Delivery Ropivicaine TAP block
Sponsor: Northwestern University
Start date: 2010-01-01; Completion date: 2017-01-01
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Since there have been no published dose-response studies investigating the effective analgesic dose of ropivacaine for use in a TAP block for post-Cesarean delivery analgesia, the investigators propose a study primarily examining the effect on 24 hour post-Cesarean delivery opioid consumption of using either a placebo, 0.25% ropivacaine, 0.5% ropivacaine, or 0.75% ropivacaine for TAP blocks.

Detailed description:
Cesarean delivery is the most commonly performed surgical procedure in the United States today, with over 1.2 million cases performed in 2005. One of the most important aspects of cesarean delivery is the provision of safe, effective postoperative analgesia for the mother, while simultaneously ensuring minimal side effects for both the mother and neonate. Studies have suggested that a multimodal approach to post-cesarean pain utilizing both intravenous, oral, and neuraxial opioids and non-steroidal anti-inflammatory drugs is highly effective in providing effective analgesia.

A significant component of post-cesarean pain is incisional pain from the Pfannenstiel incision on the anterior abdominal wall. The sensory supply to the skin, muscles, and parietal peritoneum of the anterior abdominal wall is derived from the anterior rami of T7-L1. After exiting the spinal column, these nerves proceed through the lateral abdominal wall within the transversus abdominal fascial plane, terminating in the anterior abdominal wall.

Recent studies have suggested that blocking these afferent sensory nerves with local anesthetics, as part of a multimodal postoperative pain regimen, provides superior pain relief in terms of decreased pain scores and morphine consumption for up to 48 hours postoperatively. The technique utilized for these studies employed a surface anatomical approach to the transversus abdominal fascial plane via the lumbar triangle of Petit, a technique validated in both cadaveric and radiologic studies. However, as ultrasonography has emerged as the "gold standard" for initiating many nerve blocks, reports have described the successful use of ultrasound imaging for initiation of transversus abdominis plane (TAP) blocks for both abdominal surgeries and cesarean deliveries.

In the published studies investigating the use of the TAP block for post-operative analgesia, either ropivacaine or bupivacaine was utilized in concentrations of 0.75% and 0.375%, respectively. Studies comparing ropivacaine with bupivacaine for use in interscalene, femoral, or sciatic nerve blocks have found no difference in terms of potency, time to onset or duration of postoperative analgesia between the two local anesthetics. Although no similar studies have been done with TAP blocks, one can assume that utilization of ropivacaine for this nerve block would yield similar results in terms postoperative analgesia. Moreover, the cardiotoxicity of ropivacaine has been shown to be significantly less than bupivacaine, making it a safer alternative for use in nerve blocks when used in high doses.

Risk factors for respiratory depression after the administration of neuraxial opioids in the non-obstetric population include morbid obesity and obstructive sleep apnea. For the obstetric population, a study of 856 patients revealed that all 8 patients who experienced respiratory depression after intrathecal morphine for cesarean delivery were markedly obese. Furthermore, the onset of respiratory depression after intrathecal morphine can occur up to 12 hours after administration, a time period when the patient is not being as closely monitored as she is during the 1:1 nursing care in the recovery room. Therefore, it is the investigators policy on the Labor and Delivery unit to not administer intrathecal morphine to any parturient with a history of obstructive sleep apnea or a BMI \> 40 kg/m2. These patients often require intravenous opioid patient-controlled analgesia postoperatively, which has been shown to provide inferior pain relief and greater opioid consumption than neuraxial opioids. The current clinical standard is to administer the TAP block to those patients who have not received morphine in their neuraxial anesthetic. The TAP block offers a novel addition to the management of post-cesarean pain for this patient population.

Arms: arm 1: TAP Block utilizing 15mL of 0.9% normal saline per side arm 2: TAP Block utilizing 15ml of 0.2% ropivacaine per side arm 3: TAP Block utilizing 15ml of 0.5% ropivacaine per side arm 4: TAP Block utilizing 15ml of 0.75% ropivacaine per side
Interventions: intervention 1: 0.9% Normal Saline intervention 2: 0.2% Ropivacaine intervention 3: 0.5% Ropivacaine intervention 4: 0.75% Ropivacaine
Intervention descriptions: intervention 1: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. intervention 2: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. intervention 3: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. intervention 4: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side.

