#366 Opioid Use Disorder and Acute Pain in the Hospitalized Patient

November 14, 2022 | By Matthew Watto, MD

Video

With Carolyn Chan MD and Shawn Cohen MD

Conquer acute pain in the hospitalized patient with opioid use disorder! It’s challenging to treat opioid withdrawal and acute pain simultaneously. This episode features clinical pearls on prescribing methadone, buprenorphine, low-dose buprenorphine initiation, and how to incorporate opioids as part of multimodal pain treatment responsibly. We’re joined by The Curbsiders Addiction Medicine Podcast hosts, Drs. Carolyn Chan (@carolynachan) and Shawn Cohen (@shawncohen)!

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Credits

• Writer and Producer: Matthew Watto MD, FACP
• Show Notes: Matthew Watto MD, FACP
• Cover Art and Infographic: Matthew Watto MD, FACP
• Hosts: Matthew Watto MD, FACP  
• Reviewer: Fatima Syed MD
• Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP
• Technical Production: PodPaste
• Guest: Carolyn Chan MD and Shawn Cohen MD

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CME Partner: VCU Health CE

• Show Segments
• Intro, disclaimer, guest bio
• Guest one-liner
• Acute pain in the patient on buprenorphine maintenance
• Acute pain in the patient on methadone maintenance
• Acute pain in the patient with opioid withdrawal
• Standard buprenorphine initiation
• Methadone initiation
• Low dose buprenorphine initiation
• Take-home points
• Outro

Acute Pain in OUD Pearls

1. Utilize multimodal therapy to treat acute pain in the hospitalized patient (see episode #299 Acute Pain Management for the Hospitalist; Buresh, 2020). 
2. Buprenorphine and methadone provide ~6-8 hours of analgesia (Lexicomp), so dosing 3-4 times daily helps with pain control 
3. Full agonist opioids (hydromorphone, fentanyl, oxycodone) can be prescribed on top of MOUD (medications for opioid use disorder) if needed to control acute pain (Buresh, 2020)
4. For people on MOUD, buprenorphine and methadone should be continued for all patients admitted with acute pain
5. Fentanyl is highly potent and lipophilic, so people using it often have a high opioid tolerance and may require longer withdrawal periods to start buprenorphine and decrease their risk of precipitated opioid withdrawal
6. Instead of trying to initiate buprenorphine right away in someone with acute pain in the hospital, consider prescribing a few days of full agonist opioids to allow fentanyl to dissipate, and to control pain and opioid cravings
7. Good options for rapidly  treating both opioid withdrawal and moderate to severe pain for patients not on MOUD include 1) methadone and full agonist opioids, 2) full agonist opioids alone, or 3) low-dose buprenorphine initiation plus full agonist opioids.
8. Low-dose buprenorphine initiation allows patients to take full agonist opioids for opioid withdrawal and acute pain while buprenorphine is slowly increased to therapeutic levels

Acute Pain in OUD Pearls

1. Utilize multimodal therapy to treat acute pain in the hospitalized patient (see episode #299 Acute Pain Management for the Hospitalist; Buresh, 2020). 
2. Buprenorphine and methadone provide ~6-8 hours of analgesia (Lexicomp), so dosing 3-4 times daily helps with pain control 
3. Full agonist opioids (hydromorphone, fentanyl, oxycodone) can be prescribed on top of MOUD (medications for opioid use disorder) if needed to control acute pain (Buresh, 2020)
4. For people on MOUD, buprenorphine and methadone should be continued for all patients admitted with acute pain
5. Fentanyl is highly potent and lipophilic, so people using it often have a high opioid tolerance and may require longer withdrawal periods to start buprenorphine and decrease their risk of precipitated opioid withdrawal
6. Instead of trying to initiate buprenorphine right away in someone with acute pain in the hospital, consider prescribing a few days of full agonist opioids to allow fentanyl to dissipate, and to control pain and opioid cravings
7. Good options for rapidly  treating both opioid withdrawal and moderate to severe pain for patients not on MOUD include 1) methadone and full agonist opioids, 2) full agonist opioids alone, or 3) low-dose buprenorphine initiation plus full agonist opioids.
8. Low-dose buprenorphine initiation allows patients to take full agonist opioids for opioid withdrawal and acute pain while buprenorphine is slowly increased to therapeutic levels

Scenario #1: Acute pain in a patient on buprenorphine maintenance 

Continue a patient’s baseline buprenorphine to treat opioid use disorder and if needed give additional full agonist opioids for acute pain (expert opinion, Buresh, 2020). Adequate pain control can be achieved with full agonist opioids given on top of buprenorphine (Buresh, 2020). 

