Inpatient opioid use disorder treatment for the infectious disease physician

Screening for OUD

A cross-sectional evaluation performed in 2009 of a large inpatient urban center found a substance use disorder incidence of approximately 11% (excluding alcohol, tobacco, and patients already stabilized on MOUD) [ ]. The United States Preventative Services Task Force in 2008 found insufficient evidence for universal screening in the general medical setting for drug use. These guidelines are currently being revised to respond to the national OUD crisis, and other organizational bodies such as the National Institute for Drug Abuse (NIDA) recommend universal OUD screening [ ]. We recommend consideration of OUD screening for all ID consultations, especially in those that may be IDU related. Optimally, initial ID consultation will occur early so as to potentially link to MOUD treatment and improve inpatient outcomes.

Certain infections and conditions elevate the pretest probability of having OUD. As mentioned above, HCV, HIV, and HBV infections all increase the likelihood of IDU-associated OUD. Bloodstream infections without a clear source such as Staphylococcus bacteremia or Candidiasis merit further OUD screening. Other conditions related to bacteremia or contiguous spread such as infectious endocarditis, osteomyelitis, or endophthalmitis could be injection related. Numerous noninfectious risk factors for OUD also exist. For the patient with prescribed oral opioids, four behavior patterns have been associated with illicit use: early refills, intoxication with the prescribed drug, dose increase of the patient's own volition, and oversedation [ ]. Relevant state Prescription Monitoring Program review can display patterns of medication seeking. Finally, patients with frank opioid withdrawal or intoxication can be misdiagnosed without clinical suspicion for OUD.

The NIDA Quick Screen is a single screening question for past year use of alcohol, tobacco, nonmedical prescription drug, and illegal drug use [ ]. It is meant for use by general medical practitioners and is an effective screen for OUD and other SUD. The doctor-patient discussion on screening is best prefaced by ensuring confidentiality and appropriate medical care. A positive screen reflexes to the NIDA-Modified Alcohol, Smoking, and Substance Involvement Screening Test ( NM-ASSIST ), which assesses for severity for a variety of illicit substances. The screening process is typically interpreted in tandem with a brief intervention (referred to as SBI) with a goal to frame a discussion and support deeper diagnostic evaluation. The discussion has been framed as the “5 As” of SBI: Ask, Advise, Assess, Assist, and Arrange . The provider begins by asking permission to discuss screening results, and then advises on drug use. Assessment regards the patient's readiness to quit—both readiness to start MOUD and/or harm reduction services (e.g., naloxone proficiency, needle syringe exchange) should be queried. Subsequently assistance is given in making behavioral changes, and “arrange” refers to creating follow-up care. The 5A framework should be tailored to the patient interview—if screening and OUD diagnosis occur at the same time, the intervention portion can be tailored to a discussion on MOUD initiation.

Urine toxicology screening is best used as an additional data point with a given sensitivity and specificity to be interpreted in a clinical context. Most clinical drug screening is a urine immunoassay in which an antibody panel binds against drugs or metabolites. Its major drawback is cross-reactivity, which can be assay-dependent, and includes cross reactions with naloxone (false positive for oxycodone) and both fluoroquinolones and rifampicin (false positives for opiates) [ ]. Poppy seeds are known to have minute but detectable concentrations of morphine derivative that can trigger positivity. Confirmatory testing using liquid chromatography or mass spectrometry is typically not performed in clinical labs. Positivity duration depends on opioid type: codeine, heroin, and morphine can be detected for up to 2 days and methadone can be detected for up to 3 days using specific methadone assays. The general “opiate” immunoassay will not detect oxycodone, fentanyl, or methadone, although specific screens that will check for a broader panel of opioids and metabolites are now available.

Establishing the OUD diagnosis

For those that screen positive, a full assessment of severity is merited, with the goal of establishing whether OUD is present or not. If inpatient Addiction Medicine consultation is present, this role can be referred or shared. However, part of the movement for broader MOUD prescribing involves additional providers such as ID consultants to have competency with establishing a use disorder diagnosis.

Per the DSM-5 criteria depicted in Table 10.1 , an OUD constitutes a problematic pattern of opioid use resulting in clinically significant impairment. The three broad criteria categories are (1) loss of control, (2) adverse consequences, including health, legal, etc., and (3) physiology of tolerance demonstrated in the past 12 months.

Presence of two or more criteria is consistent with a diagnosis of OUD. Severity is determined by total number of criteria, though frequency and amount of opioid use is used in conjunction with diagnostic severity for a more holistic understanding of drug-related dysfunction.

