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Evidence Brief: Managing Acute Pain in Patients with Opioid Use Disorder on Medication-assisted Treatment

Investigators: , MPH, , MD, MPP, , MPH, and , MS.

Washington (DC): Department of Veterans Affairs (US); .

The ESP Coordinating Center (ESP CC) developed this evidence brief on acute pain management in patients with opioid use disorder (OUD) who are on medication-assisted treatment (MAT) in response to a request from VA’s Health Services Research and Development Service (HSR&D). Findings from this evidence brief will be used to inform prioritization of questions for a September 2019 State-of-the-Art (SOTA) conference.

Preface

The VA Evidence Synthesis Program (ESP) was established in 2007 to provide timely and accurate syntheses of targeted healthcare topics of importance to clinicians, managers, and policymakers as they work to improve the health and healthcare of Veterans. These reports help:

  • Develop clinical policies informed by evidence;
  • Implement effective services to improve patient outcomes and to support VA clinical practice guidelines and performance measures; and
  • Set the direction for future research to address gaps in clinical knowledge.

The program is comprised of four ESP Centers across the US and a Coordinating Center located in Portland, Oregon. Center Directors are VA clinicians and recognized leaders in the field of evidence synthesis with close ties to the AHRQ Evidence-based Practice Center Program and Cochrane Collaboration. The Coordinating Center was created to manage program operations, ensure methodological consistency and quality of products, and interface with stakeholders. To ensure responsiveness to the needs of decision-makers, the program is governed by a Steering Committee comprised of health system leadership and researchers. The program solicits nominations for review topics several times a year via the program website.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, Deputy Director, ESP Coordinating Center at vog.av@dyolF.elociN.

Executive Summary

Background

The ESP Coordinating Center (ESP CC) developed this evidence brief on acute pain management in patients with opioid use disorder (OUD) who are on medication-assisted treatment (MAT) in response to a request from VA’s Health Services Research and Development Service (HSR&D). Findings from this evidence brief will be used to inform prioritization of questions for a September 2019 State-of-the-Art (SOTA) conference.

Methods

To identify studies, we searched MEDLINE®, PsycINFO, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL). We used prespecified criteria for study selection, data abstraction, and rating internal validity and strength of the evidence. See our PROSPERO protocol for our full methods.

Key Findings

  • We identified 8 studies on acute pain management for non-Veterans with opioid use disorder (OUD) taking methadone or buprenorphine. However, none directly evaluated the trade-offs of different ways of managing acute pain in OUD patients on MAT. Also, none were conducted in VHA settings, or evaluated naltrexone for OUD.
  • These 8 studies align with current guidelines which recommend continuing methadone during acute pain episodes and state that continuing buprenorphine is a reasonable approach for most patients with mild or moderate pain. Specifically, these studies found that:
    • Continuing the use of buprenorphine and methadone for patients with OUD after surgery may reduce the need for additional opioids;
    • Patients with OUD on MAT are opioid-tolerant and need higher doses of opioid agonists for effective pain control compared to patients without OUD;
    • Ineffective management of acute pain in OUD patients taking methadone can lead to disengagement in care.
  • Future research is needed to evaluate the effectiveness of adjuvant non-opioid pharmacological and non-pharmacologic acute pain management strategies for patients with OUD taking methadone and buprenorphine, as well as the benefits and harms of adjusting the dose or timing of MAT (such as increasing doses or dividing doses). Future research is also urgently needed to evaluate effective acute pain management in patients with OUD on naltrexone.

Due to the national crisis of opioid-related morbidity and mortality – including deaths from overdoses – more patients are receiving medication-assisted treatment (MAT) with methadone, buprenorphine/naloxone, and naltrexone for opioid use disorder (OUD). Acute pain management in patients who have a history of OUD can be challenging due to increased pain sensitivity and the need for higher opioid doses to achieve pain relief. Clinicians may also tend to under-treat pain in patients with OUD because of concerns for drug-seeking behavior and ongoing illicit substance use. Use of MAT adds to the complexity of acute pain management in patients with OUD because of the unique pharmacologic properties of MAT medications resulting in the need for different management strategies to effectively treat acute pain. The aim of this review is to synthesize evidence on the effectiveness of acute pain management strategies for patients on MAT in terms of benefits and harms and whether benefits and harms differ for different medications (methadone, buprenorphine, or naltrexone) or type of acute pain (such as emergency conditions vs planned surgery).

We identified 8 retrospective studies (3 studies with a control group, 1 case series, and 4 case reports) covering a range of acute pain conditions (surgical, emergency, and both) and medications (buprenorphine/naloxone alone, methadone alone, and studies that looked at both) except for naltrexone. Study size ranged from 1 in case reports to 134 in controlled studies. Most studies were conducted in hospitals/tertiary care centers or specialized pain centers and had follow-up duration ranging between 1 day to over 2 years.

Three studies with control groups provide evidence supporting the continuation of MAT in acute pain management, although detail about the timing, dosage, and rationale for administering different medications (including changes to usual MAT doses and adding opioids and non-opioid analgesics) was lacking. One study found that patients taking buprenorphine who undergo surgery and miss their buprenorphine dose the day afterwards use more patient-controlled analgesia for longer periods of time than those who do receive their dose, and similar trends were found for those taking methadone. A second study found that patients on MAT (methadone or buprenorphine/naloxone) undergoing joint replacement surgery can receive eight times the dosage of opioids at discharge, with similar outcomes on both pain and knee and hip functionality at 1 year as those without OUD. A third study found that when equivalent doses of opioids are used to manage pain in patients who are or aren’t taking MAT, patients taking MAT were less satisfied with care, which manifested as higher rates of behavioral problems and increased likelihood of discharging against medical advice. The biggest limitation of these studies is that the MAT management strategies, including adjuvant analgesics, were not adequately described (ie, timing, dosage).

Five additional studies without control groups provide information on conditions not covered by the cohort studies – especially emergency conditions – and provide more detailed descriptions of the timing, dosage, and rationale for acute pain management strategies. However, due to imprecision and other methodological limitations such as inadequate outcome assessment, these studies do not provide a reliable evidence base to guide decision-making.

While the evidence has substantial limitations, the best-conducted studies did not suggest there is a potential benefit in stopping buprenorphine or methadone, and in fact several studies found that stopping MAT can cause patients to experience increased pain (measured directly as increased pain reports or indirectly as increased use of patient-controlled analgesics). Therefore, despite the limitations of the evidence, continuing MAT for most patients with OUD during an episode of acute pain seems to be a clinically sound and patient-centered approach. Future research should therefore explore the: 1) the optimal dosage and timing of continuing MAT in acute pain management based on patient characteristics and specific MAT medications used (ie, whether to increase or divide doses); 2) the optimal use of opioids and non-opioid pain management strategies; 3) whether certain acute pain management approaches work better for certain patients; and 4) the effect of acute pain management approaches on outcomes such as risk of relapse and overdose.

Researchers should ideally apply prospective study designs to evaluate these questions, although a well-described retrospective study would also provide useful information. These studies will be most useful if they have a concurrent control group (ie, an RCT or well-controlled cohort study) to help establish the causality of pain management approaches on outcomes, and provide detailed information on the pain management approach taken (including timing, dose, duration of different medications) as well as the rationale for why any changes were made.

Introduction

Purpose

The ESP Coordinating Center (ESP CC) developed this evidence brief on acute pain management in patients with opioid use disorder (OUD) who are on medication-assisted treatment (MAT) in response to a request from VA’s Health Services Research and Development Service (HSR&D). Findings from this evidence brief will be used to inform prioritization of questions for a September 2019 State-of-the-Art (SOTA) conference.

Background

Acute pain has been defined as sudden-onset, time-limited pain that can vary in intensity, modulating factors, and impact on functionality and quality of life.1 Many cases of acute pain resolve on their own without any medical or other healthcare interventions, while others require use of pharmacological and/or nonpharmacological pain management interventions. While professional societies are reconsidering the use of opioids to manage certain acute pain conditions – such as dental procedures and ambulatory surgeries2,3 – opioids remain a common treatment for many acute pain conditions.4,5

Acute pain management in patients with opioid use disorder (OUD) can be particularly challenging due to increased pain sensitivity and the need for higher opioid doses to achieve pain relief due to opioid tolerance. Clinicians may also tend to under-treat pain in patients with OUD because of concerns for drug-seeking behavior and ongoing illicit substance use.6,7 Use of medication-assisted treatment (MAT) for OUD with methadone, buprenorphine/naloxone, and naltrexone adds to the complexity of acute pain management in patients with OUD because of the unique pharmacologic properties of these medications and the implications of using opioids for analgesia in addition to MAT (See Table 1).

Methadone and buprenorphine help patients manage OUD by reducing opioid cravings and preventing withdrawal, which are both potent drivers of ongoing opioid use.8 Methadone is an “full opioid agonist,” meaning that it activates opioid receptors in the brain and body in the same way as other prescription opioids and illicit opioids such as heroin. Methadone is a long-acting medication that can build up quickly and unpredictably with dose adjustments, thereby increasing the risk of respiratory depression and overdose, particularly when it is used at the same time as other opioids. Patients taking methadone for OUD are monitored very closely (sometimes daily) in part due to the risks of methadone if it is used at the same time as illicit opioids. A parallel risk exists when using additional opioids for acute pain management in patients on methadone in the emergency department and hospital setting. Methadone also has multiple drug-drug interactions and a risk of heart arrhythmia that requires monitoring with electrocardiograms.

