Therapeutics: Opioid Use Disorder

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The opioid crisis has been well-publicized over the last decade. After a brief decrease in opioid related deaths, there has been a sharp increase since the start of the COVID-19 pandemic. (1,2) Chronic opioid use results in the development of tolerance, requiring larger and larger doses of substance to achieve the same effects. Adaptations in cell physiology in the presence of long-term opioid use results in the syndrome of opioid withdrawal when cessation is attempted. Individuals with opioid use disorder (OUD) who attempt cessation without Medication for Opioid Use Disorder (MOUD) are at high risk for subsequent relapse and potentially fatal overdose. (3) One observational study found significant 1-year mortality (5.5%) in individuals presenting to the emergency department with a non-fatal opioid overdose. (3) Patients receiving treatment for OUD with opioid agonists are more likely to stay in treatment than those receiving non-opioid medications as treatment and have significantly reduced overall mortality compared to patients not receiving MOUD. (4,5) Furthermore, initiation of MOUD from the emergency department is associated with increased retention in treatment for OUD. (6) Below, we will review the presentation of patients to the emergency department with OUD and available treatments for these patients. We will explore using MOUD in the emergency department through a series of clinical scenarios.

Identifying patients with possible OUD and withdrawal symptoms

Table 1 - CLinical Opioid Withdrawal Score (COWS)

Some patients in the emergency department with OUD will be obvious, such as those with an acute opioid overdose requiring the administration of naloxone. Others will be completely unrevealed and may present with severe pain that is otherwise unexplained. Other patients may raise clinical suspicion for OUD based on chronic opioid prescription or documented history of overdose/withdrawal. Patients with a history of other substance use disorders are at higher risk for developing OUD.  

 A report of opioid use and/or prescription for chronic opioids should clue the provider into the possibility of a patient experiencing opioid withdrawal. Formal diagnosis of OUD may be made if the patient fulfills DSM-5 criteria. However, report or history of opioid use with symptoms consistent with opioid withdrawal should prompt the provider to initiate a discussion surrounding treatment for OUD and withdrawal. Symptoms of opioid withdrawal include dysphoria, restlessness, lacrimation, rhinorrhea, myalgias, arthralgias, and GI distress including nausea, vomiting, abdominal cramping, and diarrhea. On exam, the provider would be expected to observe mydriasis, yawning, diaphoresis, rhinorrhea, increased bowel sounds, and piloerection. A validated tool, the Clinical Opioid Withdrawal Scale (COWS), should be used to calculate the severity of the patient’s withdrawal signs and symptoms. (6,7)  The timing of development of withdrawal symptoms varies by type of opioid used as shown in table 2. (8) 

Table 2 - Timelines of withdrawal symptoms from common opiates

Treatment of opioid withdrawal in the ED is based on patient desire for treatment, last opioid use (and type of opioid used), COWS score, and the ability to arrange reliable follow-up within 3 days of presentation to the ED (ideally, next day). In the ED, options exist for both symptomatic treatment of withdrawal symptoms with agents such as clonidine and ondansetron and treatment of OUD with the partial opioid agonist, buprenorphine. Buprenorphine is a partial opioid agonist with high affinity for mu receptors but has minimal euphoric effect and a ceiling effect on respiratory depression, making it an ideal opioid-based treatment choice for OUD. Treatment with buprenorphine has been shown to reduce all-cause mortality in patients with opioid use disorder. (5) However, treatment with buprenorphine should only be initiated in patients whom there is a low potential of precipitating withdrawal. If a patient still has opioids present which are full agonists (use of short acting opioid less than 12 hours ago or long-acting opioid use, such as methadone, less than 48 hours ago), administration of buprenorphine, a partial mu agonist, will displace the full agonist and precipitate withdrawal symptoms. While it is generally accepted that opioid withdrawal is not fatal, iatrogenic precipitated withdrawal may be much more severe resulting in clinically significant autonomic hyperactivity with consequences such as pulmonary edema and make patients more reticent to continue with future medication for opioid use disorder. (8) Caution should be used in patients who have received naloxone in the last 12 hours as the patient may be at risk for precipitated withdrawal if full agonist opioids remain in their system. In these patients who would like to initiate treatment, a thorough history should be obtained to determine the opioid used, if possible, and observation may be offered until potential re-intoxication and withdrawal syndrome is seen.

