Current state of perioperative medication management of methadone, buprenorphine, and naltrexone

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Content PERIOPERATIVE MAT MEDICATION MANAGEMENT i

CURRENT STATE OF PERIOPERATIVE MEDICATION MANAGEMENT OF
METHADONE, BUPRENORPHINE AND NALTREXONE
by
Jasmine Chevalier

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

PERIOPERATIVE MAT MEDICATION MANAGEMENT ii
Distribution of Work

The following manuscript was contributed to in equal parts by
Tiffany Bolton and Jasmine Chevalier.

PERIOPERATIVE MAT MEDICATION MANAGEMENT iii
Acknowledgements
We would like to acknowledge Charles “Uncle Chuck” Griffis, PhD, CRNA for helping
us generate the idea and concept for this paper, and for being a constant source of support and
inspiration. We would like to thank Elizabeth Bamgbose, PhD, CRNA and Teresa Norris, EdD,
CRNA for their helpful feedback and editing throughout this process.

PERIOPERATIVE MAT MEDICATION MANAGEMENT iv
List of Tables and Figures

Table 1 Practice Recommendation Summary Chart ..................................................................... 33
Table 2 Gap Analysis .................................................................................................................... 41
Figure 1 PRISMA Search Documentation Flow Diagram……….………………………………42
Table 3 Literature Matrix .............................................................................................................. 43

PERIOPERATIVE MAT MEDICATION MANAGEMENT v
Table of Contents
Distribution of Work ....................................................................................................................... ii
Acknowledgements ........................................................................................................................ iii
List of Tables and Figures .............................................................................................................. iv
Abstract .......................................................................................................................................... vi
Chapter 1 ......................................................................................................................................... 1
Introduction ................................................................................................................................. 1
Clinical Problem and Specific Aims ........................................................................................... 2
Background and Significance ..................................................................................................... 3
Chapter 2 ......................................................................................................................................... 7
Methodology ............................................................................................................................... 7
Chapter 3 ......................................................................................................................................... 9
Literature Review ........................................................................................................................ 9
Methadone ............................................................................................................................... 9
Buprenorphine ....................................................................................................................... 11
Naltrexone ............................................................................................................................. 18
Chapter 4 ....................................................................................................................................... 21
Results ....................................................................................................................................... 21
Methadone and Elective Surgery .......................................................................................... 21
Methadone and Emergent Surgery ........................................................................................ 23
Buprenorphine and Elective Surgery .................................................................................... 24
Buprenorphine and Emergent Surgery .................................................................................. 26
Naltrexone and Elective Surgery .......................................................................................... 27
Naltrexone and Emergent Surgery ........................................................................................ 29
Chapter 5 ....................................................................................................................................... 30
Discussion ................................................................................................................................. 30
References ..................................................................................................................................... 34
Appendices .................................................................................................................................... 41
Appendix A: Gap Analysis ...................................................................................................... 41
Appendix B: PRISMA Search Documentation Flow Diagram ............................................... 42
Appendix C: Literature Matrix ................................................................................................ 43

PERIOPERATIVE MAT MEDICATION MANAGEMENT vi
Abstract
Opioid use disorder (OUD) is defined as the use of opioids in a problematic manner
leading to significant distress or impairment. Also known as opioid addiction, OUD involves the
misuse of prescription opioids, diverted prescription opioids, or illicitly-obtained opiates. Every
year the number of Americans misusing opiates and subsequently suffering from OUD is
increasing. Medication-assisted treatment (MAT) is the combination of counseling, behavioral
therapies, and medications approved by the United States Food and Drug Administration (FDA)
(primarily methadone, naltrexone, and/or buprenorphine) to manage OUD from a “whole-
patient” prospective. Medication-assisted treatment has demonstrated the ability to reduce the
morbidity and mortality of OUD by decreasing deaths related to overdose, increasing treatment
retention, improving the social functioning of patients, reducing criminal activity, and reducing
transmission of infectious disease. As the number of patients receiving MAT increases, it is
plausible anesthesia providers will encounter patients taking methadone, buprenorphine, and/or
naltrexone with increasing frequency for both elective and emergent surgeries. Patients receiving
MAT present unique anesthesia management challenges. This project consists of an extensive
computerized literature review regarding the perioperative management of OUD patients
prescribed methadone, buprenorphine, or naltrexone undergoing elective or emergent surgery.
The specific aim of this paper is to create an executive summary of the current state of practice
and provide anesthesia perioperative management practice recommendations for patients
receiving MAT involving methadone, buprenorphine, or naltrexone who are undergoing elective
or emergent surgeries.
PERIOPERATIVE MAT MEDICATION MANAGEMENT 1
Chapter 1
Introduction
Opioid use disorder (OUD) is defined as the use of opioids in a problematic manner
leading to significant distress or impairment (American Psychiatric Association, 2013). Also
known as opioid addiction, OUD involves the misuse of prescription opioids, diverted
prescription opioids, or illicitly-obtained opiates such as heroin (Manchikanti, Kaye, & Kaye,
2016). What started with well-intentioned but misinformed medical professionals in the 1990’s
prioritizing patient pain management has now led to a public health crisis with a death toll
surpassing that of gun violence and motor vehicle accidents (Manchikanti et al., 2016). Estimates
from 2017 approximate 40,000 Americans lost their lives in motor vehicle accidents (National
Safety Council, 2019) and 40,000 died related to gun violence (National Center for Health
Statistics, 2019), while opioid overdose claimed over 47,000 lives (Scholl, Seth, Kariisa, Wilson,
& Baldwin, 2019). These estimates indicate for the first time in United States’ history, a person
is more likely to die from an opioid overdose than from a motor vehicle accident. Every year the
number of Americans misusing opiates and subsequently suffering from OUD is increasing
(Scholl et al., 2019). In 2015, an estimated 2.4 million Americans struggled with OUD (Alderks,
2017). In 2017, the United States Department of Health and Human Services declared the opioid
crisis a public health emergency and initiated five strategies to decrease deaths related to opioid
overdose; one of these strategies includes increasing access to treatment for OUD (Price, 2017).
Medication-assisted treatment (MAT) is the combination of counseling, behavioral
therapies, and medications approved by the United States Food and Drug Administration (FDA)
(primarily methadone, naltrexone, and/or buprenorphine) to manage OUD from a “whole-
PERIOPERATIVE MAT MEDICATION MANAGEMENT 2
patient” prospective (Substance Abuse and Mental Health Services Administration [SAMHSA],
2019). Medication-assisted treatment has demonstrated the ability to reduce the morbidity and
mortality of OUD by decreasing deaths related to overdose, increasing treatment retention,
improving the social functioning of patients, reducing criminal activity, and reducing
transmission of infectious diseases (Volkow, Frieden, Hyde, & Cha, 2014). Beginning in 2003,
the use of MAT for OUD has steadily increased (Alderks, 2017). The number of methadone
patients in opioid treatment programs rose over 37% from 2003 to 2015, the number of
buprenorphine patients in opioid treatment programs rose almost 30-fold from 2004 to 2015, and
the number of patients in opioid treatment programs receiving naltrexone rose almost 50% from
2013 to 2015 (Alderks, 2017). As the number of patients receiving MAT increases, it is plausible
anesthesia providers will encounter patients taking methadone, buprenorphine, and/or naltrexone
with increasing frequency for both elective and emergent surgeries. Patients receiving MAT
present unique anesthesia management challenges (Coluzzi et al., 2017).
Clinical Problem and Specific Aims
Pain management in patients receiving MAT requires a thorough understanding of the
protocol, drug pharmacodynamics, and multimodal analgesia. Studies demonstrate patients
taking MAT medications suffer from hyperalgesia (a paradoxical pain sensitization process
related to opiate use) and opioid tolerance, rendering common opiate-based pain control
techniques minimally or ineffective and presents a complicated perioperative pain management
scenario (Zahari et al., 2016; Athanasos, Ling, Bochner, White, & Somogyi, 2019).
Insufficient knowledge, the stigmatization of the patient with OUD, and providers’ fear
of causing the OUD patient to become dependent on opioids again are among common reasons
leading to inadequate pain control of patients on MAT (Adam, Matolić, Stojčić, Mršić, & Rašić,
PERIOPERATIVE MAT MEDICATION MANAGEMENT 3
2016). Other misconceptions include opioid-tolerant patients are manipulative and seek pain
medication for reasons other than pain control, and continuing patients on their maintenance
buprenorphine or methadone provides adequate post-surgical analgesia (Coluzzi, 2017). Patients
with OUD report fearing unfair perioperative treatment, adverse judgment, inadequate pain
relief, experiencing withdrawal symptoms, and relapsing (Ward, Quaye, & Wilens, 2018).
Evidence supports poor pain management and distressing perioperative experiences increase the
risk of the OUD patient’s relapse into postoperative opiate abuse (Adam et al., 2016; Coluzzi,
2017; Ward et al., 2018). Additionally, patients with OUD have an increased risk of
postoperative morbidity, increased length of stay, and increased resource utilization postulated to
be related to opioid dose escalation in the perioperative period. It is plausible the utilization of
multimodal analgesia to optimize opioid use would be beneficial in improving patient outcomes
(Sayal, Bateman, Menendez, Eikermann, & Ladha, 2018).
The specific aim of this paper is to create an executive summary of best practice, based
on current literature, and provide perioperative anesthesia management practice
recommendations for patients receiving MAT involving methadone, buprenorphine, or
naltrexone who are undergoing elective or emergent surgeries.
Background and Significance
To aid in the treatment of OUD and addiction to opioids, the FDA has approved several
medications; the most commonly used prescription medications for OUD treatment are
methadone, buprenorphine, and naltrexone (SAMHSA, 2019). According to SAMHSA (2019),
the drugs used in the MAT protocol do not substitute an illicit drug for a MAT drug. Through
differing mechanisms of action, these medications work to prevent or relieve withdrawal
symptoms and to hinder the onset of psychological cravings without causing adverse side effects
PERIOPERATIVE MAT MEDICATION MANAGEMENT 4
on a patient’s mental or physical capabilities. Opioid use disorder is a disease of chronic nature,
and patients may take MAT medications for months, years, or their entire lifetime (SAMHSA,
2019).
Methadone was approved for use in the treatment of OUD by the FDA in 1972 and is a
synthetic full opioid mu agonist and N-methyl-D-aspartate (NMDA) receptor antagonist
(Harrison, Kornfield, Aggarwal, & Lembke, 2018). As only approximately 30% of mu opioid
receptors are bound by methadone, additional activity from either endogenous or exogenous mu
opioid agonists are allowed by methadone (“Methadone Hydrochloride,” n.d.). In MAT,
methadone works to prevent withdrawal and cravings without causing feelings of euphoria,
although it has addictive qualities. Methadone is dosed daily, with effective dosing ranging 60-
120 milligrams per day although higher doses may be seen as methadone does not experience a
ceiling effect and tolerance can develop with higher doses (Coluzzi et al., 2017; Ward et al.,
2018). According to Harrison et al. (2018) methadone has an elimination half-life and duration of
action that is significantly longer than most opioids. The half-life of methadone is generally
accepted to be 24 hours but has been documented to be as high as 5 days, which may delay the
onset of withdrawal symptoms to 4-5 days from last dose (Sen et al., 2016.). Caution must be
exercised with the use of additional methadone doses or the use of central nervous system (CNS)
depressants, as the long elimination half-life can lead to accidental overdose resulting in life-
threatening sedation, respiratory depression, and/or cardiac arrhythmias (SAMHSA, 2019).
Variables making the toxic dose of methadone difficult to predict include the long half-life, co-
administration of drugs that cause changes in metabolism, and the tolerance patients develop at
higher doses (Harrison et al., 2018). Abrupt discontinuation of methadone can precipitate
withdrawal symptoms (Strain, n.d.).

