Clinical trial NCT02579629
Conditions: Pain
Keywords: Analgesia Cesarean section Opiates
Sponsor: Emory University
Start date: 2015-07-01; Completion date: 2019-07-25
Enrollment: 64 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of this study is to examine if pain levels treated with intrathecal (IT) preservative-free morphine (PFM) after a cesarean section improve with the additional use of continuous subfascial wound infiltration with ropivacaine using the OnQ® elastomeric pump system.

Detailed description:
The main purpose of this study is to examine if pain levels treated with intrathecal (IT) preservative-free morphine (PFM) after a cesarean section improve with the additional use of continuous subfascial wound infiltration with ropivacaine using the OnQ® elastomeric pump system. As a double-blinded, randomized, placebo controlled study, women undergoing first, second or third cesarean section will be randomly assigned to one of 3 different groups. Group 1 will receive saline, group 2 will be given ropivacaine 0.1%, group 3 will be given ropivacaine 0.2%, all at a rate of 8ml/hr via the OnQ® pump system. Each group will also receive an 8mL bolus of the previously assigned infusate. The investigator will assess pain at rest and with movement at different time periods during the recovery process through 3 months post operatively. The investigator will also assess if the use of this system decreases the need for other pain medications and reduces the potential side-effects of pain treatment.

Arms: arm 1: Subjects undergoing their first,second or third cesarean sections will receive a bolus dose of 8ml of 0.1% ropivacaine followed by an infusion of 8ml/hr of 0.1% ropivacaine using the On-Q® elastomeric pump for 3 days after the cesarean section. arm 2: Subjects undergoing their first,second or third cesarean sections will receive a bolus dose of 8ml of 0.2% ropivacaine followed by an infusion of 8ml/hr of 0.2% ropivacaine using the On-Q® elastomeric pump for 3 days after the cesarean section. arm 3: Subjects undergoing their first, second or third cesarean sections will receive a bolus dose of 8ml normal saline followed by an infusion of 8ml/hr of normal saline using the On-Q® elastomeric pump for 3 days after the cesarean section.
Interventions: intervention 1: Ropivacaine 0.1% intervention 2: Ropivacaine 0.2% intervention 3: Normal saline intervention 4: On-Q ® elastomeric pump
Intervention descriptions: intervention 1: Ropivacaine 0.1% is a local anaesthetic drug and will be administered as a single bolus dose of 8ml of 0.1% ropivacaine followed by an infusion of 8ml/hr of 0.1% ropivacaine using the On-Q® elastomeric pump. The bolus dose of 8ml of 0.1% ropivacaine will be administered via a multiport, silver-impregnated catheter (6-10cm) placed above the rectus muscle parallel to the fascial incision, using a preloaded syringe. The infusion will be delivered by the On-Q® elastomeric pump pre-set to deliver 8ml/hr of 0.1% ropivacaine for 72 hours post-operatively. intervention 2: Ropivacaine 0.2% is a local anaesthetic drug and will be administered as a single bolus dose of 8ml of 0.2% ropivacaine followed by an infusion of 8ml/hr of 0.2% ropivacaine using the On-Q® elastomeric pump. The bolus dose of 8ml of 0.2% ropivacaine will be administered via a multiport, silver-impregnated catheter (6-10cm) placed above the rectus muscle parallel to the fascial incision, using a preloaded syringe. The infusion will be delivered by the On-Q® elastomeric pump pre-set to deliver 8ml/hr of 0.2% ropivacaine for 72 hours post-operatively. intervention 3: Normal saline will be administered as a single bolus dose of 8ml of normal saline followed by an infusion of normal saline using the On-Q® elastomeric pump. The bolus dose of 8ml of normal saline will be administered via a multiport, silver-impregnated catheter (6-10cm) placed above the rectus muscle parallel to the fascial incision, using a preloaded syringe. The infusion will be delivered by the On-Q® elastomeric pump pre-set to deliver 8ml/hr normal saline for 72 hours post-operatively. intervention 4: The On-Q® elastomeric pump automatically and continuously delivers a regulated flow of 0.1% or 0.2% ropivacaine or normal saline locally to the surgical site for 72 hours post-operatively. The infusion will be delivered by pre-setting the On-Q® elastomeric pump to deliver at the rate of 8ml/hr for 72 hours post-operatively.

