Picture this: it’s 11:02pm on a Friday Night. Red Team is bed-locked and you’re doing your best hospitalist impression while managing all of the boarding patients. The nurse comes up to you and says, “Hey, this patient in bed 26 is endorsing heroin withdrawal, can we give them something for it?” What’s your next move? Here we discuss the treatment of opioid withdrawal in the emergency department.
What is the recommended first-line treatment for opioid withdrawal in the emergency department?
Opioid withdrawal, although not fatal, causes significant physiological and psychological distress to patients including nausea/vomiting, diarrhea, yawning, pilorection, restlessness, anxiety, and cramping, and can occur in as little as 2-5 hours for fentanyl users and 6-12 hours in heroin users (1). Treatment of withdrawal is both humane and helpful in facilitating the overall care of the patient. In the emergency department, ACEP recommends buprenorphine for treatment of opioid use disorder, but methadone is another acceptable treatment that is frequently used (1,2).
Both buprenorphine and methadone have their pros and cons. Methadone will not precipitate withdrawal, and it has higher rates of long-term treatment retention, but it can lead to significant respiratory depression, can cause QTc prolongation, and requires enrollment in outpatient OUD clinics to continue treatment. Buprenorphine has a ceiling effect for sedation and respiratory depression, and it can also be prescribed long-term without needing outpatient clinic follow-up (or an X-waiver as of 2023!) (3). Herring et. al recommend administering buprenorphine 4-8mg SL for COWS > 8, and an additional 8-24 mg after 30-60 minutes for persistent symptoms (4). Alternatively, methadone 10 mg IM has been shown by Su et. al to treat opioid withdrawal in the ED for those unable to tolerate PO (5).
Answer: Buprenorphine and methadone are both recommended for opioid withdrawal in the emergency department. Avoid giving buprenorphine in the absence of clinically significant withdrawal (COWS < 8), as it may precipitate worsening withdrawal.
What if I can’t give methadone or buprenorphine, or the patient is only in very mild withdrawal? Is clonidine helpful?
Since buprenorphine is a partial agonist (meaning it is also a partial antagonist), administering it when there are still opioid agonists in the patient’s system can precipitate worsening withdrawal. Furthermore, methadone can cause QTc prolongation, so what can you do if you cannot administer either one? One alternative in such a situation is clonidine. Clonidine, a centrally acting alpha-2 agonist, has been shown in the literature since the 1980’s to assist with symptoms of acute opioid withdrawal. It is recommended to give clonidine 0.1 mg as needed for symptoms of withdrawal (1). Gowing et. al published a Cochrane meta-analysis in 2016 that examined 26 clinical trials that compared clonidine to alternatives in treating opioid withdrawal in the ED. They found that clonidine was superior to placebo in treating acute withdrawal (although it led to increased adverse effects related to hypotension and bradycardia) and was comparable to methadone in terms of treatment completion and management of severity of symptoms (6).
Beyond withdrawal management, clonidine may have promise as an agent to decrease the amount of opioids needed for acute pain in the ED. Rostamipoor et al. published a recent prospective study in 2023 examining patients with opioid use disorder who presented with acute orthopedic fractures. Out of 70 patients (mean age 37), half of the patients received clonidine 0.2 mg PO and the other half received placebo. Although both groups required morphine for pain control, the clonidine group required less morphine (2.7 mg on average in the clonidine group vs 4.4 mg in the placebo group (P <0.01)) (5). The study had many limitations, including its small sample size, lack of inclusion of adverse events, and heterogeneity of injuries treated, so take its conclusion with a huge grain of salt.
Answer: Clonidine is an effective treatment for opioid withdrawal in the emergency department compared to placebo. Consider using it in conjunction with other symptom-based medications like benzos, antiemetics, and muscle relaxants. However, be mindful of associated hypotension and bradycardia.
References:
Herring AA, Perrone J, Nelson LS. Managing opioid withdrawal in the emergency department with Buprenorphine. Annals of Emergency Medicine. 2019;73(5), 481–487. https://doi.org/10.1016/j.annemergmed.2018.11.032
Hawk K, Hoppe J, Ketcham E, et al. Consensus recommendations on the treatment of opioid use disorder in the Emergency Department. Annals of Emergency Medicine, 2021;78(3), 434–442. https://doi.org/10.1016/j.annemergmed.2021.04.023
Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 Feb 6;2014(2):CD002207. doi: 10.1002/14651858.CD002207.pub4. PMID: 24500948; PMCID: PMC10617756.
Herring AA, Vosooghi AA, Luftig J, et al. High-dose buprenorphine induction in the emergency department for treatment of opioid use disorder. JAMA Netw Open. 2021;4(7):e2117128.
Su MK, Lopez JH, Crossa A, Hoffman RS. Low dose intramuscular methadone for acute mild to moderate opioid withdrawal syndrome. Am J Emerg Med. 2018 Nov;36(11):1951-1956. doi: 10.1016/j.ajem.2018.02.019. Epub 2018 Mar 2. PMID: 29544903.
Gowing L, Farrell M, Ali R, White JM. Alpha2‐adrenergic agonists for the management of opioid withdrawal. Cochrane Database of Systematic Reviews. 2016; 5. DOI: 10.1002/14651858.CD002024.pub5. Accessed 10 February 2024.