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Enhanced recovery pathway for multimodal analgesia in elective cesarean surgery: literature review with practice recommendations

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Enhanced recovery pathway for multimodal analgesia in elective cesarean surgery: literature review with practice recommendations

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Content Running Head: ENHANCED RECOVERY PATHWAY

ENHANCED RECOVERY PATHWAY FOR MULTIMODAL ANALGESIA IN ELECTIVE
CESAREAN SURGERY: LITERATURE REVIEW WITH PRACTICE
RECOMMENDATIONS

by

Jacqueline Lumalu

A Doctoral Capstone Presented to the
FACULTY OF THE USC KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the Requirements for the Degree
DOCTOR OF NURSE ANESTHESIA PRACTICE

May 2020

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The following manuscript was contributed to in equal parts by Kieran Shamash, Miranda Chih,
and Jacqueline Lumalu

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Dedication
Kieran Shamash dedicates this project to her husband David, children Axel and Aviva, and to all
the strong mothers in her life, especially her mother, Jean.

Miranda Chih dedicates this project to her family.

Jacqueline Lumalu dedicates this project to her husband William and her parents.

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Acknowledgements
The authors wish to thank the following individuals for their assistance with this project:
Michele Gold, PhD, CRNA; Charles Griffis, PhD, CRNA; Elizabeth Bamgbose, PhD, CRNA;
Monique Jabbour, DNAP, CRNA; Mark Zakowski, MD; Amanda Kleiman, MD;
and Erica McCall, MPH, MS, CRNA

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Table of Contents

Dedication……………………………………………………………………………………….iii
Acknowledgements……………………………………………………………………………….iv
List of Figures………….................................................................................................................vi
List of Tables………………………………………………………………………………….…vii
Abstract.........................................................................................................................................viii
Chapter 1: Introduction................................................................................................................... 1
Definition of Clinical Problem............................................................................................ 4
Cesarean pain and maternal outcomes.................................................................... 6
Background and Significance............................................................................................. 8
Chapter 2: Methods....................................................................................................................... 10
Chapter 3: Literature Review........................................................................................................ 12
Enhanced Recovery Pathways in Cesarean Surgery......................................................... 12
Analgesia in cesarean surgery........................................................................................... 15
Intrathecal morphine with oral acetaminophen..................................................... 15
Intrathecal opioids and maternal outcomes........................................................... 16
Intrathecal morphine and continuous wound infiltration with local anesthetic.... 17
Quadratus lumborum (QL) type I block............................................................... 20
Transversus abdominis plane (TAP) block versus spinal morphine..................... 21
Chapter 4: Results and Recommendations for Practice................................................................ 24
Neuraxial Route Recommendations................................................................................. 24
Non-neuraxial Recommendations..................................................................................... 25
Chapter 5: Conclusion................................................................................................................... 27
References..................................................................................................................................... 29
Appendix ...................................................................................................................................... 36

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List of Figures
Figure 1.......................................................................................................................................... 2
Figure 2.......................................................................................................................................... 3
Figure 3.......................................................................................................................................... 5
Figure 4......................................................................................................................................... 10
Figure 5......................................................................................................................................... 11
Figure 6......................................................................................................................................... 23

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List of Tables
Table 1.......................................................................................................................................... 19

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Abstract
Women undergoing cesarean surgery experience postoperative pain that can negatively
impact mobility, breastfeeding, and maternal caring for the neonate. This extensive literature
review identifies key components of effective intra- and postoperative multimodal pain
management as part of an enhanced recovery pathway that improves post-cesarean maternal
outcomes such as pain control. An extensive literature search was performed using the databases
PubMed, EMBASE, Web of Science, and Scopus. The primary search terms were “enhanced
recovery” and “cesarean surgery”. Nine articles were reviewed and two included for final
analysis. To focus the literature review on the multimodal analgesia component of enhanced
recovery, a separate search for “multimodal analgesia” and “cesarean” was performed. A total of
six articles were included in the final multimodal analgesia component of this analysis. The two
articles included that addressed enhanced recovery pathways (ERPs) and cesarean surgery
demonstrated improved maternal satisfaction, earlier mobility, and shorter length of stay. The
six articles addressing best multimodal strategies for intra- and postoperative pain control for
cesarean surgery demonstrated improved maternal pain control with the use of intrathecal
opioids for intraoperative subarachnoid blocks. Studies that investigated adjunct modalities
found statistically significant opioid-sparing effects from the use of local anesthetic wound
infiltration catheters and quadratus lumborum (QL) regional nerve blocks. Use of long-acting
opioids in spinal anesthesia for women undergoing elective cesarean surgery is recommended,
while continued research is needed for adjunct modalities. Future research should also
standardize cesarean ERPs and consider measurement of targeted outcomes such as
breastfeeding and bonding.
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Chapter 1: Introduction

The development of an enhanced recovery pathway (ERP) for women undergoing
elective cesarean surgery may result in improved maternal-neonatal outcomes such as better pain
control, earlier mobilization, improved maternal-infant bonding, and higher rates of
breastfeeding. Along with other components, this pathway incorporates multimodal analgesia
approaches to improve these postoperative patient outcomes. Though elective cesarean surgical
procedures are common in the United States, women undergoing cesarean surgery experience
increased risk of complications, increased length of hospital stay, and higher costs (DeClercq,
2007; Hobson, 2005; Main, 2012). Cesarean surgery may be associated with postoperative pain
that can negatively impact mobility, breastfeeding, and maternal caring for the neonate
(Karlstrom, Engstrom-Olofsson, Norbergh, Sjoling, & Hildingsson, 2007; Woods, et al., 2012).
Severe postpartum pain is associated with a higher risk of chronic pain lasting more than two
months, and postpartum depression (Eisenach et al., 2008; Landau, Bollag, & Ortner, 2013).
Currently, practice in the US varies widely in the treatment of postpartum pain and may lead to
poor outcomes for women undergoing cesarean surgery (Khozhimannil et al., 2013).
Multimodal analgesic regimens, as part of an enhanced recovery pathway (ERP), may offer a
strategy to address poor pain-related outcomes for women undergoing cesarean surgery.
In the past two decades, enhanced recovery after surgery (ERAS) has become an
important intervention process to improve patient experiences in the perioperative period. ERAS
refers to a collection of evidence-based, multimodal interventions in the perioperative period to
return surgical patients to their baseline function safely and efficiently (Erikson, Miller, Mythen,
& Gan, 2017). The goals of ERAS for certain surgical populations include decreased stress
response, earlier discharge, and improved postoperative performance (Erikson et al., 2017). An
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example of an ERAS pathway can be seen in Figure 1. ERAS guidelines, published by the
ERAS Society, include perioperative evidenced-based recommendations for preoperative fasting,
multimodal anesthetic and analgesic regimens, and postoperative gut mobilization (Varadhan et
al., 2010). One of the most important components of ERAS is the emphasis on effective pain
control via multimodal approaches (Ericksen et al., 2017). Researchers have demonstrated
benefits for both patients and health care centers in a growing number of surgical populations. In
a meta-analysis of six randomized controlled trials (RCTs) of ERAS protocols in the open
colorectal surgical population, it was found patients in an ERAS program experienced decreased
hospital length of stay and a 50% reduction in complication rates (Varadhan et al., 2010). Two
recent studies by Chapman et al. (2016) and Kalogera et al. (2013) showed that ERAS programs
significantly decreased hospital length of stay and improved patient pain control in the
gynecologic surgical population. ERAS protocols provide a conceptual framework to guide the
anesthetic management of patients undergoing surgery by identifying the most effective
treatment modalities to improve outcomes.

