The Hospitalized Patient with Substance Use Disorder: Shifting from Judgment to Evidence-Based Medical Management

A Comprehensive Review for Internists

Dr Neeraj Manikath , claude.ai

Introduction

Substance use disorder (SUD) affects approximately 20% of hospitalized patients, yet many clinicians feel ill-equipped to manage these complex cases.(1) The intersection of acute medical illness and addiction creates unique challenges that demand both clinical acumen and compassionate care. This review provides evidence-based protocols for managing the hospitalized patient with SUD, emphasizing that addiction is a chronic medical condition requiring the same rigor we apply to diabetes or heart failure.

The hospitalization represents a critical window of opportunity. Patients with SUD have 4-5 times higher mortality rates than the general population, often from preventable complications.(2) By implementing evidence-based protocols for withdrawal management, initiating medication-assisted treatment (MAT), and establishing seamless transitions to outpatient care, we can fundamentally alter trajectories and save lives.

Managing Opioid and Alcohol Withdrawal: Protocols for Evidence-Based Care

Opioid Withdrawal Management

Clinical Pearl: Opioid withdrawal, while profoundly uncomfortable, is rarely life-threatening in adults. However, untreated withdrawal leads to patient elopement, against-medical-advice discharges, and missed opportunities for intervention.(3)

The COWS Score: Your Roadmap

The Clinical Opiate Withdrawal Scale (COWS) provides objective assessment:

Score 5-12: Mild withdrawal
Score 13-24: Moderate withdrawal
Score 25-36: Moderately severe withdrawal
Score >36: Severe withdrawal

Hack: Assess COWS every 4 hours initially. Pupil size, rhinorrhea, piloerection, and restlessness are early objective markers before patients complain of symptoms.

Symptom-Triggered vs. Scheduled Protocols

Symptom-Triggered Approach (Preferred for most patients):

Buprenorphine 2-4 mg sublingual when COWS ≥8-12
Reassess in 1-2 hours
Redose if COWS remains ≥8
Typical 24-hour requirement: 8-16 mg

Advantages: Uses less medication, shorter duration, individualized dosing.(4)

Scheduled Approach (For severe dependence, fentanyl exposure):

Methadone 10-20 mg PO every 4-6 hours PRN for COWS ≥8
Maximum initial dose: 40 mg/24 hours
Stabilize, then transition to daily dosing
Alternative: Buprenorphine 4 mg TID scheduled with PRN breakthrough dosing

Oyster: Fentanyl's long half-life and high receptor affinity make withdrawal unpredictable. Expect delayed onset (24-72 hours post-last use) and protracted symptoms. Consider higher buprenorphine doses (up to 24-32 mg daily) and longer induction periods.(5)

Adjunctive Medications

Create a standing order set:

Clonidine 0.1-0.2 mg PO/TD every 6 hours PRN (autonomic symptoms)
Ondansetron 4-8 mg IV/PO every 8 hours PRN (nausea)
Loperamide 2-4 mg PO PRN (diarrhea)
NSAIDs + Acetaminophen (myalgias)
Trazodone 50-100 mg qHS PRN (insomnia)
Hydroxyzine 25-50 mg every 6 hours PRN (anxiety)

Pearl: Avoid benzodiazepines for anxiety in opioid withdrawal unless co-occurring alcohol withdrawal exists. They don't treat opioid withdrawal and increase overdose risk.

Alcohol Withdrawal Management

Critical Concept: Alcohol withdrawal CAN kill. Severe withdrawal (delirium tremens) carries 5-15% mortality if untreated.(6)

CIWA-Ar: The Gold Standard

The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) guides treatment:

Score <8: Minimal withdrawal
Score 8-15: Moderate withdrawal
Score >15: Severe withdrawal, high DT risk

Hack: Don't use CIWA in delirious patients—it requires patient cooperation. In delirium tremens, treat aggressively based on clinical signs (vital instability, hallucinations, severe agitation).

