Management of acute pain in patients with opioid use disorder

INTRODUCTION — 

Opioid use disorder (OUD) is defined as a pattern of compulsive use of opioids despite negative consequences, causing clinically significant impairment. OUD has reached epidemic proportions in the United States; opioid-related overdoses, driven predominantly by illicitly manufactured fentanyl, resulted in more than 80,000 deaths in 2021 [1].

Patients with OUD may experience episodes of acute pain related to injury, illness, or surgery. This topic will discuss strategies for acute pain management in the context of medication for OUD (MOUD) treatment (eg, with methadone, buprenorphine, or naltrexone) and pain management for patients with untreated OUD.

This topic will focus primarily on patients who have physiologic opioid dependence, either because they are taking an opioid agonist for OUD or are frequently using opioids outside of treatment. Patients with OUD may present with pain during an interval in which they are not actively using opioids and therefore are not presumed to have physiological opioid dependence. Their management is similar to that of patients with OUD in remission, which is also discussed below.

Management of acute pain in patients who are chronically using opioids for pain and management of acute pain in opioid naïve patients are discussed separately.

●(See "Management of acute pain in the patient chronically using opioids for non-cancer pain".)

●(See "Approach to the management of acute pain in adults".)

●(See "Management of acute pain in opioid naïve adults in the ambulatory setting".)

ACUTE PAIN IN THE CONTEXT OF PHARMACOTHERAPY FOR OPIOID USE DISORDER — 

Adequate pain management is particularly important in patients with opioid use disorder (OUD) because undertreated pain has been shown to drive poor health outcomes for these patients, including premature discharges, in-hospital drug use, experiences of stigma, and mistrust of the healthcare system [2-5].

The only opioid agonists approved for the treatment of OUD in the United States are methadone and buprenorphine. Though each drug is often dosed once daily for addiction, their analgesic effects last only six to eight hours. Therefore, continuation of once-daily outpatient dosing for OUD alone is not sufficient for acute pain management. The amount of opioid agonist used to treat a patient's OUD should be considered their basal dose necessary to manage their opioid requirement and to avoid opioid withdrawal or craving. (See "Opioid use disorder: Pharmacologic management", section on 'Methadone: Opioid agonist' and "Opioid use disorder: Pharmacologic management", section on 'Buprenorphine: Opioid partial agonist'.)

The opioid antagonist naltrexone is also approved for prevention of recurrence of opioid use in patients with OUD who have already completed withdrawal management and are abstinent from opioids, as well as for treatment of alcohol use disorder. Management of acute pain in patients who take naltrexone poses distinctive challenges, as naltrexone blocks the effects of opioid agonists. (See "Opioid use disorder: Pharmacologic management", section on 'Naltrexone: Opioid antagonist'.)

FOR ALL PATIENTS MAXIMIZE NONOPIOID ANALGESIA — 

Both nonpharmacologic and nonopioid pharmacologic therapy should be maximized before adding further opioid therapy. Nonopioid strategies are often sufficient for treating mild acute pain (eg, after sprains, nonspecific low back pain, dental extraction, headache) and can decrease reliance upon opioids. If nonopioid strategies are not adequate, they should be continued while opioids are initiated, to reduce opioid requirement.

Nonopioid analgesics options include: acetaminophen, nonsteroidal anti-inflammatory drugs, ketamine, gabapentinoids, intravenous (IV) lidocaine and regional anesthesia techniques. Additional nonpharmacologic therapeutic measures include: physical measures (eg, cold, heat, or splinting), integrative therapies, and psychosocial or behavioral management strategies (table 1) [6,7]. These medications and techniques are discussed in detail separately. (See "Approach to the management of acute pain in adults", section on 'Options for managing postoperative analgesia' and "Nonopioid pharmacotherapy for acute pain in adults", section on 'Options for nonopioid pharmacotherapy'.)

Gabapentinoids are often used for postoperative pain control, particularly in patients who undergo very painful surgery (eg, mastectomy, thoracotomy, spine surgery, major open surgery). They should be used cautiously in older patients and in patients who are also taking opioids. Concomitant administration of opioids with gabapentin or pregabalin is associated with an increase in opioid related mortality [8]. This risk is less relevant in the monitored inpatient setting but becomes crucial when deciding on discharge medications. Given the association of gabapentinoids with an increased risk of opioid-related overdose, clinicians should weigh associated risks and benefits before initiating or continuing gabapentin at the time of discharge in a patient also being treated with opioids. For patients discharged on gabapentinoids, a postoperative analgesic transition or weaning plan should be considered.

Use of gabapentinoids for postoperative pain is discussed separately. (See "Nonopioid pharmacotherapy for acute pain in adults", section on 'Gabapentinoids'.)

For patients taking methadone, potential drug interactions should be reviewed when choosing an appropriate nonopioid analgesic. Carbamazepine, for example, induces CYP4503A, one of the main enzymes involved in methadone metabolism, and will accelerate metabolism and thereby cause acute opioid withdrawal.

PATIENTS TREATED WITH METHADONE FOR OUD

General considerations — The general approach to acute pain management in patients treated with methadone is similar to the approach used for patients treated with stable doses of other opioids on a chronic basis: continue the baseline opioid and dose and apply multimodal nonopioid analgesic strategies, supplemented with incremental opioid if necessary during the interval of acute pain. It is of critical importance to continue methadone throughout all phases of care, including immediately postoperatively, even when patients are nothing by mouth (NPO), and/or are on intravenous (IV) patient controlled analgesia (PCA) or receiving oral opioids for acute pain management. As acute pain subsides, any additional opioid is tapered.

●The plan for pain control should be based on the severity and duration of existing or expected pain. The plan must be flexible because pain intensity and the requirement for additional opioid may be unpredictable in patients who chronically use opioids and often fluctuates with activity. The expected degree and duration of acutely painful events are discussed separately. (See "Approach to the management of acute pain in adults", section on 'Strategy based on expected degree and duration of pain'.)