Figure 1. Components of a general enhanced recovery pathway. (AANA, n. d.).
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One population without ERAS guidelines is women undergoing cesarean surgery.
Protocols related to ERAS have begun to be studied in this population and are referred to as
ERPs. ERPs for cesarean surgical patients are derived from the established ERAS techniques
and continue to be developed (Wrench, Allison, Galimberti, Radley, & Wilson, 2015). Women
undergoing cesarean surgery may benefit from interventions aimed at returning them to baseline
function more efficiently and effectively, through improved pain control with the added
advantage for improved care for their newborn. This population is unique in that the patient
must not only recover from surgery but also immediately begin caring for and bonding with their
neonate (Gamez & Habib, 2018; Laronche, Popescu, & Benhamou, 2017). ERPs for women
undergoing cesarean surgery provide a framework for streamlining patient care and improving
pain-control-related outcomes (Figure 2).

Figure 2. Enhanced recovery pathway for cesarean surgery. (Laronche, et al., 2016; Ohara et al.,
2016).

The aim of this capstone project is to identify key components of effective intra- and
postoperative multimodal pain management as part of an ERP that improves post-cesarean pain
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control and mobility and may increase the likelihood for improved infant bonding and
breastfeeding for women undergoing elective cesarean surgery. This extensive literature review
concludes with recommendations for anesthesia practice. These recommendations are made
based upon current evidence supporting application of ERPs to elective cesarean surgeries and
multimodal pain management in this population.
Definition of Clinical Problem
Women who have undergone cesarean surgery report incisional pain can interfere with
activities of daily living in the first two months postpartum (Declercq, Sakala, Corry,
Applebaum, & Herrlich, 2013). Cesarean surgery is associated with high levels of postpartum
pain, difficulty breastfeeding, and difficulty caring for the neonate (Chaplin, Kelly, & Kildea,
2016; Chin, Vincent, & Wilkie, 2014; Karlstrom et al., 2007). These outcomes are unique to this
population when compared with other surgical populations. The mother-infant dyad must be
considered in all aspects of peripartum care, including anesthetic and analgesic management
(Deniau et al., 2016). Fahey and Shenassa (2013) outline the needs and considerations of women
during the peripartum period, which include maternal role attainment, and care of self, infant,
and other family members. In their health promotion model, Fahey and Shenassa (2013) present
these considerations as intertwined with physical recovery. This conceptual framework may
direct improvements in anesthetic and analgesic management in this population in order to better
facilitate physical recovery.
The maternal-infant bond has been defined as an essential psychological process whereby
the mother develops emotional and loving feelings toward the infant, which then leads to a
secure attachment between the two (Ohara et al., 2016). The mother-infant bond is an essential
component of the postpartum recovery process and is directly influenced by the amount and
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quality of physical touch between the mother and the neonate, something often limited during
cesarean surgery and recovery (Laronche, Popescu, & Benhamou, 2017). An ERP may offer
anesthetic and perioperative approaches to promote efficient return to baseline function for the
parturient, and therefore better bonding and breastfeeding outcomes for mothers (Laronche et al.
2017).
Much of the literature addressing multimodal analgesia and cesarean surgery does not
carefully consider these unique outcomes for the cesarean population, often focusing solely on
pain control. Effective multimodal analgesia, within an ERP framework, can provide an avenue
to not only improve maternal pain relief, but also improve mothers’ mobility and ability to care
for their neonates (Laronche et al, 2017). The Perinatal Maternal Health Promotion Model
(Figure 5) outlines some of the unique needs of the patient as a new mother, including her
recovery, ability to provide self-care, and her ability to form an attachment to and care for her
infant (Fahey & Shenassa, 2013). As presented in this model, these needs are closely related to
each other, making the physical recovery a new mother of paramount importance.

Adapted with permission from Fahey & Shenassa (2013)