Benzodiazepine Protocols

Symptom-Triggered Protocol (First-line for most):

Lorazepam 2-4 mg IV/PO when CIWA ≥8-10
Reassess every hour
Redose if CIWA remains ≥8
Diazepam alternative: 10-20 mg PO/IV for CIWA ≥8

Front-Loading Protocol (For severe withdrawal/DT):

Diazepam 20 mg IV every 10 minutes until light sedation
Or Lorazepam 4 mg IV every 10-15 minutes
Monitor closely for respiratory depression
Typical cumulative dose: 60-120 mg diazepam equivalents

Oyster: Lorazepam is preferred in liver disease (no active metabolites, predictable clearance). However, diazepam's longer half-life may reduce breakthrough symptoms and seizure risk in patients with normal hepatic function.(7)

Adjunctive Management

Thiamine 500 mg IV TID x 3-5 days (before glucose administration)
Folate 1 mg daily
Multivitamin with attention to magnesium, phosphate
Phenobarbital 130-260 mg loading in refractory cases
Dexmedetomidine infusion for ICU-level withdrawal

Pearl: Seizures typically occur 6-48 hours after last drink. Benzodiazepines are first-line prevention. Post-seizure, continue CIWA-based dosing—the seizure indicates inadequate treatment, not seizure disorder.(8)

Initiation of Buprenorphine in the Hospital: Seizing the Moment

Paradigm Shift: Initiating MAT during hospitalization reduces 30-day mortality by 50-75% and increases engagement with addiction treatment.(9) This is arguably the highest-impact intervention we can offer.

The "Why Now" Conversation

Before prescribing: "Your body has become dependent on opioids. Buprenorphine is a medication that prevents withdrawal, reduces cravings, and most importantly, reduces your risk of dying from overdose by over 50%. Would you like to learn more?"

Step-by-Step Buprenorphine Initiation

Step 1: Ensure Eligibility

Moderate-to-severe opioid use disorder (≥4 DSM-5 criteria)
Patient consent and interest
No contraindications (hypersensitivity, acute alcohol intoxication)

Hack: You do NOT need an X-waiver anymore (eliminated January 2023). Any DEA-licensed provider can prescribe buprenorphine for OUD.(10)

Step 2: Determine Timing

Traditional approach: Wait for withdrawal (COWS ≥8)
Microdosing/Low-Dose Induction: Start buprenorphine WITHOUT waiting for withdrawal

Pearl: For patients on long-acting opioids, methadone, or fentanyl, microdosing avoids precipitated withdrawal. Start buprenorphine 0.5-2 mg BID-TID while continuing full agonists, gradually transitioning over 5-7 days.(11)

Step 3: Initiate Dosing

Standard Induction:

Day 1: Buprenorphine/naloxone 2-4 mg SL when COWS ≥8
Observe 1-2 hours; if tolerated, give additional 4 mg
Day 1 target: 8-12 mg
Day 2: 16 mg daily (divided BID or once daily)
Adjust to 16-24 mg based on cravings/withdrawal

Microdosing Protocol (for fentanyl/methadone):

Day 1-2: Buprenorphine 0.5 mg SL TID + continue opioid PRN
Day 3-4: 1 mg TID + taper opioid by 50%
Day 5-7: 2 mg TID + discontinue opioid
Day 8+: Consolidate to 16-24 mg daily

Oyster: Precipitated withdrawal occurs when buprenorphine (partial agonist) displaces full agonists from receptors. Risk is highest with short-acting opioids within 6-12 hours and fentanyl within 72 hours. Microdosing circumvents this.(12)

Step 4: Address Pain

Critical Hack: Buprenorphine at 16+ mg daily provides analgesia for most moderate pain. For severe acute pain (trauma, surgery):

Continue buprenorphine (maintains receptor occupancy)
Add short-acting full agonists (requires higher doses; expect 2-3x typical requirements)
Regional anesthesia, multimodal analgesia (NSAIDs, gabapentin, ketamine)
Consult addiction medicine/pain service

