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The Implications of the Opioid Epidemic for the Treatment … 63
undergoing total knee or hip arthroplasty found that a 50% reduction preoperatively
resulted in improvements in multiple activity indices (compared to patients who did
not taper); furthermore, this study showed similar outcomes between individuals
who weaned opioids and the patients who were opioid naïve [62]. In a retrospective
cohort study by Jain, where chronic opioid users (defined as having used > 5000 oral
morphine equivalents over the previous year) were stratified based on timing of their
most recent prescription, those with the longest abstinence from opioids prior to spine
surgery showed significantly lower risk of long-term postoperative opioid use [63].
Notably, however, risks associated with weaning can include increased use of illicit
substances, depression and suicidality, and risk of overdose [64]. Additionally, the
importance of ensuring patient buy-in regarding the perioperative process, managing
expectations, and ensuring perioperative pain control cannot be overstated.
Perioperative/Intraoperative
Intraoperatively, several care areas may influence post-operative opioid use. Several
specialties have worked to develop enhanced recovery after surgery (ERAS) proto-
cols, which focus on improving perioperative care, minimizing complications, and
accelerating recovery [65]. Multimodal analgesia and the implementation of regional
anesthesia can help to minimize the adverse effects of opioid medications in the
recovery process.
The use of opioid-sparing pain regimens has become increasingly commonplace
in the perioperative realm. Commonly used medications include acetaminophen,
non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and celecoxib,
neuropathic medications such as gabapentin and pregabalin, intravenous alpha-2
adrenergic agonists such as dexmedetomidine and clonidine, as well as intravenous
N-methyl-D-aspartate (NMDA) antagonists such as ketamine [66, 67]. Incidentally,
there are no data to demonstrate that use of fentanyl near the start of a general
anesthetic to either treat “pain” or blunt the response to sympathetic stimulation
resulting from laryngoscopy has any bearing on postoperative opioid use.
The data behind opioid-free anesthetic plans is less clear. Opioid-free regimens
often involve the use of dexmedetomidine, lidocaine, and/or ketamine infusions. In
a Cochrane meta-analysis of 23 trials related to use of intravenous lidocaine infu-
sion, there was not clear evidence of improved pain scores, early gastrointestinal
recovery, postoperative nausea, or opioid consumption with the therapy [68]. The
use of dexmedetomidine infusions is similarly unclear with some studies showing
decreased pain scores and opioid use in the first 24 hour, along with decreased
nausea/vomiting, though other studies showed no difference in opioid use while
also observing bradycardia and hypotension [66, 69, 70]. Several meta-analyses
were performed that attempted to elucidate the benefits of intravenous ketamine.
Laskowski showed a reduction of total opioid consumption in patients who received
intravenous ketamine boluses or infusions, particularly in thoracic, upper abdominal,
and major orthopedic surgical groups, with a noted improvement in postoperative
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64 N. Xiang et al.
nausea and vomiting but an increased incidence of hallucinations and nightmares
[71]. Jouguelet-Lacoste evaluated 5 meta-analyses and 39 clinical trials that showed
use of low-dose ketamine infusions defined as less than 1.2 mg/kg/hr reduced postop-
erative opioid consumption by 40%, while no reports of major complications in the
first 48 hour [72]. Lastly, Klatt’s systematic review and meta-analysis found insuf-
ficient evidence to support a reduction in chronic pain with perioperative ketamine
use [73].
Another common aspect of a multimodal anesthetic plan is the usage of regional
anesthesia techniques, which has increased over the past decade. Regional anes-
thesia encompasses neuraxial blockade or peripheral nerve blockade. For many
surgical specialties regional anesthesia remains a key component of the multi-modal
analgesia plan, including orthopedic joint surgery, ERAS protocols for abdominal
surgeries such as sleeve gastrectomy and the procedure-specific postoperative pain
management (PROSPECT) guidelines for thoracic surgery and elective caesarean
section [66, 67, 74, 75].
Regional anesthesia was associated with improved pain scores and decreased
opioid use, primarily in hip replacement surgery, periarticular elbow surgery, and
tibial plateau fracture surgery, although these small retrospective studies do not
extend past three months postoperatively [76–78]. In contrast, there are numerous
studies that do not show a significant effect of regional anesthesia on postoperative
opioid use. Munsch et al. studied the effects of regional anesthesia for hip arthroscopy,
which took the form of L1/L2 nerve root blocks or pericapsular nerve group (PENG)
block targeting the articular branches of the femoral and obturator nerves for the hip
joint [79]. The study found no significant differences in postoperativeopioid prescrip-
tion, opioid refill requests, or number of pain-related phone calls or office encounters.