PERIOPERATIVE MAT MEDICATION MANAGEMENT 5
Buprenorphine was FDA approved for the treatment of OUD in 2002. Similar to
methadone, buprenorphine serves to reduce cravings, opiate abuse, and prevent withdrawal.
Buprenorphine can be addictive. Buprenorphine is both an opioid agonist and antagonist, acting
as a partial mu opioid receptor agonist, nociception opioid receptor-1 agonist, and antagonist of
the kappa opioid receptor. To aid in the prevention of misuse, naloxone can be added to
buprenorphine to induce withdrawal symptoms if taken inappropriately (such as if crushed or
administered intravenously). The dosing frequency and amount of buprenorphine ranges widely,
depending on the administration route and whether or not it is combined with naloxone (Harrison
et al., 2018). Buprenorphine undergoes biphasic or triphasic metabolism depending on the
administration, and subsequently has a wide range of hours for its elimination half-life
(“Buprenorphine, Buprenorphine Hydrochloride”, n.d.). As with methadone, respiratory
depression can occur when buprenorphine is co-administered with CNS depressants (Strain,
n.d.). The ceiling effect of buprenorphine helps to limit its potential for abuse, creates a margin
of safety, but also limits the potential for analgesia with subsequent doses (SAMHSA, 2019;
Harrison et al., 2018). Concerns exist regarding the use of additional opioids in the presence of
buprenorphine due to how tightly buprenorphine molecules bind to the mu receptor, potentially
blocking the additional opioids from binding and decreasing the opioid effectiveness (Harrison et
al., 2018). Respiratory depression is the most life-threatening side effect of buprenorphine and
abrupt discontinuation of buprenorphine may precipitate withdrawal symptoms (Strain, n.d.).
Naltrexone, approved by the FDA for OUD treatment in 1984, works in a manner
completely different from methadone or buprenorphine in the treatment of OUD (SAMHSA,
2019). Naltrexone blocks the euphoric and sedative effects of abused opiates if the patient
relapses and helps to reduce cravings for opiate abuse (SAMHSA, 2019). As a competitive
PERIOPERATIVE MAT MEDICATION MANAGEMENT 6
opioid antagonist, naltrexone primarily works at mu opioid receptors but also has partial agonist
effects at kappa receptors with minimal activity at delta receptors (Harrison et al., 2018). Oral
naltrexone undergoes biphasic metabolism by the liver and has a terminal elimination half-life of
approximately 11-16 hours requiring oral naltrexone to be taken daily (“Naltrexone,” n.d.).
Intramuscular naltrexone (given monthly) has a half-life of 5-10 days (“Naltrexone,” n.d.), and
can antagonize opioids for 28 days, although its opioid antagonizing effects decrease over the 28
days (Harrison et al., 2018).

Depending on when last administered, both oral and intramuscular
naltrexone can severely limit the efficacy of opiates utilized for perioperative pain management
(“Naltrexone,” n.d.).

PERIOPERATIVE MAT MEDICATION MANAGEMENT 7
Chapter 2
Methodology
This PIO project works to address current practice problems and consists of an extensive
computerized literature review regarding the perioperative management of OUD patients
prescribed methadone, buprenorphine, or naltrexone undergoing elective or emergent surgery.
Currently information about perioperative medication management for OUD in the MAT patient
population is not cohesive. There is a knowledge gap in anesthesia providers regarding the
perioperative management of methadone, buprenorphine, and naltrexone in both elective and
emergent surgical settings. This gap becomes more prominent as the number of MAT patients
increases. Consequences of the knowledge gap lead to increased patient morbidity, decreased
patient satisfaction, and potentially an increased risk of relapse. To address this gap in
knowledge about practice recommendations or guidelines, a literature review was conducted.
The goal of the literature review was to summarize current practice recommendations regarding
MAT therapy for OUD in order to increase anesthesia providers knowledge and comfort in
managing OUD medications. Potentially measurable results from the creation of practice
recommendations and an increase in anesthesia provider knowledge could include an increase in
patient satisfaction with pain management and a decrease in perioperative morbidity. See
Appendix A for the gap analysis table.
The literature review was limited to recent (within the last 5 years) published articles
when available. Databases searched include PubMed, Cochrane Library, Google Scholar,
Embase, Web of Science, and CINAHL. Search terms included opioid use disorder, OUD, OUD
anesthesia, methadone, methadone anesthesia, buprenorphine, buprenorphine anesthesia,
buprenorphine perioperative, naltrexone, naltrexone anesthesia, and naltrexone perioperative.
PERIOPERATIVE MAT MEDICATION MANAGEMENT 8
PubMed MeSH search terms were also utilized and consisted of the same search terms
previously identified. See Figure 1 in Appendix B for a complete PRISMA database search
documentation flow diagram (Moher et al., 2009).
Search inclusion criteria included adult patients taking methadone, buprenorphine, or
naltrexone undergoing an elective or emergent surgical procedure. Exclusion criteria included
studies with sample populations under 18 years old and pregnant females. The literature search
was terminated when no additional articles were found using the search criteria and terms or
when saturation of information had been obtained. At the time of this literature search there were
no randomized control trials published regarding the perioperative management of methadone,
buprenorphine, or naltrexone. The available literature consists of expert opinion based on the
pharmacology of the aforementioned medications and case reports. A literature matrix
summarizing key features of each article is included in Table 3 located in Appendix C.