There are a variety of diagnostic assessment tools to be used for establishing the diagnosis of OUD. The use of a particular assessment tool depends in part in clinical role (addiction specialist/psychiatrist vs. generalist; researcher vs. clinician) and whether there is motive for in-depth diagnosis of other substance use disorders. The SCID , or structured clinical interview for DSM-V, is the gold standard for in-depth psychiatric or research-based evaluation [ ]. It is a semistructured clinical interview based off of the DSM criteria. The Mini-International Neuropsychiatric Review, or MINI , is shorter and has been validated in relation to the SCID [ ]. All are designed to maximize diagnostic performance and interprovider reliability. For the targeted diagnosis and rapid treatment of OUD, direct use of the DSM-5 criteria serves an important role, especially in decentralized OUD treatment for nonaddiction specialty providers. The Rapid Opioid Dependence Screen (RODS ), developed by co-author S. Springer, is an eight question brief assessment tool validated against the MINI specifically for rapid diagnosis of OUD in incarcerated populations with HIV and could be used more broadly with subsequent scale validation [ , ].

Clarifying OUD for the infectious disease physician

Following diagnosis of OUD, there are two main goals: to detail the patient's opioid use with particular attention paid to infection-related risk practices and to discuss initiation of MOUD. The clarification of OUD component can be woven into the framework of an ID consult history and physical and will guide the consultation.

Type, route, and frequency of opioid will greatly affect infection risk. Often patients will have a combination of different opioid use routes (e.g., injection, snorting, oral, and/or smoked) and types (e.g., both injection-based heroin/fentanyl and oral prescription illicit opioids). Site of injection can span from low-risk sites such as the antecubital fossa or hand to more central sites with higher commensal flora burden like the groin. Very high-risk injecting such as arterial or carotid (“shooting for big red”) injection has an elevated risk for aneurysm formation and life-threatening bleeding. Skin decontamination practices should be queried especially if the patient's chief diagnosis is SSTI. Harm reduction requires hand hygiene and decontamination with proper equipment such as alcohol-based wipes. Skin-popping and muscle popping, which are subcutaneous and intramuscular injections, respectively, carry higher rates of abscess formation and spore forming bacterial infections. There is a wide spectrum of water sterility used among PWID. In ideal harm reduction settings, sterile water should be used, but sources including toilet water have been reported, often in the throes of withdrawal with limited alternative sources. This is fueled by misconceptions that the cooking of product will fully sterilize any infectious material. Paraphernalia sharing should be queried, with specific questions toward which pieces of equipment were shared and how—even if a syringe tip is replaced and a plunger is retained, residual body fluids could be reservoirs for HIV or HCV. Finally, there are a variety of real-world practices that PWID employ in attempts to sterilize paraphernalia. The most advisable form of decontamination is with undiluted household bleach retained for at least 2 min [ ]. Local availability of other harm reduction strategies such as needle and syringe exchange programs and overdose education and naloxone distribution will guide subsequent counseling.

Expanding on past substance use history is informative in anticipation of initiating MOUD treatment. A detailed history will include past use of MOUD, response, and information on relapse. History of overdose, hospitalization, and rehabilitation therapy is also relevant. The Prescription Monitoring Program database will provide historical data in regard to prescribed opioid use—methadone will not be reported here and, if prescribed, the relevant opioid treatment program (OTP) should be contacted. There is a significant heritability to substance use disorder that should be explored for family history. Social support and living situation contributes to psychosocial risk factors for use but also assistance networks for treatment. A history of legal issues regarding substances assesses adverse consequences of drug use.

Comorbid psychiatric disease can have a major impact on treatment outcomes if left undiagnosed or unmanaged. The introductory Patient Health Questionnaire (PHQ)-2 screen is a well-validated, brief screen for depression that can lead to further assessment of major depressive disorder with the PHQ-9 [ ]. Positive screening for suicidal or homicidal ideation requires psychiatric referral and stabilization. The NM-ASSIST, introduced above, can serve as a screen for other substance use disorders if performed to completion. Screening for chronic infectious diseases associated with IVDU such as HIV, HCV, and HBV should occur.

Methadone

Methadone was FDA approved for OUD in the 1970s making it the oldest and most well-studied MOUD. Methadone is a weak opioid agonist, meaning it mimics the effects of opioids such as heroin and reduces withdrawal symptoms without causing euphoria [ ]. Because of its long half-life, daily methadone in the form of methadone maintenance treatment (MMT) can curb withdrawal symptoms for 24–36 h. Doses above 60 mg have consistently shown improved outcomes compared with lower doses [ ]. By preventing withdrawal, MMT reduces illicit drug use and subsequently reduces complications of nonprescription opioids: overdose, death, injection, and additional criminalized behaviors such as drug seeking [ ]. Methadone prevents the euphoria of heroin when used concurrently due to its effect on the opioid receptor, discouraging illicit drug use and promoting recovery.

In a clinical trial setting, methadone was significantly more effective than nonpharmacological interventions in its ability to retain patients in treatment and reduce heroin use [ ]. In a review of three randomized controlled trials (RCTs) comparing methadone to nonpharmacological approaches, methadone was unable to significantly reduce criminal activity or mortality, though subsequent large-scale cohort studies have established reductions in all cause and overdose mortality with treatment [ ]. Compared with buprenorphine, methadone is more effective at both low and flexible doses in retaining patients in treatment. At fixed medium and high doses, buprenorphine may be as effective as medium and high dose methadone, respectively, at retaining patients and suppressing illicit opioid use [ ]. However, fixed doses are impractical as part of routine care. MMT has also been shown to improve drug-related HIV risk behaviors, criminal behaviors, and mortality in addition to maternal and fetal outcomes.

