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Buprenorphine induction in the ED: the missing link in a broken system?

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Why the pressure is on to help patients dealing with opioid overdoses.

Introduction: The opioid crisis has become a household term over the last few years. As deaths from opioid overdoses rise, so does the pressure to find better ways to intervene and help patients before they suffer adverse consequences or reduce the harm if they do. Rescue naloxone is one component of intervention that has reached many Emergency Departments (EDs) and EMS crews. Another opportunity that many EDs and hospital systems are exploring is medication assisted therapy (MAT) for opioid use disorder (OUD) in the ED setting.

The ED is often where patients present when they overdose, or when they want to stop using. It is often the only point of care for patients struggling with OUD and a variety of socioeconomic barriers to alternate care facilities.  As a result, ED visits by patients wanting to stop using opioids provide an important opportunity to consider induction of withdrawal treatment and bridge to maintenance therapy.

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Startling statistics show that untreated opioid withdrawal can have devastating and deadly consequences.  When untreated, opioid abstinence and withdrawal leads to higher risk of subsequent return to misuse, abuse, overdose and death following discharge.[1,2] Studies in Massachusetts showed that over half of patients who died of opioid overdose had at least one medical visit in the year before death, and almost 10% of patients who received naloxone pre-hospital for overdose were dead within one year.[3,4]

These statistics led to state-mandated ED treatment of OUD in Massachusetts, with several other states considering similar legislation at present. It is evident that the current system for access to OUD treatment is broken, and unquestionable that the ED could represent a valuable bridge in providing smooth transitions of care to enhance recovery and survival potential.  Recent success stories with buprenorphine show that ED induction is safe and effective.[5,6]  Lab studies, psychosocial intervention and desire for long-term treatment are not required prior to buprenorphine initiation, making rapid evaluation and decision to treat quite feasible in the ED setting.

Still, frequent misperceptions exist about the legal and regulatory requirements for prescribing buprenorphine induction and MAT, and the appropriate clinical methods for initiating successful care in the ED are often unfamiliar.  Here we review buprenorphine, a safe, inexpensive and non-invasive treatment that has shown significant promise as a bridging therapy from the ED.

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Patient evaluation: Buprenorphine can only be initiated in patients who are starting to experience withdrawal symptoms. If given to a patient who is still under the influence of the opiates, it can precipitate uncomfortable withdrawal symptoms. The presenting constellation of signs and symptoms of opioid withdrawal include: nausea, vomiting, diarrhea, restlessness, anxiety, diaphoresis, yawning, hiccups, dilated pupils and potential craving or seeking behavior. Time to withdrawal is widely variable, and dependent on the type, route, frequency and intensity of opioid ingestion. There are many means for scoring and assessment, but the Clinical Opiate Withdrawal Score (COWS) is a frequently used and well validated tool for assessment of withdrawal severity. COWS is evaluated on a scale of 0-36 by simple noninvasive physical assessment and should be re-assessed every 30-60 minutes both prior to and during treatment induction.[7] Correlation of COWS score to reported last opioid ingestion is important. Many existing programs recommend initiation of treatment with buprenorphine for patients with a COWS >/= 8, while more conservative models recommend initiation at scores > 13.8

Prescribing rules:  It is a misperception than any ordering or prescribing of buprenorphine in the ED requires special training and a Drug Addiction Treatment Act (DATA) waiver or X-DEA registration. In reality, short-term management of opioid withdrawal with single doses of buprenorphine while patients are in the ED is allowed for all DEA registered providers, under what is known as the Three Day Rule. This rule allows a patient to return to the ED daily for up to three days in order to receive medication until follow up care is initiated.  In order to prescribe an ongoing supply of buprenorphine outside the ED, appropriate training, DATA waiver and X-DEA license are required.

All DEA-licensed clinicians can apply for a waiver by completing an eight-hour training course and corresponding exam. Once waivered, the provider can prescribe buprenorphine for whatever time period is necessary until the patient can reach a permanent treatment provider or facility.[9] An investment in a few X-waivered providers in your ED could provide an excellent and sustainable means to treatment initiation, continuity of care and bridging to permanent treatment providers.

