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Perioperative Pain Management: Miscellaneous (Monitoring, Risk … 105
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https://t.me/med1917
Review of Eras Pain Management
Protocols
George Yacoub, Clara Nemr, and Alaa Abd-Elsayed
Abstract This chapter focuses on summarizing and reviewingrecent literature eval-
uating common pain management strategies employed by Enhanced Recovery After
Surgery (ERAS) protocols. ERAS protocols that promote effective pain manage-
ment focus on the use of multimodal analgesia methods and the implementation of
nerve blocks to reduce pain and opioid consumption in the postoperative setting.
Recent literature review shows particularly strong support for the incorporation of
perioperative administration of Cox-inhibitors in combination with NSAIDs, gluco-
corticoids, and central a-2 agonists, as well as the incorporation of an appropriate
nerveblock. Multimodal analgesia, in addition to administration of a neural block, are
well established methods that serve the goal of reducing postoperative pain, opioid
consumption, and postoperative nausea and vomiting.
Keywords ERAS
· Enhanced recovery after surgery · Pain management ·
Multimodal Analgesia · Neural block
1 Introduction
Enhanced Recovery After Surgery (ERAS) is a patient-focused program that aims
to create specialized surgical protocols with the goal of reducing a patient’s
stress response to surgery, enhancing physiological performance, and expediting
the recovery process. In addition, this multidisciplinary approach works to reduce
G. Yacoub (
B
)
University of Michigan Medical School, Ann Arbor, MI, USA
e-mail: geyacoub@med.umich.edu
C. Nemr
Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA
e-mail: clara.nemr@midwestern.edu
A. Abd-Elsayed
Department of Anesthesia, University of Wisconsin School of Medicine and Public Health,
Madison, WI, USA
e-mail: abdelsayed@wisc.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A. Abd-Elsayed and K. Schroeder (eds.), Perioperative Pain Management,
https://doi.org/10.1007/978-3-031-67648-2_8
107
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108 G. Yacoub et al.
expenses, shorten hospital stays, and mitigate postoperative complications and read-
missions [1]. The ERAS term was coined in 2001 by a group of surgeons led by
Professor Ken Fearon and Professor Olle Ljungqvist to create an evidence-based
multimodal perioperativecare pathway for patients undergoing major surgery. At that
time, physicians were practicing in a manner that failed to reflect published evidence-
based guidance and best practice. Further enhancements occurred following the
implementation of a common patient database and efforts to sustain compliance and
collaboration among medical centers, ultimately improving patient care. In 2010, the
ERAS Society for Perioperative Care was founded and quickly added membership
institutions with multidisciplinary interest in improvements in perioperative patient
care [2]. Basic ERAS protocols include preoperative patient guidance/education,
baseline nutrition assessment and supplementation, elimination/limited fasting in the
perioperative period, avoidance of nasogastric tubes, introduction of carbohydrate
intake up to two hours before surgery, implementation of standardized anesthetic
and pain management procedures (such as epidurals and non-opioid pain relief) and
initiating early patient mobilization [3].
2 Preoperative ERAS Guidelines
ERAS preoperative protocols require patients to receive counseling prior to surgery.
Patient education can be in the form of an in-person class, multimedia content, virtual
reality, or telephone interview. Counseling information is generally provided for the
patient and their support infrastructure and generally includes recovery expectations
and planning, fasting guideline review and timing of carbohydrate drink consump-
tion, prescription fulfillment, provision of contact information for questions that
may arise as surgery approaches, and meeting with an ERAS coordinator, anesthe-
siologist, and surgeon. In addition, targeted history and physical examinations are
performed to ensure optimization and preemptively address any medical titration
or diagnostic requirements. Surgical optimization may include both medical and
psychological interventions that aid in facilitating the recovery profile of patients.
These interventions might include preoperative training relevant to deep breathing
exercises, guided-imagery, and alcohol smoking abstinence for 4 weeks prior to
surgery, anemia therapy, endocrinology consult for diabetics, O-NET screening for
chronic pain patients, and showering with chlorhexidine-based scrub before surgery
[4].