●Patients on methadone maintenance treatment (MMT) typically require higher doses of additional opioid than opioid naïve patients because of cross tolerance [9-11]. As an example, in a retrospective case control study of patients on MMT who underwent total knee arthroplasty, patients on MMT had higher median daily postoperative opioid use, higher PCA use, more inpatient pain management referrals, and a longer hospital length of stay [12]. Similarly, a retrospective study of patients on MMT or buprenorphine maintenance therapy (BMT) undergoing total knee arthroplasty found that patients in the MMT/BMT group required sevenfold greater doses of opioids in the perioperative period than opioid naïve patients (793 milligram morphine equivalents [MME]/24 hours versus 109 MME/24 hours) [13]. One study of postpartum pain control found that patients on MMT required 70 percent higher opioid doses for analgesia after cesarean delivery than opioid naïve patients [14].

●It is common for severe acute pain to be inadequately controlled in the hospital and postoperative settings among patients on MMT because supplemental doses of opioids are too low or the doses are not titrated rapidly enough [15,16]. Additional short-term opioids for acute pain should not be withheld for fear of worsening the OUD. It is imperative to re-evaluate patients frequently in the initial period after adding opioids or changing doses to assess pain and sedation levels, then readjust the treatment plan as needed.

●Although it is only legal in the outpatient setting to dispense MMT in a licensed opioid treatment program (OTP) or in a qualified practice, in the inpatient setting, health care providers can legally administer methadone for addiction treatment as long as the patient is admitted for a reason other than OUD [17].

Our strategy for patients on methadone maintenance — To date, there are no trials of specific treatment protocols to guide management of acute pain in patients receiving MMT, and recommendations are based on expert opinion and retrospective studies [18-21]. Our strategy is shown in an algorithm (algorithm 1).

Continue methadone — For patients who are treated with methadone for OUD, we suggest continuing methadone during acute pain to both treat OUD and prevent withdrawal. The patient's baseline outpatient methadone dose should be confirmed with the patient's OTP.

Whether to divide the dose of methadone — Methadone is an excellent analgesic [22,23], however, the duration of action of its analgesic effect is much shorter than anticraving effects (6 to 8 hours versus >24 hours respectively). Thus, when used primarily for acute pain, methadone is dosed at approximately every eight hours, versus once daily dosing for OUD.

The patient's once daily maintenance dose of methadone is intended to treat their OUD and will not be adequate to treat acute pain. For patients who are hospitalized, there are two options for managing methadone during an episode of acute pain, particularly for those with severe pain.

●The methadone can be continued as the baseline once daily dose, relying on other analgesics for pain control for much of the day.

Or

●Methadone can be divided into three equal doses administered every eight hours to maximize the analgesic benefit, while adding other analgesics as needed.

There is a lack of evidence on the benefits of dividing the dose of methadone for patients with acute pain, and there are no related guidelines on this issue in the United States. Guidelines from the Royal College of Anaesthetists in the United Kingdom suggest splitting the dose of methadone into doses administered two or three times daily in this setting [21].

The major advantage to continuing the baseline single daily dose of methadone is to avoid the need to resume once daily dosing prior to discharge.

Any planned changes to methadone dosing should be discussed with the patient, as some patients will prefer to maintain the dose and dose schedule that have been effective for their OUD.

If the methadone dose is divided to maximize analgesic benefit, the goal should be to return the patient back to the baseline, once daily dose prior to discharge to assure a seamless transition back to outpatient methadone administration via an OTP. Thus, dividing the dose should only be considered for patients who are expected to be in the hospital for multiple days, and long enough to manage this transition back to once daily dosing.

Route of administration — If the patient cannot take oral medication, methadone can be given by the IV or subcutaneous route. Conversion from oral to parenteral methadone is complicated by its variable oral bioavailability and safety concerns, as IV administration results in more rapid and higher peak serum concentrations than oral administration [24,25]. Most experts and the US Food and Drug Administration label for injectable methadone suggest that the parenteral dose be given as one-half the oral maintenance dose, divided into two to four equal doses through the day [18,19,26]. Since there is significant variability in oral bioavailability of methadone (ie, from 40 to 100 percent) [27], some patients who receive one half the oral dose IV will be significantly undertreated. Thus, patients should be monitored for symptoms of withdrawal and doses titrated upwards rapidly as necessary.

Management based on pain severity — We manage pain according to the existing or expected degree of pain. Importantly, pain is difficult to predict; patients should be monitored closely and the pain control strategy should be adjusted as necessary (algorithm 1). (See 'For all patients maximize nonopioid analgesia' above.)

Mild pain can be expected after sprains, dental extraction, and superficial surgical procedures. Most laparoscopic and minimally invasive surgery, many soft tissue surgeries, and noncompound and noncomminuted fractures are expected to result in moderate pain that lasts for several days. Severe pain often occurs after major open surgery, spine or thoracic surgery, mastectomy, arthroplasty, and major trauma. For many patients, pain peaks at one to three days after injury or surgery and is much less by seven days. (See "Approach to the management of acute pain in adults", section on 'Pain trajectories'.)

●Mild to moderate pain – For patients who have or are expected to have mild to moderate pain, continue the usual once daily dose of methadone, and use other analgesic strategies to control the acute pain. (See 'Adding other opioids only as necessary for pain' below.)

●Severe pain – For patients who have, develop, or are expected to have severe pain, we continue methadone and use aggressive multimodal analgesia. We maximize nonopioid analgesics, use regional anesthesia techniques, consider the use of nonopioid infusions (ketamine, lidocaine), clonidine, and gabapentinoids, and add supplementary opioids as necessary, as described below. For patients for whom muscle spasm may be contributing to pain (eg, after spine surgery, orthopedic surgery, major abdominal surgery, major trauma), we add skeletal muscle relaxants (eg, cyclobenzaprine, tizanidine) as well. (See "Nonopioid pharmacotherapy for acute pain in adults" and 'Adding other opioids only as necessary for pain' below.)