PERIOPERATIVE MAT MEDICATION MANAGEMENT 9
Chapter 3
Literature Review
Methadone
A thorough review of current literature reveals a lack of clinical and experimental studies
to create evidence-based guidelines for patients chronically taking methadone. Although multiple
published papers are available with recommendations regarding the perioperative management of
chronic methadone patients, many of the recommendations are expert opinion based on the
existing knowledge of methadone’s pharmacodynamics and pharmacokinetics.
One question in regard to the perioperative care of chronic methadone patients is whether
to continue the methadone perioperatively, including on the day of surgery. Limited research
exists regarding this topic. Multiple narrative review and expert opinion articles support the
continuation of methadone for the entire perioperative period (Sen et al, 2016; Coluzzi et al.,
2017, Harrison et al., 2018, ). A 2013 retrospective cohort study of 29 patients taking methadone,
(Macintyre, Russell, Usher, Gaughwin, and Huxtable) found pain score differences were not
statistically significant between patients whose methadone was continued in the first twenty-four
postoperative hours and those patients where the usual methadone dose is withheld. Macintyre et
al. (2013) ultimately recommended methadone be continued perioperatively. One retrospective
case control study by Chan et al. (2017) of 36 patients undergoing a unilateral total knee
arthroplasty supports the perioperative continuation of methadone; however, this was not the aim
of the study.
Methadone patients are generally considered to have hyperalgesia and opioid tolerance
necessitating increased doses of opiates for acute pain management (Cornett et al., 2019;
PERIOPERATIVE MAT MEDICATION MANAGEMENT 10
Anitescu, 2019; Ward et al., 2018). Chan et al. (2017) found methadone patients whose
methadone was continued perioperatively had a 6-fold increase in postoperative opioid use,
required more referrals to pain specialists, and had longer hospitalizations as compared to
patients not taking methadone. In a prospective cohort study of 17 patients taking methadone or
buprenorphine/naloxone, Hansen et al. (2016) found these patients to have higher morphine-
equivalent requirements for pain control as compared to 34 control patients not taking either
drug. They also found adequate pain control was achievable with intravenous (IV) patient-
controlled analgesia, intermittent IV analgesia, and/or oral opioids but at higher dosages. While
Hansen et al.’s (2016) findings support the use of higher doses of opioids in methadone patients,
the study does not delineate how many of the 17 patients were taking methadone and whether or
not those patients’ methadone was continued perioperatively.
Although studies specific to methadone patients have not been conducted, it is generally
accepted by experts that opioid sparing, multimodal anesthesia is preferred (Sen et al, 2016;
Myers & Compton, 2017; Ward et al., 2018;). Narrative reviews suggest the utilization of an
intraoperative ketamine or lidocaine infusion may be helpful to reduce postoperative pain (Sen et
al., 2016; Myers & Compton, 2017; Cornett et al., 2019; Anitescu, 2019). In a 2019 randomized
control trial on 180 OUD patients, Sahmeddini, Khosravi, and Farbood found patients reported
lower pain scores, consumed less morphine, and were less drowsy or restless when an
intraoperative lidocaine infusion was utilized as compared to a ketamine or normal saline
infusion. Sahmeddini et al. (2019) found both lidocaine and ketamine infusions decreased
postoperative pain scores and morphine consumption when compared to normal saline, with
lidocaine improving postoperative pain more than ketamine, and ketamine more than normal
saline. The study by Sahmeddini et al. (2019) did not describe what preoperative medications
PERIOPERATIVE MAT MEDICATION MANAGEMENT 11
their patient population was taking, simply describing the sample population as using natural or
semisynthetic opioids; whether or not these medications were continued in the perioperative
phase was also not discussed. A postoperative ketamine infusion has been demonstrated to lower
hydromorphone consumption in opioid tolerant patients, as evidenced in a 2019 randomized
control trial by Boenigk et al. of 129 patients. A limitation to this study is the sample population,
which is not a majority nor exclusively methadone patients.
A case report of a 50-year-old male on chronic methadone having a parotidectomy under
general anesthesia (Barelli, Morelli Sbarra, Sbaraglia, Zappia, and Rossi, 2019) reported
adequate pain control, stable hemodynamics, and a lack of psychomimetic symptoms was
achieved with a multimodal pain management strategy including perioperative continuation of
the patient’s methadone, a perioperative ketamine infusion, and a postoperative tramadol
infusion.
Buprenorphine
Current recommendations for the perioperative management of buprenorphine are based
on the pharmacology of the drug, case studies, and expert opinion. As of the writing of this
manuscript there are no higher levels of evidence to guide perioperative buprenorphine
management. The articles reviewed have varying degrees of differing opinions and
recommendations.
Based off pharmacology and case reports Bryson, Lipson, and Gevirtz (2010) conclude
patients on buprenorphine require higher doses of opioid agonists due to the development of
opioid tolerance. The authors identify a case study where a patient undergoing breast implant
removal under general anesthesia had successful pain management with additional
PERIOPERATIVE MAT MEDICATION MANAGEMENT 12
buprenorphine doses (2 to 4 mg every 4 to 6 hours) in conjunction with her 24 mg per-day
maintenance dose. However, due to a possible analgesic ceiling effect, increasing the dose of
buprenorphine may not always lead to adequate pain relief. Other recommendations include
dividing the maintenance dose of buprenorphine over a 24-hour period, replacing buprenorphine
with methadone and adding other full opioid agonists, or replacing buprenorphine with a full
opioid agonist. The authors conclude standard opioid-based anesthetic techniques may not be
sufficient and alternate techniques including regional anesthesia and non-opioid medications
should be utilized. The authors do not provide a decisive recommendation for the perioperative
management of buprenorphine.
Citing the same breast implant removal case study, Gevirtz, Frost, and Bryson (2011)
came to the same general conclusion as Bryson, Lipson, and Gevirtz (2010) regarding
perioperative buprenorphine management. The authors conclude buprenorphine use will increase
a patient’s tolerance to opioid agonists thereby a higher dose will be required to achieve
analgesia and alternate methods should be utilized to achieve adequate pain control. The authors
do not suggest specific recommendations or guidelines for perioperative buprenorphine
management, only advocate the need for multimodal anesthesia in this patient population.
Harrison, Kornfeld, Aggerwal, and Lembke (2018) recommend the continued use of
buprenorphine for most patients and utilizing multimodal anesthesia for pain management. The
authors recommendations are based off four case reports involving patients maintained on
buprenorphine; two involving difficult postoperative pain management and two involving
adequate pain management when combined with multimodal anesthesia. The authors identify
extenuating circumstances in the cases where adequate postoperative pain management was not
achieved including intraoperative nerve injury, inadequate buprenorphine dosing, and failure to
PERIOPERATIVE MAT MEDICATION MANAGEMENT 13
utilize multimodal anesthesia. When full opioid agonists are needed for adequate pain
management and the patient is taking buprenorphine, the authors suggest using an opioid that has
a high mu receptor binding affinity such as sufentanil, fentanyl, or hydromorphone in order to
compete with the high receptor binding affinity of buprenorphine.
Roberts and Meyer-Witting (2005) do offer specific recommendations for
buprenorphine management based off of their expert opinion, clinical experience, and literature
recommendations. Their general recommendations include maximizing non-opioid analgesia,
local anesthetic techniques, and adjunctive therapeutic options for all types of procedures. For
elective minor procedures they recommend continuing buprenorphine at the maintenance dose
and, if additional pain management is needed, increase the dose by twenty-five percent. For
elective major procedures they recommend either increasing the buprenorphine dose by twenty-
five percent and adding additional high dose full opioid agonists, if needed, or converting the
patient to a full opioid agonist, like methadone, prior to surgery. A potential complication to
converting to a full opioid agonist is the unpredictability of the half-life of buprenorphine due to
patient age, dose-dependency, and variable absorption. For emergent procedures, the last dose of
buprenorphine should be ascertained if possible. As buprenorphine is metabolized, the dose
requirement of a full opioid agonist needed for adequate pain relief may decrease. The authors do
not provide further recommendations for buprenorphine management for emergent procedures.
Anderson et al. (2017) highlight the University of Michigan Health System’s protocol for
perioperative buprenorphine management. The protocol includes elective and urgent/emergent
procedures and continuation of buprenorphine is based on anticipated postoperative pain. If
minimal to no pain is anticipated for either elective or urgent/emergent procedures, the
recommendation is to continue buprenorphine use; consider adjuncts including NSAIDS,
PERIOPERATIVE MAT MEDICATION MANAGEMENT 14
acetaminophen, local anesthetics and regional anesthesia; and to not routinely prescribe
supplemental opioids. If moderate to severe pain is anticipated for elective procedures, the
patient is tapered off buprenorphine with discontinuation based off the maintenance dose (0-4
mg per day stopping 24 hours prior to surgery; >4-8 mg per day stopping 48 hours prior to
surgery; and >8-12 mg per day stopping 72 hours prior to surgery). For anticipated moderate to
severe pain in urgent/emergent procedures, the protocol suggests discontinuing buprenorphine,
starting patient controlled analgesia (PCA) with a full opioid agonist with proper monitoring,
utilizing regional anesthesia if appropriate, and maximizing non-opioid adjuncts. The authors
argue continued perioperative buprenorphine use should be considered in patients where regional
anesthesia will most likely minimize postoperative pain or in patients who are at high risk for
substance abuse relapse. The authors further advocate for early discussion with the patient and
well-informed providers regarding perioperative buprenorphine use, with a particular emphasis
on postoperative pain management.
After reviewing twelve articles, Jonan, Kaye, and Urman (2018) came to the same
conclusions regarding perioperative buprenorphine management as Anderson et al. (2017).
Based on information gathered from the articles (which includes six reviews, four case reports,
one prospective cohort study, and one retrospective cohort study) and the ceiling effect from
buprenorphine’s partial agonist activity, the authors conclude buprenorphine should be
discontinued in elective and urgent cases where the anticipated postoperative pain is significant.
In elective and urgent cases where the anticipated postoperative pain is not anticipated to be
significant, the authors recommend continuing perioperative buprenorphine. As with other
studies, the authors advocate for early communication and planning if buprenorphine will be
discontinued, and non-opioid adjuncts and regional anesthesia should be used when possible.
PERIOPERATIVE MAT MEDICATION MANAGEMENT 15
Ward, Quaye, and Wilens (2018) conclude, at the time of their publication, there is not a
consensus on the perioperative management of buprenorphine and there is not substantial
evidence to support the automatic discontinuation of buprenorphine preoperatively. The authors
cite several case reports involving poorly controlled postoperative pain with high doses of opioid
agonists when buprenorphine has been continued and further contradictory case reports that
recommend the continuation of buprenorphine. The authors compare protocols from the
University of Michigan Health System (previously mentioned), Boston Medical Center, and the
University of Kentucky Heath Care regarding perioperative management of patients receiving
buprenorphine-naloxone. For procedures with anticipated minimal to no pain, all facilities
recommend the continuation of buprenorphine and adding acetaminophen or non-steroidal anti-
inflammatory drugs (NSAIDs) if needed. For procedures with anticipated moderate to severe
pain, University of Michigan recommends stopping buprenorphine at least five days prior to the
procedure, Boston Medical Center recommends holding buprenorphine the day of surgery, and
University of Kentucky recommends continuing buprenorphine. The authors highlight the lack of
consistency regarding perioperative management of buprenorphine and argue for continued
buprenorphine use to prevent relapse thereby increasing patient stability. They further argue
when buprenorphine is prescribed and taken within the therapeutic range it does not occupy one
hundred percent of mu opioid receptors. The unoccupied mu receptors are available for a full
opioid agonist if additional pain management is needed. In conclusion, the authors advocate for
the use of regional and nonopioid adjuncts in addition to continuing buprenorphine
perioperatively.
After a systematic literature review involving eighteen studies, Goel et al. (2018) also
conclude there is no evidence against continuing buprenorphine perioperatively. Amongst
PERIOPERATIVE MAT MEDICATION MANAGEMENT 16
sixteen case reports, every patient whose preoperative buprenorphine was discontinued
experienced poorly controlled postoperative pain. On the other hand, all of the cases except for
one where buprenorphine was continued had controlled postoperative pain. The authors further
argue that continuing perioperative buprenorphine leads to lower relapse rates. The authors do
not make further recommendations on dosage adjustments of buprenorphine, only advocate for
continued perioperative use.
Sen et al. (2016) discuss the different options of perioperative buprenorphine
management including discontinuing buprenorphine, converting to methadone, continuing the
maintenance dose of buprenorphine, or dividing the maintenance dose into every six or eight
hour dosing cycles. However, the authors do not give a recommendation on which pathway to
follow. Due to higher relapse rates when buprenorphine is tapered rapidly over three days, the
authors recommend gradually decreasing the dose by 2 mg every two to three days over the
course of two to three weeks with complete discontinuation 72 hours prior to surgery. If the
patient is unable to tolerate tapering buprenorphine due to the development of withdrawal
symptoms they may convert to methadone. Like previous studies, the authors note if
buprenorphine is continued the patient may require higher doses of opioid agonists to compete
with mu receptor binding. Dividing the daily buprenorphine dose into every six or eight hour
dosing cycles utilizes buprenorphine’s analgesic properties. However, the authors argue this
regimen is only appropriate for anticipated mild to moderate pain due to a ceiling effect at 32 mg
per day sublingual doses. Similar to previous studies, the authors advocate for the use of
multimodal analgesia regardless of whether perioperative buprenorphine is continued or not.
A case report by Silva and Rubinstein (2016) discusses a single patient who had a total
knee arthroplasty once on each knee, two years apart. For the first procedure the patient was
PERIOPERATIVE MAT MEDICATION MANAGEMENT 17
taking sublingual buprenorphine, 24 mg per day in three divided doses, for chronic pain and
buprenorphine was continued perioperatively at the maintenance dose. The patient reported
adequate pain management with 500 mg total morphine equivalence (ME) per week of
hydrocodone in addition to buprenorphine over the thirteen week postoperative course.
Approximately two years later, the patient presented for the same procedure on the contralateral
knee and had been taking oral hydrocodone 80 mg daily for chronic pain management. The
patient declined being transitioned back to buprenorphine. The procedure was performed by the
same surgeon with the same operative anesthesia protocol and the same postoperative treatment
plan. Postoperatively the patient required higher PCA doses than the previous surgery, was in the
hospital one day longer, was taking oxycodone 1575 mg ME per week over the sixteen week
postoperative course. Despite this, the patient reported poorly controlled pain.
Silva and Rubinstein (2016) further discuss the analgesic properties of buprenorphine,
question the validity of buprenorphine having an analgesic ceiling effect, and question
buprenorphine’s ability to block the analgesic effects of other opioid agonists. In in vivo studies,
buprenorphine has achieved comparable pain control to full opioid agonists in 25 of 26 studies,
and a ceiling effect for analgesia in humans has yet to be demonstrated. A study comparing
binding affinity demonstrated sufentanil having a higher affinity and hydromorphone having a
comparable affinity to buprenorphine; therefore, buprenorphine’s binding affinity should not
negate the ability to achieve pain relief when combined with another full mu agonist. Based off
of this information, their case study, and previous studies, the authors conclude buprenorphine
should be continued perioperatively.
Lembke, Ottestad, and Schmiesing (2019) conclude buprenorphine should be continued
perioperatively, even in urgent/emergent cases, and high dose buprenorphine should be tapered
PERIOPERATIVE MAT MEDICATION MANAGEMENT 18
down to 12 mg per day two to three days prior to an elective procedure. The authors came to this
conclusion based on case reports, experience, and expert opinion. The authors argue
discontinuing buprenorphine is an unnecessary risk for the patient in regard to increasing the
management complexity of buprenorphine and increasing the potential for relapse. As of the date
of publication there are no studies involving tapering high doses of buprenorphine prior to
elective procedures. However, receptor occupancy studies using positron emission tomography
scanning reveal a dose response curve where 59% of mu opioid receptors were available with
buprenorphine 2 mg dose, 20% of receptors were available at 16 mg, and 16% available at 32
mg. The authors based their recommendation of tapering buprenorphine to 12 mg off of the
binding study and their clinical experience. At this dose it is clinically simple to taper a patient
over two to three days (unless the patient starts to exhibit withdrawal symptoms, then the authors
recommend keeping the patient on their regular dose), and there is available mu opioid receptors
to bind full opioid agonists if further pain management is needed. With buprenorphine dosages
under 12 mg the authors recommend continuing the dose throughout the perioperative period. If
a patient had been tapered down to buprenorphine 12 mg, the authors recommend returning to
the patient’s regular maintenance dose as soon as possible postoperatively. For either case, and
similar to other literature recommendations, the authors point out this patient population may
require higher doses of opioid medications than opioid naïve patients and they advocate for the
use of multimodal anesthesia.
Naltrexone
Guidelines for the perioperative management of naltrexone are mainly based off the
pharmacology followed by case reports. Since naltrexone is an opioid antagonist it will need to
be discontinued prior to surgery in order for opioid agonists to be effective for pain management.
PERIOPERATIVE MAT MEDICATION MANAGEMENT 19
Bryson (2014) and Ward et al. (2018) come to similar conclusions regarding naltrexone
management. Based off the half-life and metabolism of naltrexone, the oral formulation should
be discontinued at least 72 hours prior to a procedure and the extended release intramuscular
injectable formulation should be discontinued at least four weeks prior to a procedure. Both
authors discuss the potential for opioid receptor upregulation with chronic opioid antagonist
usage. This patient population may have an exaggerated response to an opioid agonist in the
absence of naltrexone. In the case of an urgent/emergent procedure where naltrexone is not
discontinued, the competitive blockade of opioid receptors by naltrexone may be overcome with
10-20 times the usual dose by weight of an opioid agonist (Bryson 2014). The authors further
recommend the use of multimodal analgesia and patient education regarding the discontinuation
and reinstatement of naltrexone to avoid relapse.
Curatolo and Trinh (2014) discuss a case report involving a 22-year-old woman on
extended-release naltrexone undergoing a total thyroidectomy and unilateral neck dissection for
thyroid cancer. The patient’s last dose of extended-release naltrexone was three and a half weeks
prior to the procedure. In her case, adequate pain management was achieved with multimodal
anesthesia involving intraoperative nitrous oxide along with propofol, ketamine, and remifentanil
infusions. Postoperative pain was managed with a unilateral superficial cervical plexus block
using 15 mL of 0.25% bupivacaine and acetaminophen. The patient reported adequate pain
management, was discharged home on postoperative day 1, and did not require any further pain
medications. This case suggests it is possible for the opioid receptor blockade by naltrexone to be
overcome in the fourth week of dosing. As with the previous authors, Curatolo and Trinh discuss
the potential for increased opioid sensitivity due to opioid receptor upregulation. Remifentanil
was chosen for this patient to ensure there would not be any residual opioid effect in the
PERIOPERATIVE MAT MEDICATION MANAGEMENT 20
postanesthesia care unit. The authors also recommend the use of multimodal analgesia for this
patient population.
Ninh, Kim, and Goldberg (2017) describe a case report involving a 42-year-old woman
taking oral naltrexone-bupropion extended-release (contains naltrexone 16 mg and bupropion
180 mg) for weight loss who underwent urgent anterior cervical discectomy and fusion to relieve
paresthesia due to disk herniation. The patient had taken naltrexone-bupropion within 12 hours
of surgery. Preoperatively, the patient received acetaminophen 1000 mg and gabapentin 600 mg.
Intraoperative management included intravenous fentanyl and infusions of propofol, ketamine
and remifentanil. Liposomal bupivacaine was injected by the surgeons at the end of the case.
Postoperative pain management included a hydromorphone PCA that was transitioned to oral
hydromorphone on postoperative day 1. The patient reported inadequate pain management
despite the multimodal approach. For urgent procedures the authors recommend multimodal
analgesia with the understanding that it may not adequately manage postoperative pain. Their
conclusion is that more research is necessary to develop a pain management strategy for this
patient population.