Individuals who stop or have their buprenorphine held perioperatively are at risk of not resuming buprenorphine (Wyse, 2021), which places them at increased risk for death  (Pearce, 2020).  In addition, restarting buprenorphine can be challenging if they still require full agonists for acute pain management. 

Options for dosing buprenorphine in the hospital:

1. Continue a patient’s home regimen to control opioid cravings (e.g. buprenorphine SL 1-2 times daily)
2. Split the home dose into 3-4 times daily since buprenorphine provides ≥6 hours of analgesia per dose (Lexicomp, Haber 2019)
3. Increase the dose of buprenorphine above baseline and give in divided doses

Ask the patient if they prefer to split their home dose of buprenorphine to achieve better pain control. For example, buprenorphine 16 mg daily can be split into 4 mg every 6 hours, or three times daily as 8 mg, 4mg, then 4 mg. For some cases of acute, mild pain Dr. Chan offers temporarily increased buprenorphine dosing compared to baseline (e.g. 8 mg three times daily instead of 8 mg twice daily) as this might avoid the need for additional full agonist opioids. This option is especially attractive if the patient’s baseline opioid use disorder symptoms are poorly controlled. Note, increasing the maintenance dose of buprenorphine should be done in communication with a patient’s outpatient prescriber. Finally, in cases of more severe pain, Dr. Chan uses full agonist opioids on top of a patient’s baseline buprenorphine.

Scenario #2: Acute pain in a patient on methadone maintenance

The approach here is similar to the patient on buprenorphine maintenance. Continue the patient’s baseline methadone maintenance for opioid use disorder and give as-needed medications for superimposed acute pain (expert opinion, Buresh, 2020). 

Note: Like buprenorphine, methadone’s analgesic effect is short-lived (4-8 hours) compared to its effect on opioid cravings (Lexicomp). Like with buprenorphine, split dosing of methadone can be offered to supplement pain control e.g. split methadone 120 mg daily into 40 mg given three times daily. Drs Chan and Cohen always ask before splitting the dose of methadone as some people prefer to keep it once daily.

Full agonist opioids for acute pain in OUD currently on MOUD

High-potency, full agonist opioids like hydromorphone (IV, PO) or fentanyl (IV) are typically chosen for patients on buprenorphine since it has a high affinity for the opioid receptor, and can better compete with buprenorphine at opioid receptors. Dr. Cohen points out that methadone does not have a high binding affinity at the opioid receptor, so short-acting oxycodone can be used as needed (expert opinion). As all people on MOUD will have a higher tolerance to opioids, higher doses of full agonist opioids will likely be needed for pain control. Both Drs. Chan and Cohen often start with both oral and IV opioids while getting pain controlled and then switch to only oral opioids which tend to provide longer, smoother analgesic effects (expert opinion).

Dr. Chan sometimes discharges a patient on MOUD with an oral full agonist opioid written for a taper. Both Drs. Chan and Cohen recommend primary care follow-up in 1-2 weeks to reassess pain and opioid use disorder symptoms. Dr. Cohen points out that NOT treating acute pain in the hospital and after discharge has its own risk and could push a patient towards non-prescribed opioid use, which can increase the risk of overdose. 

Kashlak pearl: For patients with chronic fentanyl use, Dr. Cohen sometimes schedules full agonist opioids around the clock at the beginning of hospitalization in addition to having PRNs available (e.g. oxycodone by mouth every four hours scheduled and additional oxycodone by mouth every four hours PRN). This serves to a) ensure frequent pain assessments b) improve pain control and c) satisfy opioid cravings. These assurances make it easier to have a productive conversation about maintenance medications for opioid use disorder (MOUD) —Kleinman, 2022. 

People who use drugs have often had negative and stigmatizing experiences in the healthcare system; addressing their needs including withdrawal and pain is critical to providing person-centered care. (McNeil, 2014)

Managing symptoms other than pain

Untreated insomnia and anxiety can worsen a patient’s discomfort so be sure to address them in the hospital. Dr. Chan offers trazodone, quetiapine, and hydroxyzine as potential treatments –expert opinion. Further, this writer recommends nicotine replacement therapy for patients with nicotine use disorder ; )

Scenario #3: Acute pain in the patient with opioid withdrawal

What is tricky about treating patients in the fentanyl era?

