INTRODUCTION — Opioid use disorder (OUD) has reached epidemic proportions in the United States. Patients with OUD commonly experience episodes of acute pain related to injury, illness, or surgery. This topic will discuss strategies for acute pain management in patients on medication-assisted treatment for OUD, eg, with methadone, buprenorphine, or naltrexone, and pain management for patients with untreated OUD.
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 "Prescription of opioids for acute pain in opioid naïve patients" and "Management of acute perioperative pain in adults".)
GENERAL PRINCIPLES — The general principles of acute pain management in patients who take opioids chronically are discussed separately. These include challenges specific to these patients, evaluation of pain and baseline opioid use, and creation of a plan for treatment based on the expected degree and duration of pain. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain".)
PATIENTS RECEIVING PHARMACOTHERAPY FOR OPIOID USE DISORDER — Acute pain management in patients receiving medication-assisted treatment for OUD often requires coordination with substance use disorder treatment specialists, particularly if supplemental opioids are required [1].
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. (See "Medication for opioid use disorder", section on 'Methadone: Opioid agonist' and "Medication for opioid use disorder", section on 'Buprenorphine: Opioid agonist'.)
The opioid antagonist naltrexone is also approved for maintenance treatment of OUD, as well as for treatment of alcohol use disorder. Naltrexone can be administered as a daily oral dose, or as a monthly intramuscular injection (see "Medication for opioid use disorder", section on 'Naltrexone: Opioid antagonist'). Management of acute pain in patients who take naltrexone poses distinctive challenges, as naltrexone blocks the effects of opioid agonists.
PATIENTS ON METHADONE MAINTENANCE THERAPY — The general approach to acute pain management in patients who take methadone is similar to the approach used for patients who take stable doses of other opioids on a chronic basis: continuation of the baseline opioid and dose and use of multimodal nonopioid analgesic strategies supplemented with incremental opioid if necessary during the interval of acute pain. Once acute pain subsides, the additional opioid is then tapered.
The plan for pain control should be based on the degree of existing or expected pain (eg, after elective surgery). 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 fluctuate with activity. The expected degree and duration of acutely painful events are discussed separately. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Creating a plan for treatment'.)
Pain may be more difficult to control in patients who receive methadone maintenance therapy (MMT). Because opioid cross-tolerance may be present in patients who take methadone [2-4], patients on MMT typically require higher doses of opioid than opioid naïve patients. 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 patient-controlled analgesia (PCA) use, more inpatient pain management referrals, and longer hospital length of stay [5]. 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 naive patients (793 milligram morphine equivalents [MME]/24 hours versus 109 MME/24 hours) [6]. 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 [7].
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 [8,9]. Additional opioids for acute pain should not be withheld for fear of worsening the OUD. As long as medications for acute pain are tapered promptly as the pain resolves, the patient's course of treatment for OUD can continue undisrupted.
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 clinical experience [10-12].
Our strategy for patients on methadone maintenance — We use the following treatment strategy for patients who are on MMT.
Continue methadone — We suggest continuing methadone during acute pain to treat OUD and prevent withdrawal. Confirm the patient's baseline outpatient methadone dose with the patient's opioid treatment program (OTP). Because of its distinctive pharmacokinetic and pharmacodynamic profile, equianalgesic dose conversion guidelines for methadone are notoriously inaccurate. Thus, whenever possible patients should be maintained on their methadone doses without attempts to convert to other agents. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'How to perform opioid rotation'.)
If the patient cannot take oral medication, methadone can be given by the intravenous (IV) or subcutaneous route (table 1). The parenteral dose should be given as one-half the oral maintenance dose, divided into two to four equal doses through the day [10]. Although it is only legal in the outpatient setting to dispense MMT in a licensed OTP or in a qualified practice, in the inpatient setting, health care providers can legally dispense methadone for addiction treatment as long as the patient is admitted for a reason other than OUD [13].