Pearl: Never abruptly stop buprenorphine perioperatively. This invites relapse.(13)

Step 5: Plan the Transition

Before discharge:

Schedule outpatient follow-up within 3-7 days (addiction medicine, primary care with buprenorphine experience)
Provide 7-14 day supply of buprenorphine (sufficient until appointment)
Warm handoff: Direct phone call/electronic referral to outpatient provider
Educate: How to take medication, side effects, naloxone co-prescription

Hack: Use the buprenorphine prior authorization process during admission to ensure seamless pharmacy access at discharge.

Infective Endocarditis in People Who Inject Drugs: Navigating Complex Terrain

Injection drug use-associated infective endocarditis (IDU-IE) has tripled over the past decade, accounting for up to 30% of IE cases in some centers.(14) These patients face dual challenges: life-threatening infection requiring weeks of IV antibiotics and ongoing addiction requiring compassionate, evidence-based management.

Medical Management Pearls

Antibiotic Selection and Duration

Right-sided IE (tricuspid/pulmonary): 4-6 weeks IV therapy
Left-sided IE (mitral/aortic): 6 weeks IV therapy, often requiring surgical intervention
S. aureus (most common): Nafcillin/Cefazolin (MSSA) or Vancomycin/Daptomycin (MRSA)
Candida endocarditis: Echinocandin + surgical debridement (nearly always required)

Oyster: Oral antibiotic step-down is emerging for select right-sided MSSA IE. Consider combination oral therapy (rifampin + fluoroquinolone or linezolid) after clinical stabilization in low-risk patients, allowing earlier discharge.(15)

Surgical Indications

Heart failure from valvular dysfunction
Perivalvular abscess or extension
Persistent bacteremia >5-7 days despite appropriate antibiotics
Large vegetations (>10 mm) with embolic events
Fungal endocarditis

Pearl: Active substance use is NOT an absolute contraindication to surgery. Evidence shows equivalent surgical outcomes in PWID when social support and addiction treatment are provided.(16)

The Ethical Minefield: Addressing Candidacy Concerns

Many teams question: "What if they relapse and reinfect the valve?" This reflects bias, not evidence.

Evidence-Based Counterpoints:

Reinfection rates: 5-15% in PWID following surgery—comparable to other high-risk groups (dialysis patients, immunocompromised hosts).(17)
Functional outcomes: Equivalent survival and quality-of-life improvements in PWID vs. non-PWID post-surgery.
The ethical imperative: Denying life-saving surgery based on predicted future behavior violates principles of justice and autonomy.

Hack: Reframe discussions. Instead of "Are they a surgical candidate?" ask "What support systems can we provide to optimize surgical outcomes?" This shifts from gatekeeping to problem-solving.

Building Surgical Candidacy

Work collaboratively with surgery, addiction medicine, social work:

Initiate MAT during admission (buprenorphine or methadone)
Behavioral support: Engage psychology/psychiatry for co-occurring mental health disorders
Social determinants: Secure housing, food access, transportation for follow-up
Addiction medicine consultation: Establish outpatient MAT and counseling prior to discharge
Multidisciplinary agreement: Document team consensus on treatment plan

Pearl: The presence of an addiction medicine consultation and MAT initiation significantly increases surgical acceptance rates.(18)

Outpatient Parenteral Antibiotic Therapy (OPAT) in PWID

Traditionally, PWID were excluded from OPAT due to concerns about line misuse. This forced prolonged hospitalizations, increasing costs and deconditioning while not addressing underlying SUD.