Figure 3. The Perinatal Maternal Health Promotion Model
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The model consists of intersecting spheres representing aspects of perinatal and maternal
health. The innermost three spheres address physical recovery, maternal role and care of the
infant, the most important components of the postpartum period. Surrounding these core
components is a sphere that addresses skills to help the mother achieve postpartum goals, which
includes self-efficacy and realistic expectations. The outermost circle represents external factors
such as health care provided to the mother. For successful infant attachment and maternal role
attainment to occur, the ability of mothers to meet their basic needs and successfully transition
into their new role is essential (Fahey & Shenassa, 2013). Poorly controlled pain may negatively
impact a new mother’s ability to achieve these core components of a successful postpartum
period (Fahey & Shenassa, 2013). An ERP may offer an external structure whereby the mother
can achieve both adequate pain control and a faster return to baseline function, enabling her to
meet the basic goals of physical recovery and caring for herself and her neonate.
Cesarean pain and maternal outcomes. The experience and dimensions of post-
cesarean pain in women with an uncomplicated singleton pregnancy undergoing elective
cesarean surgery were explored by Chin, Vincent, and Wilkie (2014). In this study, a
longitudinal mixed methodology was used to provide an understanding of the post-partum pain
experienced in these patients (n = 30). A computerized version of the McGill Pain Questionnaire
(MPQ) was used to assess the experience and quality of post-cesarean pain at two time periods:
the first, between 24-48 hours postoperative and the second, at six weeks postoperative. The
study analyzed descriptors of both nociceptive and neuropathic pain. Nociceptive pain stems
from damage to non-neural tissue and related activation of nociceptors, and neuropathic pain
arises from damage to the somatosensory nervous system (Chin et al., 2014). Findings indicated
that post-cesarean pain for these patients was multidimensional and included elements of both
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nociceptive and neuropathic pain, which are often exacerbated by activities related to infant care
(Chin et al., 2014). These results add support for more comprehensive multimodal pain control
regimens in the immediate postoperative period.
In a study about the experience of women post cesarean surgery and impact on
breastfeeding, Chaplin, Kelly & Kildea (2016), used an interpretive phenomenologic
methodology to describe the lived experience of the women and their personal perioperative
cesarean experiences. The study recorded a series of interviews with each participant (n = 8)
individually over the three months following cesarean surgery. A chart review was performed to
obtain specific information regarding labor, birth, and postnatal care. Themes were extrapolated
from the participants’ stories via a combination of computer data analysis and Van Manen’s
circular process of hermeneutical writing. This unique type of data analysis allows for
researchers to combine their knowledge and the qualitative information contained in patient
stories in a structured manner, allowing common themes and subthemes to emerge (Chaplin, et
al., 2016). Participants described nausea, drowsiness, and difficulty moving postoperatively as
having a negative impact on their ability to reach for, care for, and breastfeed their neonates.
The infants’ sleepy behavior further impeded early initiation of breastfeeding as detailed by the
study participants. Although this is a small sample and not generalizable to the larger
population, the study provides an important consideration for potential areas of improvement in
postoperative care.
Post-cesarean pain and its perceived effect on the mother’s ability to breastfeed, bond
with, and care for her neonate was assessed by Karlstrom, Engstrom-Olofsson, Nystedt, Sjoling,
& Hildingson, (2007). An anonymous questionnaire (n = 60) was distributed to women
undergoing cesarean birth to healthy neonates postoperatively and returned on postoperative day
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four or prior to discharge. Both women undergoing elective and emergency cesarean surgery
participated in the study. Pain scores were recorded retrospectively by the mothers utilizing a
visual analog scale (VAS). The results of this study indicated 62% of respondents felt their
ability to care for their newborn was greatly impacted by their postoperative pain and this effect
was strongest in the first 24 hours after surgery. Almost one-third of respondents indicated their
ability to breastfeed in the first 24 hours after surgery was negatively affected by their
postoperative pain. In addition, all the women who had problems with breastfeeding and infant
care had VAS scores of 4 or higher 2 days after surgery (Karlstrom et al., 2007). The findings in
this study also point to a possible relationship between postpartum pain and its negative impact
on the unique needs of the mother in the postpartum period, particularly the ability to breastfeed
and care for the neonate. A multimodal analgesic regimen to enhance mobility while managing
postoperative pain may decrease the negative sequelae described by the parturients and also
facilitate stronger maternal-infant bonding in the initial postoperative period.
Background and Significance
Over 1.2 million cesarean surgeries were performed in the US in 2015, making this
procedure the most common major operating room procedure in the United States (Martin et al.,
2017; Pfunter, Wier, & Stocks, 2013). There is wide variation in obstetric cesarean practice
throughout the country, and it is suggested that streamlined quality improvement aimed at
patient-centered care may help improve practice in this population (Kozhimannil et al., 2013).
Pain control and mobility remain a significant issue in postoperative cesarean care, and these
factors directly affect the patient’s ability to care for their neonate (Eisenach et al., 2008; Landau,
Bollag, & Ortner, 2013; Lavand’homme, 2006). It has also been found that the severity of acute
immediate postoperative pain is correlated with higher risk of symptoms of postpartum
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depression (Eisenach et al., 2008). Pain control, postoperative recovery, and patient satisfaction
are of great importance due to the unique concerns regarding mother-infant bonding in this
population (Bonnal et al., 2016; Laronche, Popescu, & Benhamou, 2016).
A potential solution to these issues may lie in an ERP with effective analgesia for patients
undergoing cesarean surgery. Effective multimodal analgesia is a key component of enhanced
recovery for surgical patients (Erikson et al., 2017). Enhanced recovery allows for a cohesive
patient-centered plan of care, including effective multimodal pain control balanced with early
mobility (American Association of Nurse Anesthetists [AANA], n. d.). The AANA (n. d.) has
published guidelines for cesarean surgery that advocate for the use of enhanced recovery in the
obstetric population, since its application would help to streamline the anesthesia and analgesic
protocols to improve a patient’s mobility and ability to breastfeed and care for her neonate.
The first known standardized ERP for the obstetric population was recently published,
reflecting principles found in this review (Caughey, et al., 2018). Though published too late to
be included in the literature review in this paper, multiple institutions have been evaluating the
components found in this standardized ERP focused on care of the cesarean population to see if
these interventions result in improved pain control, length of stay, bonding, breastfeeding, and
maternal satisfaction (Bonnal et al., 2016; Deniau et al., 2016; Jarraya et al., 2016; Laronche,
Popescu, & Benhamou, 2017; Wrench et al., 2015). Translation of the existing evidence into
recommendations for the anesthetic management for cesarean surgery may positively impact
maternal and neonatal outcomes, including maternal pain, mobility, ability to hold and care for
neonate, and bonding.

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Chapter 2: Methods

An extensive literature search was performed using the following databases: PubMed,
EMBASE, Web of Science, and Scopus. The first search focused on examining the application
of ERPs to the elective cesarean populations and utilized the keywords “enhanced recovery” and
“cesarean surgery” (Figure 3). Exclusion criteria consisted of studies greater than 10 years old,
studies in a language other than English, and studies on a population other than the elective
cesarean population. The results yielded 26 abstracts, which were reviewed. Seventeen abstracts
were excluded for not containing enhanced recovery or for addressing a population other than
those undergoing elective cesarean. Nine articles were reviewed and two included for final
analysis.