Buprenorphine is a “partial opioid agonist,” because it partially activates opioid receptors and thereby has a lower risk of adverse events such as respiratory depression and overdose compared to methadone and other full agonist opioids. Buprenorphine is typically co-formulated with naloxone, which helps deter misuse by blocking the effects of the opioids and causing unpleasant opioid withdrawal if the medication is crushed and injected or snorted instead of being used under the tongue as prescribed. Buprenorphine has a strong bond with opioid receptors (ie, receptor affinity) when compared with other opioids. While it is an effective pain medication for many patients, there is at least a theoretical risk that use of buprenorphine will make pain control more challenging in cases of severe acute pain because higher doses of full agonist opioids may be required to displace buprenorphine from opioid receptors.9 However, it is unclear how often this theoretical risk impacts clinical practice.

Naltrexone is an “opioid antagonist,” meaning that it blocks opioid receptor activity, and is available in an injectable form and oral form. Extended-release (injectable) naltrexone is the preferred MAT option for patients who would like to avoid taking any form of opioid or for whom methadone and buprenorphine are contraindicated. Naltrexone works differently than methadone and buprenorphine to treat OUD – by blocking the effects of opioids, it helps promote opioid abstinence. The challenge with acute pain management in patients taking naltrexone is that until enough time has elapsed that naltrexone is no longer active in the body, opioid pain medications will not be effective. Using higher doses of opioids may be a way to overcome the effects of naltrexone, but there is a risk of overdose once naltrexone starts wearing off.

Table 1. Medications used to treat OUD and clinical considerations for pain management.

Table 1

Medications used to treat OUD and clinical considerations for pain management.

The benefits of well-executed acute pain management in patients on MAT include effective management of pain; high functionality and quality of life after the acute pain event; satisfaction with care; and low healthcare utilization (including shorter hospital stays). Potential harms associated with inappropriate acute pain management for those with MAT include uncontrolled pain; risk of relapse associated with uncontrolled pain and/or gaps in MAT prescribing; and risk of respiratory depression or other adverse outcomes due to addition of high doses of full opioid agonists.

In cases of unplanned acute pain – such as injury or trauma – patients may be treated in the emergency department or hospital setting by providers who are meeting them for the first time. In this setting, patients may have heightened fears about pain control and stigma related to OUD, and providers may be more likely to view patients as drug-seeking or to have concerns about ongoing illicit drug use.13 Elective surgeries and other planned procedures present fewer challenges related to acute pain management given that planned procedures allow clinicians time to develop individualized pain management plans and allow time for MAT dose reduction and discontinuation if needed. Another difference between elective surgeries and emergency conditions is that for planned interventions, patients are more likely to have established relationships and trust with their providers.

A possible approach to acute pain management in patients taking methadone or buprenorphine/naloxone is to continue or increase their usual dose, potentially by dividing doses throughout the day, with or without the addition of other opioids or non-opioid pain treatments. Alternatively, buprenorphine may be discontinued and other opioids can be used instead until acute pain has resolved. For patients taking naltrexone, one approach is to use non-opioid and/or non-pharmacologic acute pain management strategies or to treat with higher doses of opioids to try to overcome the opioid blocking effects of naltrexone. In cases of planned procedures or surgery in which acute pain is expected, patients are often advised to stop extended-release naltrexone in advance to allow time for the medication to wear off. Given the potential challenges of using opioids for acute pain in patients MAT, clinicians may prefer to optimize non-opioid management strategies (eg, non-steroidal anti-inflammatory drugs, benzodiazepines) or use non-pharmacologic options (mindfulness and relaxation techniques, acupuncture, use of heating pads and ice packs).14 However, opioids may still be considered the best option in cases of severe acute pain.

Current guidelines addressing the management of acute pain in patients on MAT are primarily based on expert consensus and do not provide clear steps for clinicians to take in different acute pain scenarios. The American Society of Addiction Medicine’s (ASAM) 2015 guidelines on treatment for OUD – which are based on a structured consensus method – provide some suggestions but not firm recommendations for acute pain management in patients on MAT. These guidelines state that patients on methadone maintenance may require higher doses of full agonists for acute pain control in addition to their regular daily dose of methadone.14 For patients on buprenorphine, these guidelines do not conclusively recommend continuing or discontinuing buprenorphine for acute pain except in cases of severe pain, in which case these guidelines recommend stopping buprenorphine so that full agonist opioids will be more effective. For patients on naltrexone, these guidelines discuss non-opioid pain management strategies for acute unexpected pain and recommend discontinuing extended-release injectable naltrexone 30 days before elective surgery and oral naltrexone 72 hours prior to elective surgery. Educational materials produced by the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Providers Clinical Support System (PCSS) provide some suggestions for treatment, such as using intravenous ketamine and lidocaine,15 but these are not evidence-based guidelines. The Department of Veterans Affairs (VA)/Department of Defense’s (DOD) joint 2015 guidelines on management of substance use disorder do not address acute pain management for patients on MAT,16 although perioperative pain management protocols for patients on buprenorphine are being developed. Similarly, the Centers for Disease Control and Prevention (CDC) 2016 opioid guidelines encourage use of MAT for patients with OUD, but do not address acute pain management for patients on MAT.17

The most informative studies of acute pain management in patients on MAT would include patients with OUD on stable doses of methadone, buprenorphine (or buprenorphine/naloxone), or naltrexone who are undergoing elective surgery or who require emergency treatment for an acute pain condition. For patients on methadone, studies that compare the addition of opioid agonists and non-opioid treatments when baseline methadone doses are maintained would be most informative. In the case of buprenorphine, the most pressing question is whether buprenorphine should be continued or stopped for acute pain management.18 An informative study would address this question by comparing patient outcomes with use of adjuvant pain treatments when buprenorphine is continued or discontinued. Studies of naltrexone would evaluate pain management strategies prior to elective surgery when naltrexone must be stopped, as well as use of non-opioid treatments for emergency acute pain conditions. Ideal studies of MAT would also evaluate the effects of acute pain management strategies on relapse risk and other adverse events such as opioid overdose.

Use of MAT is increasing in response to the national crisis of opioid-related morbidity and mortality. Although use of these medications remains disproportionately low compared to the prevalence of OUD, multiple stakeholders, including patients, clinicians, and policy-makers, are engaged in efforts to increase MAT use, and it is likely that more patients will be treated with these medications over time.19 Determining best practices to manage acute pain in patients on MAT is therefore relevant to frontline clinicians in multiple settings. The aim of this review is to synthesize evidence on the effectiveness of acute pain management strategies for patients on MAT in terms of benefits and harms and whether benefits and harms differ for different MAT medications or type of acute pain (emergency condition vs planned surgery). Findings from this review will be used by VHA leadership, clinicians, and other decision-makers attending a 2019 VA State of the Art Conference (SOTA) to inform clinical decision-making around management of acute pain in MAT patients as well as to identify gaps for future research.

Scope

This rapid evidence review addresses the following key questions and eligibility criteria:

Key Questions

Key Question 1: What are the benefits and harms of strategies to manage acute pain in adults with OUD on MAT?

Key Question 2: Do these benefits and harms vary by patient characteristics, such as MAT medication or type of acute pain (emergency condition vs planned surgery)?

Eligibility Criteria

This review includes studies that meet the following criteria:

  • Population: Adults (excluding pregnant women) with OUD on MAT (methadone, buprenorphine [with or without naloxone], or naltrexone) with acute pain, defined as sudden onset, time-limited pain
  • Intervention: Any pain management approach (eg, discontinuation or dose change in medication used for MAT, substitution with another opioid, addition of another opioid, or non-opioid or non-pharmacological therapies)
  • Comparator: Any (ie, studies that compare different pain management approaches, or describe effects of a single pain management approach)
  • Outcomes: Pain severity, pain-related function, quality of life, patient satisfaction, healthcare utilization, opioid withdrawal symptoms, substance use relapse, opioid overdose, suicidal ideation and suicidal self-directed violence, and other adverse events
  • Timing: Any
  • Setting: Any (including primary care, emergency department, dental, perioperative, and palliative care settings)
  • Study design: Any, but may prioritize to accommodate timeline using a best-evidence approach

Methods

Searches and Study Selection

To identify articles relevant to the key questions, our research librarian searched MEDLINE, PsycINFO, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) using terms for opioid use disorder, medication-assisted treatment, and acute pain (see Supplemental Materials for complete search strategies) from database inception to April 2019. Additional citations were identified from hand-searching reference lists and consultation with content experts. We limited the search to published and indexed articles involving human subjects available in the English language. Study selection was based on the eligibility criteria described above. Titles and abstracts were reviewed by 1 investigator. Full-text articles were reviewed by 1 investigator and checked by another. All disagreements were resolved by consensus.

Quality Assessment and Data Extraction

We used predefined criteria to rate the internal validity of all included cohort studies as well as the quality of reporting for case series and case reports. For cohort studies, we used criteria from Cochrane’s ROBINS-I tool20 which evaluates the potential for bias from participant selection, classification of interventions, departure from intended interventions, measurement of outcomes, confounding, and missing/unreported data. Overall bias ratings range from low, unclear, to high risk of bias. For case series and case reports, we adapted criteria from ROBINS-I as well as the CARE Checklist21 and focused on the quality of reporting, rather than the potential for bias. Overall quality of reporting ratings range from not reported, partly reported, mostly reported, to well-reported. We abstracted data from all studies, including study characteristics, populations, comparators, intervention, and results. All data abstraction and internal validity/quality of reporting ratings were first completed by 1 reviewer and then checked by another. All disagreements were resolved by consensus.

