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Perioperative Considerations for Palliative and Terminally Ill Patients 295
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Perioperative Management of Opioid
Tolerant Patients
Lady Christine Ong Sio, Shuchita Garg, and Adil Qarni
Abstract The increase in worldwide prescription opioid use has resulted in a parallel
increase in the need to consider the analgesic management of patients who are
opioid-tolerant. Opioids provide effective analgesia; however, effective utilization
can be limited by opioid-related adverse events and abuse potential. The use of
multimodal analgesic therapy has been recommended by numerous societies and
entails the concurrent perioperative utilization of multiple pharmacologic and/or
non-pharmacologic agents with different mechanisms of action. The perioperative
period represents a vulnerable time for opioid tolerant patients due to the risk of
undertreatment of pain, risk of opioid withdrawal and relapse, not to mention the
fear of possible adverse judgment by providers. This chapter presents current recom-
mendations in the perioperative management of opioid tolerant patients. While the
management of these patients may be challenging, leveraging, multimodal thera-
pies and multi-disciplinary planning and strategies remain essential components of
optimized perioperative analgesia.
Keywords Opioid tolerance
· Opioid use disorder · Perioperative period ·
Multimodal analgesia · Chronic pain
L. C. Ong Sio (
B
)
Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville,
KY, USA
e-mail: ladychristine.ongsio@uoflhealth.org
S. Garg · A. Qarni
Department of Anesthesia and Chronic Pain Division, University of Cincinnati, Cincinnati, OH,
USA
e-mail: gargsh@ucmail.uc.edu
A. Qarni
e-mail: qarniam@ucmail.uc.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_19
297
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298 L. C. Ong Sio et al.
1 Introduction
Opioid use disorder pertains to a pattern of opioid use that is associated with physical,
mental, social, and legal problems [1]. It is a treatable chronic disorder characterized
by remission and recurrence due to loss of control of opioid use, compulsive use, and
continued use despite harms [2]. It is a chronic and relapsing disorder of the brain
caused by repeated exposure to exogenous opioids [3]. The development of opioid
tolerance, dependence, and addiction are manifestations of brain changes resulting
from chronic opioid abuse.
Data from the Centers for Disease Control and Prevention demonstrates that the
increase in opioid prescriptions that began in the 1990s was associated with a concur-
rent increase in the occurrence of drug-related overdose and death. Between the years
1999 and 2020, more than 263,000 people died in the United States due to overdoses
from prescription opioids, and the mortality rate for this cause of death increased
by five times during that period [4]. In 2021, 106,699 inclusive overdose deaths
occurred, resulting in an age-adjusted rate of 32.4 per 100,000 standard population.
The rate of drug overdose deaths involving synthetic opioids other than methadone
increased 22%, while the rate of deaths involving heroin declined 32% between 2020
and 2021. From 2020 through 2021, the rate of drug overdose deaths increased for
deaths involving cocaine and those involving psychostimulants with abuse potential
[5].
Opioid tolerance may be a consequence of prescribed use of pain medications or
illicit use. The term opioid tolerance is characterized by a reduced response to an
opioid analgesic and manifests by the need to use increasing doses to achieve the
desired effect. Tolerance occurs because brain cells with opioid receptors become less
responsive to opioid stimulation, i.e., more opioid is needed to stimulate the ventral
tegmental area brain cells of the mesolimbic reward system to release the same
amount of dopamine in the nucleus accumbens [6]. Tolerance to the analgesic and
euphoric effects develops quickly, while tolerance to respiratory depression develops
more slowly [7].
Opioid dependence is defined by the presence of withdrawal symptoms in the
absence of opioid use or use in reduced amounts. Withdrawal symptoms include
piloerection, chills, diarrhea, nausea, vomiting, muscle aches, and insomnia, and
can vary in severity and duration in each person. Opioid addiction, as defined by
the Diagnostic and Statistical Manual of Mental Disorders V, is characterized by
pronounced craving and drug-related perseveration, with an absence of inhibitory
control over efforts to refrain from drug use in the setting of compulsive and harmful
use.
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Perioperative Management of Opioid Tolerant Patients 299
2 Preoperative Evaluation
Obtaining a comprehensive pain history well in advance of surgery aids in the identi-
fication of opioid tolerance and facilitates perioperative planning. This history should
evaluate concomitant comorbidities such as anxiety, depression, and substance use
or abuse in the past. It is also important to consider that patients may deliberately
omit or fail to declare a history of opioid use or those with current opioid addic-
tion struggles may give a false history in the presence of parents, family, or friends.