Figure 4. Flowchart for enhanced recovery and cesarean surgery literature review
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In order to focus the literature review on the multimodal analgesia component of
enhanced recovery, a separate search of the databases listed above for “multimodal analgesia”
and “cesarean” was performed. The initial search yielded 180 articles, which were then
evaluated, based on inclusion and exclusion criteria (Figure 4). A total of six articles were
included in the final multimodal analgesia component of this analysis.

Figure 5. Flowchart for Multimodal Analgesia and Cesarean Surgery Literature Review

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Chapter 3: Literature Review
This extensive literature review will encompass a synthesis of existing evidence related to
enhanced recovery and cesarean surgery and a separate synthesis of existing evidence related to
multimodal intra- and postoperative analgesia for this population (Appendix A). The next
section will carefully review the published literature on ERPs and cesarean surgery followed by a
second section aimed at a discussion of specific elements of multimodal analgesia during the
intraoperative and postoperative phases.
Enhanced Recovery Pathways in Cesarean Surgery
Expert editorials address the critical importance ERPs for women undergoing cesarean
surgery to provide safer and more cost-effective care (Abell et al., 2013; Lucas & Gough, 2014).
To date, no published study investigates the effects of ERPs on the U.S. cesarean population.
However, some health care centers are implementing enhanced recovery protocols on their
obstetric units in an attempt to improve outcomes for women undergoing cesarean surgery
(Harbell & Rollins, 2017; Kett, Cherot, & Mauro, 2018; Tiouririne, Kleiman, Powlovich,
Chisholm, & Sarosiek, 2018). Two sites reported decreased opioid consumption and length of
stay after implementation of ERPs for women undergoing elective cesarean (Kett et al., 2018;
Tiouririne et al., 2018). Preliminary, non-peer-reviewed results indicated a statistically
significant improvement in pain scores and decreased opioid usage among mothers participating
in an ERP for elective cesarean at the University of California, San Francisco (Harbell & Rollins,
2017). All sites included multimodal pain management strategies as part of the ERP. While
these abstracts do not currently list specific interventions or statistics, they demonstrate the
increasing popularity of the application of an ERP in the cesarean population in the U.S.
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The published research into possible ERPs for the obstetric population consists of small
studies in areas outside the U.S. One multicenter, prospective comparative study showed
statistically significant improvements in maternal satisfaction, bonding, and breastfeeding when
an ERP was employed for women undergoing elective cesarean surgery (Laronche et al., 2017).
The ERP was employed at two centers and traditional care was continued at one center. The
ERP in this study consisted of earlier mobilization, eating, and drinking (within six to eight hours
postoperatively), earlier urinary catheter withdrawal (within 12 hours postoperatively, shorter
maintenance IV infusion (less than 24 hours postoperatively), and earlier use of oral analgesics
(within 24 hours postoperatively) than the traditional care group. The exact analgesic regimen is
not described. Measurement tools included two questionnaires based on questions from previous
bonding studies: one questionnaire focused on elements of the delivery and postoperative care
and the other focused on the mother’s subjective experience, including pain, emotions,
breastfeeding, and bonding. Mothers filled out the second questionnaire twice, on postoperative
day (POD) one and three. Pain scores upon mobilization on POD three were significantly lower
in the ERP group versus the traditional care group (p < 0.05). Maternal satisfaction, maternal
mood, and frequency of mothers carrying their babies were significantly higher in the ERP group
versus the traditional care group (p < 0.05) (Laronche, et al., 2016). The initial results from this
study show a positive impact of the ERP on mothers’ experiences and maternal perception of
bonding after cesarean surgery. In the Perinatal Maternal Health Promotion Model, a mother’s
physical recovery is directly related to maternal role attainment and infant care (Fahey &
Shenassa, 2013). In this study, it appears the ERP played a role in not only improved pain
control, but improved physical recovery and ability for the mother to care for her neonate.
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Specific details regarding the ERP in this study are not described, however, making replication
and exact recommendations difficult to extrapolate.
In an effort to provide more cost-effective care, Wrench et al. (2015) observed outcomes
during and after the implementation of a full ERP addressing every stage of the perioperative
period. This single-site quality improvement study observed an ERP that was slowly
implemented over two years and compared length of stay before and after implementation. It
included the following components: preoperative patient education, allowance of clear liquids up
to two hours pre-procedure, a high-carbohydrate drink two hours before surgery, intraoperative
warming, intra- and postoperative multimodal analgesia, early oral intake within one hour after
surgery, early mobilization within 24 hours, delayed cord clamping, and early skin to skin
contact. The primary outcomes were length of stay and readmission rates. The authors found
that discharge on POD one increased from 1.6% at baseline to 25.2% after full implementation
of the pathway. Readmissions were similar for this group (4.4%) as for the group discharged on
day 2 (5.6%). Cost savings were not analyzed for this study and the authors did not evaluate
maternal-neonatal bonding outcomes. These two studies show limited but potentially positive
effects an ERP may have on the cesarean population.
Multimodal analgesia was a consideration in all ERPs outlined in this review. As part of
an ERP for women undergoing elective cesarean surgery, analgesia plays an important role in a
mother’s physical recovery. Multimodal analgesia, as an element of an ERP, offers a method of
addressing postoperative pain that decreases overall opioid usage and enhances early mobility by
utilizing a variety of pharmacological techniques. Multimodal analgesia encompasses a variety
of analgesic methods, including pharmacological agents that target a variety of receptors, as well
as regional and neuraxial techniques (Ericksen et al., 2017).
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Analgesia in Cesarean Surgery
Multimodal analgesia is a critical component of any ERP and of added importance with
the post-cesarean population, as it impacts maternal-neonatal outcomes such as breastfeeding and
bonding (Woods et al., 2012). The focus of cesarean analgesia articles reviewed includes
multimodal strategies that involve neuraxial, non-neuraxial regional and local anesthesia