Add nonopioid analgesic strategies — Both nonpharmacologic and nonopioid pharmacologic therapy should be maximized before adding further opioid therapy. Non-opioid strategies are often sufficient for treating mild acute pain (eg, after sprains, nonspecific low back pain, dental extraction, headache) and can prevent overuse of opioids. If non-opioid strategies are not adequate, they should be continued while opioids are initiated, thereby reducing the total dose of opioids necessary for pain control. Options include nonopioid analgesics (eg, acetaminophen and nonsteroidal antiinflammatory drugs), which can be administered intramuscular (IM) or IV in acute severe pain, adjuvant medications (eg, ketamine, lidocaine, glucocorticoids, gabapentinoids), regional anesthesia techniques, physical measures (eg, cold, heat, or splinting), integrative therapies, and psychosocial or behavioral management strategies. These medications and techniques are discussed in detail separately. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Nonopioid strategies for pain control'.)
Gabapentin has been shown to reduce hyperalgesia in patients on MMT [14] and does not impact methadone metabolism. The choice of other nonopioid analgesics should be informed by their interactions with methadone. Carbamazepine and phenytoin, for example, induce CYP4503A and could lead to a reduction in methadone levels and pronounced acute opioid withdrawal.
Add opioids only as necessary — Most laparoscopic and minimally invasive surgery, many soft tissue surgeries, and non-compound and non-comminuted fractures are expected to result in moderate pain that lasts for several days. Moderate pain usually requires short-acting opioids in addition to the patient's baseline opioid and nonopioid multimodal pain control strategies.
Use of oral and IV opioids for acute pain management for patients on MMT 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:
●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 for methadone are notoriously inaccurate. Thus, we start with empiric doses that are higher than those used with opioid-naive patients (eg, oxycodone 20 to 30 mg orally), with dose titration every two to four hours based on pain control (table 2). For patients with severe pain, we initially control pain rapidly with bolus IV administration of a rapid-onset opioid (eg, fentanyl, hydromorphone, or morphine) titrated to analgesic requirements, with constant vigilance for respiratory depression, and maintenance of hemodynamic stability, in a closely monitored setting (table 3). (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Initial pain control'.)
●For inpatients maintained on oral opioids after initial control of pain, short-acting oral opioids (table 2) should be given on a schedule (every three to four hours, with omission of a dose if sedation or respiratory depression are observed) and not ordered on an as-needed basis. As with all patients on chronic opioids, mixed agonist and antagonist opioid analgesics, such as pentazocine, 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, similar to other patients on chronic opioids, we administer a trial dose 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 who require ongoing IV opioids after initial pain control, either bolus administration or PCA can be used. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Ongoing pain control'.)
Intermittent IV opioid administration allows bedside assessment of respiratory status and sedation prior to administration of the opioid. However, PCA may be preferable once a stable dose has been established because it provides a sense of control. Control over opioid administration may be particularly valuable in patients with OUD, who often fear and experience undertreatment of pain [15,16]. Setting a cumulative dose limit on the PCA (eg, over a four hour interval) may be considered to decrease the possibility of excessive self-medication with the PCA opioid. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Patient-controlled analgesia'.)
Coordinate with other care providers — To prevent destabilization of OUD treatment, it is crucial to communicate with the patient's OTP and/or primary care provider about opioids or other potentially hazardous controlled substances, such as benzodiazepines, to be prescribed at discharge. Concurrent benzodiazepine therapy increases the mortality of patients taking opioids by augmenting opioid-induced ventilatory depression [17-20], and hence must be considered only with great caution. In collaboration with the outpatient providers and with the patient, the inpatient team should establish a plan for tapering off of supplemental opioids or benzodiazepines that may have been started in the hospital. This plan for tapering should be clearly communicated to both the patient and the outpatient prescriber. If the patient's pain requires ongoing short-acting opioids, a clinician outside the methadone program, such as a primary care provider or a pain specialist, may prescribe these while the patient continues once-daily methadone dosing through an OTP. The clinician prescribing these medications for pain should regularly inform the OUD treatment provider of specific medications and doses.
PATIENTS TAKING BUPRENORPHINE — Buprenorphine is an opioid that is often used for maintenance pharmacotherapy for OUD and is also increasingly used to treat chronic pain (see "Use of opioids in the management of chronic non-cancer pain", section on 'Buprenorphine for chronic pain' and "Medication for opioid use disorder", section on 'Buprenorphine: Opioid agonist'). Buprenorphine is a partial mu-opioid receptor agonist with high affinity for the receptor but low intrinsic activity and is also an antagonist at the kappa-opioid receptor. It is associated with less opioid-induced hyperalgesia than other opioids, causes less euphoria and associated psychologic reward [21,22], and importantly, produces less respiratory depression than other full mu-opioid agonists. Buprenorphine has a ceiling effect for respiratory depression, but not for analgesia, at clinically meaningful doses [23,24].
