Buprenorphine Use in the ED

Written by: Diana Halloran, MD (NUEM ‘24) Edited by: Sean Watts, MD (NUEM ‘22) Expert Commentary by: Quentin Reuter, MD (NUEM ‘18)

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The United States has been facing a debilitating opioid epidemic, which has been partially fueled by the over-prescription of these medications in the emergency department setting. In addition, the opioid epidemic has grown exponentially during the COVID-19 pandemic. More than 40 states have reported increases in opioid-related mortality, resulting in an increased burden on an already overstrained healthcare system. (1) Prescribing the medication Buprenorphine in the emergency department offers an opportunity to ameliorate these past faults and rising statistics.

The basics:

Buprenorphine, which goes by the trade name Subutex, works by acting as both a partial mu agonist and weak kappa antagonist on opiate receptors in the brain. (2) This mechanism of action enables buprenorphine to exert analgesic effects, as well as antagonistic effects when additional opiates are consumed. In addition, buprenorphine does not carry significant sedative effects, making respiratory depression extremely rare. (3) Buprenorphine is also safe in pregnancy – a 2016 meta-analysis found no difference in pregnant patients given methadone versus buprenorphine when assessing for congenital malformations. (4) The American College of Obstetrics & Gynecology has released a committee position statement, encouraging the use of buprenorphine in pregnant patients with opioid use disorder. (5)

How to prescribe:

While the DEA X-waiver is required to write a prescription for buprenorphine for addiction treatment, withdrawal, or detox, it is not required to order or administer a dose in the hospital or emergency department. (6) This exception, called the “three-day rule”, allows a patient to come to the emergency department for three consecutive days to obtain a dose of buprenorphine if found to be in opioid withdrawal. (7)

In order to dose buprenorphine in the emergency department, the patient must be in mild acute opioid withdrawal, with a Clinical Opiate Withdrawal Score (COWS) of at least 8. (8,9) Administration of buprenorphine should not occur if the patient does not appear to be clinically withdrawing, as administration in this setting could actually precipitate withdrawal.

Dosing: (10)

• 4mg of sublingual buprenorphine can be given initially, allowing 20-40 minutes for resolution of withdrawal symptoms with repeat dosing every 1-2 hours as needed. (10)

• On Day 2, the patient’s response to Day 1 should be assessed. If the patient’s opioid withdrawal symptoms were controlled, the same dose can be continued. If not, the dose should be increased by 2-4mg. (10)

• On Day 3, the patient’s response to Day 2 should be assessed. Again, if the patient’s withdrawal symptoms are controlled then the same dose can be continued. If not, the dose can be increased by 2-4mg for Day 3. (10)

• After 3 days this dose should be continued for 3-7 days until steady-state levels are achieved (10)

• Doses should be decreased by 2mg if the patient experiences opioid intoxication (10)

Use in the emergency department:

While buprenorphine and long-term treatment of opioid use disorder may seem confined to primary care physicians and psychiatrists, emergency medicine physicians have been shown to be successful providers for initiating buprenorphine treatment versus brief intervention and referral with a result of decreased self-reported illicit opioid use. (11) In addition, Dr. Gail D’Onofrio, chair of the Department of Emergency Medicine at Yale, found that emergency department initiated buprenorphine treatment was associated with the increased self-reported engagement of addiction treatment and reduced illicit opioid use within a two-month interval. (12)  Increasing evidence demonstrates that the emergency department provides an opportunity to intervene on opioid use disorder, with more and more emergency medicine physicians becoming X-waiver certified.

References

1. Issue brief: Reports of increases in opioid and other drug-related overdose and other concerns during COVID pandemic. American Medical Association. https://www.ama-assn.org/system/files/2020-12/issue-brief-increases-in-opioid-related-overdose.pdf. Published December 9, 2020.

2. Wakhlu S. Buprenorphine: a review. J Opioid Manag. 2009 Jan-Feb;5(1):59-64. doi: 10.5055/jom.2009.0007.

3. Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. doi: 10.1038/clpt.1994.71.