The clinical importance associated with identifying these patients is highlighted in
their increased risk of prolonged postoperative opioid use, worse clinical outcomes,
increased pain, and diverse postoperative complications [8].
In the perioperative setting, patients who are opioid-tolerant can fall into one of
three categories: First are patients who are maintained on large doses of opioids for
the treatment of chronic non-malignant or malignant pain. Second are patients who
have opioid addiction and are actively misusing opioids, with or without other illicit
substances. Third are those who have a previous history of substance use disorders
and are on medication-assisted treatment (MAT) to simultaneously dampen cravings
for opioids and diminish the risk of relapse [9].
It is important to acknowledge that the acute management of perioperative pain in
opioid tolerant patients is challenging. This subset of patients may report higher pain
scores than the average patient, and their pain is often poorly managed in the hospital
setting. The mechanism involved in this difference in symptomatic pain control is
multifactorial and includes the interrelation between psychologic, physiologic, and
physical alterations that happen in individuals exposed to long-term opioid admin-
istration [10]. The goals of perioperative treatment in these patients are to prevent
opioid withdrawal, provide effective analgesia, and ensure continuity of care after
discharge [11].
Long-term preoperative opioid use is associated with a higher risk of both short-
and long-term adverse postoperative outcomes, including increased rates of surgical
infection and revision surgery, higher readmission rates, longer hospital stay, and
higher medical costs after surgery. Identifying those patients already exposed to
opioid analgesics is a core tenet of perioperative analgesic management. Fortunately,
several tools can be used to help identify these patients and screen for substance use
disorders. For patients on long term opioid therapy or with a history of substance
abuse, tools such as the ORT (Opioid Risk Tool), DIRE (Diagnosis, Intractability,
Risk, Efficacy) score, and SOAPP (Screener and Opioid Assessment for Patients and
Pain) may be used [12, 13].
In addition to obtaining a comprehensive preoperative history and physical exami-
nation, thorough discussions, counseling, and expectation settings are important. The
patient’s concerns and overall expectations should be considered as a component of
analgesic planning and in the development of a treatment approach. A reassuring
discussion is essential in reducing stress and fear of pain during the perioperative
period.
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300 L. C. Ong Sio et al.
3 Challenges in the Management of Opioid Tolerant
Patients
Opioid tolerant patients have higher pain scores than non-opioid tolerant patients
and oftentimes require higher doses of opioids. Undertreatment of pain can lead
to opioid-seeking behavior, and the patient can be perceived as ‘manipulative’ and
‘non-cooperative’ [11].
The Food and Drug Administration defines a patient as opioid tolerant if, for at
least 1 week, the patient has been receiving oral morphine 60 mg/day, transdermal
fentanyl 25 mcg/hour, oral oxycodone 30 mg/day, oral hydromorphone 8 mg/day,
oral oxymorphone 25 mg/day, or an equianalgesic dose of any other opioid [14].
Besides opioid tolerance, the risk of respiratory events, immune suppression, and
opioid-induced hyperalgesia can impact post-operative outcomes. Evidence suggests
that patients with a history of opioid tolerance may also be at increased risk for
the development of surgical site and periprosthetic infections, revision surgeries,
prolonged hospital stay, unplanned hospital readmission, non-home discharge, and
postoperative emergency room visits. Each of these adverse events has the binary
effect of worsening patient outcomes and increasing healthcare costs [12].
Another subset of patients at risk for poor perioperative pain control are those
who are in remission from an opioid use disorder and are not being maintained on
partial mu receptor agonist or antagonist therapeutics. These patients do not generally
exhibit signs and symptoms of opioid dependence but are still susceptible to triggers
and relapse. Whenever possible, regional anesthesia and/or peripheral nerve blocks
should be used in these patients to minimize pain and subsequent opioid requirements,
along with adjunct medications, to reduce the need for opioid medications. Opioid
analgesics should be given at the lowest possible effective dose and for a limited
period. Close follow-up of these patients is important to prevent the re-development
of use disorder pathologies.