For patients expected to be hospitalized three to four days or more, consider dividing the methadone dose to maximize analgesic benefits while allowing time to resume once daily dosing prior to hospital discharge, as pain improves. (See 'Whether to divide the dose of methadone' above.)

•For select patients with continued inadequate pain control after these measures, consider dividing methadone in thirds given every eight hours (if not already done) and gradually increasing the methadone dose (eg, by 10 to 20 percent per day). It is critically important to plan to return to the patient's baseline once daily methadone dose prior to discharge. Such an increase should only be considered in the following circumstances:

-The patient agrees with the increase after a discussion of the rationale and the plan to return to the baseline methadone dose prior to discharge

-The institution has the infrastructure in place (eg, addiction medicine support) for tapering back to the baseline dose as pain subsides

If methadone is increased to >100 mg per day from a lower dose, an electrocardiogram should be obtained within 12 to 24 hours after administering the first higher dose to assess for QT interval prolongation. Another electrocardiogram should be obtained after further dose increases of 10 to 20 percent or more above 100 mg per day. Methadone can cause QT prolongation, which may be dose related, and can cause life threatening arrhythmias, including torsades de pointes. This is discussed separately. (See "Opioid use disorder: Pharmacologic management", section on 'Prolonged QTc and cardiac arrhythmias'.)

•If a long-acting opioid is indicated in patients with severe acute pain in the inpatient setting, it is often safer and better tolerated to increase methadone than to add a second long-acting opioid such as extended release morphine or oxycodone. In some instances, it is conceptually easier for the patient to instead receive a different long-acting opioid that is weaned and discontinued prior to discharge than to increase then wean methadone.

•For most patients who have had the methadone dose divided, return to the once daily methadone dose prior to discharge. For very select patients with high risk of misuse or better pain control with higher doses of methadone, it may be safer to discharge the patient on a methadone dose higher than their baseline dose rather than other opioids. This must be done in coordination with addiction medicine or addiction psychiatry and with the patient's OTP.

Adding other opioids only as necessary for pain — Multimodal nonopioid analgesia may be adequate for mild pain. Moderate to severe pain often requires short-acting opioids in addition to the patient's baseline opioid and nonopioid multimodal pain control strategies. (See 'Management based on pain severity' above.)

Use of oral and IV opioids for acute pain management for patients on medication for opioid use disorder is similar to the use of opioids in patients who take other opioids chronically, and is described in detail separately (see "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Opioids for acute pain'). Issues specific to patients on MMT include the following:

●Opioid doses – The doses for oral short-acting opioids used for initial pain control in patients who are chronically taking opioids are usually calculated as a fraction of the total daily dose of opioid. However, MME estimates for methadone are notoriously inaccurate. Thus, we start with empiric doses higher than those used for opioid naive patients (eg, oxycodone 10 to 20 mg orally), with dose titration every two to four hours based on adequacy of pain control (table 2 and table 3). For patients with severe pain, we initially control pain rapidly with bolus IV morphine or hydromorphone or use a morphine or hydromorphone PCA titrated to analgesic requirements, with continuous pulse oximetry monitoring for respiratory depression (table 3). (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Initial pain control'.)

●Dosing regimen for oral opioids – For inpatients maintained on oral opioids after initial control of pain, short-acting oral opioids (table 3) should be offered as needed at three to four hour intervals to avoid gaps in analgesia that can occur with dosing at >4 hours. If methadone is maintained at once daily dosing, patients are likely to require more opioid from hour 8 to 24 after the methadone dose. As with all patients on chronic opioids, mixed agonist and antagonist opioid analgesics, such as nalbuphine and butorphanol, should not be administered to patients on methadone, as they may displace methadone from the mu receptor and precipitate acute withdrawal.

For ambulatory pain management we administer a trial dose of oral opioid before discharging patients from the emergency department or postoperative setting. If pain control is inadequate, we either admit the patient to the hospital for pain control or titrate oral opioids, as discussed separately. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Oral opioids'.)

●PCA – For patients who require frequent IV opioids after initial pain control, and who can manage a PCA pump, a PCA is preferred rather than intermittent clinician administered IV bolus. IV PCA with self-administered smaller doses provides more continuous opioid levels without the large plasma peaks and troughs associated with intermittent IV bolus (table 4). Large peaks promote reinforcing effects such as euphoria while troughs produce gaps in adequate analgesia that even further reinforce opioid-seeking behaviors.

Rarely, for patients with inadequate pain control despite frequent PCA boluses, a low dose continuous infusion could cautiously be considered (eg, starting dose of hydromorphone 0.1 to 0.3 mg/hour with slow escalation as needed). If this is done, it is critically important to monitor and evaluate patients frequently (eg, every one to two hours initially or after dose changes) to assess pain, sedation, and mental status and adjust PCA dosing. Consideration of continuous pulse oximetry and higher acuity inpatient settings (eg, ICU) that facilitate enhanced monitoring may be appropriate in some patients. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Ongoing pain control'.)

Control over opioid administration by using PCA may be particularly valuable in patients with OUD, who often fear and experience undertreatment of pain [28,29]. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Patient-controlled analgesia'.)

Post discharge pain control — For patients receiving methadone for OUD, post discharge pain should be managed in consultation with the patient's OTP. All patients should receive multimodal nonopioid analgesia, with supplemental opioids added only as necessary. For patients who require opioids for pain after discharge, the OTP should be involved in determining the duration of treatment for pain and setting a taper plan for the supplemental opioids. (See 'Coordination of care' below.)

Similar to patients who chronically take opioids for pain, patients taking methadone often require higher doses of opioids and longer durations of opioid therapy after an episode of acute pain. This is discussed separately. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Duration and taper of treatment with opioids'.)