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Review of Eras Pain Management Protocols 109
3 ERAS Guidelines: Multimodal Analgesia
for Perioperative Care
Pain management is a crucial component of ERAS protocols. Specifically, multi-
modal analgesia involves the simultaneous utilization of diverse techniques and
medications to deliver effective pain relief while minimizing reliance on opioids
and reducing opioid-related side effects [4]. Preemptive analgesic approaches have
demonstrated an ability to reduce pain, opioid requirements, inflammation, nausea,
and vomiting [5, 6]. Regional anesthetic techniques linked to perioperative multi-
modal analgesia include intrathecal morphine, thoracic epidural, transversus abdo-
minis plane (TAP) block, and erector spinae plane block (ESPB). Systemic medi-
cations encompass lidocaine, acetaminophen, nonsteroidal anti-inflammatory drugs
(NSAIDs), gabapentinoids, dexamethasone, NMDA receptor antagonists, and central
α-2 agonists [7].
4 Intrathecal Morphine
Intrathecal morphine (ITM) therapypromotes postoperative analgesia through preop-
erative injection of 3–20 mcg/kg of morphine into the cerebrospinal fluid, activating
Mu-opioid receptors in the dorsal horn of the spinal cord [8]. Morphine exhibits
hydrophilic characteristics in comparison to other opioids, resulting in an extended
stay in the cerebrospinal fluid and a prolonged duration of action. Intravenous (IV)
morphine and intrathecal morphine share similar side effects, however smaller doses
of morphine are administered intrathecally [9]. A meta-analysis performed by Musa
et al. evaluates the effects of intrathecal morphine in the pediatric spine surgery
setting, shows that ITM administration reduces total postoperative opioid consump-
tion at 24 and 48 h and increases the time until analgesic rescue. Furthermore, this
study showed no significant increase in incidence of respiratory depression, nausea
and vomiting, or pruritus with ITM use [10]. A similar meta-analysis study was
performed by Wang et al. but focuses on adult spinal surgery and shows that ITM
administration significantly reduces postoperative pain up to 24 h and reduces anal-
gesic consumption. ITM was shown to be associated with increased incidence of
pruritus in this study, but not any other opioid related side effects including respira-
tory depression or nausea and vomiting [11]. A meta-analysis study performed by
Ryu et al. and focuses on the Cesarean setting shows that ITM administration signifi-
cantly reduces postoperative pain and morphine consumption, and is especially more
effectivewhen combined with a ilioinguinal nerve and anterior transversusabdominis
plane block [12]. A randomized control trial by Cheah et al. shows ITM adminis-
tration in the setting of primary total joint arthroplasty reduces postoperative pain,
nausea and vomiting, and improves patient ambulation, but has no significant effect
on total opioid consumption [13].
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110 G. Yacoub et al.
5 Thoracic Epidural Analgesia
Thoracic epidural analgesia provides excellent pain relief in patients undergoing
upper abdominal, colorectal, thoracic, and gynecological surgeries. Thoracic epidural
analgesia blocks pain fibers from the thoracic sympathetic chain ganglia and is admin-
istered through a catheter placed in the epidural space around the spinal cord [14]. The
thoracic epidural space consists of valveless veins connecting to the azygos vein and
the basivertebral plexus. Infusions of local anesthetics or opioids within the epidural
space travel towards the nerve roots and through the intervertebral foramina [15].
Epidural analgesia minimizes opioid requirements, enhances the ability of patients
to breathe and cough, improves respiratory function, facilitates mobility, and reduces
ileus. Common side effects of epidural infusions include hypotension, pruritus, and
urinary retention [7]. Serious side effects including local anesthetic systemic toxi-
city,epidural hematoma, and sustained nerve injury are rare. A systematic review and
meta-analysis were conducted by Daghmouri et al. to evaluate a variety of analgesic
techniques and their impact on postoperative pain in the laparoscopic colonic surgery
setting. Their study shows that postoperative administration of thoracic epidural anal-
gesia is associated with significant postoperative pain reduction at 24 h and faster
bowel function recovery, but a longer length of stay [16]. A similar study by Lin et al.
analyzing the effects of regional pain management techniques in the video-assisted
thoracic surgery setting showed postoperative thoracic epidural analgesia adminis-
tration to be associated with lower resting pain compared to other strategies [ 17]. A
similar meta- analysis study by Luo et al. that evaluates analgesic techniques in breast
and thoracic surgery setting showed that thoracic epidural analgesia is significantly
less effective at reducing pain compared to other thoracic analgesic techniques [18].