4 Perioperative Pain Management Considerations (Fig. 1)
Oral Opioids
In general, when significant pain after surgery is anticipated, patients should be
advised to take their usual dose of oral opioid on the morning of surgery, with
preoperative administration of daily maintenance or baseline opioid dose occurring
before the induction of anesthesia [15]. If patients are unable to take medications by
mouth, they can be given an equivalent dose via the intravenous route. Calculating
intravenous opioid replacement dosing is often done by determining the total 24-h
dose of the current oral opioid regimen by convertingto oral morphine equivalentdose
(MED) using equianalgesic tables. Finally, the calculated oral MED can be converted
to parenteral morphine by using the conversion 3:1 oral: parenteral morphine ratio.
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Perioperative Management of Opioid Tolerant Patients 301
Fig. 1 Approach to perioperative management of patients with OUD
Transdermal Opioids
Transdermal fentanyl patches should be maintained intra-operatively to ensure main-
tenance of baseline opioid requirement. The presence of an external heat source,
however, can potentially increase cutaneous perfusion and subsequently increase
fentanyl absorption and lead to overdose [16]. In the case of major surgery, it is
preferable to remove the fentanyl patch and administer an equipotent morphine dose
as a substitute [9, 15]. In most cases, i t is prudent to coordinate with the surgical
team to ensure that fentanyl patches are reapplied following the conclusion of the
surgical procedure.
5 Intravenous Opioids
Despite a recent impetus to decrease i ntravenous opioid administration, patient-
controlled analgesia in the postoperative period can often be effectively utilized in
the management of acute pain in opioid tolerant patients. It allows for individual dose
titration and decreases staff workload. It may be challenging to determine the optimal
dose in opioid-tolerant patients, but it is recommended to consider the patient’s usual
daily 24-h opioid requirements when calculating effective dosing regimens.
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302 L. C. Ong Sio et al.
Equianalgesic tables can be used to help calculate equivalent doses of an alterna-
tive opioid but should be used with caution. When considering an opioid rotation, it
is recommended to reduce the calculated equianalgesic dose by 30 to 50% to allow
for incomplete cross-tolerance [11].
Once the patient is ready to be converted back to an oral opioid formulation, a
useful guide is to identify the intravenous opioid consumption in the previous 24 h
and convert to an equivalent oral dose. As a rule of thumb, fifty percent of this
calculated dose is given as sustained-release dosing, and the remaining fifty percent
can be divided into 4 to 6 divided doses throughout the day.
Methadone
Differing expert opinions exist on the preferred management of patients on MAT
scheduled for elective surgery. In general, patients who can tolerate oral medica-
tions should be advised to continue oral methadone on the morning of surgery and
throughout the perioperative period. If unable to do so, methadone can be given
parenterally, at a dose half to two-thirds of the maintenance dose, divided into
two to four doses throughout the day [9, 15, 17]. If parenteral methadone is not
available, methadone can be converted to morphine, however, this is challenging as
the half-life of methadone is very long (15–40 h). The challenges associated with
methadone conversions suggest that the inclusion of a dedicated pain service may
confer perioperative safety benefits.
Buprenorphine
Patients on buprenorphine often require higher doses of opioids or express higher pain
scores following surgical procedures. The etiology for these differences is related to
buprenorphine acting as a partial mu-agonist with a high affinity for opioid receptors
that outcompetes full opioid agonists. In OUD maintenance programs, buprenor-
phine is often dosed once a day or three times a week at a higher dose. Available
buprenorphine formulations include sublingual, buccal, transdermal, subdermal, or
injectable. Buprenorphine may be administered in isolation or may be a compo-
nent of a formulation that includes naloxone. Several strategies exist to address the
perioperative management of patients on buprenorphine presenting or recovering
from elective surgical procedures. One option is to continue buprenorphine and use
a different opioid for analgesia. The use of opioids with a high affinity for the opioid
receptor (i.e. fentanyl derivatives and hydromorphone) may be used and titrated to
the desired effect. It should be considered that higher doses of opioid agonists may be
necessary to provide analgesia in the setting of buprenorphine [15, 18, 19]. Buprenor-
phine dosing modifications may also provide effective perioperative pain relief. For
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Perioperative Management of Opioid Tolerant Patients 303
example, increasing dosing to three times daily or increasing the daily dose to 24–
32 mg daily may greatly enhance the analgesia provided through buprenorphine
administration.
Naltrexone
Naltrexone is an opioid antagonist that is used to prevent relapse in patients with
a history of alcohol abuse and in the treatment of fibromyalgia pain disorders. It
competitively binds to opioid receptors, causing reduced sensitivity to opioids and
can precipitate withdrawal symptoms in patients with a history of opioid dependency.
