Ms. B, a 62-year-old female with recent IV Drug Use (IVDU) and Opioid Use Disorder (on chronic methadone managed by a clinic), CAD s/p CABG, HFrEF (EF 48%), COPD presented to the hospital with acute on chronic abdominal pain found to have perforated gallbladder s/p open cholecystectomy. 

On POD #1 states that pain is localized to the R-side and describes both incisional pain and deep R-sided visceral intrabdominal pain. States that pain is constant and worsens with movement. Vitals are stable. Physical exam is notable for ~7-inch incision in the RUQ of the abdomen with mild tenderness to palpation. No abdominal guarding or rebound. 

Discussion Questions: 

1.  What type of multimodal analgesia can we offer this patient? 

Patients with opioid use disorder (OUD) on methadone maintenance treatment may experience episodes of acute pain related to injury, illness, or in the case of our patient, postoperative incisional and visceral pain. For these individuals, the daily methadone dose prescribed for the treatment of OUD is to be continued alongside aggressive multimodal analgesia (MMA) which might include non-opioid analgesics, regional anesthesia techniques, non-opioid infusions (e.g. ketamine, lidocaine), clonidine, gabapentinoids, skeletal muscle relaxants, physical modalities (e.g., cold, heat, or splinting), integrative therapies, and psychosocial or behavioral management strategies.¹ Special consideration should be given to relevant factors that may influence the selection of multimodal analgesic options such as the presence of heart failure and use of COX-2 or non-selective NSAIDs in our patient, for example.^2,3 Emphasis should be placed on maximizing the use of nonpharmacologic modalities and nonopioid agents. Should non-opioid strategies fail to adequately control the patient’s pain, MMA should be continued while opioids are initiated to reduce total opioid requirement.⁴ 

2.  Does the methadone dose prescribed for the treatment of OUD provide analgesia for the patient? 

While methadone can be effective in treating both OUD and acute pain, its typical duration of analgesic action is only about four to eight hours. Further, in the context of increased pain severity, it is unlikely that the patient's once daily maintenance dose of methadone intended to treat their OUD will be adequate to treat their postoperative acute pain.⁵

Managing acute pain in patients with OUD on methadone maintenance treatment involves the continuation and single administration of the patient’s established daily methadone dose while optimizing the utilization of non-opioid multimodal analgesia for pain control throughout the day. Of note, in some instances, methadone can be divided into three equal doses administered every eight hours in order to maximize analgesic benefit with a plan to resume baseline single-dose administration prior to discharge.¹ 

Any changes to the patient’s methadone dose or care plan should be discussed with the patient, including when it might be prudent to order supplemental opioids. At discharge, it is important to consult the patient’s licensed opioid treatment program to ensure that a solid plan has been established to help facilitate a safe return to baseline.

3.  Does use of opioid use inpatient to treat pain result in increased risk of relapse for OUD? 

Patients with OUD may face several challenges in the immediate postoperative period and risk of relapse during this time is not limited to inpatient opioid consumption alone. Physiologically, previous studies have demonstrated that individuals with a history of prolonged opioid maintenance have long term differences in pain sensitivity.⁷ This is one of the reasons why pain control in this patient population is more challenging than opioid-naïve patients. While providers and patients alike may worry about balancing inadequate pain relief, triggering opioid withdrawal and the risk of relapse, adequate pain treatment is essential as undertreated pain can drive poor health outcomes including in hospital drug use, stigma, mistrust of the health care system and patient directed discharges.⁸ To minimize the risk of relapse, all non-opioid analgesia should be maximized including nonsteroidal anti-inflammatory drugs, gabapentinoids, alpha 2 receptor agonists, dexamethasone, and ketamine or lidocaine infusions (as outlined in question 1). Anxiolytic therapies—both pharmacologic and non-pharmacologic—may prove beneficial as the anxiety surrounding surgery and hospitalization can present as a significant stressor and lead to cravings or relapse. Additionally, the use of regional anesthesia after some orthopedic surgeries has also been shown to decrease the amount of opioids consumed 0-24 hours postoperatively which may further reduce the risk of relapse.⁹ Therefore, regional anesthesia should be offered to patients postoperatively as an important component of multimodal analgesia.  Lastly, OUD medications including buprenorphine or methadone can be lifesaving. Hospitalization and acute illness can be an opportunity to initiate OUD medications,¹¹ and a new study demonstrates that these medications can also decrease the risk of overdose after surgery.¹⁰ In summary, the risk of relapse postoperatively is high, and causes are multifactorial including inadequately treated pain, psychosocial stressors, and prolonged use of prescription opioids postoperatively. Patients with OUD should also have close follow-up with an addiction specialist or chronic pain provider upon discharge. 