Protocol documents:
Prot_SAP_000.pdf: 
Principal Investigator:  Edward Yaghmour 
Version 05.0  05/27/2015 
Page 1 of 18 
Proposed Research Protocol Form 
Northwestern University Medical School 
Department of Anesthesiology Research Committee 
 
Title:  The Postoperative Analgesic Efficacy of Varied Concentrations of Ropivacaine 
Used for the Transversus Abdominis Plane (TAP) Block After Cesarean Delivery 
 
Principal Investigator:  Edward Yaghmour, M.D. 
Affiliation: Department of Anesthesiology, Northwestern University, Feinberg School of 
Medicine 
 
Institution: Northwestern Memorial Hospital 
1.0 Research Aims: 
 
.1 Research Questions(s):  Is there a difference in postoperative analgesic 
efficacy between placebo, 0.2% ropivacaine, 0.5% ropivacaine, or 0.75% 
ropivacaine for a transversus abdominis plane (TAP) block for morbidly obese 
parturients as part of a post-cesarean delivery multimodal analgesic regimen 
that does not include intrathecal morphine?  
 
.2 Hypotheses:  Utilizing 0.5% ropivacaine in a TAP block, as part of a post-
cesarean delivery multimodal analgesic regimen that does not include 
intrathecal morphine, will result in decreased 24 hour postoperative  
hydromorphone consumption compared to 0.2% ropivacaine and placebo, and 
will be equivalent in 24 hour postoperative hydromorphone consumption 
compared to 0.75% ropivacaine. 
 
 
2.0 Research significance: 
 
.1 Background: Cesarean delivery is the most commonly performed surgical 
procedures in the United States today, with over 1.2 million cases performed 
in 2005.1  One of the most important aspects of cesarean delivery is the 
provision of safe, effective postoperative analgesia for the mother, while 
simultaneously ensuring minimal side effects for both the mother and neonate.  
Studies have suggested that a multimodal approach to post-cesarean pain 
utilizing both intravenous, oral, and neuraxial opioids and non-steroidal anti-


Principal Investigator:  Edward Yaghmour 
Version 05.0  05/27/2015 
Page 2 of 18 
inflammatory drugs is highly effective in providing effective analgesia.2-4
 
A significant component of post-cesarean pain is incisional pain from the 
Pfannenstiel incision on the anterior abdominal wall.5  The sensory supply to 
the skin, muscles, and parietal peritoneum of the anterior abdominal wall is 
derived from the anterior rami of T7-L1.  After exiting the spinal column, 
these nerves proceed through the lateral abdominal wall within the transversus 
abdominal fascial plane, terminating in the anterior abdominal wall.6,7 
 
Recent studies have suggested that blocking these afferent sensory nerves 
with local anesthetics, as part of a multimodal postoperative pain regimen, 
provides superior pain relief in terms of decreased pain scores and morphine 
consumption for up to 48 hours postoperatively.8-10  The technique utilized for 
these studies employed a surface anatomical approach to the transversus 
abdominal fascial plane via the lumbar triangle of Petit, a technique validated 
in both cadaveric and radiologic studies.11  However, as ultrasonography has 
emerged as the “gold standard” for initiating many nerve blocks, reports have 
described the successful use of ultrasound imaging for initiation of transversus 
abdominis plane (TAP) blocks for both abdominal surgeries and cesarean 
deliveries.12,13 
 
In the published studies investigating the use of the TAP block for post-
operative analgesia, either ropivacaine or bupivacaine was utilized in 
concentrations of 0.75% and 0.375%, respectively.8,10  Studies comparing 
ropivacaine with bupivacaine for use in interscalene, femoral, or sciatic nerve 
blocks have found no difference in terms of potency, time to onset or duration 
of postoperative analgesia between the two local anesthetics.14-16  Although no 
similar studies have been done with TAP blocks, one can assume that 
utilization of ropivacaine for this nerve block would yield similar results in 
terms postoperative analgesia.  Moreover, the cardiotoxicity of ropivacaine 
has been shown to be significantly less than bupivacaine, making it a safer 
alternative for use in nerve blocks when used in high doses.17,18 
 
Risk factors for respiratory depression after the administration of neuraxial 
opioids in the non-obstetric population include morbid obesity and obstructive 


Principal Investigator:  Edward Yaghmour 
Version 05.0  05/27/2015 
Page 3 of 18 
sleep apnea.  For the obstetric population, a study of 856 patients revealed that 
all 8 patients who experienced respiratory depression after intrathecal 
morphine for cesarean delivery were markedly obese.19  Furthermore, the 
onset of respiratory depression after intrathecal morphine can occur up to 12 
hours after administration, a time period when the patient is not being as 
closely monitored as she is during the 1:1 nursing care in the recovery room.  
Therefore, it is our policy on the Labor and Delivery unit to not administer 
intrathecal morphine to any parturient with a history of obstructive sleep 
apnea or a BMI > 40 kg/m2.  As such, these patients often require intravenous 
opioid patient-controlled analgesia postoperatively, which has been shown to 
provide inferior pain relief and greater opioid consumption than neuraxial 
opioids.20  Moreover, the current clinical standard is to administer the TAP 
block to those patients who have not received morphine in their neuraxial 
anesthetic.8  Hence, the TAP block offers a novel addition to the management 
of post-cesarean pain for this patient population.  
 
