Methadone Induction for a Patient with Precipitated Withdrawal in the Emergency Department: A Case Report

Abstract

In the era of illicit fentanyl, reports are emerging of difficulties with buprenorphine inductions for patients with opioid use disorder. Methadone is the only other approved medication treatment with efficacy similar to buprenorphine but without risks of precipitated withdrawal. Unfortunately, outpatient methadone inductions can take days to weeks to complete, due in part to regulations that limit administration to opioid treatment programs. We describe a patient with opioid use disorder who presented to the emergency department in precipitated withdrawal who completed a same day methadone induction with next day dosing at an opioid treatment program as part of an emergency department methadone protocol. As opioid related deaths rise, emergency department-initiated methadone is feasible for patients with opioid use disorder.

Background

In an effort to combat the rise in drug related deaths in the United States, many emergency departments (ED)’s have implemented policies to initiate buprenorphine for patients with opioid use disorder (OUD).^[1,2] As a partial mu-opioid receptor agonist, buprenorphine reduces opioid related morbidity and mortality.^[3] Further, the low barrier ED model that immediately starts medication while bridging to outpatient resources decreases future opioid use and increases treatment retention.^[4]

However, reports are emerging of buprenorphine induction challenges, including precipitation of withdrawal symptoms despite prolonged abstinence, potentially due to the increased potency of illicit opioids. ^{[5, 6]} Although actual induction failures may be rare, the rise in negative experiences has resulted in hesitation to engage with buprenorphine among community members with OUD. ^[7]

Methadone is the only agonist medication approved for the treatment of OUD that does not risk precipitating opioid withdrawal. In response to a growing population of patients wary of buprenorphine, we created an ED methadone protocol that includes administration of an initial methadone dose in the ED with next day follow up at an opioid treatment program (OTP).

ED Methadone Protocol Development

The ED methadone protocol provides a pathway for patients with OUD to immediately start methadone based on their presenting symptoms, experiences, and preferences while bridging to outpatient treatment. While methadone is restricted to licensed OTPs, exemptions exist that allow outpatient methadone administration in special circumstances. One exemption, enacted in 2006, is known as the “72-hour rule” (Code of Federal Regulations, Title 21 Chapter II, Part 1306.07(b)) which allows a medical practitioner to administer narcotic medications (including methadone) for the purpose of alleviating opioid withdrawal while arranging outpatient treatment daily for a maximum of 3 days.^[8] The ED, classified as an outpatient medical center, is therefore qualified to administer methadone to patients who otherwise meet the 72-hour rule criteria.

Once the legal foundation for ED methadone was established, leaders from the local OTP collaborated with the ED to create the methadone protocol. Understanding it was not feasible to complete the OTP intake immediately after an ED visit, a next day dose pathway, modeled after guest dosing policies, was created. Guest dosing is the process of administering methadone to a “guest” patient at an OTP where they are not enrolled. Guest dosing requires a physician order and documentation of the last methadone dose to allow the OTP to continue methadone administration. Using guest dosing as a framework, protocols were created to ensure the ED provider would document criteria for OTP admission and confirm the last methadone dose to allow next-day OTP methadone administration.

Consistent with the 72-hour rule, the ED methadone protocol requires that patients be at least 18 years old, have a diagnosis of OUD, and be experiencing opioid withdrawal, defined as a clinical opiate withdrawal scale (COWS) > 0. For patients who meet criteria, an initial dose of 20-30 mg of methadone is administered in the ED based on prior drug and methadone use, with an optional 10 mg every 3 hours up to a maximum 40 mg. (Figure 1) Testing, including toxicology and electrocardiograms are left to the discretion of the clinician. Upon discharge, a last dose letter, demographics, and treatment consent forms are securely faxed to the OTP. (Supplementary materials) Upon receipt of documentation, the patient is registered and is able to continue the prior methadone dose at the OTP using the ED clinician as the qualified medical provider until intake is complete, which usually occurs in 1-3 days. As a safeguard, the OTP manager and the ED Director of Harm Reduction communicate weekly to address any issues with ED-OTP referrals.

Figure 1.

Low-Barrier Emergency Department Methadone Induction Protocol Process Flow Chart

With written consent from the patient, we present the first case of a patient who completed the ED methadone protocol.

Case Description

A 55-year-old man presented to the ED seeking assistance in treating opioid withdrawal symptoms. The patient had a history of using 0.75-1.5 grams of intranasal heroin daily for years. Prior to the ED, he wanted to start medication treatment, but was unable to arrange a timely outpatient appointment. To self-treat his OUD, he used an unknown amount of diverted methadone 30 hours prior to the ED visit. Later that night, he began experiencing withdrawal and relapsed on opioids. The next morning, he again tried to self-treat his OUD and used an unknown amount of diverted buprenorphine/naloxone, after which he began experiencing withdrawal symptoms.