4. Zedler BK, Mann AL, Kim MM, Amick HR, Joyce AR, Murrelle EL, Jones HE. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction. 2016 Dec;111(12):2115-2128. doi: 10.1111/add.13462.

5. Committee Opinion No. 711 Summary: Opioid Use and Opioid Use Disorder in Pregnancy. Obstetrics & Gynecology. 2017;130(2):488-489. doi:10.1097/aog.0000000000002229

6. Special Circumstances for Providing Buprenorphine. SAMHSA. https://www.samhsa.gov/medication-assisted-treatment/statutes-regulations-guidelines/special-circumstances. Published August 19, 2020.

7. Nagel L. Emergency Narcotic Addiction Treatment. https://www.deadiversion.usdoj.gov/pubs/advisories/emerg_treat.htm.

8. Wesson DR, Ling W. Clinical Opiate Withdrawal Scale. PsycTESTS Dataset. June 2003. doi:10.1037/t48752-000

9. D'Onofrio G, O'Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-1644. doi:10.1001/jama.2015.3474

10. Dosing Guide For Optimal Management of Opioid Dependence. The National Alliance of Advocates for Buprenorphine Treatment.

11. D’Onofrio G, O’Connor PG, Pantalon MV, et al. Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence: A Randomized Clinical Trial. JAMA. 2015;313(16):1636–1644. doi:10.1001/jama.2015.3474

12. D'Onofrio G, Chawarski MC, O'Connor PG, Pantalon MV, Busch SH, Owens PH, Hawk K, Bernstein SL, Fiellin DA. Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention. J Gen Intern Med. 2017 Jun;32(6):660-666. doi: 10.1007/s11606-017-3993-2.

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Expert Commentary

Thanks to Dr. Halloran and Watts for providing an informative discussion on buprenorphine prescribing from the ED. Buprenorphine continues to emerge as the state of the art treatment strategy for opioid use disorder (OUD) and thus, developing a working knowledge for when and how to use it is essential.

While there is little doubt that the medical field fueled the opioid epidemic through the prescribing of pain medications, EM is often given a disproportionate amount of blame for the current situation.  In 2012, EM prescriptions made up only 4.3% of all opioids in circulation (1). Furthermore, I anticipate our specialty will continue to lead the fight against the opioid epidemic as practices such as naloxone prescribing, education around safe injecting practices, reduction and optimization of opioid prescribing efforts, and buprenorphine initiation gain further traction in the ED.

Obtaining a DEA X is the first step to prescribing buprenorphine. In April of this year guidelines for the administration of buprenorphine were updated to allow practitioners to treat up to 30 patients at a time with no extra training (2). While these changes will likely expand buprenorphine prescribing from the ED, it is vital that we do not operate in a silo.

To effectively manage this complex patient cohort, a coherent system of addiction medicine services is vital.  EDs must partner with local community resources to make rapid addiction medicine appointments available. Our department utilizes specially trained addiction care coordinators, nurses with extensive training in addiction medicine to help evaluate OUD patients and navigate the fractured array of outpatient services.

Prior to the implementation of our Medication for Opioid Use Disorder (MOUD) program, our clinicians had relatively little to offer patients that directly addressed their underlying addiction.  While anecdotal, we believe that by utilizing MOUD, we have begun to rebuild trust between OUD patients and the medical system.  A once generally negative relationship between OUD patients and our ED staff has been replaced with a hopeful rapport, confident that recovery for these patients is a distinct possibility.  This therapeutic relationship continues to grow and we believe will lead to long-term sustained recovery for many of our OUD patients in the surrounding community. 

References

1. Levy B, Paulozzi L, Mack KA, Jones CM. Trends in Opioid Analgesic-Prescribing Rates by Specialty, U.S., 2007-2012. Am J Prev Med 2015;49:409-13.

2. Reuter Q, Smith G, McKinnon J, Varley J, Jouriles N, Seaberg D. Successful Medication for Opioid Use Disorder (MOUD) Program at a Community Hospital Emergency Department. Acad Emerg Med 2020.