Strength of Evidence Assessment

We graded the strength of the evidence based on the AHRQ Methods Guide for Comparative Effectiveness Reviews.22 This approach incorporates 4 key domains: risk of bias (includes study design and aggregate quality), consistency, directness, and precision of the evidence. It also considers other optional domains that may be relevant for some scenarios, such as a dose-response association, plausible confounding that would decrease the observed effect, strength of association (magnitude of effect), and publication bias. Strength of evidence is graded for each key outcome measure and ratings range from high to insufficient, reflecting our confidence that the evidence reflects the true effect.

Synthesis of Data

Due to limited data and heterogeneity, we synthesized the evidence qualitatively.

The complete description of our full methods can be found on the PROSPERO international prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO/; registration number CRD42019132924).

Results

Literature Flow

The literature flow diagram (Figure 1) summarizes the results of our search and study selection (See Supplementary Materials Appendix A for the full list of excluded studies). Our search identified 278 unique, potentially relevant articles. Of these we included 8 articles2330 that addressed our key questions. All 8 addressed Key Question 1, and none addressed Key Question 2.

Figure 1. Literature flowchart.

Figure 1

Literature flowchart.

KEY QUESTION 1. What are the benefits and harms of strategies to manage acute pain in adults with OUD on MAT?

We identified 8 retrospective studies (3 studies with a control group and 5 without): 2 studies examined patients with OUD taking buprenorphine/naloxone,24,26 4 examined those taking methadone,25,2729 and 2 examined a mixed group of MAT medications.23,30 No studies examined the use of naltrexone. Four studies examined those with emergency conditions,24,2628 3 examined those undergoing planned surgery,23,29,30 and 1 examined a mixed group of emergency and surgical patients.25 Study size ranged from 1 to 134 participants, were conducted in hospitals/tertiary care centers or specialized pain centers, and follow-up ranged between 1 day to over 2 years. Detailed descriptions of these studies appear in Appendix C and key findings appear below. For studies of buprenorphine, we first report whether the study evaluated buprenorphine alone or in co-formulation with naloxone, then subsequently refer to both medications as “buprenorphine,” as it is our assumption that these drugs were taken as prescribed and thus acted like buprenorphine alone.

Studies with control groups

The best available evidence comes from the 3 studies with control groups, although these had considerable limitations. Table 2 provides an overview of these studies, including study characteristics, patients examined, acute pain management strategies, results, and limitations. One study30 compared 2 groups of surgical patients (orthopedic, abdominal, orofacial, thoracic, and other) on MAT – those taking methadone and those taking buprenorphine – 24 hours after surgery. The study found similar pain management strategies (high doses of morphine-equivalent opioids in the intraoperative period) and outcomes (use of patient-controlled analgesia [PCA], pain severity, and adverse events like nausea, vomiting, and sedation) between groups. However, only half of patients taking buprenorphine and three-quarters of patients taking methadone received their MAT dose the day after surgery. Those taking buprenorphine who missed their dose used more PCA for longer periods of time than those that didn’t, and similar trends were found in patients taking methadone. Study authors did not know why some patients missed their dose. A second study23 compared patients with OUD taking MAT (methadone or buprenorphine/naloxone) versus non-OUD patients receiving hip or knee joint replacements. Patients taking MAT received 8 times the dose of opioids at discharge as patients not taking MAT. This difference reflected a decrease in opioid dosage from baseline for patients taking MAT and an increase in dosage from baseline for patients not taking MAT. Both groups had similar pain, functionality, and quality of life outcomes at 6 weeks and 1 year. It was unclear whether MAT was continued or discontinued in these patients, as study authors only reported overall doses of morphine-equivalent doses. It was also unclear whether these high opioid doses were titrated down over time. A third study25 compared patients with OUD taking methadone with acute pain from surgery or injury (type of surgery or injury not reported) to patients not on methadone (presumably without OUD but the study does not specify) and found that when similar doses of opioids were used to manage pain, patients taking methadone had similar number of pain reports but higher rates of behavioral problems and were more likely to discharge against medical advice. Due to limitations in how data on patients’ pain was collected, study authors could not determine why patients were discharging against medical advice. They hypothesized it may have been because either these patients were using illicit opioids in addition to MAT before hospitalization and were driven by opioid cravings, or because their pain was not being effectively managed. The study did not report any follow-up information on these patients, for example, whether they continued OUD treatment in outpatient settings.

Overall, findings from these studies align with ASAM 2015 guidelines14 on treatment for OUD which state that patients on MAT are opioid-tolerant and need higher doses of opioid agonists for effective pain control. Findings of these studies also suggest that continuing the use of methadone and buprenorphine in patients on MAT after surgery may reduce total doses of opioids. However, our confidence in these findings is low due to several limitations, including that pain management strategies, including use of MAT and adjuvant analgesics, were not adequately described (ie, timing, dosage), inadequate methods were used to assess pain severity outcomes, and few studies reported patient-important outcomes other than pain severity.

Table 2. Findings from studies with control groups.

Table 2

Findings from studies with control groups.

Studies without control groups

Additional evidence from 5 studies24,2629,31 that lacked control groups (1 case series and 4 case reports) provide information on conditions not covered by the cohort studies – especially emergency conditions – and provide more detailed descriptions of the timing, dosage, and sequence of acute pain management strategies. Table 3 provides an overview of these studies, including study characteristics, population, acute pain management strategies and key findings, and major limitations. Overall, these studies suggest that management of acute pain in emergency conditions may require some trial and error, as most studies attempted multiple strategies before achieving pain relief. These findings also support current clinical guidance that methadone should be continued in patients acute pain,27 and that higher doses of opioids may be required in patients taking MAT to achieve pain relief26 and provide one example of a case in which buprenorphine needed to be discontinued before adequate pain control was achieved.24 However, because these studies examined small numbers of patients, rarely used measurement tools to assess outcomes, and are by design at high risk of both selection and reporting bias, they do not provide a strong foundation on which to guide clinical decision-making.

Table 3. Findings from studies without control groups.

Table 3

Findings from studies without control groups.

KEY QUESTION 2. Do these benefits and harms vary by patient characteristics, such as MAT medication or type of acute pain (emergency condition vs planned surgery)?

It is not possible to determine whether benefits and harms of acute pain management strategies vary by patient characteristics or type of acute pain due to the insufficiency in descriptions of the acute pain management strategies, including adjuvant analgesics. For example, in 3 studies23,25,26 that included patients undergoing surgery who were taking methadone, detail was lacking on whether methadone was continued, whether the dosage stayed the same, increased, or decreased, and why those decisions were made. Without that information, it is impossible to know whether there were any differences in outcomes based on different management approaches.

Summary and Discussion

To our knowledge, this is the first evidence review focusing on acute pain management in patients with OUD on MAT. Because of the unique pharmacologic properties of methadone, buprenorphine/naloxone, and naltrexone, acute pain management in patients on MAT can be highly nuanced and dependent on the MAT medication used. Given the high prevalence of opioid misuse (11.4 million people or 4.2% of the population 12 and older reported misusing opioids in the past year32) and increasing use of MAT to manage patients with OUD, there is an urgent need for evidence-based strategies for managing acute pain in these patients.

Unfortunately, we identified limited evidence to address our questions, and our overall confidence in the effect of any specific strategy on the management of acute pain is low. Three retrospective studies support recent guidelines based on a structured consensus method14 that continuing the use of MAT for patients undergoing major surgery may reduce overall opioid doses, that patients on MAT are opioid-tolerant and need higher doses of opioid agonists for effective pain control, and that discontinuing MAT can lead to patient disengagement from care. The best-conducted studies did not identify a benefit of discontinuing methadone or buprenorphine, with several studies suggesting that discontinuation or missed doses can result in patients experiencing more pain (measured directly as increased pain reports or indirectly as increased patient use of patient-controlled analgesia). Only one case study found that buprenorphine needed to be discontinued to achieve adequate pain control with full agonist opioids.24 Therefore, our findings align with current guidelines which recommend continuing methadone during acute pain episodes and state that continuing buprenorphine is a reasonable approach for most patients with mild or moderate pain. Although guidelines state that discontinuing buprenorphine may be necessary in cases of severe pain, we did not identify studies supporting that statement except for one case study. Future research is needed to evaluate the effectiveness of adjuvant non-opioid and non-pharmacologic acute pain management strategies for patients with OUD taking methadone and buprenorphine, as well as the benefits and harms of adjusting the dose or timing of MAT (such as increasing doses or dividing doses). Future research is also urgently needed to evaluate effective acute pain management in patients with OUD on naltrexone.

Limitations

Primary study limitations

Primary studies in this review had several limitations that make it difficult to interpret and apply findings. First, there are no prospectively designed studies, which means that evidence is limited to information that researchers collected and aggregated from data sources not originally designed to address these questions. This practice is problematic because it means 1) researchers could introduce bias by selecting certain populations or outcomes that best support their hypothesis and 2) the data available (such as information collected from medical records) is not always the best suited to address the research question. This is most notable in patients’ assessments in pain – some studies assessed pain through a scale, but others just noted how often a patient mentioned the word pain or gave a physicians’ overall impression of a patient’s pain, which does not sufficiently address the question of whether a patients’ pain is being effectively managed. Second, there were considerable methodological limitations of the retrospectively designed studies that make it difficult to determine the causality connecting pain management approaches to outcomes. For example, 2 studies with control groups23,25 lacked detailed information on whether MAT was continued, whether the dosage stayed the same, increased, or decreased, and why those decisions were made. Without that information, it is difficult to know whether continuing MAT is a safe and effective approach towards managing pain in these patients. Furthermore, the fact that patient groups were different at baseline in all the retrospective cohort studies makes it difficult to determine whether findings are due to the intervention, or due to confounders such as patients physical and mental health status. This is especially problematic when the 2 groups being compared were so different (ie, patients on MAT vs not on MAT) that you would not expect to manage pain the same way, making it difficult to interpret data on the effects of different pain management strategies for each.