Table 3 - Common MOUD and their mechanisms, duration and potential complications

For patients who are not interested in MOUD with buprenorphine but are experiencing withdrawal symptoms, comfort medications (table 3) may be initiated and prescribed. Referral for outpatient substance use disorder treatment should also be offered. These patients, along with any patient suspected of opioid use disorder, should be sent home with naloxone to mitigate the risk of a fatal overdose. (3)

For patients experiencing opioid withdrawal symptoms and who are interested in MOUD with buprenorphine, a COWS score should be calculated to determine next steps. Patients with a COWS > 8 can be given buprenorphine until a COWS < 8 is achieved. Patients whose initial COWS score is < 8 may be offered observation until a COWS ³ 8 is present at which point treatment with buprenorphine may be initiated or discharged with a dose for home initiation as appropriate given patient characteristics and ability to follow up. The initial dose of buprenorphine is generally 4 mg sublingual (SL) or one can consider 8 mg SL for patients with COWS > 13. The maximum total dose currently recommended to be given in the ED is 16 mg, however, studies are ongoing exploring giving higher total doses up to 32 mg9. Patients are re-assessed 45 to 60 minutes after each dose of buprenorphine with the goal of achieving a subsequent COWS score < 8.  

 After evaluation for therapies, these patients may generally discharge to home. Next steps are dependent upon the institutional policies, considering the availability of next day follow up, and whether the ED provider is X-waivered for the prescription of buprenorphine. Patients for whom next day follow up can be arranged may be discharged without a prescription. For those situations when next day follow-up cannot be arranged, the patient may be prescribed a three-day supply of buprenorphine-naloxone with follow up scheduled within three days of discharge from the emergency department. Typically, buprenorphine-naloxone is prescribed which prevents parenteral use as naloxone is only active when administered parenterally. In situations when the emergency provider is not X-waivered and next day follow-up cannot be guaranteed, the patient can be directed to return to the ED for subsequent doses of buprenorphine (up to 72 hours after initial presentation) until outpatient follow-up and long term MOUD can be established.  

+ Case 1 - Let's Talk Withdrawal

A 34-year-old male with PMH significant for traumatic amputation of his left hand 6 months ago presents to the ED with a chief complaint of “anxiety.” The patient reports significant anxiety and night terrors related to the incident (crush injury in a garbage truck) which resulted in amputation of his left hand 6 months ago. A family member accompanying the patient reports the patient was initially prescribed oxycodone after the incident 6 months ago. Family reports the patient started using fentanyl after he was no longer able to obtain oxycodone. The patient confirms this and reports it has been approximately 27 hours since he last used fentanyl.

The patient reports rhinorrhea, diffuse mild myalgias, a mild headache, and nausea. He denies fever, chills, cough, vomiting, or diarrhea. His vitals are: Temp 99F HR 119 RR18 SpO2 100% BP 145/80. FSBS 114. On exam, patient is uncomfortable appearing and startles easily, he is tremulous, has somewhat large pupils and yawns once or twice. Exam is otherwise unremarkable with normal cardiopulmonary, abdominal, neurologic, and skin exam.

The patient’s history, signs, and symptoms are consistent with opioid withdrawal. He denies any other substance use. A COWS score is calculated:

  • Pulse rate: 101-120 – 2 points
  • Sweating: none, no report of chills or flushing – 0 points
  • Restlessness: Observed shifting – 3 points
  • Pupil size: somewhat larger – 1 point
  • Bone or joint pain: mild myalgias – 1 point
  • Rhinorrhea/lacrimation: rhinorrhea present – 2 points
  • GI upset: reports nausea – 2 points
  • Tremor: slightly observable – 2 points
  • Yawning: 1-2 yawns observed – 1 point
  • Anxiety/irritability: Reported – 1 point
  • Gooseflesh: none observed – 0 points

A total COWS score of 15 is calculated. MOUD education is provided to the patient and he would like to initiate treatment. With a COWS score of 15, buprenorphine 8 mg SL is given. One hour later, on reassessment, the patient has a COWS score of 9. An additional 4 mg SL buprenorphine which decreases his COWS to 5. Follow up with addiction medicine for the next day is confirmed and the patient is discharged home.