Quentin Reuter, MD

Emergency Medicine Physician

Core Faculty at Summa Health

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Halloran D., Watts S. (2021, Sept 13). Buprenorphine Use in the ED. [NUEM Blog. Expert Commentary by Reuter Q.]. Retrieved from http://www.nuemblog.com/blog/buprenorphine

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Serotonin Syndrome

Written by: Jacob Stelter, MD (NUEM PGY-3) Edited by: Elizabeth Byrne, MD,  (NUEM Graduate 2017) Expert Commentary by: Patrick Lank, MD

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The Case

A 21-yearold male with history of PTSD and depression presented to the ED complaining of “feeling anxious.” When evaluated, the patient was found to be anxious, continuously pacing around the room. His speech was pressured as he tangentially answered questions.  During the interview he stated that he was discharged a few days ago from a psychiatric hospital after he had intentionally overdosed on clonazepam. He then admited that two hours prior to arrival in your ED he took 30 pills of his prescribed sertraline 100mg tabs to “calm his nerves.” He denied any concurrent substance abuse. Despite the stated overdose, he denied any suicidal intent with his ingestion.

Physical Exam:

Vital Signs: T 98.9F oral   HR 137   BP  152/89   RR 20    Sat 99% on room air

General: Awake, alert, anxious-appearing, pacing around the room, mildly diaphoretic

Head: normocephalic, atraumatic

HEENT: PERRL,  EOMI, anicteric sclera, mydriatic pupils b/l, 8mm

Cardiac: tachycardic,  regular rhythm, no MRG

Resp: clear to auscultation, nonlabored, no crackles appreciated

Abd: Soft, not distended, not-tender to palpation, +bowel sounds

Extremities: well perfused, 2+ radial and DP pulses b/l, mildly diaphoretic

Neuro: AAOx3, 5/5 strength in all 4 extremities, +ankle clonus, hyperreflexia on patellar reflexes.

Psych: Cooperative but anxious with pressured and tangential speech., no HI , SI, hallucinations/delusions

Pertinent Labs:

WBC 12.5, Hgb 15.8, electrolytes within normal limits,  LA of 1.7.

Urine drug screen was positive for amphetamines and benzodiazepines. Acetaminophen, salicylate, and ethanol concentrations were below detection limits.

ECG:

Sinus tachycardia, QTc 457, no abnormal morphology of the QRS complexes

Diagnosis?

Serotonin Syndrome due to SSRI overdose.

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Serotonin Syndrome

Overview

Serotonin syndrome is a disorder that is precipitated by excess serotonin. It is classically described as having a combination of hyperautonomic hemodynamic changes, neuromuscular derangements, and a change in the patient’s mental status. [1]  Serotonin syndrome is a medical condition seen only in patients with exposure to serotonergic medications and has been more recently appreciated since the advent of serotonergic drugs used to treat depression and anxiety. However, in addition to pharmaceuticals, botanicals and recreational drugs of abuse can also be serotonergic.  Causative substances increase the amount of circulating serotonin in the bloodstream, which leads to an increased propensity to develop serotonin syndrome [2].  This is not a rare diagnosis; there are approximately 7,300 cases per year results in about 100 deaths [1].

Clinical Presentation

View fullsize

Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-20.

The diagnosis of serotonin syndrome will often manifest around the time of a dose increase, addition of another serotonergic agent or an overdose on a serotonergic agent [3]. Serotonin syndrome will typically manifest within 24 hours of exposure to the serotonergic agent [4]. Symptom presentation  can be separated into three main categories: cognitive, autonomic and neuromuscular. Cognitive symptoms range from restlessness and anxiety to agitation and altered mental status [2].  Autonomic signs and symptoms include tachycardia, mydriasis, hyper- or hypotension, hyperthermia and diaphoresis [2]. Neuromuscular symptoms are also usually observed, ranging from akathisia to muscle rigidity, hyperreflexia and myoclonus [2].  Serotonin syndrome can be a life-threatening condition if not promptly recognized and treated as it can progress to seizures or shock [1]. 

View fullsize

Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-20.