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How it works: Buprenorphine is a partial opioid agonist with long duration of action and high affinity for the mu-opioid receptor, and an antagonist at the kappa-opioid receptor. As a partial agonist, it does not activate mu-opioid receptors strongly enough to provide euphoria, excessive sedation or respiratory depression, but it does suppress craving and prevent withdrawal. Overdose and significant adverse reaction are exceptionally rare, making it an ideal agent for short- and long-term management of OUD. Many forms of buprenorphine are commercially available, often combined with naloxone to mitigate any potential for high from abuse or injection.

Dosing and administration:  There is currently no evidence-based standard or guideline-driven consensus for the optimal initiation dose of buprenorphine MAT in the ED, though several resources exist.10 A loading dose range of 2-32mg of sublingual buprenorphine has been described in several small studies and guidelines.  It is reasonable to expect that most ED patients will require loading doses of 8-16mg of sublingual buprenorphine for adequate relief of withdrawal symptoms and suppression of cravings.  There is minimal danger in higher induction doses of buprenorphine. Maximized loading doses of 16-32mg may be more effective than lower initiation doses of buprenorphine at suppressing craving during the dangerous period immediately following ED discharge, or precipitating opioid withdrawal by displacement of a full agonist with a partial agonist.

One option is to give all patients the 8mg dose, and then monitor them for the next 30-60 minutes, and re-dose with another 8mg if needed. In the absence of ED X-waivered providers, careful care coordination, discharge planning and handoff to ongoing clinicians is crucial.

Adverse Events: The most commonly reported adverse reaction to buprenorphine is mild sedation with higher doses.  This risk is increased if buprenorphine is combined with alcohol or other sedatives. Caution should be used in the elderly, patients with significant cardiac and respiratory disease, or those with advanced renal and hepatic dysfunction.  Buprenorphine induction with subsequent discharge is not generally recommended for patients with the following complications: pregnancy, current use of methadone, anticipated imminent surgery, co-intoxication with alcohol or other sedatives, opioid use for chronic pain therapy or immediately post opioid reversal with naloxone. Additional care, expert consultation and consideration are needed in these scenarios.

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The future: If you are interested in starting a program in your ED for MAT, numerous free helpful resources on existing program models, provider education, complicated patients, and referral tips can be found at ED-Bridge.org.[10]

References

  1. Hickman M, Steer C, Tilling K, et al. The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom. Addiction. 2018;113(8):1461-76. doi: 10.1111/add.14188.
  2. Sordo L, Barrio G, Bravo M, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. doi: 10.1136/bmj.j1550.
  3. Larochelle M, Bernson D, Land T, et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: a cohort study. Ann Intern Med. 2018;169(3):137-45. doi: 10.7326/M17-3107.
  4. Weiner S, Baker O, Bernson D, et al. One-year mortality of opioid overdose victims who received naloxone by emergency medical services. Ann Emerg Med. 2017;70:S158.
  5. D’Onofrio G, O’Connor P, Pantalon M, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-44. doi: 10.1001/jama.2015.3474
  6. Herring AA. Emergency department initiation of buprenorphine with a loading dose. Acad Emerg Med. 2018;25(suppl 1):S8-S298.
  7. Wesson D, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003;35:253-59.
  8. Herring A, Perrone J, Nelson L. Managing opioid withdrawal in the emergency department with buprenorphine. Ann Em Med. 2018. doi: 10.1016/j.annemergmed.2018.11.032
  9. Substance Abuse and Mental Health Services Administration. Buprenorphine waiver management. Available at: https://samhsa.gov/programs-campaigns/medication-assisted-treatment/training-materials-resources/buprenorphine.waiver. Accessed February 10, 2019.
  10. Herring A, Snyder H, Moulin A, et al. ED-bridge buprenorphine guide. Available at https://ed-bridge.org/. Accessed February 10, 2019.
ABOUT THE AUTHORS

Dr. Hatfield is the System Clinical Pharmacy Director for Sutter Health, where she also maintains an active practice as an emergency medicine pharmacist. She has over fifteen years of practice and faculty experience in emergency medicine, and has particular research interests in trauma, toxicology, anticoagulation reversal and advanced heart failure.

Dr. Shenvi is an assistant professor in the department of emergency medicine at the University of North Carolina. She authors RX Pad each month in EPM.

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