Rapid review limitations

In addition to primary study limitations, there were limitations in our rapid review methodology. First, our search required that a study include the term “acute pain,” which may have missed studies in which it is assumed that the patient is in acute pain but is not described that way, such as studies that look at long-term outcomes for MAT patients that include a subset of patients that underwent surgery. However, we likely identified most of the studies that explicitly sought to examine strategies for management of acute pain in MAT patients. Second, our use of first-reviewer inclusion and data abstraction with second-reviewer checking may have resulted in missing eligible studies or study data. However, given that our results align with a recent guidelines, we likely identified most of the important data on this topic.

Gaps and Future Research

There are several important gaps in the available literature that should be addressed by future research:

  1. Well-described studies (such as randomized controlled trials or cohort studies) examining specific acute pain management strategies: We did not identify any studies that adequately described a specific pain management strategy and its effects on patient outcomes. Prospective studies are the best designed to allow for the deliberate recording of intervention elements that are important to clinicians deciding which treatment approach to take (such as the specific medication including MAT medications, other opioids, and non-opioid medications; dosage; timing and justification). Prospective studies would also allow for the randomization of patients into different interventions (eg, a structured pain management approach vs clinical judgement; or continuing buprenorphine with opioids as needed vs continuing buprenorphine with non-opioid analgesics as needed). Randomizing patients into different groups would provide the most rigorous, defensible answers to what pain management approaches are safe and effective; however, even a well-described, well-controlled cohort study that adjusts for differences in patient groups at baseline would be a useful step forward.
  2. Management of patients taking naltrexone: We did not identify any evidence on the management of patients taking naltrexone, an opioid antagonist. Acute pain is especially challenging to manage in these patients as naltrexone blocks the effects of opioids. Research on management of acute pain in these patients is urgently needed.
  3. Measurement of patient outcomes: Of the best available evidence, only 1 study23 used validated tools to measure quality of life or functionality. All other studies provided limited information on how outcomes were measured, with many commenting that outcomes were retrospectively collected from medical records. We identified no studies that rigorously evaluated patient satisfaction, healthcare utilization (other than length of hospitalization), opioid withdrawal symptoms, substance use relapse, opioid overdose, or suicide ideation or suicidal self-directed violence. Furthermore, with few exceptions, studies ended when patients were discharged, so it is impossible to determine what the long-term effects of pain management strategies were on patients’ health, especially the impact of administering opioids on patients’ likelihood of relapse or overdose.

Conclusions

This review confirmed a lack of rigorous evidence on the management of acute pain in patients taking methadone, buprenorphine, or naltrexone. Although it has important limitations, the best available evidence suggests that continuing methadone or buprenorphine during an acute pain episode is a clinically sound approach for most patients taking these medications for OUD. More research is urgently needed that evaluates patient outcomes following well-characterized acute pain management interventions including MAT dose and schedule adjustments and use of non-opioid pain management strategies.

Acknowledgments

This topic was developed in response to a nomination from VA’s Health Services Research and Development Service (HSR&D), for the purpose of developing an evidence brief on acute pain management in patients with opioid use disorder who are on medication-assisted treatment. The scope was further developed with input from the topic nominators (ie, Operational Partners) and the ESP Coordinating Center.

In designing the study questions and methodology at the outset of this report, the ESP consulted several technical and content experts. Broad expertise and perspectives were sought. Divergent and conflicting opinions are common and perceived as healthy scientific discourse that results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design, methodologic approaches, and/or conclusions do not necessarily represent the views of individual technical and content experts.

The authors gratefully acknowledge Julia Haskin and Emilie Chen for their editorial support and the following individuals for their contributions to this project:

Operational Partners

Operational partners are system-level stakeholders who have requested the report to inform decision-making. They recommend Technical Expert Panel (TEP) participants; assure VA relevance; help develop and approve final project scope and timeframe for completion; provide feedback on draft report; and provide consultation on strategies for dissemination of the report to field and relevant groups.

  • William Becker, MD
    Director, Opioid Reassessment Clinic
    VA Connecticut Healthcare System
  • Amy Bohnert, PhD, MHS
    Research Investigator
    VA Center for Clinical Management Research, Ann Arbor

Peer Reviewers

The Coordinating Center sought input from external peer reviewers to review the draft report and provide feedback on the objectives, scope, methods used, perception of bias, and omitted evidence. Peer reviewers must disclose any relevant financial or non-financial conflicts of interest. Because of their unique clinical or content expertise, individuals with potential conflicts may be retained. The Coordinating Center and the ESP Center work to balance, manage, or mitigate any potential nonfinancial conflicts of interest identified.

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Supplemental Materials

APPENDIX A. Search Strategies

1. Search for current systematic reviews

Date Searched: 4/23/19

Source:Strategy:
AHRQSearch: opioid, opiate
CADTHSearch: opioid, opiate
NICESearch: opioid use disorder and “acute pain”; opiate use disorder and “acute pain”;
ECRI InstituteSearch: opioid, opiate
VA Products: VATAP, PBM, HSR&D publications, VA ART Database
Search: opioid, opiate
Cochrane Database of Systematic Reviews

Database: EBM Reviews - Cochrane Database of Systematic Reviews <2005 to April 17, 2019>

Search Strategy:

------------------------------------------------------------

  1. (Opioid Related Disorder* or Opioid-Related Disorder* or Opioid Addiction* or Opioid Dependence* or Opioid Abuse* or Opiate Abuse* or Opiate Dependence* or Opiate Addiction* or Narcotic Dependence* or Narcotic Abuse* or Narcotic Addiction*).ti,ab. (21)
  2. (buprenorphine or Probuphine or Sublocade).ti,ab. (24)
  3. (Revia or Vivitrol or naltrexone).ti,ab. (14)
  4. (Bunavail or Cassipa or Suboxone or Subutex or Zubsolv).ti,ab. (0)
  5. (medicat* adj2 assist* adj2 (treat* or therap* or regimen* or interven* or program*)).ti,ab. (0)
  6. ((opiate* or opioid* or narcotic*) adj2 (substitut* or replac* or maint*) adj2 (treatment* or therap* or regimen* or program* or interven*)).ti,ab. (5)
  7. (Opiate Substitution Treatment* or Opioid Substitution Treatment* or Opiate Substitution Therap* or Opioid Substitution Therap* or Opiate Replacement Therap* or Opioid Replacement Therap* or Medication Assisted Treatment* or Medication Assisted Therap*).ti,ab. (4)
  8. (Methadone or Biodone or Dolophine or Metadol or Metasedin or Symoron or Methadose or Methex or Phenadone or Physeptone or Phymet or Pinadone or Amidone or Methaddict).ti,ab. (27)
  9. or/2-8 (48)
  10. Acute Pain*.ti,ab. (49)
  11. 1 and 9 and 10 (0)
***************************

2. Systematic reviews currently under development (forthcoming reviews & protocols)

Date Searched: 4/23/19

Source:Strategy:
PROSPERO (SR Registry)Search: opioid, opiate
DoPHER (SR Protocols)Search: opioid, opiate

3. Current Guidelines

Date Searched: 4/23/19

Source:Strategy:
VA/DoD Clinical Practice GuidelinesSearch: NA
Guidelines TrustSearch: opioid, opiate
Guideline CentralSearch: opioid, opiate

4. Current Primary Literature

Date Searched:

Source:Strategy:
MEDLINE

Database: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) <1946 to April 22, 2019>

Search Strategy:

------------------------------------------------------------

  1. exp Opioid-Related Disorders/ (24042)
  2. (Opioid Related Disorder* or Opioid-Related Disorder* or Opioid Addiction* or Opioid Dependence* or Opioid Abuse* or Opiate Abuse* or Opiate Dependence* or Opiate Addiction* or Narcotic Dependence* or Narcotic Abuse* or Narcotic Addiction*).ti,ab. (6815)
  3. 1 or 2 (26883)
  4. exp Opiate Substitution Treatment/ (2433)
  5. exp Opioid-Related Disorders/dt, rh (9639)
  6. exp Buprenorphine/ or (buprenorphine or Probuphine or Sublocade).ti,ab. (6795)
  7. exp Naltrexone/ or (Revia or Vivitrol or naltrexone).ti,ab. (9567)
  8. exp Buprenorphine, Naloxone Drug Combination/ or (Bunavail or Cassipa or Suboxone or Subutex or Zubsolv).ti,ab. (373)
  9. (medicat* adj2 assist* adj2 (treat* or therap* or regimen* or interven* or program*)).ti,ab. (497)
  10. ((opiate* or opioid* or narcotic*) adj2 (substitut* or replac* or maint*) adj2 (treatment* or therap* or regimen* or program* or interven*)).ti,ab. (1335)
  11. (Opiate Substitution Treatment* or Opioid Substitution Treatment* or Opiate Substitution Therap* or Opioid Substitution Therap* or Opiate Replacement Therap* or Opioid Replacement Therap* or Medication Assisted Treatment* or Medication Assisted Therap*).ti,ab. (1270)
  12. exp Methadone/ (11934)
  13. (Methadone or Biodone or Dolophine or Metadol or Metasedin or Symoron or Methadose or Methex or Phenadone or Physeptone or Phymet or Pinadone or Amidone or Methaddict).ti,ab. (12911)
  14. or/4-13 (32994)
  15. exp Acute Pain/ (1721)
  16. Acute Pain*.ti,ab. (7766)
  17. 15 or 16 (8710)
  18. 3 and 14 and 17 (46)
  19. limit 18 to english language (42)
***************************