Treatment

The most important initial step to the treatment of serotonin syndrome is to remove exposure to the offending agent. Use of activated charcoal to assist with gastrointestinal decontamination can be considered in the setting of a recent ingestion [1].  Following this, the cornerstone of therapy of serotonin syndrome is symptom based supportive care, with benzodiazepines being one of the most important components of treatment [1, 2]:

• Obtain an ECG to evaluate the QTc and QRS durations.
• Begin IV fluid rehydration and resuscitation.
•  If the patient is hyperthermic, especially greater than 40 ºC, begin active external cooling.
• Antipyretics are not useful for the treatment of hyperthermia secondary to serotonin syndrome. This is because the hyperthermia is due to increased muscle activity and not secondary to change in the hypothalamic temperature set point.
• Benzodiazepines improve numerous symptoms of serotonin syndrome, especially agitation and are one of the most important elements of treatment.
• Use easily titrated medications like nitroprusside or esmolol for severe hypertension.
• If needed, vasopressors should be used for refractory hypotension.
• A recent study has suggested the potential utility of dexmedetomidine to treat serotonin syndrome (5).
• Cyproheptadine, a serotonin antagonist, has long been proposed anecdotally for the treatment of serotonin syndrome.  However, multiple studies suggest that it does not change outcomes and may only help temporarily control symptoms (6).

Unless the clinical features are very mild, these patients will likely need monitoring in an ICU setting for at least 24 hours after being initially managed in the Emergency Department (ED).  As always, especially in the case of an intentional overdose, contacting the local Poison Control Center is a valuable resource in helping to treat these patients.

What about Neuroleptic Malignant Syndrome?

One of the disorders that can present similarly to serotonin syndrome is neuroleptic malignant syndrome (NMS).  Pathophysiologically, NMS is related to an inherited genetic mutation in skeletal muscle and is provoked in the presence of certain neuroleptics [7]. Neuroleptic malignant syndrome often occurs after exposure to drugs that affect the central dopaminergic system, such as haloperidol. There are inherent differences between NMS and serotonin syndrome. Serotonin syndrome tends to present within 24 hours of exposure to the offending agent, whereas NMS will often be more delayed, presenting after 7 days of starting the neuroleptic [4]. Patients with serotonin syndrome will often be agitated and delirious while NMS patients will often have dysphagia, incontinence and increased secretions [4]. NMS will often have extrapyramidal side effects, muscle rigidity and rhabdomyolysis compared to the mydriasis, clonus and hyperreflexia of serotonin syndrome [4].

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Return to the Case

As noted above, the patient in this case exhibited all the hallmark signs of serotonin syndrome, including agitation, restlessness, diaphoresis, mydriasis, hyperreflexia and clonus.  In the emergency department, this patient was treated with multiple rounds of lorazepam and boluses of saline which helped to control his symptoms.  This patient was admitted to the medical ICU and monitored for an additional 24 hours.  After his symptoms and vital signs normalized, he was transferred to the floor and received the psychiatric evaluation and treatment that he needed.  His hospital course was uncomplicated and he was transferred to an inpatient psychiatric treatment facility for further care.

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Take Home Points

1. Serotonin syndrome can be a life-threatening condition. Keep a high suspicion for this in patients on serotonergic agents.
2. The hallmark signs and symptoms of serotonin syndrome are anxiety and restlessness, diaphoresis, mydriasis, clonus, hyperrflexia, tachycardia and hypertension.
3. Treatment is mainly supportive care and includes intravenous fluids, benzodiazepines titrated to symptom control and blood pressure control as needed.
4.  Serotonin syndrome is often confused with NMS.  Remember, NMS is in the setting of exposure to neuroleptics and tends to present later on with symptoms of extrapyramidal side effects, muscle rigidity and increased secretions.
5. Local poison control centers are a great resource in helping manage the treatment of patients with serotonin syndrome and most will require at least 24 hours in an ICU setting after ED diagnosis and management.

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Expert Commentary

Dear Dr. Stelter,

Thank you again for yet another exciting tox blog post! This case has a tremendous amount to dissect, but I want to focus on a few things.  For this case, let’s talk about the tox history, the tox physical exam, and the “supportive care” recommendation. Really, this is the definition of bread and butter medical toxicology.