PERIOPERATIVE MAT MEDICATION MANAGEMENT 21
Chapter 4
Results
Methadone and Elective Surgery
In the scenario of a methadone MAT patient coming for elective surgery, anesthesia and
pain management plans should be created well before the day of surgery. The patient should
meet with the anesthesia provider to allow the provider ample time to address patient concerns,
provide education on available pain control techniques (including self-pain management
strategies), and create a multimodal pain management plan with realistic goals for pain control
and specific indications for opioid use (Sen et al., 2016; Giron, Olson, Griffis, & Compton,
2018). At this meeting, patients should be assessed for the risk of relapse; including an inquiry
into the number of relapses in the past and possible triggering events or causes for relapse that
can be avoided (Giron et al., 2018). Ward et al. (2018) recommended discharge planning be
initiated early and must include education on the safe use of any opioids prescribed for
postoperative pain, a taper schedule for opioids, and how to properly store and dispose of
opioids. For patients at higher risk of relapse (such as those with a high number of relapse
events), discharge planning can also include arranging for a nurse to visit the patients at home for
medication dispensing, ensuring that there is no active abuse of opioids, and to assess for any
side effects from the addition of opioids (Ward et al., 2018). Giron et al. (2018) emphasized the
importance of having a mutually agreed upon perioperative plan for pain control. The creation of
a written plan and/or contract may be beneficial to reassure patients with anxieties regarding
inadequate pain control or relapsing (Giron et al., 2018). Prior to surgery, the anesthesia provider
must consult with the methadone prescriber and confirm the patient’s methadone maintenance
dosing (Ward et al., 2018).
PERIOPERATIVE MAT MEDICATION MANAGEMENT 22
On the day of surgery, the patient should take their usual methadone dose (Coluzzi et al.,
2017; Ward et al., 2018; Sen et al., 2016). The perioperative use of multimodal analgesia is
highly recommended, as is the continuation of the patient’s maintenance methadone dosing
throughout the perioperative period (Ward et al., 2018; Sen et al., 2016; Giron et al., 2018). The
anesthesia provider must anticipate potential interactions between methadone and any
medications that are co-administered as part of the anesthesia plan; increased levels of sedation
and respiratory depression may result with the administration of benzodiazepines, opiates, or
other CNS depressants (Ward et al., 2018; Sen et al., 2016). Due to opioid-induced hyperalgesia,
the anesthesia provider may also anticipate higher reported pain scores and pain levels that
decrease more slowly when compared to opioid-naive patients (Coluzzi et al., 2017). Pain is to
be treated promptly and aggressively (Coluzzi et al., 2017; Ward et al., 2018). Experts (Coluzzi
et al., 2017; Harrison et al., 2018) suggest dividing the total maintenance dose of methadone and
administering every 6-8 hours may improve pain control. While additional doses of methadone
can be used for analgesia, the methadone prescriber must be consulted before up-titration is
implemented (Harrison et al., 2018). In the event that methadone cannot be administered orally,
consultation with a pharmacist ought to be made for assistance in converting oral dosing to
intravenous. Typically, the oral daily dose of methadone is reduced by 50% and administered in
divided doses every 6-8 hours (Adam et al., 2016; Harrison et al., 2018; Sen et al., 2016). If
necessary, opioids can be given but considerations must be made for the cross-tolerance
methadone patients develop to opioids that necessitate higher doses to achieve a desired effect, in
addition to the potential increased risk of respiratory depression (Adam et al., 2016; Coluzzi et
al., 2017; Ward et al., 2018; Harrison et al., 2018). The administration of partial opioid agonists
PERIOPERATIVE MAT MEDICATION MANAGEMENT 23
(such as buprenorphine or butorphanol) is not recommended as withdrawal symptoms may be
precipitated (Adam et al., 2016; Coluzzi et al., 2017; Ward et al., 2018).
Practice Recommendations. In the planned elective surgery scenario, the anesthesia
provider should seek confirmation of the patient’s daily methadone dose to plan for continued
administration during the perioperative period; this includes ensuring the patient received their
normal scheduled dose preoperatively. Consultation with the methadone prescriber may be
beneficial in determining if dividing the maintenance dose for more frequent administration
intervals would be helpful in postoperative pain management. Anesthesia providers should
maximize non-opioid and multi-modal analgesia techniques intraoperatively and postoperatively.
The patient’s pain should be treated aggressively, with the anticipation of hyperalgesia and the
possibility for a higher opioid requirement. See Table 1 for a chart summary of practice
recommendations.
Methadone and Emergent Surgery
There are few published recommendations for the perioperative management for the
methadone-maintained MAT patient, specific to emergency surgery. Several principles from
elective surgery recommendations can be extrapolated to the emergency scenario, including
determining the patient’s maintenance dose of methadone, continuing perioperative methadone,
having awareness of existing hyperalgesia and opioid tolerance, and monitoring for over-
sedation or respiratory distress with co-administration of CNS depressants. “Methadone
Hydrochloride” (n.d.) states that because of the risk for respiratory depression and subsequent
elevation in intracerebral pressure, methadone should be used with caution in patients who have
suffered head trauma and avoided in patients with impaired levels of consciousness. Methadone
PERIOPERATIVE MAT MEDICATION MANAGEMENT 24
use may worsen biliary tract disease (such as acute pancreatitis), and should be avoided in
gastrointestinal obstruction or in suspected/known ileus (“Methadone Hydrochloride,” n.d.).
Multimodal pain management techniques should again be utilized. Infusions of ketamine or
alpha-2 agonists can provide intra- and postoperative pain relief, but patients should be
monitored for signs of withdrawal (Coluzzi et al., 2017; Sen et al., 2016). If methadone
maintenance is interrupted for more than five days, consultation with the patient’s methadone
provider must be made before restarting.
Practice Recommendations. For the emergent surgery scenario, the practice
recommendations are like those for the elective surgery scenario. Discontinuation of methadone
for hemodynamic or another reason necessitates observation of withdrawal symptoms.
Consultation with the prescribing provider should be made prior to restarting the patient’s
maintenance dosing if the methadone is held for longer five days. See Table 1 for a chart
summary of practice recommendations.
Buprenorphine and Elective Surgery
Elective surgery preparation for the patient on buprenorphine should begin with a
thorough patient assessment regarding the indication for buprenorphine use, formulation, and
dosage. In addition to treatment for OUD, buprenorphine is also used to treat chronic pain
(“Buprenorphine: Drug Information,” n.d). The two main buprenorphine formulations are
sublingual and a long acting implant. Sublingual buprenorphine dosage ranges from 4 mg to 32
mg per day with most patients falling in the 8 to 16 mg per day range. The buprenorphine
implant provides a steady, low-dose drug delivery of 8 mg or less per day (Strain, n.d). As with
PERIOPERATIVE MAT MEDICATION MANAGEMENT 25
methadone, multidisciplinary communication regarding patient concerns, pain management, and
buprenorphine management need to be addressed prior to surgery.
Current perioperative buprenorphine management strategies are based on observational
studies, case reports and expert opinion; there is no strong consensus nor higher level evidence to
guide practice (Anderson et al., 2017 and Goel et al., 2019). The main question, whether to
continue or stop buprenorphine throughout the perioperative period, remains. The patient’s
buprenorphine dosage and anticipated surgical pain should be taken into consideration when
deciding to continue or discontinue preoperative buprenorphine. Based on available studies and
case reports there is not sufficient evidence in support of automatically discontinuing
preoperative buprenorphine, and OUD patients have lower relapse rates when buprenorphine is
continued (Goel et al., 2019). However, due to buprenorphine’s high opioid binding affinity and
receptor occupancy (24 to 32 mg doses may occupy up to 95% of opioid receptors),
buprenorphine discontinuation prior to surgery may need to be considered for patients
undergoing a procedure that is anticipated to yield moderate to severe postoperative pain
(Anderson et al., 2017). It is plausible patients who are on a higher dose of buprenorphine and/or
are undergoing a moderate to severely painful procedure may not have enough opioid receptors
free to bind opioid pain medication to adequately control acute surgical pain. If buprenorphine is
to be discontinued prior to surgery, the dose needs to be tapered down over a period of 2 to 3
weeks, decreasing the dose by 2 mg per day every 2 to 3 days, and the patient should be
completely off buprenorphine for 72 hours prior to surgery to ensure adequate elimination (Sen
et al., 2016).