A systematic review by Hughes et al. evaluating the effectiveness of thoracic epidural
analgesia in the open abdominal surgery setting shows thoracic epidural analgesia
to be associated with significantly reduced postoperative pain when compared to
patient-controlled systemic opioids postoperatively [19].
6 Transversus Abdominis Plane Block
The transversus abdominis plane (TAP) block is a mode of analgesia that functions
via the administration of local anesthetics between the transversus abdominis and
internal oblique muscles. The block anesthetizes thoracolumbar nerves innervating
the anterior abdominal wall and is used in the setting of a variety of abdominal surg-
eries [20]. When used for postoperative analgesia following abdominal surgery, TAP
blocks have been shown to reduce pain and opioid consumption [21]. Risks asso-
ciated with ultrasound-guided abdominal TAP blocks include visceral organ injury,
bleeding/hematoma formation, local anesthetic systemic toxicity (including ventric-
ular arrhythmia and seizures), and transient femoral nerve palsy [22]. Daghmouri
et al.’s meta-analysis of analgesic techniques in the laparoscopic colonic surgery
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Review of Eras Pain Management Protocols 111
setting showed TAP blocks were associated with lower postoperative pain scores at
24 h, reduced opioid consumption, shorter length of stay, and faster bowel function
recovery [16]. Systematic review and meta-analysis by Brogi et al. evaluating the
effects of TAP block on postoperative pain showed that TAP block is associated
with significant postoperative pain reduction at 6, 12, and 24 h and reduced opioid
consumption in the gynecological, appendectomy, inguinal, bariatric, and urological
surgery setting [21]. However, a similar meta-analysis by Shin et al. focusing on
effects of TAP blocks in the laparoscopic hysterectomy setting showed no signifi-
cant effect of using a TAP block on postoperative pain or opioid consumption [23].
Ding et al.’s meta-analysis study on laparoscopic gynecologic surgeries shows, with
high confidence, that TAP block in combination with adjuvant analgesia signifi-
cantly reduces postoperative pain and opioid consumption at 24 h, especially when
combined with paracetamol and NSAIDs [24]. While classic approaches to TAP
blocks are effective for anesthetizing the lower abdomen, subcostal technique modi-
fications may extend analgesia and prove effective for upper abdominal procedures
as well.
7 Erector Spinae Plane Block
Erector spinae plane block (ESPB) is an additional analgesic modality that has been
reported to provide effectiveanalgesia following a large number of spine, abdominal,
breast, and thoracic surgical procedures. The mechanism of analgesia following
ESPB is, as of yet, a matter of contention but proposed mechanisms include the
blockade of ventral rami of spinal nerves, sympathetic nerve fibers, and intercostal
nerves [25]. The ESPB is performed by injecting a local anesthetic between the
anterior fascia of the erector spinae muscle group and the tip of the transverse process
of either thoracic or lumbar vertebra. ESPB is conceptually both safer and easier to
perform than a paravertebral block and procedural ease is enhanced through an ability
to realize extended dermatomal analgesia following a single injection [26]. A meta-
analysis was performed by Ma et al. to explore the analgesic effect of ESPB in spine
surgery where they found that preoperative ESPB significantly reduces postoperative
pain, opioid consumption, and post operative nausea and vomiting (PONV) [27]. A
similar study by Koo et al. focused on thoracic surgeries also demonstrated that
ESPB use is associated with lower postoperative pain scores [28]. Viderman et al.
in a meta-analysis study focusing on abdominal surgery showed that ESPB use is
associated with lower postoperative opioid consumption and an extended duration
until rescue analgesia is required [29]. A meta-analysis by Cui et al. that included
studies in the breast, orthopedic, thoracoscopic, cholecystectomy, nephrolithotomy,
and cardiac surgery settings demonstrated that ESPB reduced postoperative opioid
consumption at 24 h, PONV, and prolonged the time until rescue analgesia was
required [30].
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112 G. Yacoub et al.