Protocol documents:
Prot_SAP_000.pdf: 
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Multimodal Post-Cesarean Analgesia with Spinal Morphine and Continuous Wound 
Infiltration of Ropivacaine Using the OnQ® Elastomeric Pump:  A Dose-Ranging Study 
Using a High-Volume, Low-Dose Protocol 
 
IRB#00073292 
 
 
 
 
 
 
Multimodal Post-Cesarean Analgesia with Spinal Morphine 
and Continuous Wound Infiltration of Ropivacaine Using the 
OnQ® Elastomeric Pump:  A Dose-Ranging Study Using a 
High-Volume, Low-Dose Protocol 
 
 
 
 
 
Protocol Dated 02/06/2019 
 
 
 
 
NCT02579629 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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IRB Protocol 
 
Multimodal Post-Cesarean Analgesia with Spinal Morphine and Continuous 
Wound Infiltration of Ropivacaine Using the OnQ® Elastomeric Pump:  A Dose-
Ranging Study Using a High-Volume, Low-Dose Protocol 
PI: Dr. James Dolak 
 
Abstract: 
The purpose of the proposed study is aimed to determine whether continuous subfascial 
infusion of ropivacaine using the On-Q® elastomeric pump in combination with 
intrathecal (IT) preservative-free morphine (PFM) will improve post-operative cesarean 
section pain relative to IT PFM alone (the current standard of care).  Using a double-
blinded, randomized, placebo-controlled study design, 60 women undergoing their first, 
second or third cesarean section will be randomly assigned to one of 3 different groups 
receiving either saline (control, n=20) or ropivacaine (0.1% or 0.2%, experimental groups 
n=20 in each) subfascially via the elastomeric pump. We will enroll up to 70 subjects to 
achieve 60 randomized and treated subjects, to account for screen failures and/or early 
terminations,  All participants will receive an IT dose of 200mcg of PFM as part of a 
standardized spinal anesthetic for their operative procedure.  During closure of their 
abdomen, all patients will undergo placement of a multi-orifice, silver-impregnated 
catheter in the subfascial space.  At the conclusion of the surgery, the catheter will be 
bolused with 8ml of one of the three test solutions, after which an On-Q® elastomeric 
pump (containing the same solution as initially administered through the catheter) will be 
attached to infuse the test solution at a rate of 8ml/hr.  The infusion system will then be 
left in place for up to 72hr.  Adjunctive pain medicines (ketorolac, morphine, ibuprofen, 
and oxycodone-acetaminophen) will be available for the treatment of breakthrough pain 
during hospitalization. The primary outcome being measured in the study is post-
operative pain with movement as assessed immediately after the study bolus (baseline) 
and during the immediate post-operative period, when leaving the PACU (2hr), 6hr, 12hr, 
24hr, 48hr, and 72hr post-op.  Pain will also be evaluated by telephone at 4-6 weeks and 
3mo after surgery.  A visual acuity pain scale (VAPS) will be used to measure patient 
pain levels while hospitalized whereas pain at the 4-6 week visit and 3mo will be 
quantitated using a numeric pain scale (NPS).  Secondary outcomes to be studied include 
degree of pain at rest, time to first rescue medication, time to first opioid use, amount of 


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inpatient non-steroidal anti-inflammatory drug (NSAID) use, amount of inpatient opioid 
use, incidence and severity of opioid systemic side effects, incidence and severity of local 
anesthetic side effects, catheter related issues, breast feeding success, maternal 
satisfaction, evaluation of wound healing, categorization and quantification of outpatient 
pain medication, and cost analysis. 
 
Introduction and Background: 
The primary hypothesis of this study is that post-cesarean section pain with movement 
will be significantly improved in women treated with IT PFM by the addition of 
continuous subfascial wound infiltration with ropivacaine.  There are approximately 4 
million deliveries in the United States every year; with about 30% of these deliveries 
being cesarean sections.  This makes cesarean section one of the most common surgeries 
performed today.  Women experience significant post-operative pain after cesarean 
sections.  Cesarean section patients are unique among surgical patients in that they have 
to immediately care for their newborns after their procedure, and their infants may be 
affected by systemically-administered maternal pain medications if breastfeeding.  
Therefore, this population requires the combination of maximal pain relief with minimal 
sedation, while minimizing the exposure of infants to clinically-significant amounts of 
drugs in breast milk. This encourages further studies that will elucidate better means of 
accomplishing ideal post-operative pain. 
 
Pain, both intraoperative and postoperative, has been shown to be the anesthetic outcome 
of greatest concern to women undergoing cesarean section with the potential side effects 
of pain relief being of much less concern (1).  This was found to be true both in terms of 
absolute ranking and when using a relative value score.  Pain as part of the childbirth 
experience may predispose the parturient to the development of post-traumatic stress 
disorder (2).  It has also been suggested that pain after cesarean section decreases the 
effectiveness of breast feeding leading to more formula and pacifier use (3, 4).  In 
addition to the obvious psychological aversion to pain by patients, it is well-known that 
pain can stimulate a variety of potentially detrimental physiological effects such as 
tachycardia, hypertension, respiratory splinting, and inactivity, which in turn can lead to 


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risks of myocardial infarction, aneurysmal rupture, thrombophlebitis, post-operative 
atelectasis and pneumonia.  Poorly controlled post-surgical pain relief also influences the 
risk of developing chronic post-surgical pain (CPSP) (5, 6).  CPSP is defined as pain of at 
least 2mo duration which develops after a surgical procedure, and which is not related to 
any other causes of pain (infection, malignancy, etc.) or to pain continuing from a pre-
existing pain problem (7).  The incidence of CPSP after cesarean section is believed to be 
between 10-12% (5, 6), meaning that as many as 168,000 women might be affected with 
this each year.  Even more troubling is that an estimated 4% of the women undergoing 
cesarean section (~48,000) actually develop disabling chronic pain defined as pain > 5 on 
a scale from 0 to 10 (6).  Recognition of the above psychological and physical attributes 
of pain led to the Joint Commission recommendation to treat pain as the fifth vial sign, 
with the stated goal for US healthcare facilities to uniformly achieve pain scores ≤ 3 out 
of 10 (8). 
 
Pain after cesarean section has two well-recognized components – somatic and visceral.  
Somatic pain is often described as a well-localized, sharp, burning, or tearing pain. In 
contrast visceral pain is described as a poorly-localized, dull or cramping pain.  Somatic 
pain has both cutaneous and deep components which are transmitted via the anterior 
components of the spinal nerves, whereas visceral pain is a sympathetically-mediated 
pain whose sensation returns via afferents from the uterus to the inferior hypogastric 
plexus, and hence into the sympathetic chain, ultimately arriving at the spinal cord (8).   
It is a well-accepted theory that multimodal pain relief helps to alleviate pain by both 
working on different types of pain (somatic vs visceral) and at different pain receptors 
leading to either additive or synergistic analgesia, while minimizing the side-effect 
profile of any single drug component of the analgesic cocktail (9).  For instance, either 
systemic or neuraxial opioids are traditionally given after cesarean section to decrease 
post-operative pain.  Unfortunately, opioids given by either of these routes have several 
undesired and potentially severe side-effects including pruritus, constipation, urinary 
retention, nausea/vomiting, sedation, and respiratory depression (10). In an effort to 
mitigate these troublesome issues, NSAIDs are commonly given to reduce the 
inflammation associated with surgical injury, thereby decreasing the inflammatory 


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component of the pain with a resulting opioid-sparing effect (8, 10).   Additionally, 
NSAIDs are particularly effective against the visceral cramping pain which results from 
uterine involution (8).   
 
While the combination of neuraxial opioids with systemic NSAIDs appears to provide 
excellent postoperative pain relief at rest during the first 24hr, a significant number of 
women experience pain greater than 3/10 with movement during this same period, and 
with both rest and movement pain at time periods greater than 24hr.  These pain 
exacerbations primarily involve discomfort resulting from tension on the wound, often 
require treatment with IV or PO opioids, and appear to be due largely to cutaneous or 
deep somatic pain.  As incisional pain can often be acutely managed with local anesthetic 
(LA) infiltration, interest grew in seeing if continuous local infiltration of LA alone, 
NSAIDs alone, or combinations of NSAIDs with LAs through a catheter inserted into the 
surgical wound could reduce both post-surgical pain and postoperative opioid 
consumption.  Initial results using subcutaneous catheters were disappointing, showing at 
most modest reductions in opioid use, with little or no change in pain scores (11).  For 
example, in one study comparing the subcutaneous infusion of 4ml/hr of 0.25% 
bupivacaine with a saline infusion control showed no difference in VAS for pain at rest, 
but showed a 22 mg reduction in morphine use over 24hr (12).  However, a meta-analysis 
of a number of trials involving subsets of surgical patients showed both reductions in pain 
scores and opioid consumption in the obstetric/gynecologic surgery population, although 
only pain at rest was examined (11).  Multiple studies involving cesarean section patients 
have shown that subfascial infusions of plain 0.2% ropivacaine (13), 0.25% 
levobupivacaine (14), 0.2% ropivacaine containing diclofenac (15), or 0.2 % ropivacaine 
with ketoprofene (16) all provide good postoperative analgesia and a reduction in opioid 
usage for post-operative pain.  In one of these studies (16), wound infusion of identical 
solutions through either subfascial catheters or subcutaneous catheters was compared, 
and subfascial administration was shown to be clearly superior based on pain at rest and 
total postoperative morphine consumption.  Additionally, in two of the above studies, 
continuous wound infusion was found to provide postoperative analgesia nearly 
equivalent (14) or better (13) than epidural analgesia with either LA or PFM, 


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respectively.  In contrast to these positive studies, one negative study found that 
subfascial wound infusion with 5ml/hr of 0.375% ropivacaine was inferior to intrathecal 
PFM in terms of both pain scores and IV oxycodone use (17).  Therefore, while there are 
both theoretical and evidential grounds to support the use of subfascial wound catheters, 
their absolute efficacy as sole agents for pain relief remains to be established. 
 
To date, long-acting neuraxial opioids like PFM provide the gold standard for post-
cesarean delivery analgesia whether given via the IT or epidural route, providing excel-
lent pain relief for the first 24hr while allowing the mother to ambulate and care for her 
child (18, 19).  However, it is clear that neuraxial opioids do not provide complete 
analgesia for cesarean section when used as primary agents, with more than 70% of 
patients requesting further analgesia (19).  Even when codeine with acetaminophen is 
given prn, 33% of women in one study still experienced inadequate analgesia (18).  Pain 
with movement appears to be the most poorly treated pain phenomenon using neuraxial 
PFM (19).  Again, this points to the importance of multimodal pain control in obstetric 
patients. Surprisingly, while continuous wound infiltration has been examined as a 
primary technique for post-cesarean pain relief (13,14,15,16) and has even been 
compared for efficacy to epidural (13,14) and IT (17) post-cesarean analgesia, no one has 
tested to see if continuous wound infiltration with LAs improves the analgesia obtained 
from IT PFM. However, it is standard practice of some obstetricians in our institution to 
use the continuous wound infiltration system on every patient undergoing a cesarean 
section whether they have IT PFM or not. The purpose of the proposed study is to 
examine the hypothesis that continuous wound infusion with ropivacaine using a high-
volume, low-dose protocol will significantly improve pain with movement after cesarean 
section in patients who have received our standard dose of IT PFM.  A control group (IT 
PFM + saline wound infusion) will be compared to two groups receiving both IT PFM 
along with one of two doses of ropivacaine (experimental groups) using the OnQ® 
elastomeric pump for delivery of the infusions.  We have purposefully used lower 
concentrations of ropivacaine (0.1-0.2%) along with higher volumes in recognition that 
the nerves to be anesthetized are of smaller diameter, and therefore require lower 
concentrations of LA for this effect; while ensuring a high enough volume to completely 


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bathe the wound at the subfascial layer.  During both cesarean section under local 
anesthesia (20), and with transversus abdominis plane blocks for post-operative analgesia 
(21) - situations which involve some of the same sensory nerves blocked by continuous 
wound infusion - the importance of volume versus concentration of LAs has been 
stressed.  It is expected that ropivacaine, used in conjunction with IT PFM, will provide 
additive or synergistic pain relief as compared to IT PFM alone, and hopefully this will 
lead to better breast feeding, decreased opioid use with less opioid side-effects, fewer 
prolonged stays secondary to pain issues, increased patient satisfaction, and ultimately to 
decreased hospital costs. 
 
Objectives:  
The primary outcome measured in this study is post-operative pain with movement 
measured both during cough and 20° straight leg raise.  Pain at rest will also be 
evaluated.  All types of pain will be measured using a visual analogue pain scale (VAPS) 
determined using a 100mm line with the patient making a mark on the line between no 
pain and worst pain ever (12).  Pain scores will be collected after the bolus of study 
medication/placebo (zero time), at PACU discharge (2hr), 6hr, 12hr, 24hr, 48hr, and 72hr 
post-cesarean section.  Pain at 4-6 weeks and 3mo will be quantitated over the telephone 
using a numerical pain scale (NPS) with 0 being no pain and 10 being the worst pain 
imaginable.  In addition to the pain scores, pain with movement will be further evaluated 
qualitatively using the short-form McGill pain questionnaire (22) at all time-points in the 
study.  This will allow us to look at pain quality (sharp, burning, etc.), as well as 
examining the affective components (exhausting, fearful, etc.) of the pain. 
 
There are several secondary outcomes of this study that can be divided into rescue 
medication information, medication side effects, breastfeeding, wound evaluation, patient 
satisfaction, and cost-analysis. 
 
Rescue medication data will be collected during the hospitalization period (0-72hr).  We 
will note the time to dosing with the first rescue medication for breakthrough pain. After 
the first rescue medication is given, the patients will be eligible for further doses of IV or 


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PO pain medicines for continued breakthrough pain as needed (see Study Design and 
Methods section below for specifics). The time to first opioid use for pain will also be 
recorded whether this entails IV or PO administration.  Additionally, we will quantitate 
narcotic use in terms of morphine equivalents given (in mg) both by post-operative day 
and with a cumulative total.  The total dose of NSAIDs (in mg) will be recorded for each 
of the first three postoperative days, along with a cumulative total.  We will also be 
measuring the proportion of patients who require opioid supplementation at 0, 2, 6, 12, 
24, 48, and 72 hours post-op.  We will also ask if patients are still requiring opioids 
and/or NSAIDs for surgical discomfort along with inquiring about the amount of each 
used per day at the 4-6 week and 3 month follow-up telephone calls.   
 
As several different medications are utilized within this study, it is important to monitor 
side effects of the medications, and see if these profiles change under the conditions of 
the study.  We will collect data on the incidence and severity of opioid central and/or 
systemic side effects – pruritus, nausea/vomiting (not associated with hypotension), 
somnolence, and respiratory depression.  Somnolence will be graded using a published 
perioperative somnolence scale (23).  Measurements of nausea/vomiting and pruritus will 
make use of previously published scales (24).  Respiratory depression will be considered 
to be present if the respiratory rate is < 10 breaths/min.  We will also make note of both 
the type and amount of treatment given for these opioid-related side-effects.  In addition, 
we will collect data on the incidence and severity of ropivacaine systemic side effects – 
tinnitus, perioral numbness, metallic taste, and seizures – and will characterize both the 
type and amount of treatment required. 
 
Breast-feeding success and safety will be monitored during this study.  Breast feeding 
success will be measured using LATCH Scores (25) obtained in the PACU, and once per 
shift on the mother-baby unit for 72 hours.  These will be assigned by either the labor and 
delivery nurses or by the nurses in the post-partum ward.  We will also assess the 
proportion of mothers breast-feeding their infants at 24, 48, 72hr, and during their 4-6 
week and 3 month follow-up phone calls.  Maternal plasma and breast milk 
concentrations have been measured during epidural analgesia with ropivacaine (0.125%) 


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for labor, with the breast milk-plasma ratio being somewhere between 0.23 and 0.25 at 
18-24hr (26).  Surprisingly, the literature is silent regarding the concentration of 
ropivacaine in human breast milk after continuous wound infusion.  
 
Both the cesarean section incision and the catheter insertion site will be evaluated.  Any 
catheter- or infiltrate-related issues like wound infection and seroma formation will be 
noted.  Wounds will be assessed for infection or dehiscence at 24, 48, and 72hr. At the 4-
6 week and 3-month follow-up phone calls the patient will be asked about the presence of 
wound dysesthesia (numbness, tingling, burning, pricking, allodynia, or hyperesthesia).  
The patient will also be asked about the occurrence of infection, dehiscence, and keloid 
formation at this time. 
  
Patient satisfaction will be monitored with a satisfaction scores (100 mm scale) at 72hr.  
A cost analysis will occur for the inpatient stay.  Some of the costs we will look at are 
include those for preparation of the drugs and devices, along with monitoring/supervision 
costs based on nursing and physician interventions, as well as cost of days spent in the 
hospital (27). 
 
Study Design and Methodology 
After informed consent has been obtained, all study participants will receive spinal 
anesthetics based on their height to provide anesthesia for their cesarean sections as per 
our usual clinical practice.  Patients ≥ 64 inches will get spinal anesthetics containing 
12mg 0.75% bupivacaine (1.6ml), 10mcg fentanyl (0.2ml), and 200mcg PFM (0.4ml) for 
a total volume of 2.2ml.  Patients ≤ 63 inches will receive the same spinal anesthetic as 
those ≥ 64 inches except that the dose of 0.75% bupivacaine be reduced to 10.5mg 
(1.4ml) resulting in a total volume of 2.0ml.  The PFM dose of 200mcg was chosen as it 
is the commonly used clinical dose (28).  These spinal anesthetics reliably provide 
anesthesia for 1.5-2hr in each patient population.  The patients will have been randomly 
assigned to one of three study arms prior to initiation of the anesthetic using a computer 
generated random number list.  The randomization list has already been created using a 
randomization free-ware packet from the internet (Random Number Generator, 


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stattrek.com), and is on file at the research pharmacy.  The code is not known by any of 
the investigators.  The arms are as follows: 1) a bolus dose of 8ml of normal saline 
followed by an infusion of 8ml/hr of normal saline using an On-Q® elastomeric pump, 2) 
a bolus dose of 8ml of 0.1% ropivacaine followed by an infusion of 8ml/hr of 0.1% 
ropivacaine using an On-Q® elastomeric pump, or 3) a bolus dose of 8ml of 0.2% 
ropivacaine followed by an infusion 8 ml/hr of 0.2% ropivacaine using an On-Q® 
elastomeric pump.  The pump will be filled to its maximum capacity of 550 ml and will 
infuse    until the total volume is delivered. The patients will undergo their cesarean 
sections in the usual fashion through uterine closure.  The peritoneum may or may not be 
closed and the rectus abdominis muscles may or may not be approximated as per the 
usual practice of the attending obstetrician.  The obstetrician will insert a 20G guide 
needle/introducer assembly through the skin, subcutaneous tissue and rectus fascia about 
3cm above and just lateral to the incision. When the introducer is fixed in the desired 
location, the guide needle is removed, and a multiport, silver-impregnated catheter (6-
10cm) is placed above the rectus muscle parallel to the fascial incision.  The fascia is then 
closed above the rectus muscles, and the rest of the closure occurs as per the usual 
practice of the surgeon.  After closure is complete, one to two drops of a topical skin 
adhesive (2-octyl cyanoacrylate or SurgiSeal®) will be placed on the skin at the exit site 
of the multiport catheter and the catheter will be further secured with adhesive surgical 
strips. The exit site, along with a small length of catheter will then be covered with a 
sterile bio-occlusive dressing.   The hospital pharmacy will have delivered a 10 ml 
syringe filled to 8ml with the bolus test solution, along with an On-Q® elastomeric pump 
loaded with the same solution to the operating room prior to, or during, the cesarean 
section.  The test solutions are all water-white in color, and will have no discerning 
markings to indicate whether it is saline or one of the two concentrations of ropivacaine.  
The preparing pharmacist will be the only person not blinded to the study.  At the 
termination of the surgical procedure, the obstetrician will administer the 8ml bolus of 
test solution via the catheter using the 10ml preloaded syringe, followed by attaching and 
activating the elastomeric pump which will be pre-set to deliver 8ml/hr of test solution. 
 


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Ketorolac (30 mg IV) will always be given at the first request for additional pain 
medicine after leaving the operating room. Thereafter, the study patients will receive 
30mg ketorolac q6hr prn pain for 24hr if their pain score is > 3.  If their pain score 
remains > 3 twenty minutes after ketorolac administration, they can receive morphine 
1mg IV q1hr until their pain score is ≤ 3.  After 24hr, and through discharge, the study 
patients will receive1-2 tablets PO oxycodone-acetaminophen (5/325) q6hr for post-
operative pain for pain scores > 3.  Additional breakthrough pain still present 30 min after 
oxycodone-acetaminophen dosing will be treated with ibuprofen 600 mg PO q6hr.  
Again, if the pain score remains > 3 thirty min after ibuprofen dosing, IV morphine (1-2 
mg q1hr) will be administered until the pain score is ≤ 3. 
 
Each patient that ends up participating in our study will have a folder (see attached Data 
Collection Instrument) associated with her name.  This folder will include all of the 
VAPS scoring sheets and the McGill pain scoring sheets obtained at the different time 
periods.  It will also contain summary sheets for data abstracted from the medical, 
nursing, and pharmacy records such as uterine closure, LATCH scores, time to first 
rescue medication, time to first opioid use, and total opioid and NSAID use, etc.  These 
folders will be stored in locked file cabinets in the main office of the EUHM Department 
of Anesthesiology where other sensitive patient information is kept securely.  Data, 
without personal identifiers will be entered into Excel spread sheets and kept on the 
Emory Healthcare virtual desktop for further analysis.   
 
Participant Selection 
The study will take place at Emory University Hospital Midtown (EUHM), which cares 
for a mixed community- and university-based obstetric practice. Parturients will be 
recruited from the patient pools of both private and Emory physicians, and enrolled after 
appropriate consent has been obtained.  The inclusion criteria for the study includes all 
ASA class I-III parturients at least 34 weeks pregnant, that are 18 years or older, have 
never had a cesarean section, have had one or two prior cesarean sections, and are 
undergoing scheduled or unscheduled non-emergent cesarean sections with spinal 
anesthesia.  Exclusion criteria includes parturients who have allergies to morphine, 


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ketorolac, or amide local anesthetics; pregnancies less than 34wks gestational age; 
significant maternal cardiac, liver, or renal disease; maternal history of narcotic abuse or 
dependency; presence of a pre-operative fever (> 100.4 °F); emergent cesarean sections 
with or with-out general anesthesia; and patients in whom valid consent is questionable 
(non-English speakers or mentally-impaired individuals).  Study patients have the option 
of withdrawing from the study at any point, as the On-Q® pump infusion can be simply 
discontinued and the catheter removed.  At such time the patient would revert to our 
standard pain management protocol. 
 
Statistical Analysis 
Based on a preliminary sample size calculation using an α risk of 0.05, a β risk of 0.2, 
and an effect size involving a 40% reduction in pain scores, we estimate that 20 patients 
are needed in each arm of the study.  Data normality will be tested using the 
Kolmorgorov-Smirnov test.  Normally distributed data will be presented as means ± SD, 
whereas non-normally distributed data will be expressed as medians with interquartile 
ranges.  Categorical data will be reported as frequencies.  VAS scores will be analyzed 
using two-way ANOVA for repeated measures.  Non-normal data will be analyzed using 
the Friedman test.  Categorical data will be analyzed using the Χ2 test.  Multiple 
comparisons will use a Bonferroni correction.  Differences will be considered statistically 
significant at a P<0.05. 
 
Patient Safety and Potential Benefits 
There is no added discomfort of having the On-Q® device placed, as it is inserted during 
surgery under spinal anesthesia.  There is also minimal to no discomfort upon removal of 
the catheter which is simply pulled out when the infusion is completed, if the patient 
withdraws from the study, or if the patient is discharged from the hospital.  An adhesive 
bandage is placed over the insertion site and left in place for 12-24hr after catheter 
removal.  Control patients who end up getting the normal saline infusions will be receive 
the current standard of care for pain relief at our institution (PFM and adjunctive 
medications). 
 