Since there have been no published dose-response studies investigating the 
effective analgesic dose of ropivacaine for use in a TAP block for post-
Cesarean delivery analgesia, we propose a study primarily examining the 
effect on 24 hour post-Cesarean delivery opioid consumption of using either a 
placebo, 0.2% ropivacaine, 0.5% ropivacaine, or 0.75% ropivacaine for TAP 
blocks.   
 
 
.2 
Literature:   
 
1. 
National Center for Health Statistics: Births: Final Data for 2005. 2008; 
56: 72 PMID:  
 
2. 
Cardoso MM, Carvalho JC, Amaro AR, Prado AA, Cappelli EL: Small 
doses of intrathecal morphine combined with systemic diclofenac for postoperative pain 
control after cesarean delivery. Anesth Analg 1998; 86: 538-41 PMID: 9495409 
 
3. 
Lowder JL, Shackelford DP, Holbert D, Beste TM: A randomized, 
controlled trial to compare ketorolac tromethamine versus placebo after cesarean section 
to reduce pain and narcotic usage. Am J Obstet Gynecol 2003; 189: 1559-62 PMID: 
14710063 


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4. 
Siddik SM, Aouad MT, Jalbout MI, Rizk LB, Kamar GH, Baraka AS: 
Diclofenac and/or propacetamol for postoperative pain management after cesarean 
delivery in patients receiving patient controlled analgesia morphine. Reg Anesth Pain 
Med 2001; 26: 310-5 PMID: 11464348 
 
5. 
Loos MJ, Scheltinga MR, Mulders LG, Roumen RM: The Pfannenstiel 
incision as a source of chronic pain. Obstet Gynecol 2008; 111: 839-46 PMID: 18378742 
 
6. 
Netter F: Back and Spinal Cord. In: Netter FH, ed. Atlas of Human 
Anatomy. Summit, New Jersey, The Ciba-Geigy Corporation, 1989 
 
7. 
Netter F: Abdomen Posterolateral Abdominal Wall.  In: Netter FH, ed. 
Atlas of Human Anatomy. Summit, New Jersey, The Ciba-Geigy Corporation, 1989 
 
8. 
McDonnell JG, Curley G, Carney J, Benton A, Costello J, Maharaj CH, 
Laffey JG: The analgesic efficacy of transversus abdominis plane block after cesarean 
delivery: a randomized controlled trial. Anesth Analg 2008; 106: 186-91 PMID: 
18165577 
 
9. 
McDonnell JG, O'Donnell B, Curley G, Heffernan A, Power C, Laffey JG: 
The analgesic efficacy of transversus abdominis plane block after abdominal surgery: a 
prospective randomized controlled trial. Anesth Analg 2007; 104: 193-7 PMID: 
17179269 
 
10. 
O'Donnell BD, McDonnell JG, McShane AJ: The transversus abdominis 
plane (TAP) block in open retropubic prostatectomy. Reg Anesth Pain Med 2006; 31: 91 
PMID: 16418039 
 
11. 
McDonnell JG, O'Donnell BD, Farrell T, Gough N, Tuite D, Power C, 
Laffey JG: Transversus abdominis plane block: a cadaveric and radiological evaluation. 
Reg Anesth Pain Med 2007; 32: 399-404 PMID: 17961838 
 
12. 
Sivasubramaniam S FJ, Sadan K: Ultrasound guided transversus 
abdominis plane (TAP) block for cesarean sections. Reg Anesth Pain Med 2008; 33: e130 
PMID:  
 
13. 
Walter EJ, Smith P, Albertyn R, Uncles DR: Ultrasound imaging for 
transversus abdominis blocks. Anaesthesia 2008; 63: 211 PMID: 18211466 
 
14. 
Beaulieu P, Babin D, Hemmerling T: The pharmacodynamics of 
ropivacaine and bupivacaine in combined sciatic and femoral nerve blocks for total knee 
arthroplasty. Anesth Analg 2006; 103: 768-74 PMID: 16931694 


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15. 
Casati A, Fanelli G, Magistris L, Beccaria P, Berti M, Torri G: Minimum 
local anesthetic volume blocking the femoral nerve in 50% of cases: a double-blinded 
comparison between 0.5% ropivacaine and 0.5% bupivacaine. Anesth Analg 2001; 92: 
205-8 PMID: 11133628 
 