Trasolini et al. studied the effect of regional anesthesia for shoulder arthroscopic
procedures, finding no significant difference in the patterns of filled postoperative
opioid prescriptions between those who received a nerve block and those who did
not. However, among preoperative opioid users, there was a statistically significant
decrease of opioid prescription filling in the first two weeks postoperatively in the
group who received a nerve block [80]. In another study by Cunningham, the use of
regional anesthesia for surgical fixation of pelvic and acetabular fractures actually
showed an association with an increase in inpatient and outpatient opioid use [81].
Regardless of specific interventions, a multimodal approach using both opioid
and non-opioid medications is ideal for providing postoperative analgesia. Regional
nerve blocks certainly have a role as well, although their impact on postoperative
opioid use is equivocal. Involvement of a dedicated acute pain service, particularly
for patients noted to be at increased risk for postoperative opioid use with history of
OUD, is a good starting point in optimizing perioperative pain care.
With respect to patients with a history of OUD, care is needed to avoid overpre-
scription of opioids that may place the patient at risk for relapse balanced with the
need to achieve adequate pain control; uncontrolled pain itself can result in relapse.
If the patient is already treated with medications for OUD, such as buprenorphine or
methadone, the current expert opinion is to maintain these medications in the peri-
operative period. For buprenorphine, the recommendations from the Multi-Society
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The Implications of the Opioid Epidemic for the Treatment … 65
Working Group on opioid use disorder are generally to continue the preoperative
dose through the perioperative period [60]. Additional strategies in the perioperative
period include (1) splitting the doses into two or three doses per day for improved
analgesic effect; (2) potentially increasing above preoperative doses in the setting of
severe pain; and (3) adding short-acting full mu-opioid agonists, non-opioid medi-
cations, regional anesthesia techniques, as well as non-pharmacologic interventions
such as ice packs, positioning, relaxation techniques, and psychosocial support [60].
Kohan et al. recommend continuing methadone at the patient’s usual dose, while
supplementing with additional mu-opioid agonists. Typically, methadone is deliv-
ered as a single daily dose in an opioid treatment program; however, the single dose
can be divided into three times per day dosing for improved analgesia. Maintenance
of OUD medications can help avoid cravings, decrease the risk of relapse, and help
transition back to an appropriate outpatient regimen at discharge.
Postoperative
Surgeons, anesthesiologists, primary care physicians, and pain specialists all have
responsibilities in the postoperative period, including monitoring the healing process,
assessing for the adequacy of pain control, monitoring pain medication use with a
mindset toward gradual tapering of opioids, and consideration of safer pain control
options if needed.
One the initial inflection points in post-operative pain management is the selection
of a regimen appropriate for the procedure. There has been evidence to suggest that the
amount of opioids prescribed can be significantly decreased from historical practices
without compromising pain scores or patient satisfaction [53]. Subsequent follow-up
is needed with the patient to monitor pain symptoms and encourage gradual weaning
and (hopefully) eventual cessation of opioids. A standardized weaning schedule may
be challenging to apply for all patients, but it may be helpful as a starting point and as
a means to guide discussion and expectations. In a randomized controlled trial, Hah
et al. investigated the efficacy of motivational-interviewing (MI) along with guided
opioid tapering for a group of patients undergoing total knee and hip arthroplasty [82].
The intervention for the MI-Opioid Taper consisted of a scheduled 25% opioid dose
reduction every seven days coupled with weekly phone calls made by a pain physician
that reviewed medication adherence, reviewed response to medication, advised on
opioid weaning, provided support for the patient’sefforts, provided education on pain
management and drug misuse, and discussed over-utilization of opioids if applicable.
The results of the MI-Opioid Taper study showed that patients who underwent the
motivational interviewing taper as compared to those who did not receive weekly
phone calls, had a 62% increase in the rate of return to baseline opioid use, the
primary outcome, as well as 53% increase in the rate of complete postoperative
opioid cessation (compared to those who did not) [82].
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66 N. Xiang et al.
One important aspect of postoperative care for patients is an emphasis on collabo-
ration across specialties. If continued opioid prescriptions past several months post-
operativelyare requested, this is often referred to a primary care physician or a chronic
pain specialist. For patients without a history of chronic pain, establishing care at a
new chronic pain clinic can be challenging logistically, whether due to wait times in
the scheduling queue, insurance limitations, or local and regional opioid prescribing
policies. Without care coordination and preemptive planning, it is possible patients
may feel abandoned as they recover from surgery, which should be avoided.