PsycINFO

Database: PsycINFO <1806 to April Week 3 2019>

Search Strategy:

------------------------------------------------------------

  1. exp Drug Abuse/ or exp Drug Dependency/ or exp Opiates/ or exp Drug Addiction/ (123405)
  2. (Opioid Related Disorder* or Opioid-Related Disorder* or Opioid Addiction* or Opioid Dependence* or Opioid Abuse* or Opiate Abuse* or Opiate Dependence* or Opiate Addiction* or Narcotic Dependence* or Narcotic Abuse* or Narcotic Addiction*).ti,ab. (3956)
  3. 1 or 2 (123779)
  4. exp Drug Therapy/ (137456)
  5. exp Methadone Maintenance/ (3515)
  6. exp Buprenorphine/ or (buprenorphine or Probuphine or Sublocade).ti,ab. (2543)
  7. exp Naltrexone/ or (Revia or Vivitrol or naltrexone).ti,ab. (3314)
  8. exp Buprenorphine, Naloxone Drug Combination/ or (Bunavail or Cassipa or Suboxone or Subutex or Zubsolv).ti,ab. (105)
  9. (medicat* adj2 assist* adj2 (treat* or therap* or regimen* or interven* or program*)).ti,ab. (295)
  10. ((opiate* or opioid* or narcotic*) adj2 (substitut* or replac* or maint*) adj2 (treatment* or therap* or regimen* or program* or interven*)).ti,ab. (847)
  11. (Opiate Substitution Treatment* or Opioid Substitution Treatment* or Opiate Substitution Therap* or Opioid Substitution Therap* or Opiate Replacement Therap* or Opioid Replacement Therap* or Medication Assisted Treatment* or Medication Assisted Therap*).ti,ab. (794)
  12. exp Methadone/ (1773)
  13. (Methadone or Biodone or Dolophine or Metadol or Metasedin or Symoron or Methadose or Methex or Phenadone or Physeptone or Phymet or Pinadone or Amidone or Methaddict).ti,ab. (7068)
  14. or/4-13 (145089)
  15. Acute Pain*.ti,ab. (1707)
  16. 3 and 14 and 15 (85)
  17. limit 16 to english language (85)
***************************

CCRCT

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <March 2019>

Search Strategy:

------------------------------------------------------------

  1. exp Opioid-Related Disorders/ (1694)
  2. (Opioid Related Disorder* or Opioid-Related Disorder* or Opioid Addiction* or Opioid Dependence* or Opioid Abuse* or Opiate Abuse* or Opiate Dependence* or Opiate Addiction* or Narcotic Dependence* or Narcotic Abuse* or Narcotic Addiction*).ti,ab. (1302)
  3. 1 or 2 (2536)
  4. exp Opiate Substitution Treatment/ (263)
  5. exp Opioid-Related Disorders/dt, rh (4)
  6. exp Buprenorphine/ or (buprenorphine or Probuphine or Sublocade).ti,ab. (2178)
  7. exp Naltrexone/ or (Revia or Vivitrol or naltrexone).ti,ab. (2173)
  8. exp Buprenorphine, Naloxone Drug Combination/ or (Bunavail or Cassipa or Suboxone or Subutex or Zubsolv).ti,ab. (76)
  9. (medicat* adj2 assist* adj2 (treat* or therap* or regimen* or interven* or program*)).ti,ab. (93)
  10. ((opiate* or opioid* or narcotic*) adj2 (substitut* or replac* or maint*) adj2 (treatment* or therap* or regimen* or program* or interven*)).ti,ab. (318)
  11. (Opiate Substitution Treatment* or Opioid Substitution Treatment* or Opiate Substitution Therap* or Opioid Substitution Therap* or Opiate Replacement Therap* or Opioid Replacement Therap* or Medication Assisted Treatment* or Medication Assisted Therap*).ti,ab. (188)
  12. exp Methadone/ (1138)
  13. (Methadone or Biodone or Dolophine or Metadol or Metasedin or Symoron or Methadose or Methex or Phenadone or Physeptone or Phymet or Pinadone or Amidone or Methaddict).ti,ab. (2522)
  14. or/4-13 (6437)
  15. exp Acute Pain/ (462)
  16. Acute Pain*.ti,ab. (2289)
  17. 15 or 16 (2546)
  18. 3 and 14 and 17 (5)
  19. limit 18 to english language (2)
***************************

CINAHL

Database: CINAHL Plus with Full Text via EBSCOhost

Search Strategy:

------------------------------------------------------------

S1.

(MH “Analgesics, Opioid+”) (30707)

S2.

(MH “Substance Abuse+”) (59260)

S3.

(MH “Substance Dependence+”) (82500)

S4.

TI ( (Opioid Related Disorder* or Opioid-Related Disorder* or Opioid Addiction* or Opioid Dependence* or Opioid Abuse* or Opiate Abuse* or Opiate Dependence* or Opiate Addiction* or Narcotic Dependence* or Narcotic Abuse* or Narcotic Addiction*) ) OR AB ( (Opioid Related Disorder* or Opioid-Related Disorder* or Opioid Addiction* or Opioid Dependence* or Opioid Abuse* or Opiate Abuse* or Opiate Dependence* or Opiate Addiction* or Narcotic Dependence* or Narcotic Abuse* or Narcotic Addiction*) ) (3021)

S5.

S1 OR S2 OR S3 OR S4 (143323)

S6.

(MH “Drug Therapy+”) (149586)

S7.

(MH “Methadone”) (4360)

S8.

(MH “Buprenorphine”) (2680)

S9.

(MH “Naltrexone”) (1677)

S10.

TI ( (buprenorphine or Probuphine or Sublocade or Revia or Vivitrol or naltrexone or Bunavail or Cassipa or Suboxone or Subutex or Zubsolv) ) OR AB ( (buprenorphine or Probuphine or Sublocade or Revia or Vivitrol or naltrexone or Bunavail or Cassipa or Suboxone or Subutex or Zubsolv) ) (5277)

S11.

TI ( (medicat* N2 assist* N2 (treat* or therap* or regimen* or interven* or program*)) ) OR AB ( (medicat* N2 assist* N2 (treat* or therap* or regimen* or interven* or program*)) ) (529)

S12.

TI ( ((opiate* or opioid* or narcotic*) N2 (substitut* or replac* or maint*) N2 (treatment* or therap* or regimen* or program* or interven*)) ) OR AB ( ((opiate* or opioid* or narcotic*) N2 (substitut* or replac* or maint*) N2 (treatment* or therap* or regimen* or program* or interven*)) ) (915)

S13.

TI ( (Opiate Substitution Treatment* or Opioid Substitution Treatment* or Opiate Substitution Therap* or Opioid Substitution Therap* or Opiate Replacement Therap* or Opioid Replacement Therap* or Medication Assisted Treatment* or Medication Assisted Therap*) ) OR AB ( (Opiate Substitution Treatment* or Opioid Substitution Treatment* or Opiate Substitution Therap* or Opioid Substitution Therap* or Opiate Replacement Therap* or Opioid Replacement Therap* or Medication Assisted Treatment* or Medication Assisted Therap*) ) (969)

S14.

TI ( (Methadone or Biodone or Dolophine or Metadol or Metasedin or Symoron or Methadose or Methex or Phenadone or Physeptone or Phymet or Pinadone or Amidone or Methaddict) ) OR AB ( (Methadone or Biodone or Dolophine or Metadol or Metasedin or Symoron or Methadose or Methex or Phenadone or Physeptone or Phymet or Pinadone or Amidone or Methaddict) ) (4400)

S15.

S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 (159110)

S16.

(MH “Acute Pain (Saba CCC)”) OR (MH “Acute Pain Control (Saba CCC)”) (2)

S17.

TI Acute Pain* OR AB Acute Pain* (3202)

S18.

S16 OR S17 (3202)

S19.