16. 
Eroglu A, Uzunlar H, Sener M, Akinturk Y, Erciyes N: A clinical 
comparison of equal concentration and volume of ropivacaine and bupivacaine for 
interscalene brachial plexus anesthesia and analgesia in shoulder surgery. Reg Anesth 
Pain Med 2004; 29: 539-43 PMID: 15635512 
 
17. 
Groban L, Deal DD, Vernon JC, James RL, Butterworth J: Cardiac 
resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, 
and ropivacaine in anesthetized dogs. Anesth Analg 2001; 92: 37-43 PMID: 11133597 
 
18. 
Ohmura S, Kawada M, Ohta T, Yamamoto K, Kobayashi T: Systemic 
toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats. 
Anesth Analg 2001; 93: 743-8 PMID: 11524350 
 
19. 
Abboud TK, Dror A, Mosaad P, Zhu J, Mantilla M, Swart F, Gangolly J, 
Silao P, Makar A, Moore J, et al.: Mini-dose intrathecal morphine for the relief of post-
cesarean section pain: safety, efficacy, and ventilatory responses to carbon dioxide. 
Anesth Analg 1988; 67: 137-43 PMID: 3277478 
 
20. 
Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung 
K, Lin EE, Liu SS: Efficacy of postoperative patient-controlled and continuous infusion 
epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-
analysis. Anesthesiology 2005; 103: 1079-88 PMID: 16249683 
 
21. 
Seaton S, Reeves M, McLean S: Oxycodone as a component of 
multimodal analgesia for lactating mothers after Caesarean section: relationships between 
maternal plasma, breast milk and neonatal plasma levels. Aust N Z J Obstet Gynaecol 
2007; 47: 181-5 PMID: 17550483 
 
22. 
Kehlet H: Multimodal approach to control postoperative pathophysiology 
and rehabilitation. Br J Anaesth 1997; 78: 606-17 PMID: 9175983 
 
23. 
Chang J, Elam-Evans LD, Berg CJ, Herndon J, Flowers L, Seed KA, 
Syverson CJ: Pregnancy-related mortality surveillance--United States, 1991--1999. 
MMWR Surveill Summ 2003; 52: 1-8 PMID: 12825542 
 
24. 
Perkins FM, Kehlet H: Chronic pain as an outcome of surgery. A review 
of predictive factors. Anesthesiology 2000; 93: 1123-33 PMID: 11020770 


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25. 
Palmer CM, Cork RC, Hays R, Van Maren G, Alves D: The dose-response 
relation of intrathecal fentanyl for labor analgesia. Anesthesiology 1998; 88: 355-61 
PMID: 9477056 
 
26. 
Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, 
Schwam EM, Siegel JL: Validity and reliability of the Observer's Assessment of 
Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 
1990; 10: 244-51 PMID: 2286697 
 
27. 
Lavand'homme PM, Roelants F, Waterloos H, Collet V, De Kock MF: An 
evaluation of the postoperative antihyperalgesic and analgesic effects of intrathecal 
clonidine administered during elective cesarean delivery. Anesth Analg 2008; 107: 948-
55 PMID: 18713912 
 
28. 
Backonja MM, Krause SJ: Neuropathic pain questionnaire--short form. 
Clin J Pain 2003; 19: 315-6 PMID: 12966257 
 
29. 
Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, 
Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F: Development and validation 
of the Neuropathic Pain Symptom Inventory. Pain 2004; 108: 248-57 PMID: 15030944 
 
 
.3 Significance:   
Breakthrough pain in the postoperative period is a common occurrence.  
Currently, we attempt to effectively control this breakthrough pain with a 
combination of intravenous and oral non-steroidal anti-inflammatory drugs 
and opioids.  However, this drug regimen has its limitations, especially 
opioids.   Opioid therapy is laden with side-effects including nausea, 
vomiting, constipation, sedation and pruritus.  Opioids also cross into breast 
milk and have been detected up to 72-hours after cesarean delivery, although 
their  clinical effect on the neonate has not been determined.21  TAP blocks 
have been shown to decrease overall morphine consumption after cesarean 
delivery, as well as decrease the amount of postoperative pain reported by 
patients.8  The advantages of improved pain control include: improved patient 
satisfaction, prevention of postoperative complications associated with pain 
(e.g., atelectasis), improved ability of the mother to care for her newborn, and 
decreased side-effects from systemic opioid analgesia. In addition, the 


Principal Investigator:  Edward Yaghmour 
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reduction in need for postoperative breakthrough pain medications following 
cesarean delivery may minimize the consumption of resources (e.g., RN 
administered rescue medications) required to manage breakthrough pain on 
the postpartum wards.  Furthermore, in morbidly obese patients, the potential 
reduction in postoperative opioid consumption afforded by a TAP block 
would also decrease the risk of respiratory depression, for which these patients 
are at a higher risk.  Finally, improved postoperative pain control results in 
earlier ambulation, thereby reducing the risk of developing deep venous 
thrombosis and possible thromboembolic events, which is the number one 
cause of maternal mortality in the United States.22,23 
 