techniques. A table summarizing these articles can be found in Appendix A. The goals of
multimodal analgesia in an ERP include decreased opioid use in the perioperative period and
improved functional recovery, examples of which include the early return of gastrointestinal
transit and early mobilization (Ericksen et al., 2017). The American College of Obstetricians
and Gynecologists (ACOG, 2018) state that breastfeeding mothers need not avoid pain
medication while breastfeeding in the postpartum period. The ACOG committee opinion
advocates for the use of multimodal and opioid-sparing modalities, as excessive or long-term
opioid use may lead to both maternal and neonatal central nervous system depression. The
multimodal analgesic regimen within an enhanced recovery pathway can help facilitate opioid-
sparing pain management goals in the postpartum period. This discussion analyzes a variety of
analgesic interventions in light of these unique considerations.
Intrathecal morphine with oral acetaminophen. A synergistic use of intrathecal
morphine and oral acetaminophen can have positive impact in improving post-cesarean pain.
Booth et al. (2016) examined the multimodal nature of postoperative analgesia for women
undergoing elective cesarean in a prospective, randomized controlled trial (n = 69). This trial
was conducted in women undergoing elective cesarean surgeries who were deemed likely to be
above the 80
th
percentile for evoked pain intensity at 24 hours after surgery via a preoperative
questionnaire (Booth et al., 2016). All patients enrolled in the study received spinal anesthesia
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with 12 mg hyperbaric bupivacaine and 15-20 mcg of fentanyl. The control group received 150
mcg morphine intrathecally and one placebo tablet by mouth (PO), while the intervention group
received 300 mcg morphine intrathecally and one gram of acetaminophen PO every six hours
postoperatively. The primary outcome measure was evoked pain at 24 hours. Pain severity with
movement (evoked pain) was significantly reduced in the morphine/acetaminophen group (p =
0.009) compared with the low-dose morphine and placebo group. The visual analog scale (VAS)
scores on average (both with movement and at rest) during the first 24 hours were also
significantly lower in the morphine/acetaminophen group (p = 0.011 and p = 0.003,
respectively). There were no significant differences in the side effects or postoperative opioid
usage noted between groups. There were no significant differences in presence of persistent pain
or depression, as measured by clinical diagnosis or a score over 12 on the Edinburgh Postpartum
Depression Inventory in the eighth postoperative week. This study demonstrates that the
addition of intrathecal morphine at an appropriate dosage, together with early administration of
acetaminophen may offer benefit over traditional methods in decreasing immediate post-cesarean
pain, especially for women at high risk for postoperative pain (Booth et al., 2016). One
limitation of the study was that the morphine dose was higher in the intervention group than the
control group, making the assessment of the potential impact of acetaminophen difficult to
ascertain. Though the study does not demonstrate long-term effects of improved postoperative
pain control, the significant decrease in pain with movement in the first 24 hours may allow for
mothers to better move and care for their newborns in the immediate postpartum period.
Intrathecal opioids and maternal outcomes. One study examining analgesic regimens
for women undergoing cesarean surgery also measured the maternal-neonatal outcomes of
bonding and ability of mother to care for newborn (Karlstrom, Engstrom-Olofsson, Nystedt,
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Sjolin, & Hildingsson, 2010). This quality improvement study looked at the effect of adding
opioids to spinal anesthesia regimens prior to cesarean surgery at a county hospital, something
not previously done at this institution. Prior to the change in procedure, women undergoing
cesarean surgery in this unit received spinal anesthesia with 1.8 to 2.6 ml 0.5% bupivacaine,
depending on patient height. After the change in practice, women received an additional 5 mcg
fentanyl and 120 mcg morphine in their spinal anesthesia for cesarean surgery. Women
undergoing cesarean surgery at greater than 28 weeks gestation and with a healthy neonate (n =
121) participated in the study in two groups: the first group (n = 60) was in 2005, prior to
practice change, and the second group (n = 61) was in 2007, subsequent to the practice change.
There was a statistically significant decrease in severe pain (described as VAS score of 4-10) on
POD one from the first group (78%) to the second group (44%, p = 0.000). However, there was
no statistically significant difference in pain between the two groups on POD two, highlighting
the importance of continued pain control throughout the perioperative period. In further
investigating the effects of severe pain on breastfeeding and infant care, the study found no
statistically significant differences. However, fewer women in the second group (n = 11; 18%)
stated their ability to breastfeed was seriously impacted by postoperative pain compared with the
first group (n = 18; 30%), which may be indicative of improved pain control contributing to
positive maternal-neonatal outcomes (Karlstrom et al., 2010). This study provides support for
intrathecal opioids as part of a larger multimodal perioperative analgesic regimen for women
undergoing cesarean surgery.
Intrathecal morphine and continuous wound infiltration with local anesthetic.
Continuous wound infiltration with local anesthetic through multi-holed catheters is an effective
mode of delivering analgesia for cesarean patients. Intrathecal opioids and continuous wound
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infiltration with local anesthetic through a multi-holed catheter may offer effective analgesic
strategies, according to one study that compared both interventions to a control group. Lalmand,
Wilwerth, Fils, and Van der Linden (2017) conducted a prospective, randomized-controlled,
double-blind study to assess the duration and effect of intrathecal morphine and continuous
wound infiltration with ropivacaine compared with a control group on postoperative analgesia.
A total of 192 full-term parturients were allocated into one of three groups: a control group, a
morphine group, or a catheter group (Table 1). At the end of surgery, all participants received
multimodal analgesia with 1 g acetaminophen every six hours and 75 mg diclofenac every 12
hours. The primary endpoint measured was analgesia duration from the spinal injection to the
first delivery of morphine via a patient-controlled analgesia (PCA) pump. Secondary outcomes
included cumulative intravenous (IV) morphine consumption within the first 30 postoperative
hours, number of patients who did not receive IV morphine, incidence of adverse effects (nausea,
vomiting, and pruritis), and time to first ambulation.

ENHANCED RECOVERY PATHWAYS

19

Table 1. Intrathecal Morphine and Continuous Wound Infiltration and with Local Anesthetic
(Lalmand et al., 2017).

