What is the Clinical Institute Withdrawal Assessment (CIWA) protocol and what medications, such as benzodiazepines (e.g. diazepam, lorazepam, chlordiazepoxide), are used to manage withdrawal symptoms?

CIWA Protocol and Medications for Alcohol Withdrawal

The CIWA (Clinical Institute Withdrawal Assessment for Alcohol) protocol is a scoring tool used to assess severity of alcohol withdrawal syndrome and guide symptom-triggered benzodiazepine dosing, with long-acting benzodiazepines (chlordiazepoxide, diazepam) preferred for most patients and lorazepam reserved for those with liver failure, elderly patients, or severe comorbidities. 1

Understanding the CIWA Protocol

The CIWA is a severity assessment tool, not a diagnostic instrument. The protocol helps evaluate withdrawal severity, guide treatment planning, and facilitate communication between providers, but should not be used alone to diagnose alcohol withdrawal syndrome since high scores can occur in other conditions like anxiolytic withdrawal, anxiety disorders, sepsis, hepatic encephalopathy, and severe pain. 1

CIWA Scoring Thresholds

• CIWA-Ar score >8 indicates moderate alcohol withdrawal syndrome requiring pharmacological treatment 1
• CIWA-Ar score ≥15 indicates severe alcohol withdrawal syndrome requiring aggressive pharmacological intervention 1
• Symptom-triggered dosing based on CIWA scores is preferred over fixed-schedule dosing to prevent drug accumulation, though this approach may have higher protocol errors on general medical wards 1, 2

Benzodiazepine Selection and Dosing

First-Line: Long-Acting Benzodiazepines

Long-acting benzodiazepines (chlordiazepoxide and diazepam) are the gold standard first-line agents because they provide superior protection against seizures and delirium tremens through their prolonged duration of action and self-tapering pharmacokinetics. 1

Chlordiazepoxide Dosing

• 25-100 mg orally every 4-6 hours 1
• FDA-approved specifically for alcohol withdrawal symptoms 3
• Requires gradual tapering after extended therapy to avoid severe withdrawal symptoms including convulsions, tremor, abdominal and muscle cramps, vomiting, and sweating 3

Diazepam Dosing

• 5-10 mg orally, intravenously, or intramuscularly every 6-8 hours 1
• Has the shortest time to peak effect among benzodiazepines, facilitating rapid symptom control and accurate titration 4
• The active metabolite desmethyldiazepam has the longest elimination half-life, providing gradual self-tapering and smoother withdrawal with lower incidence of breakthrough symptoms 4

Second-Line: Intermediate-Acting Benzodiazepines

Lorazepam is specifically recommended for patients with hepatic dysfunction, advanced age, recent head trauma, respiratory failure, obesity, or other serious medical comorbidities. 1

Lorazepam Dosing

• Initial dose: 6-12 mg/day divided into 1-4 mg doses every 4-8 hours (oral, IV, or IM) 1
• Taper gradually following resolution of withdrawal symptoms 1
• Safer in hepatic dysfunction because it undergoes direct glucuronidation without active metabolites 1, 5
• Should be used with caution in severe hepatic insufficiency as it may worsen hepatic encephalopathy; lower doses may be sufficient 5
• Comparable efficacy to chlordiazepoxide in reducing withdrawal symptoms 6

Essential Adjunctive Therapy

Thiamine Supplementation

All patients with alcohol withdrawal syndrome must receive thiamine 100-300 mg/day to prevent Wernicke encephalopathy, maintained for 2-3 months after withdrawal symptom resolution. 1

• For prevention of Wernicke encephalopathy: 100-300 mg/day for 4-12 weeks 1
• For management of established Wernicke encephalopathy: 100-500 mg/day for 12-24 weeks 1
• Critical pitfall: Thiamine must be given BEFORE administering IV fluids containing glucose, as glucose administration can precipitate acute thiamine deficiency 1

Supportive Care Requirements

General management includes fluids, electrolyte replacement (especially magnesium), vitamins, and a comfortable environment. 1

• Frequent monitoring of vital signs is necessary to detect autonomic hyperactivity including high fever, tachycardia, hypertension, and sweating 1
• Carefully evaluate for comorbidities including dehydration, electrolyte imbalance, renal failure, head trauma, infection, gastrointestinal bleeding, pancreatitis, and liver failure 1

Indications for Inpatient Treatment

Admission and inpatient treatment is mandatory for serious complications including: 1

• Delirium tremens (symptoms typically worst at 3-5 days after alcohol cessation) 1
• Withdrawal seizures
• Significant alcohol withdrawal syndrome with high CIWA scores
• History of withdrawal seizures or delirium tremens
• Serious medical or psychiatric comorbidities
• Failure of outpatient treatment 1

Alternative and Adjunctive Medications

Carbamazepine

• 200 mg orally every 6-8 hours 1
• Alternative to benzodiazepines that is effective in seizure prevention 1

Haloperidol

• 0.5-5 mg orally every 8-12 hours, or 2-5 mg intramuscularly 1
• Use carefully as adjunctive therapy ONLY for agitation or psychotic symptoms (hallucinations) not controlled by benzodiazepines 1

Clomethiazole

• Used in Europe for alcohol withdrawal syndrome treatment 1
• Both benzodiazepines and clomethiazole carry abuse potential; avoid use beyond 10-14 days 1

Critical Clinical Pitfalls

Psychiatric consultation is strongly recommended (A1 recommendation) for evaluation, acute management, and long-term abstinence planning. 1

The fear of over-sedation with diazepam compared to other benzodiazepines is unfounded and based on misunderstanding of pharmacokinetics; diazepam can be safely used even in liver disease and elderly patients when using symptom-based dosing. 4

Avoid intramuscular diazepam due to its lipophilicity causing slow absorption; use lorazepam or midazolam instead when IM administration is the only option. 4

Dosage adjustments are required when benzodiazepines are combined with other medications: 5

• Reduce lorazepam dose by approximately 50% when coadministered with valproate 5
• Reduce lorazepam dose by approximately 50% when coadministered with probenecid 5
• Limit dosage and duration when combining benzodiazepines with opioids due to increased respiratory depression risk 5