4.  Is there an increased risk of respiratory depression if a patient is given more opioids on top of their maintenance methadone dose?

Patients receiving chronic methadone therapy for opioid use disorder (OUD) have developed significant tolerance to the respiratory and central nervous system (CNS) depressant effects of opioids. This tolerance is a protective factor against severe respiratory depression when additional opioids are administered for acute pain. Furthermore, acute pain itself serves as a physiological antagonist to opioid-induced respiratory depression, as evidenced by studies showing minimal respiratory complications when opioids are added in the context of acute pain. While the theoretical risk of additive respiratory depression exists, it has not been clinically substantiated, even in settings requiring higher opioid doses for pain relief. Tolerance to respiratory depression has been described as occurring rapidly, within a period of days, further supporting the recommendation that clinicians can feel comfortable adding short-acting opioid analgesics to a stable methadone regimen for a patient with a history of OUD.¹²

5.  Given that this patient is taking chronic methadone, how do we treat acute on chronic pain? 

Effective acute pain management in patients on maintenance methadone therapy necessitates a dual approach: addressing baseline opioid dependence and managing the acute pain with additional analgesics. Methadone’s analgesic effect lasts only four to eight hours, far shorter than its withdrawal-suppressing effects, leaving these patients vulnerable to inadequate pain control. Additionally, opioid tolerance and opioid-induced hyperalgesia—heightened pain sensitivity caused by long-term opioid use—require that these patients receive higher and more frequent doses of opioid analgesics compared to opioid-naïve individuals. To mitigate these challenges, the maintenance methadone dose should be continued, verified through the prescribing clinic or physician, and supplemented with short-acting opioids administered on a scheduled basis rather than as-needed.  This ensures continuous pain relief while minimizing withdrawal symptoms and hyperalgesia. To optimize outcomes, pain management strategies should prioritize multimodal analgesia, including non-opioid medications like acetaminophen or NSAIDs, and adjuvant therapies such as tricyclic antidepressants. Avoid mixed agonist-antagonist opioids to prevent withdrawal. Furthermore, physicians must complete this medicine reconciliation to communicate between the inpatient and outpatient teams to ensure that the outpatient team is aware that the patient is receiving prescribed alternative opioid analgesics in the acute care setting. This communication reduces the risk that the outpatient methadone clinic suspects misuse if alternative opioids are noted on urine drug screens.¹²

6.  Is Patient-Controlled Analgesia (PCA) safe and effective for opioid tolerant patients? 

PCA can be a safe and effective pain management strategy for opioid-tolerant patients when properly managed. These patients often have higher opioid requirements due to tolerance, and PCA allows them to self-administer analgesia within prescribed limits, reducing delays in pain relief. Additionally, PCA minimizes staff bias and variability in administering analgesia. However, careful considerations are necessary, particularly regarding the use of a basal rate, which should generally be avoided or used cautiously in opioid-naïve patients. While basal dosing may benefit opioid-tolerant patients when combined with demand dosing, it is typically reserved for those with terminal cancer pain and is not recommended for patients with OUD due to the increased risk of overdose and respiratory depression. Dosing parameters should start with higher initial demand doses and shorter lockout intervals to account for tolerance, with adjustments based on patient response and side effects. Close monitoring is essential to detect sedation, respiratory depression, or other opioid-related side effects, especially in patients with comorbidities such as COPD and HFrEF.^13,14

a.   How do you safely wean PCAs and transition to an oral regimen?

Transitioning from PCA to an oral regimen requires a structured approach. The first step is assessing the patient’s pain control and functional status, ensuring that pain is manageable with PCA demand doses alone and confirming the patient’s ability to tolerate oral intake. Next, calculate the total daily opioid requirement and convert it to an appropriate short-acting oral opioid while incorporating a cross-tolerance reduction of approximately 25-50%. Provide a short-acting opioid for breakthrough pain, typically 10-15% of the total daily dose, ensuring adequate pain relief while minimizing the risk of overuse. According to the 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain, extended-release and long-acting opioids should generally be reserved for cancer-related pain and are not recommended for patients with OUD due to the increased risk of misuse and overdose. If an extended-release opioid is considered for non-cancer pain, it should be done with careful justification, close monitoring, and a clear plan for tapering. Gradual weaning from PCA is recommended, ensuring that the patient transitions safely to oral medication. During this process, frequent monitoring to assess pain and sedation levels every one to two hours for the first 24-48 hours is crucial, as patients are at the highest risk of hypoventilation and nocturnal hypoxemia during this period. These recommendations align with the CDC guidelines, which emphasize cautious opioid prescribing, risk mitigation strategies, and individualized patient-centered approaches to pain management.¹⁵

