What is the Cows (Clinical Opiate Withdrawal Scale) protocol using buprenorphine (partial opioid agonist) cold start for managing opioid withdrawal in adults with opioid use disorder?

COWS Protocol Using Buprenorphine Cold Start for Opioid Withdrawal

Administer buprenorphine 4-8 mg sublingual only when the Clinical Opiate Withdrawal Scale (COWS) score is >8, after waiting at least 12 hours since last short-acting opioid use, with reassessment every 30-60 minutes and additional 2-4 mg doses at 2-hour intervals until withdrawal is controlled. 1

Critical Pre-Induction Requirements

Timing Since Last Opioid Use

• Short-acting opioids (heroin, oxycodone): Wait >12 hours since last use 1, 2
• Extended-release formulations: Wait >24 hours 1
• Methadone maintenance: Wait >72 hours 1
• Fentanyl: Minimum 12 hours, though higher risk of precipitated withdrawal exists 1

COWS Assessment

• Only administer buprenorphine when COWS score is >8 (moderate to severe withdrawal) 1, 2
• COWS scoring by ED nurses shows substantial agreement with physicians (82.5% concordance, weighted kappa 0.65), allowing nurses to expedite treatment 3
• Never give buprenorphine to patients not in active withdrawal—this will precipitate severe withdrawal due to buprenorphine's high binding affinity and partial agonist properties 1, 2

Standard Induction Protocol

Day 1 Dosing

• Initial dose: 4-8 mg sublingual based on withdrawal severity 1, 2
• Reassess after 30-60 minutes 1
• Additional doses: Give 2-4 mg at 2-hour intervals if withdrawal persists 1
• Target Day 1 total: 8-16 mg (most patients need 8 mg range) 1

Day 2 and Maintenance

• Day 2 dose: 16 mg total, which becomes the standard maintenance dose for most patients 1
• Maintenance range: 4-24 mg daily, with 16 mg being typical 1

Risk of Precipitated Withdrawal

The overall incidence of buprenorphine-precipitated withdrawal is low (0-13.2% across studies), and should not be a barrier to use 4. However, specific risk factors increase this risk:

High-Risk Populations

• Fentanyl users: 16.3% precipitated withdrawal rate among confirmed fentanyl users 5
• High urine fentanyl concentration (≥200 ng/mL): 8.37 times higher odds of precipitated withdrawal 5
• BMI ≥30: 5.12 times higher odds of precipitated withdrawal 5
• Methadone maintenance patients: Substantially higher risk, requiring 72-hour wait 1
• COWS 0-3: 13.5% precipitated withdrawal rate versus 3.2% for COWS 4-7 6

Definition and Recognition

• Precipitated withdrawal is defined as a 5-point or greater increase in COWS score within 4 hours of buprenorphine administration 4, 5
• Most cases occur within 1-4 hours of first dose 4, 7

Management of Precipitated Withdrawal

If precipitated withdrawal occurs:

Primary Treatment

• Give MORE buprenorphine (has pharmacological basis and proven effective in case reports) 7
• Continue with 2-4 mg doses every 2 hours as needed 1

Adjunctive Symptomatic Management

• Clonidine or lofexidine: For autonomic symptoms (sweating, tachycardia, hypertension, anxiety) 1, 8
• Antiemetics (promethazine): For nausea and vomiting 9, 1
• Benzodiazepines: For anxiety and muscle cramps 9, 1
• Loperamide: For diarrhea 9, 1

Discharge Planning

Prescribing (X-Waivered Providers)

• Prescribe buprenorphine/naloxone 16 mg sublingual daily for 3-7 days or until follow-up 1, 2
• Note: As of 2023, the X-waiver requirement has been eliminated, expanding prescribing access

Non-Waivered Providers

• Can administer (but not prescribe) buprenorphine for up to 72 hours while arranging referral 9, 1

Mandatory Harm Reduction

• Provide take-home naloxone kit and overdose prevention education—patients become more sensitive to opioid effects after withdrawal, dramatically increasing overdose risk if they resume use 2
• Offer hepatitis C and HIV screening 1, 2
• Consider reproductive health counseling 1

Comparative Effectiveness

Buprenorphine has 85% probability of being the most effective treatment, compared to 12.1% for methadone, 2.6% for lofexidine, and 0.01% for clonidine 2. For every 4 patients treated with buprenorphine versus alpha-2 agonists, 1 additional patient will complete treatment 8.

Critical Pitfalls to Avoid

• Never give buprenorphine before COWS >8—this is the most common cause of precipitated withdrawal 1, 2
• Never abbreviate waiting periods, especially for methadone (72 hours minimum) 1
• Never abandon patients who experience precipitated withdrawal—treat with more buprenorphine and supportive care 7
• Never discharge without naloxone—discontinuing buprenorphine increases relapse and overdose risk 2
• Abrupt discontinuation or rapid dose reduction constitutes unacceptable medical care except in extreme cases 1