An additional benefit of the TAP block in post-cesarean analgesia is its 
potential to reduce the incidence of post-operative neuropathic pain.  A recent 
cohort study revealed that one-third of patients who underwent a cesarean 
delivery via Pfannenstiel incision had chronic pain at the incision site two 
years later, with 7% of patients rating their pain as moderate-to-severe.5  Of 
those patients who rated their pain moderate-to-severe, neuropathic pain 
secondary to nerve entrapment was found to be the cause in 53% of the cases, 
based on history and physical exam findings.5  Furthermore, one study has 
demonstrated that the intensity of acute post-operative pain is a significant 
predictor of the development of chronic neuropathic pain.24  Therefore, based 
on this data,  it would seem that the improved post-operative analgesia 
regimen provided by the TAP block may potentially reduce the incidence of 
post-operative neuropathic pain in this patient population. 
 
The outcomes of this study will therefore allow us to establish an effective 
analgesic dose of ropivacaine, based on differences in concentration, for use in 
TAP blocks as part of a post-Cesarean delivery multimodal analgesic regimen 
that does not include intrathecal morphine. 
 
 
3.0 Investigational Plan 
 
.1 Study design: Randomized, double blind placebo controlled trial. 


Principal Investigator:  Edward Yaghmour 
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.2 Methods: 
 
.2.1 
Size of study groups(s):   
The primary outcomes for this study will be 24-hour post-TAP 
block hydromorphone consumption.  Secondary outcomes will be 
time to first request for hydromorphone, diameter of cutaneous 
sensory block from TAP block at 6 hours after placement, 
postoperative pain scores, 48-hour hydrocodone consumption in 
milligrams, 72-hour cumulative opioid consumption in morphine-
equivalents, 24 hour ketorolac consumption in milligrams, 48 hour 
ibuprofen consumption in milligrams, incidence and severity of 
postoperative neuropathic pain at 1 and 6 weeks after completion 
of surgery, and incidence of side effects from opioids (nausea, 
pruritis, sedation). 
 
There will be four groups used in this study: 
 
a.  Group 1 (Placebo Group) – 15mL 0.9% normal saline per side 
 
b.  Group 2 – 15mL 0.2% 60mg  ropivacaine per side 
 
c.  Group 3 – 15mL 0.5% 150mg  ropivacaine per side 
 
d.  Group 4 – 15mL 0.75% 225mg  ropivacaine per side 
 
For the purpose of sample size calculation, we assumed that a 
clinically important reduction in 24 hour hydromorphone 
consumption would be a 25%, 37.5% and 50% absolute reduction, 
compared with control, with increasing ropivacaine concentrations.  
The projected amount of 24 hour hydromorphone consumption in 
each group is assumed to be 4, 3, 2.5, and 2 mg.  The projected 
amount of 24-hour hydromorphone consumption in for the placebo 
group is based on data obtained from a study by Palmer, et al. 
investigating the dose-response relationship of intrathecal 
morphine for postcesarean analgesia.25  Using these assumptions a 


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one-way design with 4 groups with sample sizes of 46, 46, 46, and 
46 was derived. The null hypothesis is that the standard deviation 
of the group means is 0.0 and the alternative standard deviation of 
the group means is 0.7.  The total sample of 184 subjects achieves 
a power of 0.810 using the Kruskal-Wallis Test with a target 
significance level of 0.05 and an actual significance level of 0.046. 
The average within group standard deviation assuming the 
alternative distribution is 3.0. These results are based on a 2000 
Monte Carlo sampling from the null distributions.  However, in 
order to account for potential drop-outs, 50 patients will be 
recruited for each group, for an n=200 patients. 
 
 
.2.2 
Patient entry, exclusion and dropout criteria:        
Inclusion Criteria: ASA II-III patient > 18 years of age who is 
pregnant, presenting for a cesarean delivery via Pfannenstiel  
incision who is eligible to receive a spinal anesthetic with 0.75% 
bupivacaine and fentanyl and whose is not eligible to receive 
intrathecal morphine due to a BMI >40 kg/m2. 
 