The duration of postoperative analgesia was longer in the intrathecal morphine group
(380 minutes) and the ropivacaine wound infusion catheter group (351 minutes) compared to the
control group (247 minutes) (p < 0.01). Opioid-sparing benefits were evident in both
intervention groups. The cumulative postoperative morphine consumption was significantly
lower in the intrathecal morphine group (4 mg) and the ropivacaine catheter group (8 mg)
compared with the control group (20.5 mg) (p < 0.01). The intrathecal morphine group had the
least amount of patients that required IV morphine. There were no significant differences among
ENHANCED RECOVERY PATHWAYS

20
all groups in incidence of adverse effects and time to first ambulation. This study shows the
possible benefits of two interventions: infiltration of anesthetics into the layers of a surgical
wound or use of intrathecal morphine. Both can be safe and effective ways to provide analgesia
without side effects that can impede a mother from caring for her baby.
Quadratus lumborum (QL) type I block. An effective multimodal approach to post-
cesarean pain may also include the use of non-neuraxial regional blocks. The QL type I block
may offer relief from visceral and somatic pain after cesarean surgery due to possible spread of
local anesthetic to the thoracic paravertebral space and sympathetic nerves in the thoracolumbar
fascia (Krohg et al., Mieskowski et al.). Two recent studies investigated the use of QL blocks as
adjuncts to neuraxial anesthesia for better postoperative pain control (Krohg et al., 2018;
Mieszkowski et al., 2018). To determine the efficacy of an ultrasound-guided QL block, a
double-blind prospective RCT (n = 40) evaluated postoperative opiate consumption when
ropivacaine versus placebo was administered in the block. (Krohg et al, 2018.). Postoperative
opiate consumption was measured in amount of ketobemidone consumption by participants.
Ketobemidone is an opioid with some N-methyl-D-aspartate antagonism via its metabolite,
norketobemidone (National Center for Biotechnology Information, n. d.). Both groups
underwent the same procedure of bilateral ultrasound-guided QL block placement in the
recovery unit within one hour postoperatively. The intervention group received a total of 1.6
mg/kg of 2 mg/mL ropivacaine solution with a maximum of 120 mg. The placebo group
received 0.4 mL/kg of saline solution to a maximum of 30 mL per side. When compared with
placebo (n = 20), those who received the QL block with ropivacaine (n = 20) had significantly
lower consumption of ketobemidone at 12 hours postoperative (p <0.01; ratio of means = 0.52;
95% confidence interval (CI), 0.35 - 0.79) and lower consumption of ketobemidone at 24 hours
ENHANCED RECOVERY PATHWAYS

21
postoperative (p = 0.4; ratio of means = 0.60; 95% CI, 0.37-0.97). This opioid-sparing effect
underscores the potential benefit of a QL block, as part of a multimodal approach, to manage
postoperative pain for women undergoing elective cesarean surgery.
The opioid-sparing effects of a QL block were demonstrated again in a study by
Mieskowski et al. (2018). This clinical study randomized patients undergoing elective cesarean
into a QL block group (n = 30) and a control group (n = 30). Both groups received spinal
anesthesia with 0.5% hyperbaric bupivacaine (12.5 mg) and fentanyl (20 mcg). After wound
closure, the QL block group received a bilateral ultrasound-guided QL block with 0.375%
ropivacaine (24 mL per side) while the control group did not receive a QL block. All patients
received 1 g intravenous paracetamol every six hours postoperatively and 5 mg morphine
subcutaneously as needed for pain. The primary outcome was postoperative morphine
consumption, which was found to be significantly lower in the QL block group at 0-8 hours (p <
0.05), 12-16 hours (p < 0.05), and 24-36 hours (p < 0.05). Time to first morphine use
postoperatively was statistically significantly longer in the QL block group (618 minutes versus
221 minutes, p = 0.000), indicating improved early postoperative analgesia in the QL block
group. No differences in side effects were noted between groups. One goal of enhanced
recovery is a decrease in overall opioid consumption (Ericksen, 2017). This goal is also
reiterated as part of the ACOG guidelines encouraging a decrease in overall post-cesarean opioid
consumption (ACOG, 2018). As part of a multimodal strategy to address postoperative pain in
patients undergoing cesarean surgery, a QL block may have opioid-sparing effects that result in
improved maternal neonatal outcomes.
Transversus abdominis plane (TAP) block versus spinal morphine. Two different
analgesic interventions as part of an ERP were investigated by Jarraya et al. (2016). This
ENHANCED RECOVERY PATHWAYS

22
double-blind, prospective, randomized controlled trial compared the analgesic effects of a
transversus abdominus plane (TAP) block versus spinal anesthesia with morphine. These
interventions were tested as part of an ERP for all patients that included preoperative ranitidine
and intravenous dexamethasone administration, decreased fasting times (last liquid > 2 hours and
last solid > 6 hours), and administration of a 500 mL lactated ringers bolus prior to spinal
placement. Group 1 received spinal anesthesia with 10 mg bupivacaine, 2.5 mcg sufentanil, and
100 mcg of morphine, followed by a TAP injection with a placebo of 0.9% saline (15 mL per
side) postoperatively. Group 2 received spinal anesthesia with 10 mg bupivacaine, 2.5 mcg
sufentanil, and an unspecified placebo, followed by a TAP block with 0.2% ropivacaine (15 mL
per side) postoperatively. The results showed the patients with the TAP block ambulated
significantly earlier and had significantly shorter time to reestablish gastric transit than the group
treated with intrathecal morphine (p=.001 and p< 0.001, respectively). However, the TAP block
group reported statistically significantly higher pain scores postoperatively (3.3 versus 2.1, p <
0.05). In terms of clinical significance, however, the difference may have been smaller. There
was no difference in IV rescue morphine consumption between the groups in the post-anesthesia
care unit. As oral opioids were not available, patients could receive oral nefopam as needed for
pain postoperatively (Jarraya et al., 2016). Nefopam is a non-opioid, non-steroidal, centrally-
acting analgesic that is utilized as part of a multimodal postoperative pain control regimen
(Girard, Chauvin, & Verleye, 2016). The TAP block group utilized significantly more nefopam
compared with the intrathecal morphine group (16 patients versus none, respectively) (p <
0.001). It is notable that the morphine group experienced significantly higher rates of nausea and
vomiting (p = 0.022) and pruritis (p < 0.001) when compared with the TAP block group. This
study indicates a TAP block could be a helpful adjunct for helping mothers establish earlier
ENHANCED RECOVERY PATHWAYS

23
ambulation and gastric function, both important components of the physical recovery of the
mother. The postoperative pain scores in the TAP block group were approximately one point
higher, however this did not appear to impede movement or return of gastric motility for these
patients. The effectiveness of the ERP cannot be assessed as all patients were enrolled in the
ERP. However, preoperative education of patients receiving the TAP block on expectations of
postoperative pain may be a useful adjunct in future enhanced recovery designs.