Whether to continue buprenorphine during pain management — We agree with an increasing international consensus that buprenorphine should be continued during an episode of acute pain, whether originally prescribed for chronic pain or for OUD [25-29]. Some experts feel that buprenorphine should be discontinued prior to surgery, however growing evidence suggests that discontinuation is not necessary and is associated with inferior outcomes. Further, the process of tapering and discontinuation of buprenorphine preoperatively adds complexity to the patient management process and increases the risk of return to illicit opioid use.
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 mu receptor opioids that bind to mu-opioid receptors, due to buprenorphine's high affinity for the mu receptor. Indeed, isolated case reports describe difficulty in controlling acute pain until and unless concurrent buprenorphine is discontinued and treatment is initiated with a full mu opioid agonist or other form of analgesia [30,31]. However, the preponderance of case series, observational studies, and clinical trials demonstrate that effective analgesia for acute pain can be achieved if buprenorphine is continued perioperatively [32-37]. In some cases, patients whose buprenorphine is discontinued prior to surgery may actually require even higher doses of opioids perioperatively, likely because of the opioid deficit created by discontinuation [35,37]. 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. Clinical studies have not confirmed this, but for patients on buprenorphine it is reasonable to turn to these opioids first or to transition to them if pain is not well controlled on other opioids.
Consensus is growing as well that the optimal perioperative dosing strategy for patients on buprenorphine is to continue on their home does throughout the perioperative period. Some authors have suggested tapering buprenorphine preoperatively to doses of 12 to 16 mg over two or three days prior to major surgery [25,26], but guidelines now recommend continuing the baseline dose and trials using this approach have demonstrated good pain control [29,38].
Our strategy for patients on buprenorphine — In general, we manage acute pain for patients who take buprenorphine as we would for other patients who take opioids chronically, including an emphasis on nonopioid pain management strategies. Issues specific to patients who take buprenorphine include the following.
Continue buprenorphine — We suggest continuing buprenorphine throughout an episode of acute pain, including postoperative pain, and we administer the patient's usual home doses. One should anticipate that in the presence of buprenorphine, higher than normal doses of any full mu agonist will be required for pain control [36]. (See 'Whether to continue buprenorphine during pain management' above.)
For the vast majority of patients, the transmucosal or sublingual formulation can be administered at the patient's usual home dose. For the rare patient who is unable to tolerate sublingual or buccal buprenorphine, intravenous (IV) buprenorphine (without naloxone) can be administered; there is no empirical evidence and 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 intravenously every eight hours. For example, for a patient taking 24/6 mg sublingual buprenorphine/naloxone as an outpatient, clinicians can administer 12 mg of buprenorphine IV total daily, divided into three 4 mg doses every eight hours. Naloxone should not be administered in the IV formulation to avoid precipitating withdrawal.
In the outpatient setting, only clinicians with Drug Enforcement Administration (DEA) buprenorphine waivers can legally prescribe buprenorphine to treat OUD. However, the DEA specifically excludes inpatient health care providers from this provision, allowing buprenorphine to be dispensed in the hospital setting by prescribers who have not obtained the X license waiver associated with their DEA registration if the patient is admitted for a reason other than OUD [13].
Employ nonopioid analgesic strategies — Both nonpharmacologic and nonopioid pharmacologic therapy should be maximized before adding opioid therapy, and should be continued if opioid therapy is used. (See 'Our strategy for patients on methadone maintenance' above and "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Nonopioid strategies for pain control'.)
Increase buprenorphine for mild to moderate pain — For patients who take buprenorphine for OUD once per day, mild to moderate pain that requires treatment over and above nonopioid analgesics (eg, sprained ankle or limited cellulitis) may be adequately controlled by increasing the patient's buprenorphine dose up to 32 mg/day, divided into doses every six to eight hours. The same approach applies to patients taking 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 with buprenorphine implants or receiving long-acting depot injections, we do not adjust the buprenorphine dose level and instead proceed to the addition of supplementary full mu agonist opioids if necessary.