S5 AND S15 AND S18 (202)

S20.

limit 19 to Academic Journals (162)

S21.

limit 20 to english language (158)

***************************

5. Primary literature currently under development (forthcoming studies & protocols)

Date Searched: 4/23/19

Source:Strategy:
Clinicaltrials​.gov

Search: opioid and “acute pain”; opiate and “acute pain”

Effect of Buprenorphine/Naloxone Continuation on Pain Control and Opioid Use

APPENDIX B. List of Excluded Studies

Exclude reasons: 1=Ineligible population, 2=Ineligible intervention, 3=Ineligible comparator, 4=Ineligible outcome, 5=Ineligible timing, 6=Ineligible study design, 7=Ineligible publication type 8=Outdated or ineligible systematic review

#CitationExclude reason
1Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Annals of Internal Medicine. 2006;144(2):127-134.E7
2Anderson TA, Quaye ANA, Ward EN, Wilens TE, Hilliard PE, Brummett CM. To Stop or Not, That Is the Question: Acute Pain Management for the Patient on Chronic Buprenorphine. Anesthesiology. 2017;126(6):1180-1186.E7
3Bean HK, Gannon R. Treatment of acute pain in opioid tolerant patients. Connecticut Medicine. 2010;74(3):143-148.E7
4Book SW, Myrick H, Malcolm R, Strain EC. Buprenorphine for postoperative pain following general surgery in a buprenorphine-maintained patient. American Journal of Psychiatry. 2007;164(6):979.E7
5Broglio K, Matzo M. CE: Acute Pain Management for People with Opioid Use Disorder. American Journal of Nursing. 2018;118(10):30-38.E7
6CADTH. Research Gaps: Acute Pain Management: Non-Opioid Treatments (Pharmacologic and Non-Pharmacologic). 2018.E7
7Chapman C, Davis J, Donaldson GW, Naylor J, Winchester D. Postoperative pain trajectories in chronic pain patients undergoing surgery: The effects of chronic opioid pharmacotherapy on acute pain. Journal of Pain. 2011;12(12):1240-1246.E1
8Chua K-P, Brummett CM, Waljee JF. Opioid Prescribing Limits for Acute Pain: Potential Problems With Design and Implementation. JAMA: Journal of the American Medical Association. 2019;321(7):643-644.E7
9Compton P, McCaffery M. Treating acute pain in addicted patients. Nursing. 2001;31(1):17.E7
10De Pinto M, Cahana A. Medical management of acute pain in patients with chronic pain. Expert Review of Neurotherapeutics. 2012;12(11):1325-1338.E7
11Dever C. Treating Acute Pain in the Opiate-Dependent Patient. Journal of Trauma Nursing. 2017;24(5):292-299.E7
12Eyler EC. Chronic and acute pain and pain management for patients in methadone maintenance treatment. American Journal on Addictions. 2013;22(1):75-83.E7
13Gorman E, Warfield CA. The opioid-dependent patient with acute pain. Hospital Practice. 1987;22(11):113, 115, 117-120.E7
14Hay JL, White JM, Bochner F, Somogyi AA. Antinociceptive effects of high-dose remifentanil in male methadone-maintained patients. European Journal of Pain. 2008;12(7):926-933.E1
15Huxtable CA, Macintyre PE. An alternative way of managing acute pain in patients who are in buprenorphine opioid substitution therapy programs. European Journal of Anaesthesiology. 2013;30(11):717-718.E7
16Kraft L, Wiechula R, Conroy T. The effectiveness of acute pain management for opioid tolerant or opioid dependent patients: a systematic review protocol. JBI Database System Rev Implement Rep. 2015;13(9):120-135.E7
17Manfredi PL, Gonzales GR, Cheville AL, Kornick C, Payne R. Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy. Journal of Pain and Symptom Management. 2001;21(2):169-174.E1
18Mehta V, Langford R. Acute Pain Management in Opioid Dependent Patients. Rev Pain. 2009;3(2):10-14.E7
19Mehta V, Langford RM. Acute pain management for opioid dependent patients. Anaesthesia. 2006;61(3):269-276.E7
20Mercadante S, Ferrera P, Arcuri E, Mercadante S, Ferrera P, Arcuri E. The use of fentanyl buccal tablets as breakthrough medication in patients receiving chronic methadone therapy: an open label preliminary study. Supportive Care in Cancer. 2011;19(3):435-438.E1
21Mercadante S. Opioid titration in cancer pain: A critical review. European Journal of Pain. 2007;11(8):823-830.E1
22Nielsen RV, Fomsgaard JS, Siegel H, et al. Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial. Pain. 2017;158(3):463-470.E1
23Paschkis Z, Potter ML. CE: Acute Pain Management for Inpatients with Opioid Use Disorder. American Journal of Nursing. 2015;115(9):24-32; quiz 33, 46.E7
24Rapp SE, Ready LB, Nessly ML. Acute pain management in patients with prior opioid consumption: a case-controlled retrospective review. Pain. 1995;61(2):195-201.E1
25Schug SA. Acute pain management in the opioid-tolerant patient. Pain Manag. 2012;2(6):581-591.E7
26Shah S, Kapoor S, Durkin B. Analgesic management of acute pain in the opioid-tolerant patient. Current Opinion in Anaesthesiology. 2015;28(4):398-402.E1
27Streltzer J. Pain management in the opioid-dependent patient. Curr Psychiatry Rep. 2001;3(6):489-496.E7
28Stromer W, Michaeli K, Sandner-Kiesling A. Reply to: an alternative way of managing acute pain in patients who are in buprenorphine opioid substitution therapy programmes. European Journal of Anaesthesiology. 2013;30(11):718-719.E7
29Tauben D, Klein JW, Merrill JO, Gordon DB. Acute Pain Management in Patients with Opioid Use Disorder. NIH.E7
30Taveros MC, Chuang EJ. Pain management strategies for patients on methadone maintenance therapy: a systematic review of the literature. BMJ supportive & palliative care. 2017;7(4):383-389.E1
31Wilson JL, Poulin PA, Sikorski R, Nathan HJ, Taljaard M, Smyth C. Opioid use among same-day surgery patients: Prevalence, management and outcomes. Pain Research & Management. 2015;20(6):300-304.E1

APPENDIX C. Evidence Tables

Data Abstraction of Included Observational Studies

Study and Patient Characteristics

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Intervention Characteristics

Download PDF (62K)

Questions for Quality Assessment of Included Cohort Studies

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Quality Assessment of Included Cohort Studies

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Questions for Assessing Quality of Reporting for Included Case Series and Studies

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Assessment of Quality of Reporting for Included Case Series and Studies

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APPENDIX D. Peer Review Comments