Modern Approach:

Assess individually: Not all PWID are actively using; many are in recovery
Structured OPAT programs: Daily witnessed infusions at infusion centers, combined with addiction treatment
Harm reduction: If line misuse occurs, offer non-judgmental re-engagement rather than permanent exclusion
Alternative long-acting antibiotics: Weekly dalbavancin (lipoglycopeptide) or ertapenem for select organisms eliminates line need(19)

Oyster: Prolonged hospitalization itself increases relapse risk post-discharge. A 42-day hospital stay disconnects patients from community supports, increases institutionalization, and creates jarring transitions. Structured OPAT allows continuity of addiction care.(20)

Harm Reduction at Discharge: Closing the Loop

The discharge transition is the most vulnerable period. Without deliberate planning, patients often return to prior use patterns, with overdose risk heightened by reduced tolerance.

Essential Elements of Harm Reduction Discharge Planning

1. Naloxone Prescription and Education

Non-negotiable: Every patient with OUD should receive naloxone at discharge.

Prescribe: Naloxone nasal spray 4 mg (2-pack) or injectable kit
Educate patient and family: Recognition of overdose, administration technique, calling 911
Frame positively: "This is like an EpiPen for allergies—we hope you never need it, but it can save your life or someone else's"

Hack: Pre-printed naloxone prescriptions in discharge paperwork reduce omission. Many states have standing orders allowing pharmacy dispensing without individual prescriptions.

2. Medication-Assisted Treatment Linkage

Buprenorphine: Prescribe 7-14 day supply with outpatient follow-up <7 days
Methadone: Direct referral to opioid treatment program (OTP); cannot be prescribed for take-home use outside OTPs
Naltrexone: Consider extended-release injectable (Vivitrol) for patients declining agonist therapy, ensuring 7-10 days opioid-free before administration

Pearl: The "warm handoff"—direct communication between inpatient and outpatient addiction providers, ideally with patient present—doubles engagement rates compared to giving a phone number.(21)

3. Harm Reduction Resources

Provide tangible resources:

Syringe service program locations: Clean needles, naloxone, wound care, hepatitis/HIV testing
Fentanyl test strips: Allow testing drugs for fentanyl contamination
Safer use education: Never use alone, start with small test doses, avoid mixing substances
Crisis hotlines: SAMHSA National Helpline (1-800-662-4357), local mobile crisis teams

Hack: Create a standardized "harm reduction discharge kit" containing naloxone, fentanyl test strips, safer use information, and local resource list. Normalize provision for all SUD patients.

4. Address Social Determinants

Housing: Connect with transitional housing, recovery residences, or shelter services
Transportation: Arrange medical transport for initial outpatient appointments
Insurance/Benefits: Ensure Medicaid enrollment, application for disability if appropriate
Legal advocacy: Referrals for assistance with legal issues that may impede treatment engagement

Pearl: Unmet social needs are stronger predictors of relapse than substance use severity. A patient discharged to homelessness will struggle to prioritize MAT adherence over basic survival.(22)

5. Mental Health Integration

Over 50% of patients with SUD have co-occurring mental health disorders.(23) Address during hospitalization:

Initiate treatment for depression, anxiety, PTSD
Prescribe and educate on psychiatric medications
Coordinate integrated mental health and addiction follow-up

Oyster: Untreated depression/anxiety dramatically increases relapse risk. Don't assume "they need to be sober first"—treat concurrently.

Practical Pearls and Clinical Hacks: Summary

Reframe your mindset: Addiction is a chronic relapsing medical condition, not a moral failing. Treat it like diabetes—with protocols, compassion, and persistence.
COWS and CIWA are your friends: Objective scoring prevents under- and over-treatment.
Symptom-triggered beats scheduled: Uses less medication, shorter courses, better outcomes.
Buprenorphine during admission saves lives: 50-75% reduction in post-discharge mortality. This is the single highest-impact intervention.
Microdosing conquers fentanyl: Avoids precipitated withdrawal in complex inductions.
Surgical candidacy is about optimization, not exclusion: Partner with addiction medicine to build support structures.
Harm reduction is healthcare: Naloxone, test strips, and safer use education reduce deaths.
The warm handoff is essential: Direct provider-to-provider communication doubles outpatient engagement.
Don't forget pain management: Buprenorphine provides analgesia; full agonists can be added for severe acute pain.
Social determinants matter more than we think: Housing and food security predict outcomes better than drug use severity.