The Perioperative Surgical Home (PSH) is one model that focuses on interdisci-
plinary collaboration and aims to guide a patient through a surgical process, beginning
from the initial decision to undergo surgery and into the recovery and rehabilitation
phase post-discharge [83]. Vetter’sreview of the PSH model notes the need to address
inadequate treatment of postoperative pain, to minimize opioid-related side effects,
and to improve upon opioid prescribing patterns so as to avoid negative outcomes.
One concept of the PSH for the postoperative period is the establishment of a transi-
tional pain service or clinic (TPS), which usually includes a team of pain specialists,
internal medicine providers, addiction medicine specialists, mental health providers,
licensed social workers, and advanced practice nurses [83]. The goal of the clinic
or service is to optimize pain control, wean patients off high-dose opioids, decrease
unnecessary readmissions, reduce healthcare costs, and minimize disability related
to chronic post-surgical pain.
One of the earliest models for a TPS originated at Toronto General Hospital,
which was established in 2014 [84]. The services that were provided included “mul-
timodal medication optimization by anesthesiologists, postsurgical physical therapy
and acupuncture, and a pain psychology intervention consisting of pain education,
mindfulness training, brief hypnosis, and a form of cognitive–behavioral treatment
called acceptance and commitment therapy (ACT)” [84]. There have been two cohort
studies investigating the TPS at this institution, with additional randomized controlled
trials ongoing. One team studied the effect of ACT on patients at increased risk for
chronic postsurgical pain and persistent opioid use; the use of ACT in this cohort
showed greater reductions in opioid use, pain interference, and depressed mood as
compared to the non-ACT group, despite starting at a higher level for each category
[85]. A separate study evaluating opioid consumption in the transitional pain clinic
found that, at the conclusion of the six month study period, opioid-naïve patients
had reduced consumption by 69%, with 46% having completely weaned off; in the
opioid-experienced group, opioid use was reduced by 44% and 29% of patients had
been completely weaned off [86]. Similar programs have been started at other insti-
tutions, which is often dependent upon incentivizing institutional support in the form
of improved quality of care and decreased system costs, buy-in from surgeons, and
collaboration of providers across multiple disciplines [87].
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The Implications of the Opioid Epidemic for the Treatment … 67
Key Takeaways
1. While the elements that created the opioid epidemic are multifactorial, its impacts
on American society and healthcare as a whole have been profound and continue
to reverberate.
2. While surgery remains a launching point for chronic opioid use and OUD in
some, multidisciplinary teams can play a major role in significantly reducing the
likelihood of a poor outcome.
3. Setting reasonable expectations for pain and opioid use in the perioperative
period is critical to ensure medication stewardship and appropriate taper or
discontinuation of opioids.
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Genetics of Acute Pain
Danial Shams
Abstract Pain is one of the primary complaints following surgery and has major
impacts on recovery, not to mention the costs (emotionally, physically, and finan-
cially) on the individual and society at large. In fact, survey studies show more than
70% of patients report moderate to extreme pain after surgery, with more than 70%
also complaining of these same levels of pain after discharge [ 1]. This makes the
treatment of acute post-operative pain an important mainstay of today’s surgical
and acute pain services. There is a growing body of literature describing the role that
genetics may play in how and to what degree a person perceives pain. Further research
into these topics may help guide future practitioners in identifying those patients at
greatest risk for the development of significant post-operative and chronic pain. In
addition, an individual’s genetic makeup may contribute to the ability to develop
individualized treatment plans that result in safer and more efficacious treatments.
Keywords Acute pain
· Pain · Genetics · Chronic pain · COMT · GCH1 ·
SCN9A · CYP2D6 · OPRM1
1 Introduction
Pain is both universal and incredibly personal. It is experienced by all animals,
including humans, at some point in their lives; it is an evolutionary advantage which
allows organisms to protect themselves from injury. Yet, given the same type of
injury or trauma, there still exists incredible interindividual variability in the percep-
tion of intensity and duration of pain. This variation is likely secondary to an intri-
cate interconnection of environmental and genetic factors. As our knowledge of
pain genetics has improved, certain genes and their products have been identified
D. Shams (
B
)
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA
e-mail: danial.shams@vumc.org
© 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_5
73
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