Comment #Reviewer #CommentAuthor Response
Are the objectives, scope, and methods for this review clearly described?
0011YesNone.
0022YesNone.
0033YesNone.
0045YesNone.
Is there any indication of bias in our synthesis of the evidence?
0051NoNone.
0062NoNone.
0073NoNone.
0085NoNone.
Are there any published or unpublished studies that we may have overlooked?
0091NoNone.
0102NoNone.
0113NoNone.
0125NoNone.
Additional suggestions or comments can be provided below.
0131Good executive summary. Good introduction to problemThank you.
0141Even though there is likely no literature, does type of surgery have implications for management (I think it is considered in the context of VA/DoD guidelines for post-op pain; should these be referenced?). Page 10 (or 5) mentions other guidelines but not VA/DoD post-op guideline. In this context, it might be informative to cite the published taxonomy of acute pain conditions. (Kent ML et al. The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) multidimensional approach to classifying acute pain conditions. Journal of Pain, 2017;18:479-489. (Also published in Pain Medicine, 2017;18:947-958).Yes, type of surgery has implications for the management of acute pain. We added details to the “findings” section to indicate what types of surgery patients were undergoing in each study, as it is helpful in interpreting findings. Unfortunately, no studies conducted subgroup analyses based on different types of surgery, so we do not know whether certain acute pain management strategies worked better or worse for patients undergoing certain types of surgery. We have also added the ACTTION-APS-AAPM Pain Taxonomy’s definition of acute pain to the “background” section.
0151The description of MAT and three medications is excellent; Table 1 is helpful summaryThank you.
0161Good summary of considerations and differences for managing emergent pain versus planned surgeries.Thank you.
0171How important is it to distinguish use of BUP versus BUP/Naloxone and consider their indications and plans for acute pain management separately?It was our assumption that patients in these studies were taking buprenorphine or buprenorphine/naloxone as prescribed, which would mean the medications would act in the same way (i.e., the naloxone component was not activated for patients taking buprenorphine/naloxone). We clarified this in our report by adding the following statement in the findings: “for studies of buprenorphine, we first report whether the study evaluated buprenorphine alone or in co-formulation with naloxone, then subsequently refer to both medications as “buprenorphine,” as it is our assumption that these drugs were taken as prescribed and thus act like buprenorphine alone.”
0181At least a brief qualifying discussion of the presumed role of opioids for the management of acute pain would likely be helpful. Increasingly, prescribers are reevaluating the analgesic requirements for management of many acute pain conditions, such as dental procedures, factures other than long-bone fractures, and ambulatory and other surgeries.We added a sentence to the first paragraph of the background indicating: “While professional societies are reconsidering the use of opioids to manage certain acute pain conditions – such as dental procedures and ambulatory surgeries – opioids remain a common treatment for many acute pain conditions.”
0191How important is it to be clear that most acute pain conditions don’t require any medical or other healthcare interventions? Most acute pain conditions resolve on their own (e.g., acute low back pain).We added a sentence to the first paragraph of the background indicating: “Many cases of acute pain resolve on their own without any medical or other healthcare interventions, while others require use of pharmacological and/or nonpharmacological pain management interventions.”
0201I’m not sure that listing some “ideal studies” on page 11 (or 6) is indicated before considering the review. This suggests some potential bias of the reviewers that could have influenced their search and review of the findings.We disagree that pre-specifying which studies are most relevant to our study questions would introduce bias. We have, however, changed the terminology in this section from “ideal studies” to “most informative studies,” to make it clear that these types of studies would theoretically offer the most relevant information to address our questions.
0211Some more explicit background on the evidence of effectiveness of non-opioid analgesics and co-analgesics and non-pharmacological approaches would also likely be informative and provide important context for the focus of this review. (Page 11 [or 6], line 21).We have added a section describing the potential use of non-opioid and non-pharmacological management strategies to manage acute pain in patients on MAT to the “background” section: “Given the potential challenges of using opioids for acute pain in patients on MAT, clinicians may prefer to optimize non-opioid management strategies (e.g. non-steroidal anti-inflammatory drugs, benzodiazepines) or non-pharmacologic options (mindfulness and relaxation techniques, acupuncture, use of heating pads and ice packs). However, opioids may still be considered the best option in cases of severe acute pain.”
0221What is the domain of “acute pain management strategies” being considered? The eligibility criteria are not clear regarding these issues; the use of “etc” is concerning. Why the term “adjuvant” therapies in this context?We added our definition of acute pain to the inclusion criteria. We also replaced “non-opioid adjunctive” with “non-opioid and non-pharmacological therapies.“
0231Although there is reference to an interest in non-opioid and nonpharmacological approaches, it did not appear that the search strategy included this focus. If not, why not? And, if not, references to this broader interest should be deleted and it should be clear that the aims were limited to examining use of opioid therapy and “adjuvant medications” for the management of acute pain.We were interested in any type of acute pain management strategy. Our search strategy was based on our population of interest (patients with opioid use disorder, taking some form of MAT, with acute pain) and therefore would have captured any type of acute pain management. Our description of our search erroneously included opioids as a search term, which we have corrected to opioid use disorder instead.
0241Outcomes: “Pain relief” is recommended as a primary or secondary outcome in acute pain trials. Why wasn’t this outcome included in the search and evaluation of the findings? (Cooper SA et al, Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain, 2016;157:288-301)We agree that pain relief is important and did include it as an outcome of interest. However, it is not our standard approach to limit by outcome in our search, as it can result in results that are overly exclusive.
0251What about other “patient characteristics” beyond the nature of acute pain and type of MAT, including comorbidities, history of SUD, overdose, suicide, and so forth?We specifically mention MAT medication and type of acute pain as examples of relevant patient subgroups, but we would have included analyses of any patient subgroups that study authors conducted. Unfortunately, we did not identify any studies that conducted these types of analyses.
0261Overall, the approach is appropriate, other than the question about non-opioid strategies.None.
0271How is “opioid requirements” defined, and what does it mean to say that an intervention “reduced opioid requirements?” The authors are encouraged to reconsider this kind of terminology, since it suggests a bias in favor of sole reliance on opioids in the acute pain management setting and a sense of a reliable, objective approach to measuring pain and pain relief.Here and throughout the report, we changed the reference to “high opioid requirements” to “high doses of opioids” so we do not inadvertently suggest opioids are the only viable option to achieve pain relief.
0282Page 6, line 58: What does multiple MAT types mean?This means we identified studies that examined more than 1 type of MAT (for ex, in MacIntyre 2013, some patients were taking methadone and some were taking buprenorphine). We added language to clarify that MAT types includes “buprenorphine/naloxone alone, methadone alone, and studies that looked at multiple MAT medications.”
0292Page 7, line 12: [“than those that”] WhoChanged “that” to “who.”
0302Page 7, line 15: [“receive 8-fold the dosage of opioids at discharge with similar outcomes”] Compared to?Clarified that this is compared to those not taking MAT.
0312Page 7, line 18: [“non-MAT patients, MAT patients”] Would use person first language e.g. patients on MAT.Changed “MAT patients” to “patients taking MAT” as appropriate.
0322Page 7, line 25: [“cohort studies - especially emergent conditions – and“] These look like hyphens but should be dashes. Same on next page.Changed to dashes.
0332Page 8, line 54/55: [ “the naloxone component is not activated” ] The naloxone component is eliminated by the first pass of the liver.Clarified “the naloxone component is eliminated by the liver and therefore not activated.”
0342Page 8, line 58: [ ”with opioid receptors” ] I.e. receptor affinity.Added “ie, receptor affinity.”
0352Page 8, line 59/60: [ “it may be difficult to achieve adequate pain control” ] I’m struggling with this clause – “it may be difficult to achieve adequate pain control…” Reality may be a little more nuanced. It may be that being on BUP means higher dose IV opioids are needed in patients for whom anesthesiologists are trying to make unconscious and also have total analgesia. However, in the post-operative period, in my experience, buprenorphine is a great long acting opioid for many patients and they can still use short acting opioids on top of buprenorphine with good effect. As written, this sentence seems to imply that stopping buprenorphine may be the best way to go (b/c otherwise it may be difficult to achieve adequate analgesia…) when in fact, the data, as weak as they are, seems to suggest the opposite.We re-wrote the section on how MAT medications work. We now say: “while it is an effective pain medication for many patients, there is at least a theoretical risk that use of buprenorphine will make pain control more challenging in cases of severe acute pain because higher doses of full agonist opioids may be required to displace buprenorphine from opioid receptors. However, it is unclear whether this theoretical risk is relevant to clinical practice.”
0362Page 9, line 4/5: [ “patients can experience withdrawal symptoms” ] Would say ‘typically experience withdrawal symptoms’ rather than can experience.We re-wrote the section on how MAT medications work. This now says: “Methadone and buprenorphine help patients manage OUD by reducing opioid cravings and preventing withdrawal, which are both potent drivers of ongoing opioid use.”
0372Page 9, line 10/11: [ “patients who do not want to use any form of an opioid” ] Or are court ordered.We re-wrote the section on how MAT medications work. This now says: “Extended-release naltrexone is the preferred MAT option for patients who would like to avoid taking any form of opioid or for whom methadone and buprenorphine are contraindicated.”
0382Page 9, line 14: [ “over time may help prevent opioid cravings” ] It doesn’t prevent cravings.We re-wrote the section on how MAT medications work. The relevant sections now say: “Methadone and buprenorphine help patients manage OUD by reducing opioid cravings and preventing withdrawal, which are both potent drivers of ongoing opioid use.” And “Naltrexone works differently than methadone and buprenorphine to treat OUD – by blocking the effects of opioids, it helps reduce cravings and increase opioid abstinence.”
0393Thanks for the opportunity to review the VA review of acute pain management in persons with OUD on MAT. I was kind of surprised how little and how poor the available data is. Given the very limited lack of evidence and the timeliness of something our group here has accepted for publication (Dale et al., in press) I wanted to share it with you as it seems to provide some data that the authors may wish to consider. We are correcting the author questions this week.We reviewed this article for potential inclusion. Unfortunately, because it looks at patients with untreated OUD, it does not meet our inclusion criteria.
0405Page 6, line 8: [ “The ESP Coordinating Center (ESP CC) is responding to a request from VA’s Health Services Research” ] Possible make this past tense, and more clear that the evidence brief was what the request was for.Here and in the introduction, we rephrased to say, “The ESP Coordinating Center (ESP CC) developed this evidence brief on acute pain management in patients with opioid use disorder (OUD) who are on medication-assisted treatment (MAT) in response to a request from VA’s Health Services Research and Development Service (HSR&D).”
0415Page 6, line 13: [ “recent guidelines that:” ] that recommend:Changed to “suggest that” since guidelines did not provide strong recommendations on treatment.
0425Page 6, line 27: [ “We identified no studies of naltrexone. Studies of methadone and buprenorphine” ] I think that this is unclear, should note that the naltrexone, etc is the MAT therapy in the background, and the rest of this paragraph is referring to acute pain management techniques, doses, etc.We revised this to say, “We did not identify any studies conducted in VHA settings, or among Veterans or non-Veterans taking naltrexone for OUD.”
0435Page 6, line 34: [ “Cochrane Central Register of Controlled Trials (CCRT).” ] I’m pretty sure that Cochrane change this to ‘CENTRAL’ several years ago.Changed to CENTRAL.
0445Page 6, line 38/39: [ “for opioid use disorder (OUD).” ] Suggest adding the list of 3 meds used for this here.Added “including methadone, buprenorphine/naloxone, and naltrexone” here.
0455Page 6, line 42: [ “Clinicians may also have a tendency to under-treat pain in patients with OUD” ] Do you have a citation for this statement?We do not typically include citations in the executive summary. Citations supporting this statement are available in the full report, under “background.”
0465Page 6, line 48: [ “these 3 medications work to treat OUD,” ] Manage? I don’t think that we are ally treating OUD, just trying to contain it.Changed to “manage.”
0475Page 6, line 56/57: [ “and MAT types” ] As a pharmacist, I guess I would object to using the word ‘types’ – can you just say drugs or medications? Drug treatmentsHere and throughout the report, changed “MAT types” to “MAT medications.”
0485Page 7, line 9: [ “rationale for different medications was lacking” ] As in the summary above, I find it unclear whether you are referring to the MAT meds or acute pain meds here.Changed to “rationale for administering different medications (including MAT, opioids, and non-opioid analgesia) was lacking.”
0495Page 7, line 15: [ “outcomes on pain” ] Does this mean pain at one year, or just function at one year? This finding also makes me wonder if they were able to taper off these large doses of opioids?Clarified that both pain and hip/knee functionality was measured at 1 year. Unfortunately, study authors do not report what the average dosage of opioids was like at 1 year, so we do not know if patients were tapered off these or not. We added a sentence to the “findings” section indicating “It was also unclear whether these high opioid doses were titrated down over time.”
0505Page 7, line 37: [ “the ideal use” ] Appropriate? Best?Changed to “best.”
0515Page 7, line 39/40: [ “outcomes such as risk of relapse and overdose” ] Did any of these mention other forms of therapy, psychosocial interventions?None of these studies addressed psychosocial or other types of therapeutic interventions.
0525Page 8, line 11: [ “is responding to” ] As above, the report represents the finished work so seems like this sentence should be re-framed.Revised so this is in past tense.
0535Page 8, line 34: [ “Because of the different ways these 3 medications work to treat OUD, patients taking these medications may require different management strategies to effectively treat acute pain. (Table 1).” ] This sentence is just slightly awkward, maybe just simplify it.Changed to “Patients taking these medications may require different management strategies to effectively treat acute pain, as these medications work in different ways to manage OUD.”
0545Page 8, line 42/43: [ “effects” ] I don’t think that effects is the right word. It can have unpredictable pharmacokinetics, which may affect the effects by building up in the body. But it doesn’t have unpredictable effects on the Mu receptors.Changed to “Methadone is a long-acting opioid medication whose use can result in serious adverse events.”
0555Page 8, line 42/43: [ “with” ] afterChanged to “after.”
0565Page 8, line 42/43: [ “It can build up quickly and unexpectedly with dose adjustments and increase the risk of respiratory depression and overdose, particularly when it is used at the same time as other opioids.” ] This sentence too is a bit awkward and might be better to simplify or break it up.Revised so this is now 2 sentences: “It can build up quickly and unexpectedly after dose adjustments. It can also increase the risk of respiratory depression and overdose, particularly when it is used at the same time as other opioids.”
0575Page 8, line 42/43: [ “Like other opioids, it can cause withdrawal symptoms if stopped abruptly” ] Yes, but with a long half-life, it is probably less of a risk than with other opioids that are shorter acting.Added “although this risk is lower with methadone than with shorter-acting opioids.”
0585Page 8, line 47-57: [ “Buprenorphine/naloxone is different than methadone and other opioids because it only partially activates the opioid receptor (“partial agonists”). For this reason, buprenorphine/naloxone is useful in treating OUD because it prevents opioid withdrawal symptoms and has a lower risk of overdose. Buprenorphine is co-formulated with naloxone in order to prevent abuse. Naloxone blocks opioid receptor activity (“opioid antagonist”). When buprenorphine/naloxone is taken as prescribed in a sublingual form (under the tongue), the naloxone component is not activated. However, if the medication is crushed and injected or snorted, naloxone is activated to block the effect of opioids and can therefore cause immediate withdrawal symptoms.” ] I suggest reversing the order of this – starting with the explanation that it is a combination product. Maybe start with buprenorphine is used to treat OUD, and that naloxone is added to the product to prevent abuse. Later on in this section it may be confusing to a reader that it partially activates but binds very tightly with the receptors.We re-wrote the section on how MAT medications work. We now start with a description of buprenorphine as a partial opioid agonist and its properties, then later discuss how it is typically formulated with naloxone
0595Page 8-9, line 57-6: [ “Another important feature of buprenorphine/naloxone is how strongly the buprenorphine component bonds with opioid receptors. It has a stronger bond with the receptor than other opioids, so it may be difficult to achieve adequate pain control in patients taking buprenorphine/naloxone because the addition of other opioids (such as morphine or oxycodone) may not be as effective. Like opioids, patients can experience withdrawal symptoms if buprenorphine/naloxone is stopped abruptly.” ] I suggest simplifying by combining these sentences.See comment above, this section has been re-ordered for clarity.
0605Page 8, line 59/60: [ “achieve adequate pain control” ] Might be good to add in acute, or some way to more clearly indicate that you mean treating pain on top of treating OUD.Added “acute.”
0615Page 9, line 4/5: [ “experience withdrawal symptoms” ] Above, you noed that this combo drug prevents withdrawal symptoms.We re-wrote the section on how MAT medications work. We now discuss in the text that MAT medications can help prevent withdrawal symptoms from opioids but note in table 1 there is a risk that patients may experience these symptoms when their MAT is discontinued.
0625Page 9, line 14: [ “The challenge with acute pain management in patients taking naltrexone is that is also blocks the analgesic effects of opioids. Therefore, until enough time has elapsed that naltrexone is no longer active in the body, opioid pain medications will not be effective. Using higher doses of opioids may be a way to overcome the effects of naltrexone, but there is a risk of overdose once naltrexone starts wearing off.” ] Alternative forms of treating pain may need to be used? Both drug and non-drug forms are potentials.In the following paragraph, we discuss that non-opioid and non-pharmacological treatments are possible approaches towards managing acute pain.
0635Page 9, line 56/57: [ “typical approach” ] For both of these sentences it seem like a citation is needed. Where do these statements come from?We clarified that these are “possible approaches.” We also discuss the American Society of Addiction Medicine’s 2015 guidelines in the next paragraph to clarify what guidelines suggest when managing acute pain in patients on MAT.
0645Page 10, line 7-9: [ “For patients taking naltrexone, a typical approach is to stop naltrexone and use non-opioid pain treatments or higher doses of opioids until naltrexone effects wear off.” ] It seems like the use of non-pharm or non-opioid treatments is left out in these scenarios. I hear that IV Tylenol is quite effective, for example.We have added examples of non-opioid (e.g., ketamine, benzodiazepines, non-steroidal anti-inflammatory drugs) and non-pharmacological (e.g., relaxation techniques, heating pads, aromatherapy) treatments for managing acute pain to the beginning of this paragraph, as these approaches are being considered for all patients on MAT.
0655Page 10, line 17: [ “leading to disengagement from care (such as leaving a hospital or clinic against medical advice);” ] Was this potential harm specifically identified a priori? It just seems a bit unusual to have this be exactly what the findings of some studies showed too. Might re-word this to say stopping OUD treatment? I’d think leaving AMA is a bit different, affects the current acute pain episode but potentially not the OUD treatment.Deleted the clause that uncontrolled pain can lead to disengagement from care as this was indeed informed by our findings.
0665Page 10, line 22/23: In cases of unexpected acute painChanged to “unplanned.” We believe it’s important to leave this word in as it distinguishes between unplanned (i.e., emergency) acute pain and planned (i.e., surgical) acute pain, which may require different management strategies.
0675Page 11, line 5/6: [ “emergent” ] I’m sure the definition of this word includes emergency as it is unfolding, but it seems a bit odd here, and elsewhere in tis report. Can you just use emergency?Replaced “emergent” with “emergency” here and throughout to report.
0685Page 11, line 48/49: [ “with acute pain” ] I see that acute was not pre-defined. Cancer pain, reported below, seems like it may not always be acute, or rarely is. It may be new pain, but less likely to only be expected to have a short duration.We added our definition of acute pain to the inclusion criteria. We also agree that the Manfredi 2011 article does not meet inclusion criteria, because they did not exclusively examine patients with acute pain (some had acute pain and cancer-related pain, others just had cancer-related pain.) We have removed it from the report.
0695Page 11, line 53: [ “non-opioid adjunctive therapies” ] Did you search for these explicitly? Or was that not necessary as the search was based on the population only?Our search was based on the population only.
0705Page 13, line 9: [ “(CCRT)” ] As above, the correct term is now CENTRAL.Changed this to CENTRAL.
0715Page 15, line 13: [ “1 examined those with cancer pain” ] As above, is this really acute pain? The study report may have only covered an acute period, but is the pain expected to really resolve?See comment #68 above. We have removed this study from the report.
0725Page 15, line 38: [ “MAT patients received 8 times the dose of opioids at discharge, which reflected a decrease from baseline for MAT patients and an increase from baseline for non-MAT patients.” ] I don’t understand the second half of this sentence. Obviously, comparing OUD to non-OUD patients is not very useful, but still I’d rather understand what is going on here.Revised to say: “MAT patients received 8 times the dose of opioids at discharge as non-MAT patients. This difference reflected a decrease in opioid dosage from baseline for MAT patients and an increase in dosage from baseline for non-MAT patients.”
0735Page 15, line 48: [ “discharge against medical advice.” ] Might note here that they did not report on follow-up, e.g. whether the patient went back to OUD treatment as an outpatient.Added: “Authors also did not report any follow-up information on these patients, for example, whether they continued OUD treatment in outpatient settings.”
0745Page 22, line 13: [ “such as patients physical and mental health status” ] Does this cover the comparison of OUD patients with non-OUD patients? Seems like maybe not quite clear – that is a huge limitation as the findings are apples and oranges.Added: “This was especially problematic when the two groups being compared were so different (i.e., MAT vs non-MAT patients) that you would not expect to manage pain the same way, making it difficult to interpret data on the effects of different pain management strategies for each.”
0755Page 22, line 22: [ “underwent surgery.” ] Similarly the criteria used did no defined ‘acute’.We selected studies of sudden onset, time-limited pain and have clarified this definition in the eligibility criteria.
0765Page 22, line 33/34: Add that non-drug and non-opioid interventions need to be studied.