Conclusion

Managing hospitalized patients with substance use disorder requires a paradigm shift—from judgment and gatekeeping to evidence-based medical management and advocacy. By implementing standardized protocols for withdrawal management, seizing the opportunity to initiate MAT, navigating complex ethical situations like IDU-IE with equity and compassion, and providing robust harm reduction resources at discharge, we can transform outcomes for this vulnerable population.

The evidence is clear: these interventions work. Buprenorphine initiation, naloxone distribution, and warm handoffs reduce mortality and increase treatment engagement. Our role as internists is not to solve addiction in a single hospitalization—it's to stabilize, engage, and build bridges to ongoing care. Every admission is an opportunity. Let's not waste it.

References

Ronan MV, Herzig SJ. Hospitalizations related to opioid abuse/dependence and associated serious infections increased sharply, 2002–12. Health Aff. 2016;35(5):832-837.
Degenhardt L, et al. Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis. Addiction. 2011;106(1):32-51.
Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) national practice guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med. 2015;9(5):358-367.
Ducharme S, et al. Acute opioid withdrawal management. CMAJ. 2020;192(9):E230.
Gudin JA, et al. Risks, management, and monitoring of combination opioid, benzodiazepines, and/or alcohol use. Postgrad Med. 2013;125(4):115-130.
Jesse S, et al. Alcohol withdrawal syndrome: mechanisms, manifestations, and management. Acta Neurol Scand. 2017;135(1):4-16.
Mayo-Smith MF. Pharmacological management of alcohol withdrawal: a meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-151.
Schmidt KJ, et al. Treatment of severe alcohol withdrawal. Ann Pharmacother. 2016;50(5):389-401.
Larochelle MR, et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality. Ann Intern Med. 2018;169(3):137-145.
HHS removes federal barrier to treating opioid use disorder. January 2023. Available at: https://www.hhs.gov/about/news/2023/01/12/hhs-removes-federal-barrier-treating-opioid-use-disorder.html
Hämmig R, et al. Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence. J Subst Abuse Treat. 2014;47(4):275-281.
Azar P, et al. Low-dose buprenorphine for opioid use disorder: a pragmatic approach. Psychiatr Serv. 2021;72(10):1165-1171.
Alford DP, et al. Acute and chronic pain management for patients receiving buprenorphine. Ann Intern Med. 2006;144(2):127-134.
Schranz AJ, et al. Trends in drug use-associated infective endocarditis and heart valve surgery, 2007 to 2017. Ann Intern Med. 2019;170(1):31-40.
Iversen K, et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Engl J Med. 2019;380(5):415-424.
Shrestha NK, et al. Injection drug use and outcomes after surgical intervention for infective endocarditis. Ann Thorac Surg. 2015;100(3):875-882.
Shmueli H, et al. Outcomes of cardiac surgery in patients with drug addiction: a retrospective study. Isr Med Assoc J. 2019;21(3):185-189.
Rosenthal ES, et al. Addressing the ethical challenges of treating endocarditis in patients who inject drugs. Clin Infect Dis. 2020;71(5):1338-1342.
Ramirez JA, Peyrani P. Outpatient parenteral antimicrobial therapy in patients with injection drug use. Infect Dis Clin North Am. 2020;34(1):163-175.
Fanucchi L, et al. In-hospital illicit drug use and patient-centered discharge planning. Drug Alcohol Depend. 2016;159:143-147.
D'Onofrio G, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence. JAMA. 2015;313(16):1636-1644.
Binswanger IA, et al. Release from prison—a high risk of death for former inmates. N Engl J Med. 2007;356(2):157-165.
Quello SB, et al. Mood disorders and substance use disorder: a complex comorbidity. Sci Pract Perspect. 2005;3(1):13-21.