8 Lidocaine
Lidocaine, a local anesthetic, provides multimodal pain control by inhibiting propa-
gation of nerve impulses through blocking voltage-gatedsodium channels in neurons,
preventingdepolarization [7]. Perioperativelidocaine infusions decrease pain, opioid
usage, ileus duration, nausea, and length of stay. In addition, lidocaine infusions miti-
gate the proinflammatory effects caused by surgery by blocking polymorphonuclear
neutrophil priming [31]. The mechanism by which lidocaine inhibits intracellular
G-protein signaling molecules explains the low concentrations of active lidocaine
needed and its prolonged duration of effect at those low concentrations [32]. A
systematic review was performed by Chu et al. in 2020 that evaluated the role
of IV lidocaine in the management of acute and chronic postoperative pain. Chu
et al.’s study demonstrated that dosing guidelines for IV lidocaine are inconsis-
tent. Different studies performed a starting intraoperative IV lidocaine bolus ranging
from 1.5–2 mg/kg. Maintenance doses ranged from 1.5 mg/kg/hr to 3 mg/kg/hr. The
studies also differed on the use of post-operative continuous IV infusions, with some
studies discontinuing IV lidocaine postoperatively and others performing a contin-
uous infusion that ranged in duration between 4–24 h postoperatively. Furthermore,
the efficacy of IV lidocaine in reducing pain and reducing opioid use and side effects
has not been shown to be consistent across the studies. Some studies demonstrate
lidocaine’s efficacy in reducing pain while no significant pain reduction is found in
other studies across a variety of different surgical specialties including laparoscopic
abdominal, open abdominal, breast, and ENT surgeries [33]. A systematic review
by Boswell et al. that focuses on cardiac surgery shows that perioperative IV lido-
caine administration has not been shown to significantly reduce pain or improve
surgical outcomes [34]. Stone et al. published ERAS guidelines for minimally inva-
sive gynecologic surgery that recommends not including IV lidocaine broadly due
to lack of literature evidence supporting its benefits [35]. A randomized clinical trial
by Casas-Arroyave et al. demonstrated intravenous lidocaine demonstrates compa-
rable efficacy to thoracic epidural analgesia in controlling acute postoperative pain
following major abdominal surgery at the 24-h postoperative mark [36].
9 Acetaminophen and NSAIDS
Acetaminophen is a fundamental component of many supplementary analgesic treat-
ment regimens where it has demonstrated an ability to decrease postoperative pain
and opioid requirements. Acetaminophen reduces the release of proinflammatory
and pain-amplifying mediators, leading to antinociceptive effects at peripheral sites
[37]. Oral and IV acetaminophen are both available for administration, however IV
acetaminophen may be more feasible in anesthetized patients or with contraindi-
cations to oral intake and peaks faster in cerebrospinal fluid [38]. NSAIDs mecha-
nism of action is the inhibition of cyclooxygenase (COX) enzymes. COX converts
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Review of Eras Pain Management Protocols 113
arachidonic acid into prostaglandins, prostacyclins, and thromboxanes, with the ther-
apeutic effects arising from the lack of these eicosanoids. Thromboxanes contributeto
platelet adhesion, while prostaglandins induce vasodilation, elevatethe hypothalamic
temperature set-point, and participate in anti-nociception [39]. The combination of
NSAIDs and acetaminophen results in a much more significant reduction of postop-
erative pain and opioid consumption than acetaminophen alone [37]. Meta-analysis
of a variety of studies in different fields including thoracic, orthopedic, gynecolog-
ical, obstetric, and general surgery demonstrated that postoperative co-administration
of paracetamol, NSAIDs, and COX-2 inhibitors with patient-controlled analgesia
morphine resulted in a significant reduction of morphine administration in the first
24 h post-surgery. Co-administration of NSAIDs significantly reduced morphine
administration and significantly reduced the risk of PONV [38]. A meta-analysis by
Heybati et al. evaluating the effects of non-opioid analgesic administration perioper-
ativelyin the adult cardiac surgery s etting demonstrated, with moderate to high confi-
dence, that acetaminophen use significantly reduces postoperative pain at 24 h [40]. A
meta-analysis study by Ding et al. evaluated nonopioid analgesics and regional tech-
niques for perioperative pain management in laparoscopic gynecological surgery.