PATIENTS TAKING BUPRENORPHINE — 

Buprenorphine is an opioid that is often used for maintenance pharmacotherapy for opioid use disorder (OUD) and is also increasingly used to treat chronic pain. Buprenorphine is a partial mu-opioid receptor agonist with a high affinity for the receptor but low intrinsic activity; despite being a partial mu-opioid receptor agonist, it is a potent analgesic. The doses used for pain are typically lower than doses used for OUD. The recommended starting dose of the buccal film for chronic pain is 75 mcg buccal, compared with a range of 8 to 16 mg on the first day initiating buprenorphine for OUD therapy. Buprenorphine is increasingly used for acute pain as well, in both opioid naïve and opioid tolerant patients with doses ranging from 75 mcg to 2 mg buccal. Formulations used for OUD usually include naloxone; naloxone has no treatment effect in these formulations. It has low sublingual bioavailability and is included only to deter injection misuse. (See "Use of opioids in the management of chronic pain in adults", section on 'Buprenorphine for chronic pain' and "Opioid use disorder: Pharmacologic management", section on 'Buprenorphine: Opioid partial agonist'.)

Our strategy for patients on buprenorphine — The general approach to acute pain management in patients treated with buprenorphine is similar to the approach used for patients treated with stable doses of other opioids on a chronic basis: continue the baseline opioid dose (in this case buprenorphine) and use multimodal nonopioid analgesic strategies, supplemented with incremental opioid, if necessary, during the interval of acute pain. As the acute pain subsides, the additional opioid is tapered. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain".)

Our strategy for managing acute pain in patients taking buprenorphine appears in algorithms, one for perioperative pain control, and another for management of acute nonsurgical pain (algorithm 2 and algorithm 3).

Continue buprenorphine — Issues and questions regarding the perioperative management of buprenorphine include the following:

Whether to continue buprenorphine — We suggest continuing buprenorphine (with or without naloxone) during an episode of acute pain, whether it was originally prescribed for chronic pain or for OUD [30-34]. For most patients, pain can be effectively managed while they are taking buprenorphine. Discontinuation of buprenorphine preoperatively complicates preoperative management and for patients with OUD, increases the risk of return to illicit opioid use. Our approach is consistent with 2021 guidelines from a multi-society expert panel including representatives from anesthesiology, pain medicine, addiction medicine, and pharmacy societies [34].

In the past, concerns over continuation of buprenorphine have centered on the idea that acute pain may be more difficult to control because of competition by buprenorphine with other opioids that bind to mu-opioid receptors, due to buprenorphine's high affinity for the mu receptor. However, the preponderance of evidence, which consists of case series, observational studies, and clinical trials including patients with acute pain, supports continuation of buprenorphine, even in patients who are taking high doses for OUD [35-42].

In the presence of buprenorphine, higher than normal doses of any full mu agonist will be required for pain control [39].

For most patients, the transmucosal or sublingual buprenorphine formulation can be used during an episode of acute pain. For the rare patient who is unable to tolerate sublingual or buccal buprenorphine, IV buprenorphine (without naloxone) can be administered; there is no empirical evidence, and there is minimal clinical experience to guide dosing. For patients who require IV buprenorphine, a reasonable strategy based on bioavailability studies is to reduce the patient's usual daily buprenorphine dose by 50 percent and divide the reduced dose into three equal doses administered every eight hours. For example, for a patient taking 24/6 mg sublingual buprenorphine/naloxone as an outpatient, administer 12 mg of buprenorphine IV total daily, divided into three 4 mg doses every eight hours. Naloxone should not be included in the IV formulation with buprenorphine to avoid precipitating opioid withdrawal.

In the United States, any practitioner with a Drug Enforcement Administration license to prescribe controlled substances can prescribe buprenorphine for OUD, and there is no longer special licensure required.

Whether to taper buprenorphine — Whereas there is consensus for continuing buprenorphine in the perioperative period, there is less agreement on the dose at which buprenorphine should be maintained. We agree with experts who suggest that it is reasonable to consider tapering from higher doses to a dose of 12 to 16 mg per day over several days prior to surgery for patients who are expected to have severely painful surgery [30,31,34]. Importantly, whether to taper buprenorphine should be part of shared decision making with the patient and should be coordinated with an addiction medicine specialist or the patient's buprenorphine prescriber. The potential analgesic benefit of tapering buprenorphine must be balanced against the possibility of relapse of OUD.

Preclinical and human studies have found that at increasing doses there are fewer free mu opioid receptors unoccupied by buprenorphine and therefore available to bind to other opioids [43-45]. However, data that confirm the degree of mu opioid receptor occupancy required for analgesia are lacking, and there are a number of reports of adequate analgesia in patients maintained on high doses of buprenorphine preoperatively [41,46,47].

Whether to divide the buprenorphine dose — Buprenorphine is an excellent analgesic, but the duration of action for analgesia is shorter (6 to 12 hours) than its anticraving effects [48,49]. Whereas buprenorphine is usually taken as a single daily dose for OUD, to take full advantage of the analgesic effects, buprenorphine should be administered every six to eight hours. We base the decision to split the dose on the existing or expected degree of pain. For patients who will likely need opioids to manage acute pain (ie, patients with moderate to severe pain), we divide the patient's total baseline buprenorphine dose into three doses administered every eight hours. Unlike methadone, the patient can continue divided dosing of buprenorphine as an outpatient if necessary for optimal analgesia. Single daily dose methadone is required for ambulatory patients who receive methadone maintenance therapy, which is administered by an OTP, but this is not required for buprenorphine. The need to discharge the patient on a daily dose of methadone is discussed above. (See 'Whether to divide the dose of methadone' above.)

Patients taking long-acting buprenorphine preparations — For most patients who take weekly or monthly subcutaneous buprenorphine preparations, the medication is continued through an episode of acute pain at the usual dose, even for patients who are scheduled for severely painful elective surgery well in advance. There is limited evidence to guide management for patients taking long acting buprenorphine [50]. The complexity of changing to an alternative buprenorphine preparation and the risks of recurrence of opioid use in these patients may outweigh the potential benefits from tapering. (See "Opioid use disorder: Pharmacologic management", section on 'Injectable buprenorphine'.)