On arrival, the patient had a temperature of 99.1, heart rate of 64, blood pressure of 154/64 and an oxygen saturation of 99% on room air. He appeared awake and alert in mild distress. He had opioid withdrawal symptoms consistent with a COWS of 6, reporting increased irritability, joint aches, stomach cramps and was observed to have a slight tremor. His exam was otherwise unremarkable.

The patient was unaware that the ED could offer medications for OUD. He was offered buprenorphine but declined, concerned about precipitated withdrawal. He was interested in methadone and was administered 20mg of methadone in the ED with improvement in his withdrawal symptoms. Upon discharge, the patient was given a last dose letter, next day OTP follow up instructions and reasons to return to the ED.

The next day, the patient was administered 20mg of methadone at the OTP based on the last dose letter. His initial urine toxicology was positive for fentanyl, cocaine, buprenorphine and methadone. After confirming the patient was not receiving treatment at another OTP, he was evaluated by the clinician and enrolled in the OTP. On one month’s follow up, the OTP confirmed that the patient had stabilized at 70mg of methadone, had only missed one dose, and had not returned to the ED. His most recent urine toxicology results were only positive for methadone.

Discussion

Methadone is a long-acting opioid agonist approved for the treatment of OUD that works by managing cravings and withdrawal symptoms, allowing patients to re-engage with family, work, and life. Methadone maintenance reduces rates of illicit drug use, increases treatment retention, and decreases future opioid related health complications. ^[9,10]

Compared to buprenorphine, methadone has multiple advantages, including the opportunity to start medication without prolonged abstinence or withdrawal symptoms, frequent visits with clinicians, and the ability to titrate to effect. With respect to risks, although overdose rates are higher during methadone induction compared to buprenorphine, engagement in either methadone or buprenorphine halves the mortality for ED patients after an initial nonfatal overdose. ^[11]

The greatest barriers to methadone are government regulations, many of which have not changed in 50 years. According to federal regulations, apart from the 72-hour rule, methadone for outpatient treatment of OUD can only be dispensed after completing an in-person exam with a clinician at an accredited OTP. Further, methadone for OUD can never be prescribed and historically was administered daily for the first 90 days of treatment, though daily administration regulations were relaxed during COVID-19. Combined with state laws that restrict the accreditation or reimbursement of OTPs, the barriers patients with OUD face to engage in methadone are substantial. ^[12]

The ED serves as important safety net for patients with OUD, providing an opportunity to engage in treatment irrespective of demographics, legal status or ability to pay.^[13] Over the last decade, many EDs have implemented low barrier models to incorporate buprenorphine into practice.^[14] However, methadone in the ED remains rare, limited to continuing established therapy and occasionally to treat opioid withdrawal.^[15] There are no published reports of ED methadone induction with OTP linkage; the only reports of outpatient methadone inductions occurring outside an OTP are at a single substance use urgent care facility.^[16,17]

Fundamental to the success of the ED methadone protocol is the collaboration between the ED and the OTP. Established over years of working together on community opioid harm reduction initiatives, ED and OTP providers had already built a level of trust and shared goals that ensured honest discussions regarding testing, methadone dosing, and the safe transfer of health information. The implementation of the ED methadone protocol has continued to improve collaboration between the ED and OTP, resulting in increased communication, shared provider education initiatives and addressing patient problems that fall outside the ED methadone protocol.

There are multiple advantages to the ED methadone protocol. Like buprenorphine, the low barrier ED methadone protocol allows patients to immediately start and continue medication while establishing outpatient care. Further, the initial dose of 20-30mg is well tolerated, does not require an observation period, and eliminates the risk of precipitated withdrawal. Additionally, as safety net resources, ED’s may help to address existing inequities by engaging community members with OUD that have historically struggled to connect with traditional outpatient facilities. ^[18–19]

The limitation of the ED methadone program is that it relies on the capacity of the OTP, which could limit feasibility in certain geographic areas. Unfortunately, there is no exemption that allows outpatient methadone treatment for patients with OUD beyond 72 hours by non-licensed providers. We believe that all FDA-approved medications for opioid use disorder should be available in all venues and hope that the successful treatment of patients through low barrier programs may serve as a call to regulatory agencies to reevaluate antiquated laws that continue to limit access to medication treatments for OUD. ^[20]

Conclusions

In the setting of increasingly potent illicit opioids such as fentanyl, not all patients are achieving adequate treatment with buprenorphine. As a full agonist medication, methadone is particularly useful in patients with precipitated withdrawal. There is an exception to federal regulations that allows for the treatment of acute opioid withdrawal and linkage to care by providers who are not licensed as OTPs. A protocol based on an ED-OTP relationship inclusive of the 72-hour rule is a feasible method to initiate patients with OUD on methadone.