Add supplementary opioids for severe or undertreated pain — Rather than temporarily increasing the dose of buprenorphine during severe acute pain, a short-acting oral or parenteral full mu opioid agonist should be added as needed, since full mu receptor agonists have greater intrinsic analgesic efficacy. 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 "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, milligram morphine equivalents (MME) cannot be reliably calculated for buprenorphine. Thus, we start with empiric doses that are higher than those used with opioid-naive patients (eg, oxycodone 20 to 30 mg orally), with dose titration every two to four hours based on pain control (table 2).
●For patients whose pain is not well controlled with higher doses of full-agonist opioids, we transition patients to a full agonist opioid with a high affinity for the mu opioid receptor (eg hydromorphone or fentanyl). It is reasonable to start with one of these agents.
●For inpatients who are maintained on oral opioids, after initial control of pain, short-acting oral opioids (table 2) should be administered on a schedule (every three to four hours, with omission of a dose if sedation or respiratory depression are suspected) and not ordered on an as-needed basis. As for all patients on chronic opioids, mixed agonist and antagonist opioid analgesics, such as pentazocine, nalbuphine and butorphanol, should not be administered to patients on buprenorphine, as they may precipitate acute withdrawal.
For ambulatory patients, as with other patients on 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 severe pain, we initially control pain rapidly with bolus IV administration of a full mu opioid agonist titrated to analgesic requirements, closely watching for respiratory depression, and maintaining hemodynamic stability in a monitored setting (table 3). (See "Management of acute perioperative pain in adults", section on 'Parenteral opioids' and "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Initial pain control'.)
●For patients who require IV opioids after initial control of pain, management is similar to patients who are on methadone as described above. (See 'Our strategy for patients on methadone maintenance' above.)
Coordinate care — Pain in patients receiving buprenorphine therapy for substance use disorder should be managed in consultation with the patient's addiction medicine team or provider. If the patient will need additional opioids for pain control after discharge from the hospital, it is important to develop a taper plan in collaboration with the outpatient team and with the patient. For patients who take buprenorphine for chronic pain and who require either a change in buprenorphine dose or additional opioids, the patient's chronic opioid prescriber should be involved in determining the duration of treatment and setting a taper plan.
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 [39]. 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 [40]. 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 perioperative pain control, including ketamine and regional anesthesia if possible.
●If opioids are required while naltrexone is still in effect (ie, within three days of oral naltrexone or within one month of XR naltrexone), opioids should be titrated to effect with monitoring in an intensive care unit.
●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 OUD is associated with reduced mortality and increased rates of recovery, 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. Patients in sustained remission from OUD may prefer to use nonpharmacologic or nonopioid pain management because of this risk. Any pain management plan for this population should be made in collaboration with the patient and 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 when possible.
With severe pain that cannot otherwise be controlled, it is sometimes necessary and appropriate to initiate opioid medications. Opioid tolerance is typically lost within weeks to months after cessation of opioids, so patients in sustained remission have likely lost all opioid tolerance and should be treated with the same doses of opioids as opioid naïve individuals. (See "Management of acute perioperative pain in adults", section on 'Parenteral opioids' and "Prescription of opioids for acute pain in opioid naïve patients".)
For mild to moderate pain requiring opioids, we recommend buprenorphine in this population. Though not specifically studied among people with behaviorally treated OUD, the limited euphoria associated with buprenorphine may reduce the risk of return to uncontrolled OUD. As a kappa-opioid antagonist, buprenorphine also reduces the intensity of opioid abstinence syndrome. A starting buprenorphine dose of 2 mg three times daily can be titrated upwards every eight hours in the hospital or every one to three days in the outpatient setting. For more severe pain, full agonist opioids (eg, oxycodone 5 mg) are more appropriate.
If an outpatient or discharge prescription is necessary, opioids should typically be prescribed for a short (three to five day) course. For pain that is expected to last longer, a clear plan for tapering should be discussed with the patient and their outpatient prescriber. We recommend short durations of prescriptions (five to seven days) with frequent visits to assess impact and titrate dose. Patients with OUD can also benefit from increased psychosocial support and increased engagement with their addiction treatment team both during and for the months following the opioid prescription.