Management based on pain severity — We manage pain according to the existing or expected degree of pain in addition to using multimodal nonopioid analgesia (eg, acetaminophen and nonsteroidal anti-inflammatory drugs [NSAIDs], regional anesthesia techniques, physical measures [eg, cold, heat, or splinting], ketamine, IV lidocaine, gabapentinoids). Importantly, pain is difficult to predict; patients should be monitored closely and the pain control strategy adjusted as necessary. (See 'For all patients maximize nonopioid analgesia' above.)

●Mild pain (eg, after sprains, dental extraction, superficial surgical procedures)

•Continue the current dose of buprenorphine

•Add low doses of short acting opioids only as necessary (see 'Adding other opioids only as necessary for pain' above)

●Moderate pain (eg, after laparoscopic and minimally invasive surgery, most soft tissue surgeries, and noncompound and noncomminuted fractures)

•Continue the current daily dose of buprenorphine. For patients who will be hospitalized for several days, split into doses administered every six to eight hours.

•Add opioids as necessary, expecting to need higher doses than for opioid naïve patients. For additional opioids, we suggest either increasing the buprenorphine doses, and/or adding short acting full mu opioid receptor agonist opioids.

Buprenorphine can be increased modestly to provide additional analgesia, with a maximum of 32 mg/day, including in patients who take concurrent buprenorphine and naloxone. Because naloxone is only minimally bioavailable via the sublingual route, it will not interfere with pain management unless injected. For patients receiving long-acting depot injections at less than maximal doses, we add supplemental transmucosal buprenorphine. For patients already on maximum long-acting buprenorphine doses, we proceed to the addition of supplementary full mu agonist opioids if necessary. (See 'Use of supplemental opioids for patients taking buprenorphine' below.)

●Severe pain (eg, after major trauma, major spine surgery, thoracotomy, mastectomy)

•Continue buprenorphine, split into equal doses administered every six to eight hours. For surgical patients, if regional anesthesia will be used and is expected to provide most analgesic needs, continue the current daily dose of buprenorphine. If regional anesthesia is not expected to be adequate, consider tapering the buprenorphine daily dose to 12 to 16 mg/day over 2 or 3 days prior to surgery. Plan to return to the usual daily dose by the time of discharge.

•Add full mu opioid receptor agonist (eg, fentanyl, hydromorphone, morphine) as needed, as described below.

Use of supplemental opioids for patients taking buprenorphine — Use of supplementary oral and IV opioids for acute pain management for patients who take buprenorphine is similar to the use of opioids in patients who take other opioids chronically, as described in detail separately. (See 'Adding other opioids only as necessary for pain' above and "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Opioids for acute pain'.)

Issues specific to patients who take buprenorphine include the following:

●The doses for oral short-acting opioids used for initial pain control in patients who are chronically taking opioids are usually calculated as a fraction of the total daily dose of opioid. However, MME cannot be reliably calculated for buprenorphine. Thus, we start with empiric doses that are higher than those used for opioid-naive patients (eg, oxycodone 10 to 20 mg orally), with dose titration every three to four hours based on pain control (table 3).

For ambulatory patients, as with other patients taking chronic opioids, we administer a trial dose to ensure efficacy before discharging patients from the emergency department or postoperative setting and provide close follow-up in the outpatient setting for dose titration. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Oral opioids'.)

●For patients with or expected to have severe pain, we suggest using a full mu opioid receptor agonist with a high affinity for the mu opioid receptor (eg hydromorphone or fentanyl) rather than other opioids. We transition to one of these opioids for patients who have pain that is not well controlled with other full mu opioid receptor agonists. Receptor binding studies suggest that high-potency, full mu-agonist opioids such as fentanyl and hydromorphone might provide better pain relief than other opioids for patients on buprenorphine, however there are no clinical studies that have confirmed this.

Post discharge pain control — For patients receiving buprenorphine for OUD, post discharge pain should be managed in consultation with the patient's regular buprenorphine prescriber. For patients who require either a change in buprenorphine dose, divided dosing, or additional opioids, the patient's buprenorphine prescriber should be involved in determining the duration of treatment for pain, setting a taper plan for the supplemental opioids, and/or return to the original buprenorphine maintenance dose. (See 'Coordination of care' below.)

Similar to patients who chronically take opioids for pain, patients taking buprenorphine often require higher doses of opioids and longer durations of opioid therapy after an episode of acute pain. This is discussed separately. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Duration and taper of treatment with opioids'.)

PATIENTS TAKING NALTREXONE — 

Management of acute pain may be particularly challenging in patients who take naltrexone, especially for patients who receive monthly injections (XR naltrexone). Naltrexone occupies and blocks activation of mu opioid receptors and therefore blocks the effectiveness of opioid analgesics for acute pain. However, based on animal studies, it is thought that chronic opioid antagonism with naltrexone increases the density of opioid receptors in the brain, thereby increasing sensitivity to opioid agonists [51-55]. Thus, the risk of side effects (eg, respiratory depression) may be increased if opioid antagonism is overcome or if naltrexone is discontinued during opioid therapy. Opioid antagonism wanes over the course of the month after a dose of XR naltrexone, and case reports describe opioid overdose and death in patients who used opioids at the end of the dosing interval [56]. In addition, reinstitution of naltrexone therapy in patients who have been receiving opioids for pain control can precipitate withdrawal.

Our approach to treatment of acute pain in patients who take naltrexone is as follows:

●Consult the clinician who prescribed naltrexone.

●For elective surgery, discontinue oral naltrexone at least three days prior to surgery, and XR naltrexone at least one month prior to surgery.

●Maximize nonopioid methods for acute pain control, including ketamine, lidocaine infusion and regional anesthesia if possible. (See 'For all patients maximize nonopioid analgesia' above and "Nonopioid pharmacotherapy for acute pain in adults", section on 'Options for nonopioid pharmacotherapy'.)

●If opioids are required while naltrexone is still in effect (ie, within three days of oral naltrexone or within one month of XR naltrexone), high doses of opioids will be required. Opioids should be titrated to effect with pulse oximetry and electrocardiogram monitoring.