The patient history described above is incredibly common, and that makes sense! Patients with a known history of psychiatric disease have higher risk of having psychiatric emergencies and have access to psychiatric medications. So whether by misunderstanding the purpose of their medication or by intentionally trying to harm oneself, it is common that we as medical toxicologists have to consider the effect a patient’s psychiatric medications have had (or will have) on their current clinical state. So what I want to know out of this patient is what all he could have been exposed to and when. Here are examples of questions I ask:

•  “When did you take this medication?” (Looking at the clock) “Ok. It’s 3pm. You took it 2 hours ago, so at 1pm you sat down and swallowed 30 pills?” In essence, I want the patient to describe exactly how he was exposed – this can also clue me into his intent.
• “Did you take anything else?” (Answer is commonly “no” – always dig deeper) “Are you on any other medication? When is the last time you took that medication? When you started to feel sick before you came into the emergency department, did you take anything else to help with your symptoms?”
•  “This may sound silly to you, but I also care about anything else you are taking. Are you on any vitamins or diet pills or herbals or cleanses? Is there anything you have purchased and taken in the last week which was not food or a prescription medication we have already talked about?”
• “Do you do any drugs?” I purposely leave the word “illicit” out. I don’t really care about legality. I just want to make them better. “I have seen many patients use all sorts of things that make them feel as sick as you feel now. Is there anything you can think of that you’ve taken which could make you this sick?”

This physical examination gave you your diagnosis! Usually we are clued into these diagnoses based on hyperthermia, which this patient frustratingly did not have. But that “hot tox” differential is something all emergency physicians should be aware of and facile in differentiating between. It includes serotonin syndrome, NMS, sympathomimetic toxicity (including cocaine, amphetamines, MDMA, cathinone derivatives, etc.), anticholinergic toxicity, and severe salicylate toxicity just to name a few.  Although this patient did not have hyperthermia, he did have almost every other finding associated with serotonin syndrome with the most specifically-associated being clonus. Once I see clonus, I take a step back and see if serotonin syndrome fits into the clinical picture.

Finally, I greatly appreciate your description of symptom-focused supportive care in this clinical scenario. As you have displayed, “supportive care” is not super simple. It is nuanced and multifaceted and very frequently life-saving. Before fellowship I was frustrated that there wasn’t necessarily a specific antidote or procedure we could do to reverse toxicity in all poisoned patients. With time, however, I have gained great respect for “supportive care” – regretting when it is not performed adequately and truly appreciating when it is life-saving.

So in this single case you have touched on the key major aspects of the specialty of medical toxicology. I hope some of my points were helpful to you in further appreciating the stellar medical care you provided this sample patient.

Sincerely,

Patrick Lank, MD

Associate Program Director Northwestern Emergency Medicine 

Assistant Professor of Emergency Medicine

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How to cite this post

[Peer-Reviewed, Web Publication] Stelter J,  Byrne E (2017, Nov 13). Serotonin Syndrome [NUEM Blog. Expert Commentary By Lank P]. Retrieved from http://www.nuemblog.com/blog/serotonin-syndrome

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References

1. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-20.
2.  LoVecchio F, Mattison E. Atypical and serotonergic antidepressants. In Tintinalli’s emergency medicine: A comprehensive study guide. J Tintinalli (Ed.) (pp. 1219-24). 2016. New York, NY: McGraw-Hill.
3. Pedavally S, Fugate JE, Rabinstein AA. Serotonin syndrome in the intensive care unit: Clinical presentations and precipitating medications. Neurocrit Care 2014;21:108-13.
4. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: A brief review. Can Med Assc J 2003;168:1439-42.
5.  Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacotherapy 2014;14:1651-4.
6.  McDaniel WW. Serotonin syndrome: Early management with cyproheptadine. Ann Pharmacother 2001;35:870-3.
7.  Keck PE, Caroff SN, McElroy SL. Neuroleptic malignant syndrome and malignant hyperthermia: End of a controversy? J Neuropsychiatry Clin NeuroSci 1995;7:135-44.

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