We added additional detail under gap #1 that more detailed information is needed on the “specific medication type (including MAT medications, other opioids, and non-opioid medications) …” to address this.

Non-drug pain management strategies were outside the scope of this review.

0775Page 23, line 17: This review confirmed there is a lack of rigorous evidenceDeleted “there is.”

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Prepared for: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development Service, Washington, DC 20420. Prepared by: Evidence Synthesis Program (ESP), Coordinating Center, Portland VA Health Care System, Portland, OR, Mark Helfand, MD, MPH, MS, Director

Suggested citation:

Veazie S, Mackey K, Bourne D, Peterson K. Evidence Brief: Managing Acute Pain in Patients with Opioid Use Disorder on Medication-Assisted Treatment. Washington, DC: Evidence Synthesis Program, Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-199; 2019. Posted final reports are located on the ESP search page.

This report is based on research conducted by the Evidence Synthesis Program (ESP) Center located at the Portland VA Health Care System, Portland, OR, funded by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development. The findings and conclusions in this document are those of the author(s) who are responsible for its contents; the findings and conclusions do not necessarily represent the views of the Department of Veterans Affairs or the United States government. Therefore, no statement in this article should be construed as an official position of the Department of Veterans Affairs. No investigators have any affiliations or financial involvement (eg, employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties) that conflict with material presented in the report.

Copyright Notice

This publication is in the public domain and is therefore without copyright. All text from this work may be reprinted freely. Use of these materials should be acknowledged.

Bookshelf ID: NBK549201PMID: 31670924

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