Exclusion criteria: < 18 years of age; contraindication to 
placement of a spinal anesthetic; contraindication to use of non-
steroidal anti-inflammatory drugs (NSAIDs);  patients receiving 
medical therapies considered to result in tolerance to opioids; 
patients with a history of established chronic pain, (e.g. chronic 
low back pain, fibromyalgia or headaches), defined as requiring 
regular medical follow-up with pain specialists, as well as recent 
use (within the year preceding pregnancy) of opioid analgesics as 
an outpatient; patients with a history of diabetes mellitus; patients 
undergoing a vertical midline skin incision; patients who are 
undergoing a cesarean delivery after a failed vaginal trial of labor 
with neuraxial analgesia already in place;  


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Dropout criteria: intraoperative conversion to general anesthesia, 
failure of spinal anesthetic to achieve an adequate surgical level 
(loss of T4 dermatome to pinch bilaterally), failed spinal anesthetic 
requiring repetition of neuraxial blockade, and patients requiring 
>100 μg of intraoperative fentanyl for supplemental analgesia. 
 
 
.2.3 
Protocol specific methods:  
Eligible women for elective cesarean delivery admitted to the 
Labor and Delivery Unit of Prentice Women’s Hospital will be 
approached for study participation immediately after the routine 
preanesthetic evaluation or immediately after completion of the 
surgical procedure.  Women who agree to participate will give 
written, informed consent at this time. 
 
Subjects will be prepared preoperatively in the usual fashion with 
intravenous (IV) access, aspiration prophylaxis and intraoperative 
monitoring. Preincision antibiotics will be given and uterotonic 
medications will be used as per usual practice after delivery.  
 
The anesthesiologist will perform a spinal anesthetic per routine 
with the subject in the sitting position using sterile technique at the 
L3-4 interspace (± one vertebral interspace) utilizing a 25-gauge 
Pencan spinal needle. The spinal anesthetic will consist of 12 mg 
of hyperbaric 0.75% bupivacaine + 15 μg fentanyl. The subject 
will be placed supine with left lateral tilt to alleviate aortocaval 
compression. Cesarean delivery will commence after adequate 
anesthesia is assured to a T4 sensory level to pinprick. 
Vasopressors and IV fluids will be administered at the 
anesthesiologist’s discretion per usual practice. 
 


Principal Investigator:  Edward Yaghmour 
Version 05.0  05/27/2015 
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Upon completion of the cesarean delivery, the subject will be 
transported to the post-anesthesia care unit (PACU).  At the time of 
presentation to PACU, the subject will be randomized to one of 
four groups using a computer generated random number table: 
placebo (0.9% normal saline), 0.2% ropivacaine, 0.5% ropivacaine, 
or 0.75% ropivacaine. Randomization assignments will be kept in 
sequentially numbered opaque envelopes. The envelope will be 
opened by a research nurse who will prepare 2 x 20 mL syringes, 
each containing 15 mL of the assigned solution, with each syringe 
labeled “study drug”. Subjects randomized to one of the 
ropivacaine groups will receive a total of 30 mL (15 mL per side) 
of ropivacaine according to group assignment.  Subjects 
randomized to the placebo group will receive a total of 30 mL 
preservative free saline (15 mL per side). 
 
TAP blocks will be performed within 15 minutes of arrival into the 
PACU room.  All TAP blocks will be performed by one of five co-
investigators (CC, AD, NH, AL, or EY), each of whom has 
significant experience in placement of these blocks.  During block 
placement, the patient will be continuously monitored with non-
invasive blood pressure measurement, EKG, and pulse oximetry.  
All patients will be placed in the supine position, with arms 
elevated above their heads.  Utilizing a Sonosite M-Turbo 
Ultrasound machine with an L-25 transducer (5.0-10.0 MHz) 
(SonoSite, Inc., Bothell, WA),  the abdominal muscle layers will 
be located by placing the ultrasound transducer perpendicular to 
the coronal anatomic plane at the T-10 dermatome level in the 
patient’s midaxillary line.  Three muscle layers (from superficial to 
deep: external oblique, internal oblique, and transversus 
abdominis) and three fascial layers (from superficial to deep: layer 
between subcutaneous fat and external oblique, layer between 


Principal Investigator:  Edward Yaghmour 
Version 05.0  05/27/2015 
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external oblique and internal oblique, and layer between internal 
oblique and transversus abdominis) will be identified.  Under 
ultrasound guidance utilizing an in-plane approach, a 70mm or 
90mm, 21 gauge blunted Stimuplex needle will be advanced from 
the skin until the tip reaches the fascial layer between the internal 
oblique and transversus abdominis.  After negative aspiration, 15 
mL of the study drug will be injected incrementally, while 
simultaneously observing for distention of this fascial plane with 
local anesthetic.  The needle will then be removed and the process 
repeated in the same manner on the patient’s opposite side. 
Following completion of the TAP block, the patients will be 
monitored in the PACU per routine Labor and Delivery Unit 
guidelines.   
 