With a high confidence level, they found that NSAID administration, with and
without acetaminophen, significantly reduces total opioid consumption at 24 h, and
co-administration with acetaminophen and a topical analgesic or a peripheral nerve
block reduces pain at 24 h [24]. Use of prophylactic acetaminophen combined with
NSAIDs is shown to reduce morphine intake, reduce post-operative pain, and signif-
icantly improve patient ambulation in total knee arthroplasties more effectively than
using acetaminophen or NSAIDs alone [41]. Implementation of ERAS pathways
prior to elective cesarean section was shown to drive an eightfold increase in IV
acetaminophen use and a twofold decrease in morphine use controlling for age, race,
ethnicity, pre-pregnancy body mass index, and patient reported pain score. Further-
more, there was a significant increase in the proportion of patients reporting accept-
able pain scores, decrease in outpatient opioid prescription on discharge, decrease in
hours to postsurgical ambulation, and decrease in hours to postsurgical solid intake
[42].
10 Gabapentinoids
Gabapentinoids are structural analogs of the inhibitory neurotransmitter γ-
aminobutyric acid (GABA) and are antiepileptic, anticonvulsant drugs used to treat
neuropathic pain. When administered preoperatively, gabapentinoids block hyper-
algesia surrounding wounds in postoperative patients [43]. In addition, gabapenti-
noids are effective for reducing perioperative pain, development of chronic pain,
and surgically related nausea and vomiting [7]. However, current literature does not
provide sufficient evidence supporting the routine perioperative administration of
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114 G. Yacoub et al.
gabapentinoids to provide significant pain reduction. Furthermore, dosing guide-
lines are unclear with different studies administering gabapentin ranging from 600–
1200 mg and pregabalin ranging from 100–300 mg. Timing of administration also
varied between studies with administration being either preoperative, postoperative,
or both [44–47]. Verret et al. performed a meta-analysis in 2020 evaluating the
role of gabapentinoids in the management of acute and chronic postoperative pain.
The meta-analysis included data from a variety of surgical specialties like ortho-
pedic, spinal, non-endoscopic abdominal, endoscopic abdominal, ophthalmologic,
maxillofacial, ENT, plastic, breast, thoracic and cardiac surgeries. The results show
a mild analgesic effect of gabapentinoids at 6, 12, 24, and 48 h, but not at 72 h.
However, this effect on pain control was determined to not be clinically signifi-
cant since it did not exceed the minimal clinically important difference for any of
the time points measured. The results show that administration of gabapentinoids
reduced opioid administration with a mean difference of 8 mg I V morphine equiva-
lents. However, the difference observed in opioid administration is not supported by
a high degree of evidence in this analysis. Furthermore, the group observed a statis-
tically significant increased incidence of adverse side effects from gabapentinoid
administration including dizziness and visual disturbance [46]. Stone et al. similarly
advise against the use of gabapentinoids in their ERAS guidelines for minimally
invasive gynecologic surgeries due to the FDA reported side effects of respiratory
depression when using gabapentinoids in combination with opioids [35]. A similar
meta-analysis performed by Fiore et al. in 2023 that specifically focuses on cran-
iotomies showed with a low degree of confidence that gabapentin administration
slightly reduced postoperative pain at 24 h without evidence of pain reduction at
any other time points [47]. Overall, literature evidence to support the broad use of
gabapentinoids in ERAS protocols is inconsistent and controversial as of now.
11 Glucocorticoids and Dexamethasone
Dexamethasone, a glucocorticoid drug, is commonly used to reduce perioperative
pain and PONV. Glucocorticoids bind to the glucocorticoid receptors (GR) expressed
throughout the body, inducing or repressing transcription of genes through binding
directly to DNA [48]. This mechanism of action is used to treat inflammation, aller-
gies, asthma, arthritis, skin, and kidney conditions [49]. Important side effects related
to dexamethasone administration include impaired wound healing, muscle atrophy,
and hypertension [48]. A meta-analysis by Weibel et al. that evaluated the effective-
ness of different prophylactic pharmacologic interventions demonstrated that > 4 mg
IV dexamethasone administration prior to surgery or at anesthesia induction is effec-
tiveat reducing PONV [50]. A systematic review by Korwin-Kochanowskaon hallux
valgus RCT studies found evidence that preoperative administration of dexametha-
sone reduces postoperative pain [51]. A systematic review study by Macfater et al.
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