PATIENTS WITH UNTREATED 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, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis", section on 'Epidemiology'.)
Some patients with OUD repeatedly report acute pain in an effort to obtain opioids. Even when this behavior pattern is recognized, a physiologic cause for pain should always be sought.
Screening for OUD — OUD is a potentially life-threatening medical condition that responds well to treatment. For patients without a diagnosis of OUD, clinicians who suspect it can use structured assessment tools to confirm the diagnosis. Screening and assessment for OUD is discussed separately. (See "Screening for unhealthy use of alcohol and other drugs in primary care" and "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis".)
Treating OUD — Intervention for OUD is indicated for patients who screen positive for OUD with a screening tool and/or urine drug testing, with confirmation using Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) criteria (see "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis", section on 'Diagnosis'). Once the acute pain period has subsided, it is critical to discontinue opioids to prevent ongoing misuse, and to engage the patient in compassionate, non-judgmental discussions about their OUD and offer treatment. For patients who are amenable to starting pharmacotherapy for OUD, they can be transitioned from opioids to buprenorphine or methadone. This transition can be made in the hospital setting if a patient remains hospitalized during this phase of treatment, or in the outpatient setting if the patient has been discharged [41-43]. The choice of medication to start for OUD should be a shared decision made with the patient. It should be informed by whether the patient has contraindications to a given medication and what is available with the patient's insurance in the patient's geographic region. Methadone should only be prescribed by clinicians familiar with its use, and with consideration of its unique risk profile and drug interactions. These considerations are discussed separately. (See "Medication for opioid use disorder", section on 'Adverse effects'.)
In some settings, methadone is more easily available whereas in others, buprenorphine or naltrexone are easier to arrange after discharge. 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 waived buprenorphine provider or a licensed OTP for ongoing methadone. If a patient is off of opioids for seven or more days during their hospitalization, they may also consider IM naltrexone to treat their OUD. Emergency departments, hospitals, urgent care clinics, labor and delivery units, and primary care providers can all initiate buprenorphine treatment for OUD if clinicians have received proper training and certification [41-44] (see "Medication for opioid use disorder", section on 'Regulation of methadone in United States' and "Medication for opioid use disorder", section on 'Regulation of buprenorphine in United States'). If the patient is referred elsewhere for treatment, the patient's pain should be managed in collaboration with substance use disorder treatment clinicians and counselors.
Outpatient pain management — Patients with OUD who have mild pain can often be managed as outpatients, with nonopioid measures for pain control. For moderate pain, prescription of opioids for outpatient treatment 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 a prescription for naloxone. There is no evidence to suggest that one opioid is safer than another in this situation. Some providers believe that hydromorphone or oxycodone have a higher potential for misuse, but all short-acting opioids can be inhaled or injected and provide similar euphoric experiences. Buprenorphine, because of its limited euphoric effect, is less likely to be misused, but in patients who are actively using opioids it 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 represents a contraindication to prescribing further opioids, or requires workup to determine why the patient requires opioids. (See "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Prescription monitoring programs'.)
Inpatient pain management — Pain should be treated aggressively to achieve effective analgesia in patients with OUD, with opioid doses titrated upwards rapidly as necessary. The setting of severe acute pain is not the time to attempt opioid weaning and detoxification. On the contrary, undertreated acute pain is a risk factor for chronification of acute pain and persistent opioid use [45-49].
Preventing or treating withdrawal — Inpatient pain management may be complicated by untreated withdrawal, as patients do not have access to their usual supply of opioids. It is important to prescribe sufficient opioids to both treat or prevent withdrawal and to sufficiently 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 of opioid withdrawal are discussed separately. (See "Opioid withdrawal in adults: Clinical manifestations, course, assessment, and diagnosis", section on 'Clinical manifestations'.)
Before initiating treatment for withdrawal, it is important to discuss with patients their intention to continue pharmacotherapy for OUD after discharge. If they intend to continue medications for OUD after treatment, it is useful to determine which medication they prefer. For patients who would like to take methadone or buprenorphine after discharge it may be preferable to start their preferred medication to treat withdrawal. The factors a patient and provider should consider together when choosing a long term treatment strategy are discussed separately. (See "Medication for opioid use disorder".)