To optimize pain control, multimodal analgesia should be the foundation of therapy, with non-opioid medications serving as the mainstay of treatment. Acetaminophen, NSAIDs (if not contraindicated), and adjuvants such as gabapentinoids should be prioritized to provide effective baseline analgesia. Opioids should be used as adjuncts for breakthrough pain rather than as the primary modality, helping to enhance pain relief while minimizing opioid-related side effects and risks. By following these steps, health care providers can safely transition patients from PCA to oral analgesia, ensuring effective and comprehensive pain management.^13,14 

7.  What are the ethical considerations and challenges in managing pain for patients with a history of intravenous drug use, and how can health care providers address potential biases to ensure equitable care?

When managing pain in patients with a history of intravenous drug use, several ethical principles come into play. Autonomy requires respecting the patient’s right to pain relief and honoring their established treatment plans, such as chronic methadone therapy. Beneficence emphasizes the need to provide optimal pain management to enhance recovery and minimize suffering, while nonmaleficence urges providers to carefully balance effective pain control against the risks of exacerbating a substance use disorder or inducing overdose. Justice demands that health care providers deliver equitable care without bias or discrimination, ensuring that all patients receive appropriate treatment regardless of their history.

Despite these guiding principles, health care providers often face hesitations when managing pain in this population. Concerns about drug misuse or diversion may lead to reluctance in prescribing opioids, driven by fear that such treatments could worsen the patient’s addiction. Stigma and bias further contribute to the under-treatment of pain, as misconceptions about individuals with a history of drug use influence clinical decision-making. Additionally, determining appropriate opioid doses for a tolerant patient can be challenging, as providers must avoid both under-dosing and the risks associated with overdose or withdrawal. Regulatory pressures, including heightened scrutiny of opioid prescriptions, also compound hesitations, making some providers wary of prescribing adequate pain medications.

To address these challenges, health care providers can take several steps. Education is essential to help providers balance addiction management with ethical pain treatment. Evidence-based guidelines for managing pain in patients with OUD offer a structured approach to care. Engaging addiction specialists and pain management teams fosters a collaborative, multidisciplinary strategy. Open communication with the patient builds trust, allowing providers to discuss care goals, pain expectations, and safe opioid use. Finally, tools like prescription drug monitoring programs and naloxone education can help mitigate risks and support safer prescribing practices. By combining ethical principles with practical strategies, providers can ensure that patients with a history of intravenous drug use receive compassionate, equitable, and effective pain management.^{16,17,18 s} 

8.  What community resources should we connect patients with upon hospital discharge? 

Community resources play a crucial role in the management of OUD providing patients with support beyond clinical settings. Physicians should connect patients with medication-assisted treatment (MAT) programs, such as those that provide buprenorphine, methadone, or naltrexone, which are evidence-based approaches proven to reduce opioid cravings and prevent relapse.¹⁹ Unfortunately, only a small percentage of people eligible for MAT in the United States participate in treatment, and MAT programs often have patient retention issues.²⁰

Physicians should become familiar with harm reduction services, including syringe exchange programs and naloxone distribution, which are essential for minimizing the risks associated with opioid use while maintaining patient safety.²¹ Peer support groups, such as Narcotics Anonymous or SMART Recovery, provide patients with social support, self-empowerment, and accountability which are vital for overcoming a substance use disorder.²² Additionally, social service agencies that address housing, employment, and food insecurity can help stabilize patients’ lives and reduce relapse triggers. 

Physicians should collaborate with multidisciplinary teams within their help system, including case managers, social workers, and community health workers, to ensure patients have access to these resources. Evidence shows that comprehensive, community-based approaches improve long-term outcomes for individuals with OUD. 

References:

1. Wakeman S, Zeballos J. (2024). Management of acute pain in patients with opioid use disorder. UpToDate. Retrieved December 22nd, 2024 from https://www.uptodate.com/contents/management-of-acute-pain-in-patients-with-opioid-use-disorder
2. Goodlin, S. J., Wingate, S., Albert, N. M., Pressler, S. J., Houser, J., Kwon, J., Chiong, J., Storey, C. P., Quill, T., Teerlink, J. R., & PAIN-HF Investigators (2012). Investigating pain in heart failure patients: the pain assessment, incidence, and nature in heart failure (PAIN-HF) study. Journal of cardiac failure, 18(10), 776–783. https://doi.org/10.1016/j.cardfail.2012.07.007 
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