●An addiction medicine specialist should be consulted prior to reinstitution of naltrexone therapy after opioid administration for pain. In most cases, naltrexone should be withheld until the patient has been off opioids for at least seven days.

PATIENTS WITH OPIOID USE DISORDER IN REMISSION WITHOUT PHARMACOTHERAPY — 

While pharmacotherapy for opioid use disorder (OUD) is associated with reduced mortality and increased rates of remission, some patients successfully achieve sustained remission from OUD without medication. Treating acute pain with opioids in this population can place them at risk for returning to uncontrolled OUD. It may be preferable to avoid opioids, if at all possible, in some patients in remission, including using regional anesthesia techniques when they would not ordinarily be used.

General principles — Principles for pain management in patients with OUD in remission are as follows:

●Patients in sustained remission from OUD may prefer to rely on nonpharmacologic or nonopioid pain management because of the risk of relapse. Any pain management plan for these patients should be made in collaboration with the patient, the acute pain management service, and ideally with an addiction care team.

●As with other patients, nonpharmacologic and nonopioid pain management should be optimized prior to considering opioid analgesia, and regional anesthesia should be considered whenever feasible. (See 'For all patients maximize nonopioid analgesia' above.)

●Opioid tolerance is typically lost within weeks to months after cessation of opioids. Thus, if opioids are required for patients in sustained remission, the doses used should be similar to the doses that would be used for opioid naïve patients. (See "Use of opioids for acute pain in hospitalized patients" and "Management of acute pain in opioid naïve adults in the ambulatory setting", section on 'Opioids'.)

●For patients who require intravenous opioids, choice of opioid and administration requirements should be similar to patients without a history of OUD. (See "Use of opioids for acute pain in hospitalized patients", section on 'IV opioids'.)

●For patients for whom oral opioids are appropriate, it may be preferable to use buprenorphine rather than other opioids. (See 'Buprenorphine for acute pain' below.)

●For patients who require opioids after discharge or on an ambulatory basis, there should be a clear plan for tapering and discontinuation while continuing nonopioid analgesics. (See "Use of opioids for acute pain in hospitalized patients", section on 'Discontinuing opioids'.)

●Patients with OUD who receive opioids for acute pain may benefit from increased psychosocial support and increased engagement with their addiction treatment team both during and for the months following the opioid prescription.

Buprenorphine for acute pain — Though not specifically studied among people with behaviorally treated OUD, the diminished euphoria associated with buprenorphine may reduce the risk of return to uncontrolled OUD, compared with other opioids.

Buprenorphine preparations prescribed for OUD are typically combination preparations that include naloxone, whereas the formulations prescribed for acute pain typically do not contain naloxone. For acute pain, the most commonly used buprenorphine preparation is the buccal film, though sublingual tablets have also been used. Doses administered for pain are typically much lower than doses used for maintenance pharmacotherapy for OUD. The onset of the buprenorphine buccal film is longer than for oral immediate release full mu opioid receptor opioids. The onset of buprenorphine is in 30 to 60 minutes, and peak effect in 1 to 4 hours, with duration of action from 6 to 12 hours. Buprenorphine can also be prescribed for ambulatory patients, with a clear plan for tapering and discontinuing.

●Dose – Starting dose 75 to 150 mcg buccal every eight hours; may be titrated with additional doses two hours after a dose.

PATIENTS WITH UNTREATED OPIOID USE DISORDER — 

Opioid use disorder (OUD) has reached epidemic proportions in the United States and should be considered in all patients who present for medical treatment. (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment", section on 'Epidemiology'.)

For patients without a diagnosis of OUD, clinicians who suspect it can use structured assessment tools to confirm the diagnosis. OUD is a potentially life-threatening medical condition that responds well to treatment. If OUD is first diagnosed during preoperative evaluation for elective surgery, the possibility of initiating medical treatment prior to surgery should be explored with the patient. Screening and assessment for OUD and the choice of medication for opioid use disorder are discussed separately.

●(See "Screening for unhealthy use of alcohol and other drugs in primary care".)

●(See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment".)

●(See "Opioid use disorder: Treatment overview".)

Occasionally, repeatedly reporting acute pain in an effort to obtain opioids may be a presenting symptom of OUD. A physiologic cause for pain should always be explored even when this behavior pattern is suspected or recognized.

Outpatient pain management — Patients with untreated OUD who have mild pain can often be managed as outpatients with nonopioid measures for pain control. For moderate pain, outpatient opioid prescription should be considered carefully, and if absolutely necessary, a short course (eg, oxycodone 10 mg every six hours for three days) should be prescribed, along with overdose education and a prescription for naloxone for overdose reversal. In 2023, over the counter naloxone (ie, without a prescription) became available in the United States and is another option for patients. (See "Prevention of lethal opioid overdose in the community".)

There is no evidence that one opioid is safer than another in this situation. Some providers believe that hydromorphone or oxycodone has a higher potential for misuse, but all short-acting opioids can be inhaled or injected and provide similar euphoria. Buprenorphine is less likely to be misused because of its limited euphoric effect. Most patients who use nonprescribed buprenorphine do so to self-manage opioid withdrawal or to maintain abstinence from other opioids [57]. In patients who are actively using full agonist opioids, buprenorphine can precipitate withdrawal and is not recommended.

A prescription drug monitoring program database should always be checked prior to prescribing opioids in patients with known or suspected OUD. Opioid prescription from another provider that cannot be explained by the patient's clinical history requires further exploration. (See "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Prescription monitoring programs'.)

Inpatient management — Management of pain in patients with untreated OUD who are actively using opioids depends on the intensity of their pain and their preference for initiating medication for opioid use disorder (MOUD).

Inpatient pain management in patients with OUD may be complicated by withdrawal, as patients do not have access to their usual supply of opioids. It is important to administer sufficient opioids to both treat or prevent withdrawal and to adequately treat pain. In our experience, this is best accomplished by providing methadone or buprenorphine to minimize symptoms of withdrawal, while adding additional treatment for analgesia. Signs and symptoms and treatment of opioid withdrawal are discussed separately. (See "Opioid withdrawal: Clinical features, assessment, and diagnosis", section on 'Clinical manifestations' and "Opioid withdrawal in adults in the emergency setting", section on 'Management'.)