Patients in opioid withdrawal with mild to moderate pain — For patients with mild to moderate pain in the hospital (eg, cellulitis) who are in some degree of withdrawal, we suggest administering buprenorphine to manage both withdrawal and pain. We typically administer buprenorphine three times a day, starting at a dose of 4 mg sublingual and titrate upwards as necessary every one to four hours.
Patients in opioid withdrawal with moderate to severe pain — For patients with moderate to severe pain who are in opioid withdrawal and who have no preference for buprenorphine treatment after discharge, we suggest administering methadone rather than buprenorphine to treat symptoms of withdrawal and to provide a degree of analgesia, adding short-acting opioids for further pain control. We start methadone at doses of 20 to 30 mg, titrated as described below, and taking into account methadone's adverse effects and drug interactions. (See "Medication for opioid use disorder", section on 'Methadone: Opioid agonist'.)
We use methadone for patients with moderate to severe pain because it has greater intrinsic analgesic efficacy than buprenorphine. However, if the patient intends to continue treatment for OUD after discharge and prefers buprenorphine for treatment, starting methadone can make it more difficult to transition to buprenorphine after discharge. In this case, prescribers may consider using a different long-acting opioid (eg, oral long-acting morphine) to treat or prevent withdrawal and transitioning to buprenorphine when the patient's pain has improved sufficiently to tolerate 12 hours without opioids.
Patients not in opioid withdrawal on admission or patients with severe pain — For patients with OUD who are not in withdrawal or who are in severe pain, the following is a reasonable strategy:
●Administer long-acting opioid to prevent withdrawal, as follows:
•Start methadone 20 to 30 mg orally once daily for withdrawal prevention. We do not recommend starting buprenorphine on patients with OUD who are in acute moderate to severe pain and who are not in withdrawal. Patients with OUD who are not in withdrawal may have high systemic opioid levels; buprenorphine may precipitate withdrawal in this setting. (See "Medication for opioid use disorder".)
•Four hours after the initial dose, if the patient has withdrawal symptoms, administer additional methadone 10 mg orally.
•Do not exceed 40 mg of methadone on the first day to avoid oversedation and respiratory depression. A steady state of methadone takes 4.5 days to achieve, so slow titration is critical.
•Patients should be supported in enrolling in long term pharmacotherapy to treat OUD and to reduce the risk of death from overdose after discharge.
-For patients intending to enter methadone maintenance therapy (MMT), methadone should be titrated up by 10 mg each day on subsequent days to eliminate withdrawal symptoms and reduce cravings. At a daily dose of 60 mg, we recommend pausing for five days to achieve a steady state serum level. After that, the dose can be increased by 10 mg each week in collaboration with the patient's accepting OTP. This titration is more rapid than recommended in the outpatient setting, but is considered appropriate in the inpatient setting because of the higher degree of monitoring and the urgency to prevent or treat withdrawal. (See "Medication for opioid use disorder".)
-If the patient does not intend to continue MMT as an outpatient, their dose should be titrated to eliminate withdrawal (typically achieved by daily doses of 40 mg), but should not be titrated to the high levels required to eliminate cravings (typically 80 mg or higher). Because the patient will be discharged without methadone, the severity of withdrawal on discharge can be somewhat limited by keeping the dose 40 mg or lower in the hospital and titrating down to 20 mg on the day of discharge.
-Patients who prefer to take buprenorphine for medication-assisted treatment after discharge can be transitioned to buprenorphine with the help of an addiction specialist.
●Diagnose and treat the pain — After administration of medication to prevent withdrawal, diagnosis and treatment of acute pain in patients with OUD is similar to treatment for other patients who chronically use methadone, buprenorphine, or other opioids. A multimodal approach should be used, starting with nonpharmacologic and nonopioid pharmacologic strategies, with oral or parenteral opioids added as necessary. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Creating a plan for treatment'.)
For patients with untreated OUD, the doses of opioids they use on a daily basis may be difficult or impossible to determine. Thus, if opioids are required for acute pain control an empiric starting dose may be required, followed by rapid titration and observation. Increased tolerance to opioids and therefore higher required doses can be expected. (See 'Our strategy for patients on methadone maintenance' above.)