If buprenorphine will be maintained throughout the perioperative period, the daily dose
can be divided into every 6 or 8-hour dosing cycles to utilize its analgesic effects. If opioids are
PERIOPERATIVE MAT MEDICATION MANAGEMENT 26
required to achieve adequate pain control, higher doses may be required and opioids that have
higher mu binding activity should be used such as fentanyl or hydromorphone (Sen et al., 2016).
Regardless of whether or not buprenorphine therapy will be continued throughout the
perioperative period, multimodal anesthesia should be utilized to ensure adequate pain
management (Ward, Quaye, & Wilens, 2018).
Practice Recommendations. Practice recommendations for the elective surgical
scenario vary depending on the expected amount of postoperative pain. If minimal pain is
anticipated postoperatively, the verified dose of buprenorphine should be continued throughout
the perioperative period. Consideration could be made to divide the daily maintenance dose for
administration every 6-8 hours to maximize analgesia. If the postoperative pain is expected to be
moderate or severe, it is considered optional to continue buprenorphine perioperatively.
Discontinuing buprenorphine preoperatively necessitates a planned tapering of the dose, with
discontinuation occurring 24-72 hours prior to surgery. Should buprenorphine be continued
perioperatively, the daily maintenance dose could be divided and administered every 6-8 hours to
aid in pain management. The anesthesia provider should maximize multi-modal analgesia
techniques and anticipate the possible need for higher opioid dosages (should opiates be
necessary to achieve pain control). Consultation with the buprenorphine subscriber and patient
should take place prior to the procedure to make a pain management plan. See Table 1 for a chart
summary of practice recommendations.
Buprenorphine and Emergent Surgery
The same decision tree for elective surgery may be used on a patient with buprenorphine
use who is presenting for emergent surgery. If post-surgical pain is expected to be minimal,
PERIOPERATIVE MAT MEDICATION MANAGEMENT 27
buprenorphine use may be continued throughout the perioperative period (Anderson et al., 2017).
Pain management should include non-opioid adjuncts like acetaminophen and NSAIDs. If
moderate to severe pain is anticipated, buprenorphine use may be discontinued to ensure
adequate opioid receptor availability for acute pain management. Regional anesthesia and
adjuncts should also be utilized. Patients on buprenorphine may also have increased tolerance to
opioid medications, and larger doses may be required in order to achieve adequate analgesia
(Athanasos et al., 2019, and Anderson et al., 2017).
Practice Recommendations. For the emergent surgery scenario, practice
recommendations are identical as those for the elective scenario. Should minimal pain be
anticipated postoperatively, the verified dose of buprenorphine should be continued throughout
the perioperative period. If the postoperative pain level is expected to be moderate or severe,
continuation of buprenorphine perioperatively is optional. Should buprenorphine be continued be
continued perioperatively, the daily maintenance dose could be divided and administered every
6-8 hours to aid in pain management. The anesthesia provider should maximize multi-modal
analgesia techniques and anticipate the need for higher opioid dosages. The buprenorphine
subscriber should be consulted regarding post-surgical pain management. See Table 1 for a chart
summary of practice recommendations.
Naltrexone and Elective Surgery
When evaluating a patient on naltrexone prior to elective surgery, the reason for
naltrexone use should be established. In addition to naltrexone’s use in treating OUD, it is also
used in the treatment of alcohol use disorder, has an off-label use for the treatment of cholestatic
pruritus (“Naltrexone: Drug Information,” n.d.), and is used as a weight loss medication in
PERIOPERATIVE MAT MEDICATION MANAGEMENT 28
combination with bupropion. Multidisciplinary conversations regarding opioid agonist use in the
perioperative setting should take place prior to surgery in order to address patient questions and
concerns, and to ensure adequate patient education about proper opioid use for acute pain,
tapering medication, and proper disposal (Ward et al., 2018).
Due to naltrexone’s opioid receptor antagonism, it should be discontinued prior to
surgery. Oral naltrexone should be discontinued at least 72 hours prior to surgery. Extended
release intramuscular naltrexone should be discontinued at least 30 days prior to surgery and oral
naltrexone may be used temporarily (“Naltrexone: Drug Information,” n.d.). If opioid agonists
are needed to manage acute perioperative pain, extra caution should be taken regarding the
dosage. Opioid use disorder patients on naltrexone experience a loss of tolerance to opioids, and
naltrexone use is associated with an increase in density of opioid receptors due to receptor
upregulation (Ward et al., 2018, and Strain, n.d., and Bryson 2014). A loss of tolerance to opioid
agonists coupled with an increase in opioid receptors places this patient population at a particular
risk of experiencing an exaggerated response to the effects of opioids. Pain management should
include non-opioid strategies like regional anesthesia and nonopioid adjuncts (Ward et al., 2018).
Practice Recommendations. For the elective surgical scenario, naltrexone must be
discontinued preoperatively for standard opioid doses to be effective in pain management
intraoperatively and postoperatively. Pre-operative naltrexone medication adjustments and
alternative therapies need to be discussed with the naltrexone provider and the patient to ensure a
perioperative pain management strategy is in place. Orally administered naltrexone should be
discontinued 72 hours prior to surgery while extended release injections of naltrexone should be
discontinued 30 days prior to surgery. Non-opioid analgesia strategies should be maximized.
PERIOPERATIVE MAT MEDICATION MANAGEMENT 29
Should opiates be necessary for adequate pain control, sensitivity to administered opioids should
be monitored for. See Table 1 for a chart summary of practice recommendations.
Naltrexone and Emergent Surgery
The patient on naltrexone who presents for emergent surgery is particularly challenging
in regards to pain management. Non-opioid pain management strategies should be utilized since
standard dosing of opioid agonists may not be effective (Ward et al., 2018). The competitive
opioid receptor blockade by naltrexone may be overcome by dosing opioid agonists 6 to 20 times
the usual dosage by weight (Harrison, Kornfield, Aggarwal & Lembke, 2018, and Bryson, 2014).
These patients should be closely monitored postoperatively due to their potential for having an
altered response to opioids (Ward et al., 2018). Discharge planning should include patient
education regarding proper opioid use, tapering, and disposal as well as a plan to re-start
naltrexone once the patient is no longer taking opioid agonists for acute pain management.
Practice Recommendations. The emergent surgical scenario will necessitate high
dosages of opioids be administered to achieve pain control. Non-opioid analgesia techniques
should be utilized to the fullest extent. The naltrexone prescriber, in conjuction with the patient,
should be consulted regarding postoperative pain management medications, tapering opioid
medications, and when to resume naltrexone. See Table 1 for a chart summary of practice
recommendations.

PERIOPERATIVE MAT MEDICATION MANAGEMENT 30
Chapter 5
Discussion
The perioperative management of the OUD patient on methadone, buprenorphine, or
naltrexone is a complex clinical problem. With an increasing OUD population, it is probable
anesthesia providers will encounter an increasing number of patients maintained on one of the
aforementioned drugs. In elective procedures a discussion regarding the perioperative
management of the patient’s OUD medication, pain management, and, if needed, a plan
regarding postoperative opioid medication usage should take place in advance of the procedure.
Regardless of what OUD medication a patient is maintained on, multimodal anesthesia and
analgesia should be maximized to decrease, or completely eliminate, the amount of additional
opioid medication needed to achieve adequate postoperative pain management.
Regarding the perioperative management of methadone, existing evidence and expert
opinion supports the continued use of perioperative methadone in both elective and emergent
procedures. However, methadone should be held in cases of known or suspected biliary tract
disease, gastrointestinal obstruction or ileus. Dividing the maintenance dose of methadone and
administering every 6-8 hours may improve pain control in combination with multimodal
analgesia. This patient population may exhibit hyperalgesia and opioid tolerance requiring
increased doses of opioids for adequate pain management.
Current evidence and expert opinion of the perioperative management of buprenorphine
concludes there is not significant evidence to support the automatic discontinuation of
preoperative buprenorphine, and the current recommendation is to continue buprenorphine in
elective or emergent cases where anticipated postoperative pain is mild. As with morphine,
buprenorphine’s analgesic properties may be further utilized when the maintenance dose is
PERIOPERATIVE MAT MEDICATION MANAGEMENT 31
divided into 6-8 hour intervals. In cases where the anticipated postoperative pain is moderate to
high, most case reports and opinions recommend discontinuing preoperative buprenorphine and,
in cases where the patient may not tolerate the taper due to withdrawal symptoms, may be
converted to methadone for OUD management. The recommendation to discontinue
buprenorphine in cases where moderate to high pain is anticipated is based on buprenorphine’s
partial opioid receptor antagonistic property, which may inhibit further opioid receptor binding
by full opioid agonists leading to inadequate pain control. However, Lembke et al. (2019) argue
high dose buprenorphine may be tapered down to 12 mg per day allowing for adequate mu
opioid receptor availability, thereby enabling adequate pain management with opioid agonists.
Given the current lack of further studies regarding specific buprenorphine tapering management,
the decision to taper down or discontinue preoperative buprenorphine in procedures with
anticipated moderate to high postoperative pain should be left to the discretion of the anesthesia
provider.
Due to naltrexone’s full opioid antagonistic properties it should be discontinued in
elective procedures, which is 72 hours for the oral formulation and 4 weeks for the long acting
intramuscular injection. However, one case report by Curatolo et al. (2014) documents adequate
postoperative analgesia when long acting naltrexone was given 3.5 weeks prior to the procedure,
calling into question the need for a patient to be off long acting naltrexone for 4 weeks. Patients
maintained on naltrexone may have an increase in opioid receptors due to receptor upregulation
leading to increased sensitivity to opioid agonists. Pain management may be particularly difficult
in patients taking naltrexone who present for urgent or emergency surgery. Maximizing
multimodal analgesia, including regional anesthesia, is crucial in this patient population since
PERIOPERATIVE MAT MEDICATION MANAGEMENT 32
adequate pain management may not be achievable with opioid agonists, even at much higher
doses.
Overall, patients with OUD presenting for surgery have unique perioperative
considerations that should be addressed in order to mitigate psychological stress the patient may
have due to concerns regarding pain and/or changes to their medication routine. Planning needs
to take place well in advance of the procedure date to ensure proper medication management and
to monitor for signs of withdrawal or urges to relapse. The use of multimodal analgesia should
be fully utilized to limit the need for postoperative opioid use. Adequate patient education and
support regarding proper use and disposal, as well as a plan for transitioning back onto their
MAT medication should be in place if postoperative opioids are needed after discharge.
Anesthesia providers will continue to see a growing number of patients on methadone,
buprenorphine, and naltrexone and it is imperative these patients are managed appropriately. See
Table 1 for a practice recommendation summary for each MAT medication and surgery scenario
based off current practices and the limited available recent research.
One limitation of this PIO project is the lack of current, high level research upon which to
build practice recommendations. Current recommendations for perioperative management are
based mostly on pharmacological knowledge of the drugs, expert opinion, and case reports.
Higher level research is necessary to better inform clinical practice.

PERIOPERATIVE MAT MEDICATION MANAGEMENT 33
Table 1 Practice Recommendation Summary Chart
Drug Surgery Type Recommendation
Methadone Elective
Surgery

Continue maintenance dosing throughout perioperative period.

Consider dividing total daily maintenance dose and administer every 6-8
hours.
Methadone Urgent/
Emergent
Surgery
Determine maintenance dose and continue throughout perioperative period.

Consider dividing total daily maintenance dose and administer every 6-8
hours.
Buprenorphine Elective
Surgery

MINIMAL TO NO PAIN ANTICIPATED
Continue maintenance dose throughout perioperative period.

Consider dividing total daily maintenance dose and administer every 6-8
hours.

MODERATE TO SEVERE PAIN ANTICIPATED
Consider continuation of buprenorphine throughout perioperative period.

Consider discontinuation of buprenorphine 24-72 hours prior to surgery.

If patient’s dose is >12 mg/day, consider tapering dose to <12 mg/day prior
to surgery.

Consider dividing total daily maintenance dose, administer every 6-8 hours.
Buprenorphine Urgent/
Emergent
Surgery
MINIMAL TO NO PAIN ANTICIPATED
Determine maintenance dose, consider continuation throughout
perioperative period.

Consider dividing total daily maintenance dose, administer every 6-8 hours.

MODERATE TO SEVERE PAIN ANTICIPATED
Determine maintenance dose, consider continuation throughout
perioperative period.

Consider discontinuation of buprenorphine and start PCA.

Consider dividing total daily maintenance dose and administer every 6-8
hours.
Naltrexone Elective
Surgery
Discontinue oral formulation at least 72 hours prior to surgery.

Discontinue extended release injection 30 days prior to surgery.
Naltrexone Urgent/
Emergent
Surgery
Maximize non-opioid pain management strategies.

Opioid receptor blockade by naltrexone may be overcome with high dose (6-
20 times usual dose by weight) opioid agonists.

Closely monitor patients postoperatively for potential altered response to
opioids secondary to opioid receptor upregulation.

PERIOPERATIVE MAT MEDICATION MANAGEMENT 34
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https://doi.org/10.18433/j3ns49

PERIOPERATIVE MAT MEDICATION MANAGEMENT 41
Appendices
Appendix A: Gap Analysis
Table 2 Gap Analysis
Classify the Problem Define Best Practice Measure Goals
Increasing numbers of
patients on MAT therapy for
OUD
Research available literature
on perioperative MAT
medication management
Increase in anesthesia
providers knowledge/comfort
regarding pain management
for MAT patients
Increasing number of patients
coming to surgery on MAT
Gather pain management
recommendations specific to
OUD patients taking MAT
Increase patient satisfaction
with pain control
MAT medications complicate
pain control for patients
Extrapolate current research
on MAT medications to
emergency surgery pain
management principles
Decrease morbidity for MAT
patients
Anesthesia providers lack
knowledge regarding MAT
implications for both elective
and emergent procedures
Write practice
recommendations for elective
and emergent surgery
scenarios

Patients on MAT face
consequences of providers’
knowledge deficit, including
inadequate pain control
Disseminate practice
recommendations

PERIOPERATIVE MAT MEDICATION MANAGEMENT 42
Appendix B: PRISMA Search Documentation Flow Diagram
Figure 1 PRISMA Search Documentation Flow Diagram

883 articles from PubMed
380 articles from CINAHL
258 articles from Cochrane Library
208 articles from Web of Science
218 articles from Embase
127 articles from Google Scholar

Screening Included Eligibility Identification

entification
Additional articles identified
through other sources
(n = 7)
Articles after duplicates removed
(n = 884)
Articles screened
(n = 884)
Articles excluded
(n = 806)
Full-text articles assessed
for eligibility
(n = 78)
Full-text articles excluded,
with reasons
(n = 48)
Articles included in
present literature review
(n = 30)
PERIOPERATIVE MAT MEDICATION MANAGEMENT 43
Appendix C: Literature Matrix
Table 3 Literature Matrix

Reference Summary of Main
Concept
Type Methods (Design,
instruments,
questionnaires)
Main Findings
Giron, S. E., Olson, R.
A., Griffis, C. A., &
Compton, P. (2018).
Guest editorial: The
opioid crisis and the
CRNA: caring for
opioid use disorder
patients in drug-free
recovery. AANA
Journal, 86(5), 82-87.
Retrieved from
https://www.aana.com/d
ocs/default-source
/aana-journal-web-
documents-1/guest-
editorial-aana-journal-
october-
2018.pdf?sfvrsn=4f075
4b1_4
Perioperative care of
OUD patient in
recovery
Quantitative

Small literature review OUD patients in drug free
recovery require perioperative
care, starting before surgery;
Myers and Compton
ComfortCare model has
recommendations for
management of OUD patient
Ward, E. N., Quaye, A.
N., & Wilens, T. E.
(2018). Opioid use
disorders: Perioperative
management of a
special population.
Anesthesia and
Analgesia, 127(2), 539-
547.
doi:10.1213/ANE.0000
000000003477
Buprenorphine,
methadone, and
naltrexone treatment
for OUD complicate
perioperative pain
management, need
multidisciplinary team
approach, use
multimodal anesthesia
Quantitative Literature review Preop planning, stopping or not
stopping med, pain
management, discharge
planning
Coluzzi, F., Bifulco, F.,
Cuomo, A., Dauri, M.,
Leonardi, C., Melotti,
R. M., . . . Corcione, A.
(2017). The challenge
of perioperative pain
management in opioid-
tolerant patients.
Therapeutics and
Clinical Risk
Management, 2017(13),
1163-1173. doi:
10.2147/TCRM.S14133
2
Inadequate pain
control for opioid
tolerant patients is
very common;
signs/symptoms of
opioid abuse and
withdrawal should be
assessed for
preoperative; patients
should be referred to
psychiatrists and
addition specialists
preoperative; gives
suggestions for
perioperative
management and
opioid conversion
Quantitative Narrative review,
expert opinion
Increasing probability of
needing to care for opioid
tolerant patient; opioid users
should take their usual opiate
dose the day of surgery;
Addiction Risk Questionnaire
can help ID patients w/opioid
tolerance; opioid dependent
patients have increased
morbidity and mortality;
suggestions for multimodal,
written opioid pain plan
agreement; use PCA; opioid
rotation allows for reduction in
dosing; analgesia nociception
index monitoring can be helpful
intraoperatively in addition to
assessing HR, pupil dilation,
PERIOPERATIVE MAT MEDICATION MANAGEMENT 44
BP; wound infiltration with
local, low dose ketamine,
regional help to control pain but
do not prevent withdrawal;
postoperative patient on
buprenorphine: if possible, stop
3 days preoperative as efficacy
of full agonists will be
decreased; if not possible, use
fentanyl or sufentanil; have
pain follow postop; don’t
withhold adequate pain control;
continue methadone
perioperative, acute pain
control on methadone requires
3-4 doses/day; first choice for
buprenorphine is to continue
perioperative then add short
acting opiate unless patient on
low dose, then give daily dose
every 6-8 hours, plan for patient
to have higher opiate needs;
naltrexone: timing of last dose
determines if patient will be
sensitive or tolerant to opioids,
discontinue use 1-3 days
preoperatively if possible and
opioids are planned to be used
intraoperatively (otherwise use
NSAIDS, ketamine, regional)
Sayal, P., Bateman, B.
T., Menendez, M.,
Eikermann, M., &
Ladha, K. S. (2018).
Opioid Use Disorders
and the Risk of
Postoperative
Pulmonary
Complications.
Anesthesia &
Analgesia, 127(3), 767-
774.
OUD likely have
opioid dose escalation
(r/t increased risk of
severe postop pain) in
the perioperative
period that increase
the risk of postop
pulmonary
complications
Quantitative Retrospective cross-
sectional analysis of
patients undergoing
one of 6 elective
surgical procedures,
data collected from
Nationwide Inpatient
Sample from 2002-
2011; total sample-
weighted cohort of
7,533,050 patients,
OUD pts more likely
to suffer complications
than non-opioid
dependent patients
(4.2% to 1.6%, P<
0.001), had 1.62 times
higher odds (95% CI,
1.16-2.27)
OUD patients are at an
increased risk for postop
pulmonary complications
(prolonged ventilation,
reintubation, acute respiratory
failure), prolonged LOS,
increased resource
utilization/cost of care;
multimodal pain control
approach would be beneficial,
OUD is a modifiable risk factor
that can be addressed
preoperatively
Harrison, T. K.,
Kornfield, H.,
Aggarwal, A. K., &
Lembke, A. (2018).
Perioperative
considerations for the
patient with opioid use
disorder on
buprenorphine,
methadone, or
Perioperative
management of MAT
medications
Quantitative Literature review,
expert opinion
Methadone: take day of
surgery, likely will need
additional opioids for pain
management due to opioid
tolerance, dividing dose into 3
doses may improve pain
management (references article
from 2003)
PERIOPERATIVE MAT MEDICATION MANAGEMENT 45
naltrexone maintenance
therapy. Anesthesiology
Clinics, 36(3), 345-359.
doi:
10.1016/j.anclin.2018.0
4.002
Adam, V.N., Matolić,
M, Stojčić, E.G., Mršić,
V., & Rašić Ž. (2017).
Acute pain management
in patient on opioid
substitution therapy
with methadone or
buprenorphine. Acta
medica Croatica, 70(3),
173-178.

A lack of education
and preexisting
misconceptions
regarding patients on
methadone and
buprenorphine
contribute to these
patients having
inadequate pain
control in the
perioperative setting
Quantitative Expert opinion,
literature review
Discusses preexisting
conceptions that contribute to
inadequate pain control of OUD
patients on methadone or
buprenorphine by health care
providers. Makes practice
recommendations
Hansen, L. E., Stone, G.
L., Matson, C. A.,
Tybor, D. J., Pevear, M.
E., & Smith, E. L.
(2016). Total joint
arthroplasty in patients
taking methadone or
buprenorphine/naloxone
preoperatively for prior
heroin addiction: a
prospective matched
cohort study. The
Journal of arthroplasty,
31(8), 1698-1701.
“The purpose of this
study is to compare
clinical outcomes of
patients undergoing
elective TJA while
concurrently being
treated with
methadone or
buprenorphine/naloxo
ne for prior heroin
addiction to a matched
control group.”
Quantitative Prospective cohort
study, 17 MAT pts, 34
control pts “From an
electronic medical
record, we collected
age, gender, body mass
index, the presence of
back pain, smoking
status, history of
alcohol abuse,
preoperative use of a
pain clinic, and use of
antipsychotics,
antidepressants, or
systemic
corticosteroids.
Validated outcome
measures including the
12-Item Short Form
Survey, Knee Society
Score (KSS), and
Harris Hip Score were
used to assess
functional outcomes
preoperatively and
postoperatively.
Perioperative data
were retrospectively
obtained from patient
charts. Postoperative
functional outcomes
were prospectively
collected at follow-up
visits. Subjects were
matched to 2:1 control
group on the basis of
procedure, sex,
diagnosis, age (±5
years), and body mass
index (±5 kg/m(2)).
Average follow-up was
27.2 months.”
“Significant preoperative
differences between the groups
included mean morphine-
equivalent requirements (997.1
mg for study group vs 24.8 mg
for controls), 12-Item Short
Form Survey Mental
Component Scores (MCS-12;
37.8 for study group vs 49.0 for
controls), smoking history, and
antipsychotic medication use.
Perioperative referral to
inpatient Acute Pain Service
and mean in-hospital morphine-
equivalent narcotic usage (793
mg/24 h for study group vs 109
mg/24 h for controls) also
significantly differed between
groups. Knee range of motion
differed significantly between
the cohorts at 1 year (77.5 for
study group vs 109.4);
however, no significant
difference in KSS pain (87.6 vs
84.4), KSS function (61 vs
80.9), Harris Hip Score (89.2 vs
85.3), MCS-12 (47.1 vs 52.9),
or complications was
observed.”
PERIOPERATIVE MAT MEDICATION MANAGEMENT 46
Sen, S., Arulkumar, S.,
Cornett, E. M., Gayle, J.
A., Flower, R. R., Fox,
C. J., & Kaye, A. D.
(2016). New pain
management options for
the surgical patient on
methadone and
buprenorphine. Current
Pain and Headache
Reports, 20(3), 16. doi:
10.1007/s11916-016-
0549-9

“Perioperative
management of
patients receiving
opioid addiction
therapy presents a
unique challenge for
the anesthesiologist...
Patients on long-term
opioid management
therapy with
methadone and
buprenorphine require
special considerations.
Recommendations and
options for treating
postoperative pain in
patients on methadone
and buprenorphine are
outlined”
Quantitative Expert opinion,
literature review
Verify dose preoperatively,
continue methadone to the day
of surgery and perioperatively,
use of PCAs can be helpful but
be careful with sedation,
supports multi-modal analgesia
techniques including low dose
ketamine infusion
intraoperatively although these
have not been specifically
studied in MAT patients
Athanasos, P., Ling, W.,
Bochner, F., White, J.
M., & Somogyi, A. A.
(2019). Buprenorphine
maintenance subjects
are hyperalgesic and
have no antinociceptive
response to a very high
morphine dose. Pain
Medicine, 20(1), 119–
128.
doi:10.1093/pm/pny025
Very high doses of
morphine are
ineffective in
overcoming opioid-
induced hyperalgesia
to methadone
maintained patients in
an experimental
setting
Quantitative Randomized Double
Blind
Buprenorphine subjects
hyperalgesic, did not
experience pain relief despite
high plasma morphine
concentrations
Anderson, T. A.,
Quaye, A. N. A., Ward,
E. N., Wilens, T. E.,
Hilliard, P. E., &
Brummette, C. M.
(2017). To stop or not,
that is the question:
Acute pain management
for the patient on
chronic buprenorphine.
Anesthesiology, 126(6),
1180-1186. doi:
10.1097/ALN.0000000
000001633
Pain management
approaches for
patients on
buprenorphine
presenting for elective
and urgent/emergent
surgery
Qualitative Literature Review Perioperative protocols for
buprenorphine management
Goel, A., Azargive, S.,
Lamba, W., Bordman,
J., Englesakis, M.,
Srikandarajah, S., . . .
Clarke, H. (2019). The
perioperative patient on
buprenorphine: a
systematic review of
perioperative
management strategies
and patient outcomes.
Canadian Journal of
Anesthesia, 66(2), 201-
Perioperative
management of
patients on
buprenorphine is
inconsistent
Qualitative Literature Review
1 controlled study, 4
observation studies
Current understanding is
limited by lack of high quality
evidence about bup. use
PERIOPERATIVE MAT MEDICATION MANAGEMENT 47
217.
doi:10.1007/s12630-
018-1255-3
Barelli, R., Morelli
Sbarra, G., Sbaraglia,
F., Zappia, L., & Rossi,
M. (Epub ahead of print
2019). Prevention of
post‐operative
hyperalgesia in a
heroin‐addicted patient
on methadone
maintenance. Journal of
Clinical Pharmacy and
Therapeutics. doi:
10.1111/jcpt.12798
“Ketamine can
effectively reduce
opioid requirements in
chronic opioid users
on methadone
maintenance therapy
and should therefore
be considered
promptly as part of a
multimodal
perioperative
analgesia management
in this category of
patients.”
Case report Case report; one
patient (80kg, 50-year-
old male) on chronic
methadone having
parotidectomy under
GA
Multimodal pain control
consisted of: giving patient
regular AM dose of methadone;
restarting methadone per
patient’s home schedule 6 hours
after surgery end; ketamine drip
0.2mcg/kg/min started post-
induction and discontinued 2
hours postop ; tramadol
infusion 0.1mg/kg/h started 30
mins before surgery end and
continued for 24 hours
postoperatively; intermittent
fentanyl boluses
intraoperatively (totaling 5
mcg/kg); acetaminophen and
ketoralac utilized for pain
control for 2 days
postoperatively.
No psychomimetic symptoms
observed, VS WNL, pain
“adequately” controlled
Bryson, E. O. (2014).
The perioperative
management of patients
maintained on
medications used to
manage opioid
addiction. Current
Opinion in
Anaesthesiology, 27(3),
359-364.
doi:10.1097/ACO.0000
000000000052
Buprenorphine,
Naltrexone,
Methadone use
perioperative
Qualitative Overview of current
recommendations
Naltrexone receptor
upregulation
Chan, F.J., Schwartz, A.
M., Wong, J., Chen, C.,
Tiwari, B., & Kim, S. J.
(2017). Use of chronic
methadone before total
knee arthroplasty. The
Journal of Arthroplasty,
32(7), 2105-2107. doi:
10.1016/j.arth.2017.02.
048
Patients chronically on
methadone require
more opioids, have
longer
hospitalizations, need
referral to pain service
more frequently
Quantitative Retrospective, case
control study; 36
patients on chronic
methadone (continued
perioperatively)
compared to 36
matched control group
of patients not taking
chronic methadone
Greater than 6-fold increase of
opioid use, greater PCA use,
greater use of pain service
referrals
Macintyre, P. E.,
Russell, R. A., Usher,
K. A. N., Gaughwin,
M., & Huxtable, C. A.
(2013). Pain relief and
opioid requirements in
the first 24 hours after
surgery in patients
taking buprenorphine
and methadone opioid
Generally, it is agreed
that methadone should
be continued
perioperatively but
continuing
buprenorphine
perioperatively is not
as equally supported.
No good evidence
exists to support
Quantitative Retrospective cohort
study of patients taking
either buprenorphine
or methadone
preoperatively,
receiving IV PCA
opioids after any type
of surgery, comparing
pain relief and opioid
requirements within
Pain scores, nausea/vomiting,
nor sedation scores were not
significantly different between
buprenorphine and methadone
patients overall NOR b/t
patients who did and did not
receive methadone on the day
after surgery; patients who did
not receive their usual dose of
buprenorphine the day after
PERIOPERATIVE MAT MEDICATION MANAGEMENT 48
substitution therapy.
Anaesthesia and
Intensive Care, 41(2),
222-230. doi:
10.1177/0310057X1304
100212
continuing
buprenorphine or not
perioperatively.
the first 24 hours
postoperative in 22
buprenorphine patients
and 29 methadone
patients
surgery used statistically
significant more PCA opioid
compared to those patients who
did receive their usual dose:
confirmed doses of methadone
or buprenorphine with
prescriber preop; 12 of 51
patients given intraoperative
ketamine infusion (4-8mg/h);
all received acetaminophen
No neuraxial anesthesia utilized
Jonan, A. B., Kaye, A.
D., & Urman, R. D.
(2018). Buprenorphine
formulations: clinical
best practice strategies
recommendations for
perioperative
management of patients
undergoing surgical or
interventional pain
procedures. Pain
Physician, 21, E1-E12.
Best practice
recommendations for
perioperative
buprenorphine
management
Quantitative Literature review, 12
total
Management dependent on type
of surgery/postoperative pain
level, elective vs emergent.
Buprenorphine can be used for
post-operative analgesia,
continue if anticipated post op
pain is mild. Discontinue if
post-operative pain anticipated
to be high. Emergent-continue
if pain level expected to be low,
stop if pain level expected to be
high
Roberts, D. M., &
Meyer-Witting, M.
(2005). High-dose
buprenorphine:
perioperative
precautions and
management strategies.
Anaesthesia and
intensive care, 33(1),
17-25.
Buprenorphine should
be continued, use non-
opioid analgesia,
regional, full opioid
agonist (fentanyl,
morphine
Expert opinion Expert opinion based
on pharmacology,
clinical experience,
recommendations from
literature
Continue buprenorphine, use
adjuncts, only convert to opioid
agonist prior to procedure if
absolutely necessary
Gevirtz, C., Frost, E. A.,
& Bryson, E. O. (2011).
Perioperative
implications of
buprenorphine
maintenance treatment
for opioid addiction.
International
anesthesiology clinics,
49(1), 147-155.
Patients on
buprenorphine may
need adjunct/higher
doses of opioids to
control pain
Expert opinion Pharmacology, case
studies
Use shorter acting opioids in
addition to buprenorphine, can
divide buprenorphine dose over
24 hours replace buprenorphine
with methadone or another
opioid agonist, use regional
Bryson, E. O., Lipson,
S., & Gevirtz, C.
(2010). Anesthesia for
patients on
buprenorphine.
Anesthesiology clinics,
28(4), 611-617.
Buprenorphine pharm,
alternate anesthesia
techniques must be
used
Expert opinion Pharmacology, case
studies
Alternate anesthesia pain
techniques should be used for a
patient on buprenorphine
Silva, M. J., &
Rubinstein, A. (2016).
Continuous
perioperative sublingual
buprenorphine. Journal
of pain & palliative
Continue
buprenorphine
perioperatively
Case report Same patient, same
surgery 2 years apart,
one with
buprenorphine, one
without, better pain
Buprenorphine should be
continued perioperatively for
better pain management
PERIOPERATIVE MAT MEDICATION MANAGEMENT 49
care pharmacotherapy,
30(4), 289-293.
control with
buprenorphine
Curatolo, C., & Trinh,
M. (2014). Challenges
in the perioperative
management of the
patient receiving
extended-release
naltrexone. A&A
Practice, 3(11), 142-
144.
Perioperative
management of patient
on extended release
naltrexone can be
challenging due to
pharm of naltrexone
Case report 22yo F on XR
naltrexone, last took
3.5 weeks prior to
scheduled surgery,
pain well controlled
Pain management depends on
timing of last dose of
naltrexone, multimodal
analgesia
Ninh, A., Kim, S., &
Goldberg, A. (2017).
Perioperative Pain
Management of a
Patient Taking
Naltrexone
HCl/Bupropion HCl
(Contrave): A Case
Report. A&A Practice,
9(8), 224-226.
Post op pain
management of patient
on naltrexone is
difficult
Case report Patient on Contrave
(weight loss), urgent
spine surgery
Postoperative pain not
adequately controlled despite
multimodal pain medication
regimen
Lembke, A., Ottestad,
E., & Schmiesing, C.
(2019). Patients
Maintained on
Buprenorphine for
Opioid Use Disorder
Should Continue
Buprenorphine Through
the Perioperative
Period. Pain medicine
(Malden, Mass.), 20(3),
425.
Buprenorphine should
be continued
perioperatively
Expert opinion Expert opinion Continued buprenorphine use
leads to better pain
management, if on high dose
buprenorphine, taper dose to
free up opioid receptors,
buprenorphine should not be
discontinued
Cornett, E.M., Kline,
R.J., Robichaux, S.L.,
Green, J.B., Anyama,
B.C., Gennuso, S.A.,
Okereke, E.C., &Kaye,
A.D. (2019).
Comprehensive
perioperative
management
considerations in
patients taking
methadone.
Current Pain and
Headache Reports,
23(7):49. doi:
10.1007/s11916-019-
0783-z
OUD patients on
methadone require a
multidisciplinary
approach to pain
management,
including thorough
preoperative
evaluation,
multimodal pain
management
strategies, and opioid-
sparing techniques in
both the intraoperative
and postoperative
periods
Quantitative Literature review,
expert opinion
MMT patients have increased
risk for serotonin syndrome and
QT prolongation. Continue
methadone perioperatively.
Anticipate increased doses of
anesthetic agents. A non-opioid
based intraoperative plan is
preferred. If opioids are needed,
dose may need to be increased
50-100%. Intraoperative
remifentanil may be helpful.
Avoid giving doses of mixed
opioid agonist-antagonist.
Inadequate pain management
may increase risk of relapse.
Use immediate-release, short
acting opiates sparingly. Low
dose ketamine is helpful as a
continuous infusion for 1-3
days postop. Use regional/local
when possible.
PERIOPERATIVE MAT MEDICATION MANAGEMENT 50
Anitescu, M. (2019).
The patient with
substance use disorder.
Current Opinion in
Anaesthesiology,
32(3):427-437. doi:
10.1097/ACO.0000000
000000738.
Review of OUD,
MAT, and
perioperative
recommendations
Literature
review
Methadone: involve patient
with perioperative pain
planning, verify dose preop,
continue perioperatively but in
divided doses, avoid partial
agonists, consider adjuvants
and short acting opioids,
consult with pain service
Buprenorphine-naloxone:
continue, consult pain for PCA,
regional, adjuvants, divide dose
every 6-8 hrs
Injectable naltrexone: stop if
oral for >3 days or > 4 weeks if
injectable; for elective surgery
monitor response to opioids
closely; for emergent, consider
non-opioid techniques
Overall pain management
technique: start with
regional/NSAIDS/tylenol →
lidocaine/magnesium →
ketamine, precedex → opioids

Asset Metadata

Creator Chevalier, Jasmine (author)

Core Title Current state of perioperative medication management of methadone, buprenorphine, and naltrexone

Contributor Electronically uploaded by the author (provenance)

School Keck School of Medicine

Degree Doctor of Nurse Anesthesia Practice

Degree Program Nurse Anesthesiology

Publication Date 05/13/2020

Defense Date 05/12/2020

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

Tag anesthesia,buprenorphine,elective surgery,medication assisted treatment,methadone,naltrexone,OAI-PMH Harvest,opioid use disorder,perioperative medication management,urgent surgery

Language English

Advisor Bamgbose, Elizabeth (committee member), Darna, Jeffrey (committee member), Norris, Teresa (committee member)

Creator Email jgallahe@usc.edu,jlgallaher@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c89-306282

Unique identifier UC11663790

Identifier etd-ChevalierJ-8500.pdf (filename),usctheses-c89-306282 (legacy record id)

Legacy Identifier etd-ChevalierJ-8500.pdf

Dmrecord 306282

Document Type Capstone project

Rights Chevalier, Jasmine

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

Abstract (if available)

Abstract Opioid use disorder (OUD) is defined as the use of opioids in a problematic manner leading to significant distress or impairment. Also known as opioid addiction, OUD involves the misuse of prescription opioids, diverted prescription opioids, or illicitly-obtained opiates. Every year the number of Americans misusing opiates and subsequently suffering from OUD is increasing. Medication-assisted treatment (MAT) is the combination of counseling, behavioral therapies, and medications approved by the United States Food and Drug Administration (FDA) (primarily methadone, naltrexone, and/or buprenorphine) to manage OUD from a “whole-patient” prospective. Medication-assisted treatment has demonstrated the ability to reduce the morbidity and mortality of OUD by decreasing deaths related to overdose, increasing treatment retention, improving the social functioning of patients, reducing criminal activity, and reducing transmission of infectious disease. As the number of patients receiving MAT increases, it is plausible anesthesia providers will encounter patients taking methadone, buprenorphine, and/or naltrexone with increasing frequency for both elective and emergent surgeries. Patients receiving MAT present unique anesthesia management challenges. This project consists of an extensive computerized literature review regarding the perioperative management of OUD patients prescribed methadone, buprenorphine, or naltrexone undergoing elective or emergent surgery. The specific aim of this paper is to create an executive summary of the current state of practice and provide anesthesia perioperative management practice recommendations for patients receiving MAT involving methadone, buprenorphine, or naltrexone who are undergoing elective or emergent surgeries.