Naltrexone is available in oral and injectable forms and should be discontinued at least
24–72 h prior to planned surgical procedures if opioid-based anesthesia is planned
[15]. The recommendation for injectable naltrexone is to postpone elective surgery
for 30 days following the last injection. Daily oral naltrexone should be discontinued
72 h before surgery [20–22].
Regional Anesthesia
Neuraxial and peripheral nerve blocks are widely used techniques that are frequently
utilized to manage acute perioperative pain. For example, the use of brachial plexus
blocks and catheter techniques can be utilized as either the sole anesthetic during
surgery or for postoperative pain control in the setting of significant shoulder or arm
surgery. Thoracic paravertebral blocks, erector spinae blocks, transversus abdominis
plane blocks and catheters can be used for truncal surgeries. Neuraxial techniques
such as spinal and epidural are safe and effectivefor lower extremity procedures. With
an improved understanding of anatomy and ultrasound technology, there is an ever-
expanding scope of surgical procedures that might benefit from regional anesthesia
and the thoughtful application of these techniques should be strongly considered in
patients with a history of opioid use or abuse.
Adjuvant Medications
Non-opioid adjuvant medications can be combined with opioids to improve pain
control and potentially decrease opioid consumption. The use of non-steroidal
anti-inflammatory drugs and acetaminophen should be strongly considered unless
otherwise contraindicated.
Acetaminophen inhibits prostaglandin synthesis in the central nervous system,
leading to inhibition of inflammation in the peripheral nervous system. It is available
in oral, intravenous, or rectal forms.
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304 L. C. Ong Sio et al.
Gabapentinoids such as gabapentin and pregabalin are antiseizure medications
with analgesic and anxiolytic properties [20]. These medications are believed to act
as inhibitors of voltage-gated calcium channels. There is no consensus that exists
for optimal dosing and caution should be exercised in patients who are elderly or
otherwise at risk for sedation and respiratory depression.
Clonidine and dexmedetomidine are alpha-2 adrenergic agonists that have anal-
gesic properties and have been used to reduce perioperative pain. Clonidine is partic-
ularly useful as a component of an analgesic program aimed at preventing opioid
withdrawal symptoms and may have efficacy comparable to buprenorphine [23].
Opioid antagonists (naloxone and naltrexone) as well as mixed agonist-antagonist
types of opioids (nalbuphine, pentazocine, butorphanol), should be used with tremen-
dous caution in patients on chronic opioid therapy because these drugs can precipitate
acute opioid withdrawal.
Non-pharmacologic Therapies
A multi-disciplinary pain approach consisting of non-opioid and non-pharmacologic
modalities is helpful in managing opioid-tolerant patients. Not only does it help
decrease postoperative pain, but it also limits opioid dose requirements and subse-
quently reduce opioid-related side effects. Non-pharmacological treatments include
cognitive behavioral therapy, mindfulness training, relaxation strategies and phone
applications, physical therapy, peer, and family support. Other support groups such
as narcotics anonymous may also be helpful. Acupuncture and topical analgesics,
such as ice, can be beneficial [24].
6 Conclusion
Perioperative pain management in the setting of preoperative opioid use or abuse,
introduces tremendous analgesic management complexity and is associated with a
significant potential to impact recovery outcomes well beyond the immediate post-
operative period. These patients should be monitored not only for achievement of
analgesic milestones but also for signs of withdrawal and cravings that might be
associated with dangerous use or misuse of opioids. If a perioperative interruption in
baseline opioid administration does occur, there needs to be communication with the
patient’s outpatient opioid prescriber such that arrangements could be done to restart
medications. Difficulties encountered with these multifaceted management strate-
gies highlight why it is most frequently prudent to continue baseline opioid dosing
throughout the postoperative period and supplement with additional analgesics as
needed. Finally, a multidisciplinary team approach and evidence-based treatment
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Perioperative Management of Opioid Tolerant Patients 305
strategy are critical to safely manage opioid tolerant patients in the perioperative
arena and ensure adequate analgesia while reducing the risk of relapse.
Key Takeaways
1. Early identification of opioid-tolerant patients undergoing surgery is an essential
component of successful perioperative care and management.
2. The goals of perioperative treatment are to prevent opioid withdrawal, provide
effective analgesia, and ensure continuity of care post-discharge.
3. A multi-disciplinary team approach is important to safely manage opioid tolerant
patients and at the same time, ensure adequate analgesia while avoiding relapse.
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