1. The drug supply is highly toxic because it is unpredictable and contaminated. About 73 percent of seized street-supply fentanyl is really fentanyl (DEA National Drug Threat Assessment), but the other 25 percent comprises substances like xylazine (Alexander, 2022), fentanyl analogs, and other high-potency opioids.
2. Fentanyl is a high-potency opioid (Armenian, 2018). Thus, patients with opioid use disorder using fentanyl have a high tolerance and require high doses to satisfy opioid cravings and treat acute pain. 
3. Fentanyl is lipophilic and builds up in fat stores leading to protracted clearance from the body (Huhn, 2020). 

Options for acute pain and withdrawal 

Below we discuss a range of options for treating acute pain and opioid withdrawal in the hospitalized patient with opioid use disorder not currently on MOUD. People presenting to the hospital with opioid use disorder not on MOUD, particularly those in pain, will need opioids at minimum to prevent withdrawal and likely to address their pain as well. This should include offering to start buprenorphine and/or methadone for MOUD. It is never wrong to start full agonist opioids while determining the best next step that fits your patient’s goals.

Patients with moderate to severe pain are less likely to tolerate withdrawal periods required for standard buprenorphine initiation. Drs. Cohen and Chan work with the patient to develop a plan for both acute pain and opioid withdrawal. Note: All patients should receive multimodal therapy for acute pain. Full agonist opioids (FAO) can be given for acute pain in patients receiving buprenorphine or methadone for opioid withdrawal symptoms. 

1. Buprenorphine, standard initiation
2. Methadone initiation plus full + FAO as needed for pain
3. Scheduled full agonist opioids plus as needed doses for opioid cravings/acute pain
4. Low-dose buprenorphine initiation (Cohen, 2022) + FAOs as needed for pain

Buprenorphine: standard initiation

This option is most feasible for the patient with mild acute pain who is willing to go through a withdrawal period before starting buprenorphine. Waiting for withdrawal minimizes the risk of causing precipitated withdrawal (discussed below)

• Wait at least 12-24 hours (or as long as possible) and for 3 symptoms of opioid withdrawal (or a COWS>8-13), then give buprenorphine 8-12 mg. Assess every 1-2 hours and repeat dosing to a maximum of 24 mg in the first 24 hours (see Curbsiders Addiction Medicine #7 Do The OBOT). 
• Give adjunctive meds for anxiety, restlessness, nausea, diarrhea, pain, etc. during the withdrawal period (can include benzodiazepines)
• As discussed above, after the buprenorphine is started splitting into three or four times daily dosing can further supplement pain control. 
• After buprenorphine initiation, full agonist opioids can be given as needed to supplement pain control 

Kashlak pearl: If doing a standard buprenorphine initiation, Dr. Cohen sometimes prescribes a short-acting full agonist opioid (e.g. oxycodone IR) to prevent withdrawal symptoms for a few days to allow fentanyl to leave a patient’s system (Kleinman, 2022). Once stabilized, the patient can undergo a 12-hour withdrawal period overnight, then start buprenorphine at 8-12 mg in the morning. 

Precipitated withdrawal and the speeding car analogy

Think of full agonist opioids (heroin, fentanyl, hydromorphone, oxycodone) as fuel that will send a car speeding at 120 mph (Cohen, 2022). Now consider buprenorphine, a partial opioid agonist with a high affinity for the opioid receptor, that sends a car only 60 mph at maximum. Precipitated withdrawal occurs when a person riding 120 mph on full agonist opioids suddenly drops to 60 mph after a dose of buprenorphine, which abruptly slows the car because buprenorphine displaces full agonist opioids (due to buprenorphine’s higher affinity for the opioid receptor) —Cohen, 2022. 

Heroin and other short-acting full agonist opioids typically require a withdrawal period of 6-12 hours before a patient is in enough opioid withdrawal to give buprenorphine. Notably, fentanyl seems to carry a heightened risk for precipitated withdrawal (Varshneya, 2022, Huhn, 2020) because it is lipophilic and builds up in fat stores. Thus, it may require a longer period of abstinence (to allow fentanyl to dissipate) before giving buprenorphine (often ≥24 hours). Returning to the car analogy discussed above, we want to ensure the car is going 60 mph or less on opioids before giving a full dose of buprenorphine to avoid precipitated withdrawal. 