As part of their postoperative pain control management, all patients 
will receive ketorolac tromethamine 30mg IV q6h x 24 hours, 
beginning within 30 minutes after completion of the TAP block.  
After 24 hours, ibuprofen 600mg per os will be administered q6 
hours prn pain x48 hours. The patient will also receive patient-
controlled intravenous hydromorphone analgesia (PCA), which 
will be set up within 30 minutes upon arrival to the PACU.  The 
PCA will be set at 0.3mg bolus, lockout interval 10 minutes, with a 
4 hour maximum dose of 5 mg. The PCA will be activated at 
patient’s first request for supplemental analgesia and a VAS pain 
score will be documented at this time.   
 
Prior to transfer to the floor, the labor and delivery nurse will 
notify the accepting floor nurse, through the nursing handoff 
report, of the patient’s participation in this study.  Also, a sheet will 
be placed on the front of the patient’s chart, identifying the 
patient’s participation in this study and instructing the floor nursing 


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staff to contact the anesthesia nurse clinician (and not the obstetric 
housestaff, as per routine) for evaluation and management of 
breakthrough pain. If the anesthesia nurse clinician deems that a 
change in the patient’s pain management regimen is necessary, she 
will consult an anesthesiology physician on call, who will adjust 
the pain medications accordingly.  
 
The patient will remain on the PCA for 24 hours after the time of 
TAP block placement, after which time the patient will be 
converted to acetaminophen/hydrocodone 325mg/10mg per os q4 
hours prn pain x48 hours.  These are routine oral analgesic 
medications for postoperative cesarean delivery analgesia in 
patients who do not receive intrathecal morphine.   
 
Standard orders will be written for monitoring sedation and 
respiratory rate, and treatment of side effects (nausea, vomiting, 
pruritus and respiratory depression). The total amount of 
hydromorphone and hydrocodone given will be determined for 
each subject after 24 and 72 hours, and will be reported in 
milligrams; the total opioid consumption of 72 hours will be 
reported in morphine-equivalents.  The total amount of ketorolac 
given will be determined for each subject at 24 hours; the total 
amount of ibuprofen given will be determined for each subject at 
72 hours. 
 
Time to first request for hydromorphone PCA; presence and 
severity of pain, nausea, and pruritus; extent of cutaneous sensory 
block; and 1 and 6 week postoperative follow-up will be made by 
an anesthesia nurse clinician blinded to group allocation, as 
follows:  
 


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Pain, nausea, sedation, and pruritus will be assessed at 2, 6, 24, and 
72 hours after TAP blockade.  Pain severity will be assessed both 
at rest and with movement (hip flexion) utilizing a verbal pain 
scale (0 = no pain, 10 = worst pain imaginable).  Pain severity will 
also be assessed at the time of first request for PCA analgesia. 
 
Nausea will be measured using a categorical scoring system (0 = 
none, 1 = mild, 2 = moderate, 3 = severe).  Rescue antiemetics will 
be offered to any patient complaining of nausea or vomiting, per 
standard postoperative order regimen.  Pruritus will be measured 
using a categorical scoring system (0 = none, 1 = mild, 2 = 
moderate, 3 = severe).  Sedation will be measured using the 
Observer’s Assessment of Alertness/Sedation Scale, a validated 
scale of sedation (see figure below).26 
 
 
 
 
Assessment of cutaneous sensory block will be made at 6 hours 
post-TAP blockade, utilizing a similar method described in a study 
by Lavand’homme, et al. 27  Using an alcohol-sterilized von Frey 
hair (396 m Newton) the patient’s abdomen will be stimulated, 
starting at the umbilicus and moving cephalad by 1-cm steps until 
the patient reports a distinct change in perception. Then, the 
Observer’s Assessment of Alertness/Sedation Scale (OAA/S)24  


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abdomen will be stimulated in the same fashion, again beginning at 
the umbilicus and moving laterally in one direction in 1-cm 
increments until the patient reports a distinct change in perception, 
and then laterally from the umbilicus in the opposite direction in 1-
cm increments.  Finally, the inguinal creases will be stimulated  in 
the same fashion, beginning immediately beneath the bandage and 
moving in 1-cm increments caudad until the patient reports a 
distinct change in perception.  These measurements will then be 
transcribed onto graph paper and the total surface area will be 
calculated.   
 
The following data will be collected in addition to the primary and 
secondary outcome data:  maternal age, height, weight, gestational 
age, history of previous abdominal surgery, and history of previous 
cesarean delivery. 
 
Protocol specific analgesic regimens will end at 72 hours post-TAP 
blockade.  72 hours is chosen as the time to end the standardized 
analgesic regimens as this is the average time when post-cesarean 
delivery patients are typically discharged from the hospital.   
 