Pain control strategy — Pain should be treated aggressively in patients with untreated OUD. All patients should receive nonopioid analgesics, and these agents may be sufficient in patients with mild pain. Intravenous opioids are usually required for the initial treatment of acute severe pain and may also be required for some patients with moderate pain. Escalated opioid dosing requirements should be expected and opioid dosing should be increased in the setting of poorly controlled pain. Efforts should be made to maximize the use of regional anesthesia techniques.

For patients with untreated OUD, the precise doses of opioids they use on a daily basis may be difficult or impossible to estimate. Thus, if opioids are required for acute pain control, an empiric starting dose may be required, followed by rapid titration. The patient should be assessed frequently for pain control, opioid related side effects (eg, sedation), and symptoms of withdrawal, adjusting the dose, interval, route of administration, and choice of opioid as needed. Increased tolerance to opioids and therefore higher required doses can be expected. (See 'General considerations' above.)

The setting of severe acute pain is not the time to attempt opioid weaning and associated withdrawal management; indeed, undertreated acute pain is a risk factor for chronification of acute pain and persistent opioid use [58-62].

Will the patient start MOUD? — Before initiating treatment for prevention or treatment of withdrawal, if the clinical situation permits, the patient's preference for starting MOUD after discharge should be considered. The choice among options for treating OUD is beyond the scope of this topic and is discussed separately. (See "Opioid use disorder: Treatment overview", section on 'Shared decision-making'.)

●For patients who want to start treatment with methadone or buprenorphine, it may be preferable to start their desired medication in the hospital to prevent or treat withdrawal.

•Buprenorphine – Patients with active OUD who are not in withdrawal on admission have likely used opioids up until hospital admission. We do not recommend starting buprenorphine at standard doses for these patients unless they are experiencing opioid withdrawal (eg, Clinical Opioid Withdrawal Scale ≥12) (calculator 1), as they may have high systemic opioid levels; buprenorphine may precipitate withdrawal in this setting. For patients not in withdrawal, their pain can be controlled with other opioids as necessary, and they can be transitioned to buprenorphine during hospitalization or after discharge. For patients not in withdrawal, low dose (microdose) buprenorphine induction is an option. Inpatient initiation of MOUD is discussed separately. (See "Opioid use disorder: Pharmacologic management", section on 'Alternative induction methods for specific circumstances'.)

•Methadone – Starting patients on methadone for maintenance therapy requires collaboration with addiction medicine and acceptance by an opioid treatment program. Early communication with an opioid treatment program will avoid delays in discharge. For patients who will start methadone, it can be started along with other opioids for pain. Prior to discharge the total dose of opioids, including methadone, should be used to calculate the discharge dose of methadone, in coordination with addiction medicine and the opioid treatment program (OTP) or pain specialist. (See 'Transition to outpatient treatment' below.)

If an OTP is not available to accept the patient immediately after discharge, it may be necessary to transition to another opioid for pain prior to discharge.

●For patients who are unsure or not interested in starting MOUD with methadone or buprenorphine or who do not yet have a provider to start MOUD, short-acting opioids may be used to manage withdrawal and acute pain. Alternatively, buprenorphine can be used for patients who are in withdrawal. Higher doses and more frequent dosing may be necessary compared with opioid naïve patients.

●Patients who plan to start naltrexone will need to undergo medically supervised withdrawal once they no longer need opioids for pain. (See 'Transition to outpatient treatment' below.)

Transition to outpatient treatment — Once the acute pain period has subsided, it is critical to engage the patient in compassionate, nonjudgmental discussions about their OUD and offer treatment. For patients who are amenable to starting pharmacotherapy for OUD, they can be transitioned from opioids or the doses of MOUD described above to therapeutic maintenance doses of MOUD. This should ideally be done before hospital discharge or with direct linkage to ongoing outpatient OUD treatment [63-65]. (See "Opioid use disorder: Treatment overview" and "Opioid use disorder: Pharmacologic management".)

When a patient is transitioned to buprenorphine or methadone, it is incumbent on the treating team to ensure that the patient has a follow-up plan with a provider who will continue their buprenorphine or a licensed OTP for ongoing methadone. If a patient is off opioids for seven or more days during hospitalization and prefers antagonist therapy, they may also consider intramuscular naltrexone as a second-line treatment option to prevent recurrence of opioid use. If the patient is referred elsewhere for treatment, the patient's pain should be managed in collaboration with substance use disorder treatment clinicians.

COORDINATION OF CARE — 

Acute pain management in patients receiving medication for opioid use disorder (MOUD) is best coordinated with substance use disorder treatment specialists and outpatient pain specialists if they were involved in the patient's care, particularly if supplemental opioids are required [66]. However, management of pain should not be delayed while waiting for input from these specialists.

●For patients taking methadone, it is crucial to communicate with the patient's opioid treatment program (OTP) about any changes to methadone doses and with the patient's outpatient pain provider, if they had one. OTPs prefer no changes to patients' preoperative methadone dosing, and the patients should typically be discharged on the same dose they were taking prior to admission. The OTP and/or primary care provider should be aware of additional opioids or other sedatives or analgesics prescribed at discharge. For patients who require opioids in addition to methadone after discharge, a clinician outside the OTP (eg, primary care provider or pain specialist) can prescribe them while the patient continues once daily methadone dosing through an OTP.

●For patients who take buprenorphine and who require either a change in buprenorphine dose or additional opioids, the patient's buprenorphine prescriber should be involved in determining the duration of treatment and setting a plan for returning to the buprenorphine maintenance dose and taper of any additional opioids.

Prior to discharge, a plan for tapering supplemental opioids and other sedatives or analgesics should be established in coordination with the outpatient prescriber, the patient, and the patient's family. The clinician prescribing the medications for pain should regularly inform the OUD treatment provider of specific medications and doses.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opioid use disorder and withdrawal" and "Society guideline links: Acute pain management".)