Methadone initiation

See Curbsiders Addiction Medicine #1 Methadone, the Canadian Guidelines on Methadone by Bromley et al accessed 30 Oct 2022.

Methadone initiation is a good option for patients with moderate to severe pain because it avoids an opioid withdrawal period. Patients can receive methadone to treat opioid cravings and in addition use as needed full agonist opioids to treat acute pain. As discussed above, splitting methadone into three to four daily doses can further supplement pain control. For someone with high tolerance (regularly using fentanyl) methadone can be uptitrated more rapidly as below (expert opinion):

• Day 1: Give 20-30 mg methadone (depending on baseline opioid use). An additional 10 mg can be given on day one 4 hours after the first dose
• Day 2-5: Give the total dose from day one (e.g. 40 mg). An additional 10 mg can be given each day if needed*.
• Hold for a few days once the methadone dose reaches 60-70 mg daily.
• Give as needed full agonist opioids in addition (e.g. oxycodone, hydromorphone) to treat acute pain and withdrawal

*Note: Don’t ramp up the dose of methadone above 30-40 mg daily unless you can connect the person to an opioid treatment program (OTP) where they can continue methadone.  Patients with lower opioid tolerance or risk for complications should be started on lower doses (e.g. methadone 10-20 mg daily) and uptitrated more slowly.

Note: Experts have recognized the need for more rapid methadone induction protocols in the fentanyl era (Buresh, 2022) although data on regimens is lacking.

Low-dose initiation of buprenorphine

Dr. Cohen mentions that he still most often starts buprenorphine through “standard initiation,” but in certain situations, such as acute pain requiring opioids, alternative initiation strategies can be helpful. Note: Theis process can be complicated so consider reaching out to an addiction medicine expert for help guiding if unfamiliar with it.

Low-dose initiation of buprenorphine is an alternative method of starting buprenorphine that allows someone to continue on full agonist opioids for pain/withdrawal during the process. The concept is to give small gradually escalating doses of buprenorphine over days while a patient still receives full agonist opioids.  The goal is for the buprenorphine to slowly displace full agonist opioids without precipitating withdrawal. Returning to the analogy of our car traveling at 120 mph on FAOs, we slowly bring down the car’s speed by 10 mph per day as we slowly increase the buprenorphine until we reach a therapeutic dose of buprenorphine (usually 16-24mg). This avoids an abrupt deceleration (precipitated withdrawal). Dr. Cohen points out that the literature supporting this practice is observational, but it can be a useful tool to start people on buprenorphine requiring full opioid agonists for pain.

Due to requiring doses lower than the smallest buprenorphine film (<2mg), low-dose buprenorphine initiation depends on other formulations of buprenorphine that are not available in every hospital (buccal, transdermal, IV, or splitting films/tabs). Remember to schedule full agonist opioids until buprenorphine reaches a therapeutic dose. Dr. Chan asks patients to keep open communication during low-dose initiation because some withdrawal symptoms may still occur. In these cases, the pace of initiation can be slowed down, or comfort meds can be given. 

What if my patient experiences precipitated withdrawal?

Precipitated withdrawal might occur despite our best efforts. In the event of precipitated withdrawal during standard buprenorphine initiation (2, 4, 8 mg doses), Drs. Cohen and Chan recommend giving more buprenorphine and adjunctive meds for anxiety (clonidine and even benzodiazepines), pain, nausea, diarrhea, etc. This approach is consistent with published case reports Oakley, 2021.

For patients who experience mild withdrawal symptoms during low-dose buprenorphine initiation, Dr. Chan slows down buprenorphine dose escalation (expert opinion).

Key take-home points

• Treat opioid withdrawal. It is absolutely life-threatening
• It’s okay to give full agonist therapy on top of MOUD.
• Listen to your patients. Treat their acute pain and opioid withdrawal. 
• Do not stop MOUD. 
• Lose the term “drug seeking”. 

Links

Links are included in the text above.

Goal

Listeners will develop an approach to managing acute pain and opioid withdrawal in the hospital 

Learning objectives

After listening to this episode listeners will…

1. Learn to treat acute pain in a hospitalized patient with opioid use disorder
2. Treat opioid withdrawal and opioid cravings in the hospitalized patient

Disclosures

Drs. Chan and Cohen report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Watto MF, Chan CA, Cohen S, Syed F. “#366 Opioid Use disorder, Acute Pain in the Hospitalized Patient”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date November 14, 2022.