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24
Chapter 4: Results and Recommendations for Practice

Based upon this extensive review of the extant literature, recommendations for anesthesia
practice for improved outcomes in post-cesarean care include multimodal pain management
methods and recommendations to establish a more robust body of knowledge related to
postoperative care of this distinct population (Figure 6).

Figure 6. Results summary: Multimodal analgesia for cesarean surgery. Light blue shading
indicates studies that compare spinal anesthesia interventions. Dark blue shading indicates
studies that compare non-neuraxial regional adjunct treatments.

The recommendations for practice include consideration of multimodal analgesic
interventions and associated patient education for the parturient undergoing elective cesarean
surgery. According to Ericksen (2017), patient education is an integral part of the success of a
multimodal analgesia program aimed at faster return to baseline physical function.
Neuraxial Route Recommendations
Long-acting opioids added to spinal anesthesia for women undergoing elective cesarean
surgery will significantly improve postoperative maternal pain relief. This modality was shown
ENHANCED RECOVERY PATHWAYS

25
to decrease pain scores in the immediate postoperative period in four studies (Booth et al. 2016;
Jarraya et al., 2016; Lalmand et al. 2017; Karlstrom et al., 2010). Intrathecal morphine was
associated with a statistically significant decrease in overall opioid consumption in one study
(Lalmand et al., 2017). The dosages of morphine administered in conjunction with local
anesthetics and with or without a short-acting opioid ranged from 100 mcg (Jarraya et al., 2016;
Lalmand et al., 2017) to 300 mcg (Booth et al., 2012). The benefits of long-acting spinal opioids
in this scenario include improved pain control during the immediate postoperative period,
increased sensory block, decreased motor block, decreased dose of local anesthetic, and
decreased overall consumption of opioid-based pain medication (Booth et al., Lalmand et al.,
Karlstrom et al.). Decreased pain in the immediate postoperative period may also help new
mothers better hold and care for their neonate, though pain control must be maintained
throughout the postoperative period after the effects of the intrathecal morphine have diminished
(Karlstrom et al.). It is important to note two of the studies reviewed showed increased risk of
adverse effects such as nausea and pruritis (Booth et al., 2016 & Jarraya et al., 2016), which can
impact a mother’s recovery and ability to care for their neonate. Although these side effects can
be treated with targeted medications, they should be considered when designing a multimodal
analgesic regimen.
Non-neuraxial Route Recommendations
Although it is recommended that all women undergoing elective cesarean surgery
receive neuraxial anesthesia as outlined above, other multimodal analgesic considerations should
include local anesthetic wound infiltration infusions and regional blocks as adjuncts. Lalmand et
al. (2017) reported a subfascial wound infusion of local anesthetic provides superior pain relief
and opioid-sparing effects when compared to placebo. This study, which utilized a multi-
ENHANCED RECOVERY PATHWAYS

26
pronged design to test two interventions, reported that the effects of the infusion were similar
when compared with intrathecal morphine, making it a possible alternative or adjunct when
using intrathecal morphine. The QL block was shown to have both significant analgesic effects
and significant opioid-sparing effects in Krohg et al., 2018 and Mieskowski et al., 2018, and is
recommended as part of a multimodal analgesic strategy for women undergoing elective
cesarean surgery. Placement of this block could occur immediately post-wound closure in the
operating room for postoperative analgesia. While a TAP block may offer narrower coverage, it
is included in these recommendations as it was shown to be associated with earlier ambulation
and earlier return of gastric motility, both key goals of an enhanced recovery pathway (Jarraya et
al., 2016).

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27
Chapter 5: Conclusion

ERPs that include an evidenced-based, multimodal approach to perioperative pain
management may lead to improved outcomes for women undergoing elective cesarean surgery.
As outlined in the Perinatal Maternal Health Promotion Model, physical recovery in the
postpartum period is linked with maternal role attainment and care of the neonate (Fahey &
Shenassa, 2013). The authors define maternal well-being as not just the absence of medical
complications, but the ability to successfully adapt to their new role as a parent through realistic
expectations, self-efficacy, and positive coping strategies (Fahey & Shenassa). Providers play a
role in this conceptual framework by optimizing maternal recovery after cesarean. Adequate
pain control, balanced with improved mobility and faster return to baseline function, may allow
new mothers to achieve this physical recovery and better bond with and care for their neonates.
Multimodal approaches to pain management, as part of an ERP, must focus on adequate pain
control with a faster physical recovery (Ericksen, 2017). The evidence outlined in this paper
underscore the potential benefits of a multimodal approach combining neuraxial and regional
anesthetic and analgesic techniques to better manage pain and pain-related outcomes in this
patient population. The effectiveness of ERPs for the cesarean surgical patient and the focus of
the PMHP framework underscore a critical need for future research into improved care for
women undergoing cesarean surgery. Institutions considering implementation of ERPs for this
population must build pathways around current best practice for this population. Further
considerations unique to women undergoing elective cesarean surgery may include early skin-to-
skin contact, breastfeeding support, and in-home follow-up care (Laronche et al. 2016; Wrench
et al., 2015). Notably, much of the literature on multimodal analgesia for women undergoing
elective cesarean surgery did not address crucial outcomes unique to this population, namely: the
ENHANCED RECOVERY PATHWAYS

28
effect on mother-infant bonding, breastfeeding, and ability of the mother to care for her
neonate. Future research should consider careful measurement of these outcomes in addition to
outcomes related to pain control and physical recovery.