As noted above, initiation of buprenorphine in the ED has been shown to improve patient’s adherence to treatment for OUD and MOUD has been shown to decreased overall mortality for these patients. (4–6) This case is a classic example of a patient with OUD and subsequent opioid withdrawal. The case demonstrates the appropriate management of OUD and withdrawal in the emergency department.

+ Case 2 - I Just Need Help

Six months after the initial encounter with the patient from case 1, the same patient returns to the emergency department with left arm pain. On exam, there is apparent cellulitis of the left forearm just proximal to his stump. He is afebrile and without signs of necrotizing soft tissue infection, compartment syndrome, or abscess. He reports recent heroin use as it helps with his anxiety related to the garbage truck accident which had resulted in his amputation. He states he had been doing well with recovery from OUD until a friend offered him some heroin to help with his anxiety. He last used heroin around 7 hours ago. He reports some mild anxiety currently but otherwise denies any other symptoms of withdrawal. He reports lack of housing due to financial difficulties and job loss after he started using heroin. His relationship with his family has also suffered since his relapse. He would like to restart treatment for OUD but feels overwhelmed with the idea of trying to coordinate this and is unsure where to start. His calculated COWS score at initial presentation is 1.

After discussing options for re-initiating treatment, the patient would prefer to be observed in the ED until he reaches a COWS score sufficient to initiate treatment with buprenorphine. He is started on cephalexin for his cellulitis. A COWS score of 10 is calculated later that evening and he is given buprenorphine 4 mg SL which improves his COWS score to 4. Follow up with addiction medicine is arranged for the following morning.

+ Case 3 - Acute Pain Control

A 52-year-old female with past medical history of HTN, HLD, and OUD (tx with buprenorphine for the last 2 years) presents to the emergency department with right ankle pain after tripping on an icy step. The patient reports severe right ankle pain and deformity of the right ankle. She has been unable to bear weight since the incident. She did fall during the incident but denies head strike or any other injuries. Her vitals are: Temp 97.8F HR 106 BP 156/94 RR 20 SpO2 98%. On exam, she has obvious deformity of the right ankle with significant swelling and tenderness, NVID. Her exam otherwise is unremarkable. Plain films of the right ankle show a trimalleolar fracture. She remains in significant pain. A discussion is had with the patient regarding administering narcotic pain medications for her pain. She is agreeable to this and does not feel it will put her in jeopardy of relapse. She states she had a previous injury to her right wrist 9 months ago which required analgesia with opioid pain medications and did not interfere with her MOUD. She is initially given 1 mg hydromorphone which does not improve her pain. An additional 1 mg is given with some relief of pain. Her fracture is reduced and splinted. Her buprenorphine prescriber is contacted and agrees with the plan to treat her pain effectively. They will follow up with her closely to ensure she is given the best opportunity to remain in recovery. The patient is discharged with a 2-day supply of oxycodone 10 mg every 4-6 hours as needed for pain and referral for ortho follow up is scheduled for 2 days later.

There is very little data on optimal acute pain management strategies for patients receiving MOUD. A recent systematic review found only observational studies exploring this area and only three of those studies were comparative. (13) The consensus, at this time, is to continue the patient on MOUD, as there may be increased risk of relapse if it is held. (13,14) Patients may require higher doses of opioids to achieve analgesia than patients not on MOUD. (13,14) Finally, if possible, the patient’s MOUD prescriber should be contacted to discuss the plan and made aware that the patient will be discharge with a prescription for opioids.

Post by David Jackson, MD

Dr. Jackson is a PGY-1 in Emergency Medicine at the University of Cincinnati

Editing by Colleen Laurence, MD and Ryan LaFollette, MD

Dr. Laurence is a PGY-4 and Chief Resident at the University of Cincinnati and Dr. LaFollette is an Associate Professor of Emergency Medicine at the University of Cincinnati and co-Editor of TamingtheSRU

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