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 in patients treated with opioid use disorder (OUD) frequently requires coordination with substance use disorder treatment specialists. (See 'Coordinate with other care providers' above and 'Coordinate care' above.)
•The general principles of acute pain management for patients who receive methadone or buprenorphine are similar to the principles used for patients who take other opioids chronically: continue the baseline opioid, maximize nonopioid and nonpharmacologic analgesic strategies, and administer supplemental opioid only if necessary. (See 'General principles' above.)
•For inpatients with severe pain requiring IV opioids, we seek to control pain rapidly with IV boluses in a closely monitored setting. For ongoing pain control with IV opioids, either bolus administration or patient-controlled analgesia (PCA) can be used. (See "Management of acute perioperative pain in adults", section on 'Parenteral opioids'.)
●Patients who take methadone
•For patients who take methadone, we suggest continuing maintenance methadone during an episode of acute pain (Grade 2C). For patients who cannot take oral medications, methadone can be administered by the intravenous (IV) or subcutaneous routes, at a dose one-half the oral maintenance dose divided into two to four equal doses throughout the day. (See 'Patients on methadone maintenance therapy' above.)
•Dose conversions between methadone and other opioids are problematic. Thus, for patients on methadone who require oral opioids for initial pain control, we start with empiric doses of short-acting oral opioids at doses higher than would be used for opioid naïve patients (eg, oxycodone 20 to 30 mg orally), with dose titration every four hours based on pain control. More rapid titration of IV opioids is appropriate for more severe pain. (See 'Add opioids only as necessary' above.)
●Patients who take buprenorphine
•For patients who take buprenorphine for either OUD or chronic pain, we suggest continuing buprenorphine during an episode of acute pain (Grade 2C), and we continue the patient's home dose. (See 'Whether to continue buprenorphine during pain management' above and 'Continue buprenorphine' above.)
•If opioids are required for mild acute pain in patients who take buprenorphine, after maximizing nonopioid analgesic strategies, the dose of buprenorphine can be increased up to 32 mg per day, divided into doses every six to eight hours. For moderate to severe pain, other opioids can be added to the regimen, similar to patients on methadone. (See 'Add supplementary opioids for severe or undertreated pain' above.)
•Dose conversions between buprenorphine and other opioids are problematic. Thus, for patients on buprenorphine who require oral opioids for initial pain control, we start with empiric doses of short-acting oral opioids at doses higher than would be used for opioid naïve patients (eg, oxycodone 20 to 30 mg orally), with dose titration every four hours based on pain control. More rapid titration of IV opioids is appropriate for more severe pain. (See 'Add supplementary opioids for severe or undertreated pain' above.)
●Patients who take naltrexone – Naltrexone blocks the mu-opioid receptor, rendering the use of opioids for acute pain management problematic. Oral naltrexone should be discontinued at least three days prior to elective procedures. Naltrexone XR should be held 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 untreated OUD
•For patients with untreated OUD, outpatient opioids should be considered only with great caution and after exhaustion of alternatives. If absolutely necessary, a short course (ie, ≤3 days) should be prescribed along with a prescription of naloxone for treatment of overdose and in collaboration with the outpatient prescribing team. (See 'Outpatient pain management' above.)
•A key goal for pain management in inpatients with untreated OUD is prevention or mitigation of opioid withdrawal.
-For patients who are in some degree of opioid withdrawal and have mild pain, we suggest administering buprenorphine to manage both pain and withdrawal (Grade 2C). (See 'Patients in opioid withdrawal with mild to moderate pain' above.)
-For patients with moderate to severe pain who are in opioid withdrawal and who have no preference for buprenorphine treatment after discharge, we suggest administering methadone rather than buprenorphine to treat symptoms of withdrawal and to provide a degree of analgesia, adding short-acting opioids for further pain control (Grade 2C). (See 'Patients in opioid withdrawal with moderate to severe pain' above.)
-For patients who are not in opioid withdrawal or who have severe pain, we suggest administering methadone to prevent withdrawal (Grade 2C). After administration of methadone to prevent withdrawal, treatment of pain is similar to treatment with other patients who chronically use opioids. (See 'Inpatient pain management' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Diana Coffa, MD, who contributed to earlier versions of this topic review.