ENHANCED RECOVERY PATHWAYS

29
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Appendix
Reference Study aim Study design Methods Results
Booth et al.,
2016
Multimodal pain
management for
women determined
to be at high risk
for severe post–
cesarean delivery
pain
Prospective,
randomized
controlled trial, n =
69
Control: MS 150mcg
intrathecally + 1 placebo
tablet PO
Intervention group: MS
300 mcg intrathecally +
Acetaminophen 1gm PO
Q6hrs post op
Intervention group
pain score
significantly
reduced
immediately post
op and for the next
24H
Karlstrom
et al., 2010
Evaluate new
anesthetic routine
with spinal opioids
for cesarean
surgery
Descriptive patient
survey, quality
improvement, n =
121
Group 1 received 1.8 –
2.6ml of 0.5%
bupivacaine (depends
on patient's height).
Group 2 had the same
regimen as (1), but
received an additional
Fentanyl 5mcg and MS
120mcg intrathecally

Group 2 had
statistically
significant
decrease in pain
score POD 1 and
less ability impact
on breastfeeding
Lalmand et
al., 2017
To compare
efficacies of
intrathecal
morphine and
continuous wound
infusion with local
anesthetic versus
control group
Prospective,
double-blind,
randomized
controlled trials into
three groups:
control, morphine,
and catheter, n =
192
Control: intrathecal
0.5% bupivacaine
10mg, Sufentanil 5mcg,
NS 0.1ml, and a local
catheter infusion of NS
10ml/hr for 30H) at
surgical site
Morphine: intrathecal
0.5% bupivacaine
10mg, Sufentanil 5mcg,
MS 100mcg, and a local
catheter infusion of NS
10ml/hr for 30H) at
surgical site
Catheter: intrathecal
0.5% bupivacaine
10mg, Sufentanil 5mcg,
NS 0.1ml, and a local
catheter bolus 0.2%
ropivacaine 15ml,
followed by infusion of
10ml/hr for 30H at
surgical site
Morphine and
catheter group had
longer pain relief
and decreased
overall opioid use
ENHANCED RECOVERY PATHWAYS

37
Krohg et
al., 2018
Evaluate post
cesarean analgesic
effect of an US
guided lateral QL
type I block with
ropivacaine when
compared with
placebo

Prospective,
randomized,
placebo-controlled,
double blind trial
with parallel-group
comparison, n = 40
Control: placebo with
NS 0.4ml/kg to a max of
30ml per side
Intervention: 1.6mg/kg
of 2 mg/ml ropivacaine
with a max of 120mg
Intervention group
had significant
lower opioid
consumption at 12
and 24 hours post
op
Mieskowski
et al., 2018
Looking at the
effect of QL block
on postoperative
morphine
consumption
Randomized
controlled trial, n =
60
Control: intrathecal
0.5% bupivacaine
12.5mg, fentanyl
20mcg. And
paracetamol 1gm IV
Q6hrs and MS 5mg SQ
as needed for pain.
QLB group: same
regimen as above +
bilateral US guided QL
block with 0.375%
ropivacaine 24ml per
side. And paracetamol
1gm IV Q6hrs and MS
5mg SQ as needed for
pain
QLB group had
significantly lower
MS consumption at
0-8 hr, 12-16 hr, and
24-36 hr post op

Jarraya et
al., 2016
Demonstrate the
efficacy of one
type of regional
anesthesia (TAP
blocker) over
another
(subarachnoid MS)
Prospective,
double-blind,
randomized
controlled trial, n =
86
Group 1: intrathecal
bupivacaine 10mg,
sufentanil 2.5mcg, MS
100mcg. And a placebo
TAP block 0.9% NS
(15ml per side)
Group 2: intrathecal
bupivacaine 10mg,
sufentanil 2.5mcg, an
unspecified placebo.
And a TAP block with
0.2% ropivacaine (15ml
per side)
Group 2
ambulated
significantly
earlier and had
shorter time to
reestablish gastric
transit

C/S = cesarean section. GI = gastrointestinal. MS = morphine sulfate. PO = orally. Post op = post-
operative. PCOA = patient-controlled oral analgesia. N = sample size (total from all groups). NS =
normal saline. Q6hrs = every 6 hours. QL = quadratus lumborum. SQ = subcutaneous. TAP block =
trans-abdominal plane block. US = ultrasound

Abstract (if available)

Abstract Women undergoing cesarean surgery experience postoperative pain that can negatively impact mobility, breastfeeding, and maternal caring for the neonate. This extensive literature review identifies key components of effective intra- and postoperative multimodal pain management as part of an enhanced recovery pathway that improves post-cesarean maternal outcomes such as pain control. An extensive literature search was performed using the databases PubMed, EMBASE, Web of Science, and Scopus. The primary search terms were “enhanced recovery” and “cesarean surgery”. Nine articles were reviewed and two included for final analysis. To focus the literature review on the multimodal analgesia component of enhanced recovery, a separate search for “multimodal analgesia” and “cesarean” was performed. A total of six articles were included in the final multimodal analgesia component of this analysis. The two articles included that addressed enhanced recovery pathways (ERPs) and cesarean surgery demonstrated improved maternal satisfaction, earlier mobility, and shorter length of stay. The six articles addressing best multimodal strategies for intra- and postoperative pain control for cesarean surgery demonstrated improved maternal pain control with the use of intrathecal opioids for intraoperative subarachnoid blocks. Studies that investigated adjunct modalities found statistically significant opioid-sparing effects from the use of local anesthetic wound infiltration catheters and quadratus lumborum (QL) regional nerve blocks. Use of long-acting opioids in spinal anesthesia for women undergoing elective cesarean surgery is recommended, while continued research is needed for adjunct modalities. Future research should also standardize cesarean ERPs and consider measurement of targeted outcomes such as breastfeeding and bonding.

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Asset Metadata

Creator Lumalu, Jacqueline (author)

Core Title Enhanced recovery pathway for multimodal analgesia in elective cesarean surgery: literature review with practice recommendations

School Keck School of Medicine

Degree Doctor of Nurse Anesthesia Practice

Degree Program Nurse Anesthesiology

Publication Date 04/27/2020

Defense Date 04/26/2020

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag cesarean,cesarean surgery,enhanced recovery,multimodal analgesia,OAI-PMH Harvest

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Gold, Michele (committee chair), Bamgbose, Elizabeth (committee member), Griffis, Charles (committee member)

Creator Email lumalu@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c89-288632

Unique identifier UC11663568

Identifier etd-LumaluJacq-8356.pdf (filename),usctheses-c89-288632 (legacy record id)

Legacy Identifier etd-LumaluJacq-8356.pdf

Dmrecord 288632

Document Type Capstone project

Rights Lumalu, Jacqueline

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA