Opioid Use Disorders: Perioperative Management of a Special Population

Abstract

Opioid-related overdose deaths have reached epidemic levels within the last decade. The efforts to prevent, identify, and treat opioid use disorders (OUDs) mostly focus on the outpatient setting. Despite their frequent overrepresentation, less is known about the inpatient management of patients with OUDs. Specifically, the perioperative phase is a very vulnerable time for patients with OUDs, and little has been studied on the optimal management of acute pain in these patients. The preoperative evaluation should aim to identify those with OUDs and assess factors that may interfere with OUD treatment and pain management. Efforts should be made to provide education and assistance to patients and their support systems. For those who are actively struggling with opioid use, the perioperative phase can be an opportunity for engagement and to initiate treatment. Buprenorphine, methadone, and naltrexone medication treatment for OUD and opioid tolerance complicate perioperative pain management. A multidisciplinary team approach is crucial to provide clinically balanced pain relief without jeopardizing the patient’s recovery. This article reviews the existing literature on the perioperative management of patients with OUDs and provides clinical suggestions for the optimal care of this patient population.

METHODS

In this report, we conducted a systematic computerized search of all studies relevant to perioperative pain management in individuals with opioid use disorders (OUDs). The search was conducted using PubMed and Ovid MEDLINE from 1982 to September 2017. We included case series and reports, reviews, cross-sectional and controlled studies, guidelines, and editorials. The MeSH terms included buprenorphine, methadone, naltrexone, perioperative, postoperative, pain management, opioid, addiction, abuse and dependence (Supplemental Digital Content, Figure 1, http://links.lww.com/AA/C412).

OUD OVERVIEW

In the 1980s, opioid pain medications began to play a role in the management of noncancer chronic pain. The risk of addiction was believed to be rare.¹ Pain experts advocated for pain to become a vital sign.² The opioid pain medications sales increased 4-fold between 1990 and 2010, and there was a parallel increase in overdose death rates and admissions for the treatment of OUD.³ In fact, in 2010, the US consumed 80% of the global opioid supply.⁴ From 1999 to 2016, >200,000 people died in the United States from overdoses related to prescription opioids.⁵ In 2015 alone, >33,000 people died from overdoses related to opioid pain medication and heroin combined.⁶ According to the 2016 National Survey of Drug Use and Health, 1.8 million people had prescription pain medication use disorder, and 626,000 had a heroin use disorder.⁷

With the rapidly increasing sales of opioid analgesics and corresponding overdose death rates, many federal and state agencies as well as professional medical organizations have published guidelines to modify prescribing practices in efforts to decrease the number of opioid analgesic prescribed.^8–10 Similarly, many states have adopted regulations to increase education on safe prescribing, to limit the amount of opioid analgesic prescriptions, and to require prescribers to check the online prescription monitoring program.^11,12 In 2013, prescriptions for opioid analgesics started to show a decline. Despite these efforts, overdose death rates continue to rise, especially with nonprescription opioids such as heroin and illicit fentanyl-like drugs.^13,14

There are existing effective treatments for OUDs. Medication management with methadone, buprenorphine–naloxone (bup-nx), and intramuscular naltrexone are among the first-line treatment options. The medication management of OUDs is associated with decreased illicit opioid use and relapse, increased treatment engagement, and decrease in mortality.^15–17 A multisite randomized study sponsored by the National Institute of Drug Abuse showed that illicit opioid relapse rates were over 90% when bup-nx was tapered off after 12 weeks of treatment. This study highlighted the clinical importance of continuing medication treatment and cautioned against stopping medication treatment prematurely.¹⁸ Similarly, the relapse rates and risk of opioid-related overdose are very high after an inpatient detoxification unless those individuals continue to receive medication treatment after discharge.¹⁹ Unfortunately, many patients who could benefit from medication assistance for OUDs are not receiving treatment. In 2015, it was estimated that a total of 356,000 individuals received treatment with methadone and 75,000 individuals with bup-nx.²⁰ Barriers to treatment include a lack of trained clinicians, poor understanding of the effectiveness of medication treatments, stigma against individuals with substance use disorders (SUDs), and poor insurance coverage.¹⁶

Psychosocial interventions play an important role in SUD treatment as many individuals suffer from homelessness, unemployment, legal problems, lack of social support, isolation, and comorbid psychiatric illness. Ancillary services and counseling are commonly used by patients with OUDs to address coexisting psychiatric and psychosocial issues and other substance use in conjunction with medication treatment.^21,22

Most research is focused on the management of OUDs in outpatient settings. Despite their frequent overrepresentation, less is known about inpatient and emergency department management of patients with OUDs. The management of such patients can be complex often compounded by acute pain, medical and surgical conditions, and psychosocial problems.

Inpatient acute pain management of hospitalized patients with OUDs has been an area of great clinical challenge.²³ Undertreated pain conditions and concurrently unaddressed OUD may result in less desirable outcomes such as premature discharge, worsening of medical conditions, readmissions, relapse, and overdose during both inpatient stay and immediately after discharge. Acute pain management requires specific considerations and planning for individuals who are receiving medications to treat OUD.

Patients With OUDs: A Special Population

The perioperative phase is a very vulnerable time for patients with OUDs. Individuals with OUD may fear that they will face unfair treatment and adverse judgment by medical providers during their hospital stay. Shame and self-stigma are common among individuals with SUDs and known to confound their help seeking.²⁴ These patients worry about receiving inadequate pain relief, experiencing opioid withdrawal symptoms, and relapsing.

The difficulties in controlling pain for this special population have been reported previously. Patients with OUD have been shown to have lowered pain tolerance, increased sensitivity to pain, and comorbid chronic pain conditions compared to that of opioid-naive control groups.^25,26

Although several perioperative pain management strategies have been proposed, there is a paucity of research and lack of standardized protocol or consensus to guide the clinical practice of anesthesiologists, surgeons, and providers who treat patients with OUD.²⁷

Preoperative Preparation

Guidelines on the management of perioperative pain recommend that preoperative patient evaluation and preparation include obtaining a pain history, undergoing a physical examination, identifying any medication whose cessation may lead to withdrawal, and assessing for psychiatric and SUD comorbidities.^28,29 Screening for high-risk comorbid conditions can help guide perioperative pain management. There are brief screening tools validated in primary care patients to identify those who have generalized anxiety, have depression, use illicit substances, and are at risk for problem drinking.^30–33 A urine toxicology screening specifically testing for methadone, buprenorphine, and fentanyl in addition to other opioids can be helpful to gather objective information. Online prescription drug monitoring program databases should be reviewed for controlled substance prescriptions.

Anxiety and catastrophic thinking have been associated with higher risk of opioid misuse in chronic pain patients and those with a history of SUDs.^34,35 The Pain Catastrophizing Scale is a reliable and valid scale that can help identify those who may experience significant helplessness and catastrophic thinking about their pain and inform decisions related to pain management.³⁶ Negative affect such as anxiety is known to trigger drug craving.³⁷ Pain Catastrophizing Scale can be a useful tool to screen patients with OUD for anxious, catastrophizing thinking before a surgical procedure. The Opioid Risk Tool identifies those with chronic pain who may be at high risk if opioid analgesics are prescribed and can help guide postoperative pain management.³⁸

Perioperative Management of Patients With OUD

OUD in Remission Without Medication Treatment.

Patients with OUD who are in remission and without medication treatment no longer have signs and symptoms of physical dependence, but they continue to be susceptible to triggers and negative impact of stressful life events and can therefore relapse. According to the neurobiological model of SUD, the hallmarks of the disease are loss of control over substance use, impaired executive functioning, and poorly functioning antistress systems.³⁷ The anxiety surrounding surgery and postoperative pain are significant stressors and can easily elicit a conditioned response, trigger powerful memories of drug use, and ultimately result in drug cravings.³⁹ Similarly, access to prescription opioid analgesics without clinical planning and monitoring can lead to strong urges to use and impair one’s ability to “not use.” On the other hand, poorly controlled pain can lead to cravings and relapse.^40,41 Therefore, discussing the risks and benefits of postoperative pain management modalities focusing on relapse prevention is crucial (Table 1). An acute pain consult should be obtained to develop a safe perioperative management plan and minimize the risk of relapse. Regional anesthesia should be considered to reduce postoperative opioid analgesics, as well as adjunct nonopioid medications and nonpharmacological alternatives.⁴² If opioid analgesics are necessary, patient and family education, cognitive behavioral approaches to manage anxiety, craving, and pain should be considered. After discharge, facilitating self-help group attendance, involving sponsor and/or a peer support, when applicable, and collaboration with patient’s current mental health or SUD clinician are some of the strategies to increase support and mitigate risk of relapse. Discharge planning should include safe medication use and storage and disposal of unused opioids. The opioid analgesics should be prescribed at the lowest effective dose and for a limited period. A responsible support person can be involved to hold/dispense the opioid analgesic medications. Due to the loss of tolerance during abstinence, relapse can lead to overdose and death. Overdose prevention education and nasal naloxone prescription (OPENP), the opioid receptor antagonist to reverse opioid overdose, should be considered.⁴³ Effective strategies to prevent relapse while providing adequate pain relief requires further research; however, identifying those who are at risk for relapse is crucial.

Table 1.

Perioperative Pain Management of Patients With OUD in Remission Without Medication

	Preoperative Planning	Inpatient Management	Discharge Planning
Patients with OUD in remission	High risk for relapse	Consider nonopioid medications	Arrange follow-up with SUD clinic
	Involve patient and support person for pain management planning, provide education, and discuss risk of relapse	Consider adjuncts therapies	Maximize strategies for relapse prevention
	Consider SUD consult	Consider APS and SUD consult	Close follow-up for pain management
			Consider OPENP

Abbreviations: APS, acute pain service; OPENP overdose prevention education and naloxone prescription; OUD, opioid use disorder; SUD, substance use disorder.

OUD on Methadone Treatment.

Methadone is a synthetic opioid analgesic approved by Food and Drug Administration (FDA) in 1972 for the treatment of OUD. An effective daily methadone dose varies between 60 and 120 mg/d, but higher doses are not uncommon. The optimal daily dose for an individual should successfully suppress withdrawal symptoms and eliminate cravings and have minimal side effects. During a hospital stay, daily outpatient methadone dose should be continued after verifying with the Opioid Treatment Program (OTP; Table 2). It is also imperative to note that a daily methadone dose for OUD is inadequate to provide acute pain relief and additional medications, and strategies to manage acute pain are required.^44,45 Partial agonist opioid analgesics such as butorphanol and buprenorphine should be avoided as they will precipitate withdrawal symptoms. According to the Guidelines on the Management of Postoperative Pain, for those on methadone, clinicians should consider nonpharmacological interventions and nonopioid medications depending on the surgery and severity of acute pain.⁴⁶ For moderate to severe pain, peripheral, regional, and neuraxial analgesia or PCA with opioids may be appropriate. Postoperatively, patients should be closely monitored for pain control as well as side effects such as sedation, euphoria, opioid-induced constipation, and respiratory depression. For additional risk assessment, a brief mental status examination to monitor mood and anxiety, sleep, cravings or urges to use, and safety should be considered. As clinically indicated, inpatient acute pain and SUD consultation should be considered.

Table 2.

Perioperative Pain Management of Patients With OUD on Methadone

	Preoperative Planning	Inpatient Management	Discharge Planning
Patients with OUD on methadone	Contact methadone clinic	Continue methadone	Continue methadone
	Involve patient, methadone clinic, and support person for decisions, and provide education	Consider adjunct nonopioid and short-acting opioids for pain	Provide last methadone dose verification letter
	Consider SUD consult	Avoid partial opioid agonists	Clear instructions for pain medication management and opioid taper and follow-up
			Consider OPENP

Abbreviations: APS, acute pain service; OPENP overdose prevention education and naloxone prescription; OUD, opioid use disorder; SUD, substance use disorder.

Discharge planning includes communication with OTP including a letter verifying the last inpatient dose of methadone given, list of postdischarge medications, dosing directions, and the number of pills prescribed for pain. If discharged with opioid analgesics, a safe use and taper plan, storage, and disposal instructions should be given. For high-risk patients, arranging a visiting nurse who can dispense medications, ensure opioid analgesic adherence, and monitor symptoms and side effects should be considered. OTPs can arrange “medical take home” arrangements for those who are physically unable to attend daily methadone dosing due to medical conditions. Sometimes, a supportive person can be identified to help with medication adherence. For safe storage, obtaining a locked box is encouraged. The discharge plan should include OPENP.

OUD on bup-nx Treatment.

bup-nx sublingual tablet was the first approved medication to be prescribed to treat OUD in the outpatient office setting under the Drug Addiction Treatment Act of 2000 and was approved by FDA in 2002.⁴⁷ The combination bup-nx is indicated for detoxification and maintenance of OUDs. FDA-approved formulations are sublingual tablet and film, buccal film, and recently available 6-month subdermal implant.⁴⁸ Sublingual buprenorphine without naloxone is indicated to be used for pregnant patients with OUD.

Buprenorphine is a partial agonist at the μ receptor and an antagonist at the kappa receptor. It has high affinity and slow dissociation properties. Its intrinsic activity at the receptor level is about 40%. If taken by an individual with OUD during withdrawal, that is, μ receptors are not occupied, buprenorphine will relieve withdrawal symptoms by its opioid agonist effect. If taken during euphoric state, that is, μ receptors are occupied with full agonist such as heroin and buprenorphine, as a function of its high affinity, will uncouple and replace the full agonist. The patient will then experience a decrease in agonist effect, resulting in a precipitated withdrawal.

The treatment of OUD with bup-nx is relatively straightforward. Before taking the first dose, patients with OUD need to be exhibiting signs and symptoms of withdrawal. Clinical Opiate Withdrawal Scale is a validated tool commonly used to assess the severity of opioid withdrawal and monitor symptoms over time.⁴⁹ The treatment is typically initiated with 2–4 mg of bup-nx and can be increased to 8–12 mg over the next 24 hours.⁵⁰ The effective dose of buprenorphine is 8–24 mg/d. At the therapeutic range, buprenorphine occupies g receptors and prevents other full agonists from binding if used concurrently, thus blocking the euphoric effect of the full agonist. A dose of 16 mg of buprenorphine blocks >80% of μ receptors.⁵¹

Predictable side effects of bup-nx include sedation constipation and diaphoresis. Unless it is mixed with other substances and central nervous system depressants such as alcohol and benzodiazepines, respiratory depression is uncommon. Of note, deaths have been reported with the intravenous use of buprenorphine with benzodiazepines.⁴⁸

Acute pain management of patients treated with bup-nx has been challenging for both outpatient and inpatient providers because of its pharmacological properties and associated clinical concerns (Table 3). The critical question for clinicians is whether buprenorphine should be stopped to achieve effective analgesia. If it needs to be stopped, when should it be discontinued before the surgery? If it does not have to be stopped, what type of analgesic regimen will be effective postoperatively? How about patient preference? How about patient’s abstinence and risk of relapse?

Table 3.

Perioperative Pain Management of Patients With OUD on Bunrenornhine–Naloxone

	Preoperative Planning	Inpatient Management	Discharge Planning
Patients with OUD on bup-nx	Contact bup-nx provider	Continue bup-nx if minimal to no pain is expected	Coordinate with bup-nx provider for follow-up
	Involve patient, provider, and support person for decisions regarding bup-nx and pain management	Consider adjuncts—NSAIDs, acetaminophen, dividing bup-nx dose 3–4 times a day	Clear instructions for pain medications and follow-up
	Consider APS/SUD consult	Continue bup-nx for moderate to severe pain	Consider OPENP
		Consult APS for PCA
		Consider regional anesthesia
		Close nursing monitoring
		Maximize adjuncts—dexmedetomidine, acetaminophen around the clock, gabapentin/pregabalin
		If bup-nx has been discontinued, consider SUD consult
		Consider methadone or ER/LA opioids for OUD to avoid withdrawal and cravings

Abbreviations: APS, acute pain service; bup-nx, buprenorphine–naloxone; ER/LA, extended release/long acting; NSAIDs, nonsteroidal anti-inflammatory drugs; OPENP overdose prevention education and naloxone prescription; OUD, opioid use disorder; PCA, patient-controlled analgesia; SUD, substance use disorder.

A review of the literature showed contradictory results and conflicting views.^27,44,52 Several case reports described poorly controlled postoperative pain despite high doses of opioid analgesics.^53–55 Suggestions included discontinuation of buprenorphine before the surgery if elective; continuation of treatment with full opioid agonists, anticipating higher than normal doses; and use of nonopioid analgesic strategies with regional anesthesia when possible. As much as there is no consensus, some reports suggest discontinuing bup-nx between 2 and 5 days ahead of surgery.^56,57

The University of Michigan Health Systems (Table 4) developed a protocol on the Management of Sublingual Buprenorphine in the Acute Perioperative Setting.⁵⁸ The protocol suggests that the patient should be off bup-nx for at least 5 days before surgery and transitioned to short-acting opioids. The rationale for stopping bup-nx is to ensure opioid receptor availability for pain management purposes.

Table 4.

Summary of Protocols of Perioperative Pain Management of Patients on Buprenorphine–Naloxone^43,57,67

	Minimal to No Pain	Moderate to Severe Pain
University of Michigan Health System	Continue bup-nx and contact provider	Cancel surgery
	Consider adding NSAIDS or acetaminophen	Coordinate with bup-nx provider to stop bup-nx ≥5 d, transition to shortacting opioids before surgery
	If off bup-nx ≥5 d, treat with regular opioids	If off bup-nx ≥5 d, use opioid analgesics for pain
		Consider adjuncts—acetaminophen, NSAIDs, gabapentin/pregabalin, alpha-2 agonist, low-dose ketamine infusion
		Consider regional anesthesia
		Return to bup-nx provider for reinduction
Boston Medical Center	Continue bup-nx and contact provider and consider	Hold bup-nx on the day of the surgery
	Adding NSAIDs and acetaminophen	Give single-dose ER/LA before the surgery and continue ER/LA opioid to address baseline pain control
	Dividing bup-nx dose q6–8 h	Use PCA with no basal dose or IR/SA opioid analgesic for breakthrough pain
	Increasing bup-nx dose	Return to bup-nx provider within a week for consideration to reinduce bup-nx
	Adding short-acting opioid analgesics
University of Kentucky Health care	Continue bup-nx and contact provider	Continue bup-nx and contact provider
	Consider adjuncts—acetaminophen/NSAIDs, opioids up to 3 d if necessary	Consider acute pain consult for potential PCA or regional modality
	Consider dividing bup-nx dose every 6–8 h	Admit in close observation unit to assess analgesia
	If off bup-nx, consider adjunct therapy with acetaminophen/NSAIDS or opioids	Continue opioid therapy for postoperative pain after discharge

Abbreviations: bup-nx, buprenorphine–naloxone; ER/LA, extended release/long acting; NSAIDs, nonsteroidal anti-inflammatory drugs; PCA, patient-controlled analgesia.

The protocols recommending bup-nx discontinuation preoperatively vary in regards to the analgesics medications to bridge the patient. Per the University Michigan Health System Protocol, the bup-nx provider assumes responsibility over the choice of short-acting opioid prescription before surgery. However, bup-nx providers may not have expertise prescribing opioids for pain and knowledge regarding how to convert bup-nx dose to a short-acting opioid analgesic equivalent. Furthermore, short-acting opioid analgesics are not ideal for the treatment of opioid withdrawal or stabilization of OUDs, in part due to their short half-life and euphoria-inducing properties and misuse potential. According to the 2015 Behavioral Health Barometer, 80% of patients with OUD had initiated opioid misuse with prescription opioid analgesics²⁰ and may be vulnerable to relapse if they are exposed to opioids.

In contradistinction, case reports recommend ongoing bup-nx treatment perioperatively. These reports showed that postoperative pain was successfully managed with additional opioid analgesics and nonopioid alternatives without interrupting bup-nx, concluding that there was no benefit in discontinuing bup-nx perioperatively.^59–62

Buprenorphine alone has been increasingly prescribed to treat pregnant women with OUD.⁶³ With regards to the pain management of pregnant women, there is consensus on continuing buprenorphine before delivery. In a retrospective study, postpartum patients on buprenorphine were treated with opioid analgesics.⁶⁴ Studies that compared pregnant women on methadone with those on buprenorphine showed no difference in pain scores and peripartum pain management between the 2 groups.^65,66 The ASAM National Practice Guideline for the use of Medications in the Treatment of Addiction involving Opioids recommends continuation of buprenorphine before elective cesarean delivery to avoid fetal opioid withdrawal.⁶⁷

Boston Medical Center has developed a patient-centered perioperative acute pain management protocol for patients with OUD⁴⁴ (Table 4). Their protocol accounts for the anxiety and possible destabilization caused by the cessation of bup-nx. In the protocol, patients are to continue their bup-nx except the day of the surgery. To minimize withdrawal and discomfort, patients are maintained on long-acting/extended release opioids such as methadone 30–40 mg throughout their hospital stay, with short-acting opioid analgesics added for pain management and breakthrough pain.

Similarly, the University of Kentucky Health Care System developed a protocol with emphasis on continuing bup-nx and managing postoperative pain with multimodal analgesia (Douglas R. Oyler, PharmD, email communication, June 15, 2017; Table 4). The advantage of their approach is that patients are maintained on stable doses of bup-nx throughout the perioperative period without fluctuations in the serum levels of the drug. The benefits of multimodal approach as well as effective pain management strategies for those who are on bup-nx have been previously reviewed by our group.²⁷ Acute pain can be managed by multimodal analgesia such as short-acting opioids, acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentinoids, ketamine, and alpha 2 agonists. Regional anesthesia can provide additional postoperative analgesia and may obviate need for opioid analgesics.

The analgesic ceiling of bup-nx has not been well understood. A case report of a patient on bup-nx for OUD showed that pain relief was achieved by increasing the dose of the bup-nx.⁶⁸ Further research is needed to understand if bup-nx dose increase can play a role in acute pain management for patients with OUD.

Bup-nx is viewed as a lifesaving medication by patients. Discontinuing a stabilizing medication, coupled with the preoperative anxiety and anticipation of pain, can be unbearable and lead to stress-triggered relapse. It is imperative to weigh the risks and benefits of discontinuing bup-nx before surgery, especially given that the risk of mortality is substantially higher immediately after stopping bup-nx treatment.¹⁷ Given the accumulating evidence of tolerability and favorable outcomes of patients receiving bup-nx and adjunct opioid therapy perioperatively, automatically discontinuing bup-nx 2–5 days before surgery does not appear to be supported by high-level evidence and may be unsafe given the increased risk of mortality on treatment cessation.¹⁷

Patients and their supportive others need to be take part in decision-making.⁴⁶ It is crucial to provide detailed education, identify goals for pain control, and discuss pain management. Specifically, discussions about bup-nx should include the outpatient prescriber and the risk of relapse. Information about patient’s preference, fears and beliefs, prior surgical and acute pain experience, current psychosocial stressors, and the state of SUD and behavioral health status should be gathered.

During hospitalization, patients should not only be monitored for pain but also for signs and symptoms of withdrawal, cravings, urges to take the drug, anxiety, and safety. Delivering an empathic approach to management including listening, reassurance, and transparency are crucial to help patients feel that they have some control and their medical and psychological needs managed. The inpatient team should be in communication with the bup-nx provider and/or SUD inpatient consult team to ensure that the patient’s needs are addressed. If opioids are needed postoperatively, safe use, storage, and disposal instructions as well as OPENP should be provided. For those who discontinued bup-nx for surgery and need to restart the medication, arrangements should be made with the outpatient provider for an appointment as soon as possible to ensure a safe transition back to bup-nx treatment.

OUD on Injectable Naltrexone Treatment.

Naltrexone is an opioid antagonist and competitively binds to opioid μ receptors. Naltrexone blocks the effect of endogenous and exogenous opioids such as medications and illicit drugs such as heroin. Naltrexone has an oral formulation and a monthly intramuscular injectable form also known as extended release.⁶⁹ Serious side effects include the risk of overdose, precipitated withdrawal, injection site reactions with intramuscular use, depression, and mild-to-severe hepatitis. Because of the loss of tolerance, the risk of opioid overdose is high during the 7–10 days preceding the initial dose of naltrexone and toward the end of 4 weeks before the next injection. In addition, after opioid antagonist (eg, naltrexone) is started, there is an increase in the density of opioid receptors commensurate with the increase in patient’s sensitivity to the effect of opioids.⁷⁰

Postoperative pain management is a clinical challenge for patients receiving naltrexone for the treatment of OUD and should include communicating with the naltrexone prescriber⁷¹ (Table 5). The patient and the provider’s preferences of postoperative pain management modality need to be considered, and the risks and benefits of different options should be discussed. For those who are on oral formulation, a 72-hour washout period is needed after the last dose before surgery. The surgery should be ideally set for at least 4 weeks after the last injection of extended-release naltrexone. Patients should be asked about their experience with illicit opioid use while on naltrexone.⁷² If the surgery is performed while the patient is on injectable naltrexone, routine doses of opioids may not be effective as higher doses of opioids are required to overcome the opioid-blocking effect of intramuscular naltrexone.⁷³ In contrast, when naltrexone is no longer occupying the receptors, opioid analgesics can elicit an exaggerated response as a result of opioid receptor upregulation, resulting in increased sensitivity.⁷⁴

Table 5.

Perioperative Pain Management of Patients With OUD on Injectable Naltrexone

	Preoperative Planning	Inpatient Management	Discharge Planning
Patients with OUD on injectable naltrexone	Contact naltrexone provider	For elective surgeries, consider close observation to monitor response to opioids.	Coordinate with provider for restart of naltrexone
	Involve patient, provider, and support person for decisions regarding pain management, discuss risk of relapse	Consider adjuncts	Consider OPENP
	Stop naltrexone presurgery	For emergency surgery, consider pain management with nonopioid strategies such as regional anesthesia and analgesia, systemic nonopioid agents, and nonpharmacological interventions
	>72 h for tablet
	>4 wk for injection
	Consider APS, SUD consult

Abbreviations: APS, acute pain service; OPENP overdose prevention education and naloxone prescription; OUD, opioid use disorder; SUD, substance use disorder.

An individualized approach must be developed to best manage postoperative pain and prevent relapse. Depending on the surgery, the management plan should include nonopioid strategies such as regional anesthesia and analgesia, systemic nonopioid agents, and nonpharmacological interventions. Unfortunately, there is a lack of standardized protocols addressing this topic. The published case reports describe successful perioperative management using various perioperative management strategies including general and regional anesthesia and nonopioid analgesia.^75,76

For the patient on oral or injectable naltrexone, a preoperative consult with a pain and addiction specialist can be very informative. If opioid agents are required perioperatively, patients should be well informed about the risks and benefits, and a relapse risk management plan should be developed with input from the patient’s outpatient providers. Patient and family education is essential. Given the possible altered response to opioids, patients should be under close observation during their hospital stay. Postoperatively, safe practices such as education and support around safe medication use, storage and disposal, short opioid prescription, follow-up appointment with patient’s outpatient provider, monitoring signs and symptoms of cravings, and symptoms of withdrawal and anxiety should be followed. Closer monitoring is needed for such patients to ensure that they continue their treatment of OUD and receive support and necessary help. Due to heightened overdose risk, OPENP is advised.

OUD With Continuous Use.

The hospital admission rates involving opioid misuse have increased >150% between 1993 and 2012.⁷⁷ An increasing number of these admissions are due to medical consequences of OUD including infection and trauma.

SUD and pain consultation should be in place for patients with untreated OUD (Table 6). For those cases, the presence of perioperative (particularly postsurgical) withdrawal symptoms should be anticipated. Active withdrawal will complicate postoperative recovery and increase pain sensation. This unfortunate but common scenario is particularly observed in patients who are hospitalized for nonelective surgeries, trauma, or acute medical conditions.

Table 6.

Perioperative Pain Management of Patients With OUD With Continuous Use

	Preoperative Planning	Inpatient Management	Discharge Planning
Patients with OUD, with continuous use	Plan for inpatient opioid withdrawal management and initiate medication for OUD with patient consent	Obtain SUD consult	Arrange outpatient follow-up for OUD treatment and pain management
		Manage OUD withdrawal/craving with methadone or bup-nx	Maximize recovery support efforts
		Involve patient and support person to initiate OUD treatment	Consider OPENP
		Management of pain should be like persons who are on methadone or bup-nx treatment

Abbreviations: bup-nx, buprenorphine-naloxone; OPENP overdose prevention education and naloxone prescription; OUD, opioid use disorder; SUD, substance use disorder.

Data indicate that bup-nx and methadone are equally effective in treating signs and symptoms of withdrawal and are far superior to the alpha agonists such as clonidine.⁷⁸ For surgeries where moderate to high postoperative pain is anticipated, methadone may be preferred to treat the withdrawal symptoms and manage pain postoperatively. Nonpharmacological or adjunct medications can be added to existing methadone treatment protocols. Per federal regulations, methadone’s first dose cannot exceed 30 mg, and total dose during day 1 should not exceed 40 mg unless the provider has a clinical justification. It is noteworthy that the dose of methadone used to manage withdrawal, usually in the range of 30–40 mg/d, may be insufficient (a) to adequately cover urges and cravings for opioids and (b) for pain management. Patients who are treated with methadone per detoxification protocols continue to have pain and drug cravings and maybe at high risk for relapse during an inpatient stay. Bup-nx detoxification protocols follow the same principles as previously explained for the induction protocol.

When choosing between methadone and bup-nx, the treatment team should consider patient preference, drug-drug interactions, side effect profile, and existing cardiac conduction problems (eg, increased corrected QT interval [QTc] syndrome) and acute pain management options.

Commonly, the general hospital inpatient settings only provide treatment for opioid withdrawal management. Methadone or bup-nx doses are tapered off over the course of the inpatient stay before discharge. Patients with SUDs are known to be at a disadvantage when it comes to receiving appropriate medical care and have high rates of discharge against medical advice.^79,80 The reasons are believed to be mostly related to unmanaged ongoing substance use.

There has been a changing attitude among practitioners in providing more clinically appropriate care. Ideally, with the patient’s agreement, patients should not be tapered, but a transition to an OTP for methadone or a bup-nx provider should be arranged. For that purpose, an inpatient SUD consult is required to arrange such referral and follow-up. A recent study showed that a significantly higher percentage of those who received inpatient bup-nx and linkage to outpatient treatment followed up with their outpatient bup-nx treatment compared to those who were on a 5-day bup-nx detoxification protocol.⁸¹ Similarly, in a randomized clinical trial, patients who received bup-nx and referral to outpatient medication follow-up visits in the emergency department setting had significantly superior engagement in SUD treatment, reduction in self-reported illicit drug use, and decreased use of inpatient SUDs services in the following 30 days.⁸² These studies highlight the feasibility of engaging patients with OUD and initiating medication treatment in general hospital settings. Efforts should be made to ensure collaboration between inpatient care teams and linkage to outpatient SUD treatment.

CONCLUSIONS

Perioperative management of patients with OUD in the general hospital setting is complex and requires a multidisciplinary approach. Furthermore, the pain management of patients with OUD is quite challenging, and a multimodal analgesia should be considered. Although there is agreement in continuing methadone perioperatively, clinicians should be reminded that methadone treatment for OUD does not provide adequate pain relief and additional opioids/adjuvant therapies are often required. There is no agreement on perioperative approaches to patients on bup-nx. The case reports and hospital protocols vary greatly in the conclusions they reach. The risks and benefits of discontinuing bup-nx have not been extensively studied. Given the increased mortality rate immediately after discontinuing bup-nx, we strongly recommend continuing bup-nx preoperatively to ensure overall patient stability and prevent relapse from stopping and restarting the medication. It is important to note that the p receptor occupancy is not 100% when bup-nx is prescribed within therapeutic range.⁵¹ The (unoccupied) p receptor availability can allow patients to achieve pain relief in varying degrees if a full opioid agonist is added to bup-nx. Patients with OUD may also require higher doses of opioid analgesics due to tolerance and increased pain sensitivity. The role of escalating bup-nx dose in postoperative pain management has not been fully understood. To decrease the need for opioid analgesics, regional and nonopioid treatment modalities should be optimized. There is consensus for pregnant patients to continue buprenorphine treatment to avoid withdrawal during delivery. Patients on naltrexone should be prepared to discontinue the medication preoperatively and be closely monitored for risk of relapse and overdose. Patients who are in remission without any medication treatment should receive individualized care to minimize risk of relapse and adequate pain care. Inpatient admission should be an opportunity to engage patients who are suffering from untreated OUD and efforts should be channeled toward initiating and linking patients to medication treatment. A patient-centered treatment planning and collaboration between treatment teams including anesthesia, surgery, SUD specialists, primary care physician, and the patient and their family are essential to provide safe, compassionate, and nondiscriminatory care. Patients require clear instructions about how to take prescribed opioid analgesics and taper them as outpatient. Due to possible medication side effects, risk of relapse, and adverse events, patients and families should receive opioid analgesic safe use, storage, and disposal education as well as OPENP. ⊞