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All medications utilized in this study are currently employed on the labor and delivery 
and postpartum wards at EUHM.  The spinal anesthetics described earlier constitute our 
standard of care for the provision of intraoperative anesthesia for cesarean section.  The 
treatment of post-operative pain with IV ketorolac, and further with IV morphine for 
unremitting pain, represents our usual standard during the first 24hrs after cesarean 
delivery.  Pain relief on the second and third postsurgical days is commonly provided by 
our obstetricians using oxycodone-acetaminophen (5/325) and ibuprofen, with IV 
morphine being occasionally used in refractory cases. 
 
Several of our obstetricians routinely place the OnQ® pain system post-cesarean delivery, 
and administer 0.5% bupivacaine at 5 ml/hr through a subfascial catheter.  In this study, 
we propose changing the LA infused from 0.5% bupivacaine at 5 ml/hr to either 0.1% or 
0.2% ropivacaine, at 8 ml/hr.  This change should actually enhance patient safety as not 
only does this represent a reduction in LA dose/hr (from 25mg/hr with bupivacaine to 
either 8 or 16mg/hr with ropivacaine, respectively), but also constitutes a change from a 
relatively cardiotoxic LA (bupivacaine) to one considered significantly less so 
(ropivacaine) (29).  Ropivacaine is widely used in obstetric anesthesia for labor epidurals, 
and in fact, 0.2% ropivacaine at 8-12ml/hr forms our standard labor epidural infusion at 
EUHM.  Finally, it should be noted that the highest daily ropivacaine dose utilized (day 1 
which includes the hourly infusion plus an 8ml bolus (which works out to either 200mg 
or 400 mg for the two infusions) in this study is well below the maximum recommended 
daily dose of 800mg (30).   
 
Additionally, patients in the study will be immediately unblinded via phone call to the 
pharmacy in the three following situations: a) if they experience any 2 of 4 minor LA 
toxicities (perioral numbness, metallic taste in mouth, tinnitus, or light-headedness); b) 
any signs of severe systemic toxicity (seizures, arrhythmia, obtundation, cardiac arrest); 
or allergic reactions which appear by timing as due to LA administration (hives, 
angioedema, anaphylaxis).  Minor toxicities will be treated by simply stopping the 
infusion and watching the patient for 6hr (approximately 3 half-times in circulation - 
product insert).  Major toxicities will be treated by stopping the infusions and providing 


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appropriate supportive or resuscitative care.  It is felt that major toxicity is very unlikely 
considering the drug utilized, the drug dosage, the use of a clinically-approved delivery 
device, and the restrictions on recruiting patients with LA allergies. 
 
The OnQ® elastomeric pump and silver-impregnated catheter are FDA-approved devices 
for the treatment of post-surgical pain after all types of surgery including cesarean 
section.  Theoretically, it could be argued that there is a small risk of skin or wound 
infection due to the presence of a tunneled percutaneous catheter for three days.  This risk 
will be mitigated in three ways.  First, sterile technique will be used throughout the 
procedure and the patients will be given antibiotic prophylaxis before the cesarean 
section.  Second, the silver-impregnated catheter has inherent antimicrobial properties 
which prevent formation of a bacterial microfilm with subsequent catheter colonization; 
and also elutes silver directly into the implantation site where it may have direct 
antimicrobial activity (31).  Finally, LAs themselves have intrinsic bacteriostatic and/or 
bactericidal properties against a wide range of pathogenic bacteria, and thereby 
continuous wound infusion with these agents might create an unfavorable milieu for 
infection (32). 
 
There are possible benefits of being enrolled in the study.  If our hypothesis is correct, 
both acute postoperative pain (at rest and with movement) and chronic postsurgical pain 
will be reduced in patients that receive the ropivacaine infusions.  These patients would 
likely experience a reduction in the use of opioids and other adjunctive pain medicines.  
This could lead to a reduction in the incidence and treatment of medication-related side-
effects.  The reduction in pain, as well as a decrease in medication use, might result in 
more successful and safer breastfeeding.  Pain and side-effect reduction might also lead 
to the need for fewer nursing interventions, along with a potential decrease in the length 
of stay after a cesarean section.  If these goals are met, this truly multimodal technique of 
postoperative pain control might also decrease the cost of these patients’ hospitalization. 
 
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