Two telephone follow-up evaluations will be made (one at 1 week 
post-delivery and one at 6 weeks post-delivery) to assess the 
incidence and extent of postoperative neuropathic pain.  These two 
follow-up evaluations will each use a combination of 2 pain 
questionnaires: the Neuropathic Pain Questionnaire—Short Form 
(NPQ-SF) and the Neuropathic Pain Symptom Inventory (NPSI) 
(see attached form).  The NPQ-SF will be used to assess for the 
presence of neuropathic pain, while the NPSI will be used to assess 
for the type and severity of neuropathic pain. The NPQ-SF has 
been shown to have 64.5% sensitivity, 78.6% specificity, and 73% 


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accuracy for the presence of neuropathic pain28;  the test-retest 
reliability and validity of the NPSI has also been demonstrated in 
the literature.29  
 
 
.2.4 
Risks/Benefits:  The risks of the spinal procedure itself are 
unchanged by participating in this study.  These risks include: 
ineffective anesthesia, pruritus, nausea, vomiting, and hypotension.  
Less common risks include fetal bradycardia or maternal postdural 
puncture headache.  Rare complications include maternal or fetal 
respiratory depression, total spinal anesthesia, a toxic reaction to 
the anesthetic agents, and bleeding or infection in the epidural or 
spinal space that may lead to nerve damage.  There is always a risk 
of inadequate analgesia after surgery with the proposed pain 
management regimen. Participation in this study does not increase 
this risk above baseline. 
The risks of ropivacaine: 
hypotension (37.0%)  
 nausea (24.8%) 
 vomiting (11.6%) 
 bradycardia (9.3%) 
 fever (9.2%) 
 pain (8.0%)  
 postoperative complications (7.1%) 
 anemia (6.1%)  
 paresthesia (5.6%) 
 headache (5.1%) 
 pruritus (5.1%) 
 back pain (5.0%) 
Additional potential risks are present with the administration of a 
TAP block.  These risks include: ineffective analgesia, soreness 


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around injection site, and mild bruising around injection site.  Rare 
complications include inadvertent peritoneal puncture, systemic 
toxicity from local anesthetic, and bleeding or infection.  The risk 
of inadvertent peritoneal puncture is potentially reduced by usage 
of ultrasound to confirm needle position.   
 
Finally, risks due to participation in this study include loss of 
confidentiality.  There is also a risk the patient may become 
emotionally uncomfortable since research nurses will be contacting 
patients at home for follow-up. 
 
2.2.5       Confidentiality: 
Subjects’ identity will be guarded by assigning a numerical code  
which is only known by the principal investigator. Data is stored in 
department computer which is password protected. Each study subject 
will be assigned a study code number. The code will be used to link 
study data to patient identification (name) in a separate database. 
Subject data will be stored on secure computers at Northwestern 
University. Data access will be password protected and only available 
to study investigators. The surveys will have the study code affixed 
after they have been received from the mail. 
 
 
4.0  Data Analysis: 
 
.1 Data collection form:  See attached. 
.2  Data evaluation: The primary outcome (24-hour hydromorphone 
consumption) will be compared among groups using the Kruskal-Wallis test.  
Post hoc testing will be performed using the Mann-Whitney test with 
Bonferroni correction.  The time to first request for analgesia will be 
compared using the log-rank test.  The area of abdominal analgesia, 48-hour 
hydrocodone consumption, 72-hour cumulative opioid consumption, 24 hour 


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ketorolac consumption, 48 hour ibuprofen consumption, VAS pain scores and 
NRS scores for nausea, pruritus and sedation, and follow-up questionnaires 
will be compared using ANOVA or the Kruskal-Wallis H test.  The incidence 
of side effects will be compared using a 2 statistic.  A P<0.05 will be required 
to reject the null hypothesis. 
 
.3 Interpretation of Anticipated Results:   It is anticipated that a concentration 
of ropivacaine will be found that will provide effective post-cesarean delivery 
analgesia as part of a multimodal analgesic regimen that does not include 
intrathecal morphine. In turn, anesthesiologists will be able to provide 
superior post-cesarean analgesia with the TAP block for those patients who 
are ineligible to receive intrathecal morphine.  Furthermore, it is anticipated 
that use of the TAP block will decrease the incidence of post-operative 
neuropathic pain after cesarean delivery. 
5.0 Budget: 
 
.1 Materials: all materials and medications utilized for this study are readily 
available on the Labor and Delivery Unit or from the Prentice Women’s 
Hospital Pharmacy. 
 
.2 Labor Requirements:  existing anesthesia personnel on Labor and Delivery 
Unit. 
 
.3 Presentation Cost:  anticipated presentations at SOAP and ASA meetings. 
 
 
6.0 Consent:   See Attached