SUMMARY AND RECOMMENDATIONS

●General principles

•Acute pain management should be guided by pain specialists in coordination with substance use disorder treatment specialists. (See 'Coordination of care' above.)

•For patients taking medication for opioid use disorder (MOUD), the baseline opioid should be continued while maximizing nonopioid and nonpharmacologic analgesic strategies and adding supplemental opioid if necessary. (See 'Acute pain in the context of pharmacotherapy for opioid use disorder' above and 'For all patients maximize nonopioid analgesia' above and 'Adding other opioids only as necessary for pain' above.)

•It is imperative to re-evaluate patients frequently in the initial period after adding opioids or changing doses to assess pain and sedation levels, then readjust the treatment plan as needed.

●Patients who take methadone

•For these patients we suggest continuing methadone during an episode of acute pain to both treat opioid use disorder and prevent withdrawal (Grade 2C) (algorithm 1).

-For patients with mild to moderate pain, we continue the usual once daily dose of methadone, and use other analgesic strategies to control the acute pain. (See 'Management based on pain severity' above.)

-For patients with severe pain and who will be in the hospital for several days (ie, long enough to allow transition back to the once daily maintenance dose prior to discharge), we consider administering one-third of the usual daily dose every eight hours. The duration of action of methadone's analgesic effect is much shorter than its anticraving effects. (See 'Whether to divide the dose of methadone' above.)

-If the dose or dosing interval of methadone is changed, the goal should be to return to the baseline daily maintenance dose prior to discharge, to facilitate a seamless transition to outpatient MOUD.

●Patients who take buprenorphine

•We suggest continuing buprenorphine during an episode of acute pain rather than discontinuation (Grade 2C). We manage pain according to the existing or expected degree of pain (algorithm 2 and algorithm 3). (See 'Continue buprenorphine' above and 'Management based on pain severity' above.)

-Mild pain – For patients with or expected to have mild pain, we continue the patient's home baseline dose and add low dose short acting opioids as necessary.

-Moderate to severe pain – For patients with or expected to have moderate to severe pain, we continue the baseline buprenorphine dose, but we suggest dividing it into thirds, with doses administered every six to eight hours, rather than giving it as a single daily dose (Grade 2C). (See 'Whether to divide the buprenorphine dose' above.)

For additional analgesia, we suggest either modestly increasing buprenorphine doses or adding short acting full mu opioid agonists (Grade 2C).

•For patients having elective surgery expected to be severely painful, who are taking >16 mg per day of buprenorphine, and for whom regional anesthesia is not likely to provide adequate analgesia, we consider tapering buprenorphine preoperatively on an individualized basis. We aim to taper to 12 to 16 mg/day over 2 or 3 days prior to surgery, in coordination with the buprenorphine prescriber and after shared decision making. (See 'Whether to taper buprenorphine' above.)

●Patients who take naltrexone – Naltrexone blocks the mu-opioid receptor and therefore blocks the analgesic effects of opioids. Oral naltrexone should be discontinued for at least three days and naltrexone XR for 30 days prior to elective procedures. If opioids are required while naltrexone is still in effect, they should be titrated to effect with close ventilatory monitoring. (See 'Patients taking naltrexone' above.)

●Patients with OUD in remission – These patients are at risk for return to uncontrolled OUD if opioids are administered. The plan for pain management should be made in collaboration with the patient and an addiction medicine specialist when possible. (See 'Patients with opioid use disorder in remission without pharmacotherapy' above and 'General principles' above.)

•It is particularly important to maximize nonopioid analgesic options to avoid opioids if possible.

•Opioid tolerance is most often lost within weeks or months of abstinence; the doses of opioids for patients in sustained remission from OUD should be similar to opioid naïve patients.

•For patients who require intravenous opioids, choice of opioid and administration should be similar to patients without a history of OUD.

•For patients for whom oral opioids are appropriate, it may be preferable to use buprenorphine rather than other opioids. (See 'Buprenorphine for acute pain' above.)

●Patients with untreated OUD

•Outpatients – For patients with untreated OUD, outpatient opioids should be avoided if possible. If necessary, a short course (ie, ≤3 days) should be prescribed along with naloxone for treatment of overdose and in collaboration with the outpatient treatment team. (See 'Outpatient pain management' above and "Prevention of lethal opioid overdose in the community".)

•Inpatients – These patients must receive sufficient opioids to both prevent or treat opioid withdrawal and to adequately control pain. Patients in severe acute pain should have opioids and other analgesics titrated to treat their pain. This is usually adequate to prevent opioid withdrawal. (See 'Inpatient management' above.)

-Pain control – For patients who require opioids for pain, empiric doses should be used, since the patient's usual daily dose may be difficult or impossible to determine. Doses should be titrated rapidly, expecting opioid tolerance. (See 'Pain control strategy' above.)

-Patients who will start MOUD – The possibility of starting MOUD should be discussed with all patients with untreated OUD. Patients who are not in withdrawal should not start buprenorphine at standard initiation doses, as this may precipitate withdrawal; they can be transitioned to buprenorphine after discharge or undergo low dose buprenorphine initiation. (See 'Will the patient start MOUD?' above.)

Patients who plan to start naltrexone will need medically supervised withdrawal once they no longer need opioids for pain.

●Coordination of care

•Acute pain management in patients receiving MOUD ideally requires coordination with substance use disorder treatment specialists. A plan for tapering supplemental opioids and other sedatives or analgesics and for return to baseline MOUD (if necessary) should be established in coordination with the outpatient prescriber, the patient, and the patient's family. (See 'Coordination of care' above.)

•For patients with untreated OUD who agree to start treatment, the team managing their acute pain should ensure follow up for ongoing MOUD. (See 'Transition to outpatient treatment' above.)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Diana Coffa, MD, who contributed to earlier versions of this topic review.

The UpToDate editorial staff also acknowledges Daniel Carr, MD, who contributed to earlier versions of this topic.