Though methadone is a sufficient medication for treatment of inpatient opioid withdrawal, there can be dose and duration restrictions on inpatient prescribing which vary state by state, often making buprenorphine a more practical choice.

Clinicians and patients should appreciate the risks associated with MMT, including death, respiratory depression, and QT prolongation. For this reason, methadone dose should be slowly increased, and MMT should be avoided altogether in patients with a long QT. Patients receiving MMT should avoid additional respiratory suppressants including alcohol and benzodiazepines and medications that might increase the QT interval [ ]. Both methadone and buprenorphine are extensively metabolized by the CYP450 system (see Table 10.3 ).

Buprenorphine

Buprenorphine is a semisynthetic derivative of thebaine with both partial agonist effect at the mu opioid receptor and antagonistic effect at kappa receptors [ ]. Due to these partial agonist properties, it exhibits a dose response curve with limited additional analgesia and euphoria, giving it a functional ceiling effect [ ]. Buprenorphine is highly potent and adherent to mu opioid receptors, and at moderate doses reduces cravings of illicit opioids through cross-tolerance and high-level receptor occupancy. This high-level occupancy, however, functions to displace other mu agonists which can lead to precipitated withdrawal.

Buprenorphine is ineffective via an oral route but is absorbed well via sublingual (i.e., transmucosal) and transdermal formulations. Naloxone has poor oral and sublingual bioavailability and as such plays no role in buprenorphine coformulated regimens (e.g., Suboxone) except to dissuade from snorting or injection of the medication. The four current formulations of buprenorphine are daily sublingual (tablet/film) or buccal (film), 6-month implantable (Probuphine), and monthly subcutaneous (Sublocade).

Drug allergies to buprenorphine are relatively rare, and it is advisable to educate patients on the difference between allergy and precipitated withdrawal symptoms. While the overdose potential is certainly lower than other full agonist opioids, it still exists—the risk of respiratory depression is increased when coadministered with benzodiazepines or alcohol [ ]. Buprenorphine can be used in situations of liver disease. Combination naloxone products are not recommended in severe hepatic impairment (Childs B or C); even the negligible amount of sublingual naloxone absorbed can become clinically significant given impaired hepatic metabolism and can cause precipitated withdrawal [ ]. Buprenorphine monotherapy can be used with dose reduction and caution for signs and symptoms of opioid toxicity. Hepatitis with fulminant hepatic failure has occurred in rare cases, typically in those with underlying liver disease such as underlying HBV and HCV. Unless there is known acute hepatitis, it is reasonable to prescribe and monitor closely without assessing LFTs prior to initiation [ ]. Notably, additional concurrent substance use disorders such as stimulant use are not contraindications to starting therapy. Buprenorphine is metabolized via the CYP3A4 hepatic system and as such is affected by other medications that either inhibit or induce this system as depicted in Tables 10.3 .

An abstinence period between last full mu opioid dose and initiation is required to avoid precipitated withdrawal. The abstinence period varies from approximately 12–16 h for short-acting opioids, 16–24 h for intermediate-acting opioids, and up to 48 h for high dose methadone dependence. In particular for the inpatient setting, it should be ensured that the patient is not receiving short-acting opioids for pain control. Typically at least mild withdrawal as noted by a COWS score of 5 or greater is sufficient to start treatment; however, some sources recommend a COWS score >12 as the goal prior to the first dose. An advantage to inpatient initiation of buprenorphine is the availability of a broad array of oral and IV medications to minimize withdrawal symptoms in the abstinence period; these should be liberally used. See Chart 10.1 for a depiction of initiating buprenorphine in the inpatient setting.

Patients should be informed not to swallow the sublingual medication and to allow for up to 10 min for it to fully dissolve before swallowing. The majority of patients stabilize on a maintenance dose of 8–16 mg, and the data for doses above 24 mg is currently limited [ ].

Two additional buprenorphine formulations of consideration are the subdermal implant, brand name Probuphine®, and extended-release buprenorphine, brand name Sublocade®. The implantable formulation deploys a steady state of 8 mg or less of buprenorphine over the course of 6 months. The extended-release formulation medication is administered monthly (300 and 100 mg doses) and designed for patients who have already been stabilized on at least 7 days of transmucosal buprenorphine at a dose of at least 8 mg [ ]. The inpatient setting may be an ideal time for transition to subdermal implantation or the extended-release buprenorphine formulation. Some patients will still require typically small doses of additional transmucosal agonist therapy to achieve resolution of cravings.

There is a subset of patients, particularly those with concurrent chronic pain, for which a period of opioid abstinence prior to induction might be infeasible. Transdermal buprenorphine (trade name Butrans®) appears to produce a more gradual exposure of opioid receptors to drug and is not associated with precipitated withdrawal when short-acting opioids are added. Regimens with initial transdermal buprenorphine with subsequent maintenance transition to sublingual dosing have been successfully reported and should be considered for those with chronic pain [ ].