CIWA Protocol: Fraser Health Rajwant Minhas Pharmacy Resident

Overview Introduction: Alcohol Withdrawal Timeline (pictures, graph) Overview of CIWA Protocol Scoring Drugs we use Why? Why not Phenytoin How much? How long? Why are labs ordered and how to interpret them? Patient Case: typical patient and course of treatment DRPs that could come up Handout DART resolution

Alcohol Withdrawal

Diagnostic Criteria A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged. B. Two (or more) of the following, developing within several hours to a few days after criterion A: 1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 beats per minute) 2. Increased hand tremor 3. Insomnia 4. Nausea or vomiting 5. Transient visual, tactile, or auditory hallucination s or illusions 6. Psychomotor agitation 7. Anxiety 8. Grand mal seizures C. The symptoms in criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

Acute Alcohol Withdrawal Clinical features follow the cessation of regular high-dose alcohol ingestion as soon as blood alcohol level decreases significantly Within 6-24 hours after stopping drinking, tremors, nausea and vomiting, anxiety, mild agitation, tachycardia, hypertension, insomnia and diaphoresis may occur. Symptoms usually peak b/w 24-36 hours and may dissipate after 48 hours.

Hallucinations occur in 3%–10% of patients and are usually visual; their onset and duration are variable but typically begin after several days of abstinence. Convulsions, which are usually 1 or 2 grand mal seizures, occur in 5%–15% of patients during acute alcohol withdrawal and typically occur within 6 to 48 hours after alcohol cessation

Alcohol consumption is more strongly associated with seizures than is alcohol withdrawal. Delirium tremens (disorientation and global confusion) occur in < 5% of patients, usually 3-5 days after withdrawal, and last for 2-3 days. The overall rate of death from delirium tremens is estimated at 2%–10%, with death usually due to cardiovascular, metabolic or infectious complications.

Basic laboratory investigations include a complete blood count, liver function tests, a urine drug screen, and determination of blood alcohol and electrolyte levels.

Routine care Abnormalities in fluid levels, electrolyte levels, or nutrition should be corrected. Intravenous fluids may be necessary in patients with severe withdrawal because of excessive fluid loss through hyperthermia, sweating, and vomiting. Intravenous fluids should not be administered routinely in patients with less severe withdrawal, because these patients may become overhydrated. Routine administration of magnesium sulfate has not been shown to improve withdrawal symptoms,9 but supplementation is appropriate if a patient is hypomagnesemic. Multivitamins and thiamine (100 mg per day) should be provided during treatment for alcohol withdrawal. If intravenous fluids are administered, thiamine (100 mg intravenously) should be given before glucose is administered, to prevent precipitation of Wernicke’s encephalopathy.

Clinical Institute Withdrawal Assessment 10 item scale Likert-type scale (0–7 in most cases) Maximum possible total score = 67 Mild withdrawal: <15 or less Moderate withdrawal:16 and 20 Severe withdrawal: >20 To quantify the severity of alcohol withdrawal syndrome, and to monitor and medicate patients going through withdrawal Symptom triggered regimen for medication administration Symptom triggered: less medication, shorter duration of therapy

Alcohol enhances the effect of GABA on GABA-A neuroreceptors, resulting in decreased overall brain excitability. Chronic exposure to alcohol results in a compensatory decrease of GABA-A neuroreceptor response to GABA, evidenced by increasing tolerance of the effects of alcohol. Medications used are cross-tolerant with alcohol

Alcohol inhibits NMDA neuroreceptors, and chronic alcohol exposure results in up-regulation of these receptors. Abrupt cessation of alcohol exposure results in brain hyperexcitability, because receptors previously inhibited by alcohol are no longer inhibited. Brain hyperexcitability manifests clinically as anxiety, irritability, agitation, and tremors. Severe manifestations include alcohol withdrawal seizures and delirium tremens.

Thiamine Thiamine deficiency reported in 30-80% of patients with alcohol dependance To prevent Wernicke’s encephalopathy This vitamin should be administered before intravenous glucose because it is a cofactor necessary for glucose metabolism. Severe and irreversible cerebellar and brain-stem damage has been reported when glucose was administered to patients suffering acute alcohol withdrawal who were not given concomitant thiamine therapy. The value of multivitamin or other B vitamin prophylactic therapy for patients in alcohol withdrawal remains unproven.

Mild withdrawal: supportive care

Benzodiazepines Keystone therapy for alcohol withdrawal Sedating and anticonvulsant effects Shown to be safe and effective for seizure prevention and treatment Preferred agent

Diazepam (Valium) and chlordiazepoxide (Librium) are long-acting agents that have been shown to be excellent in treating alcohol withdrawal symptoms. Because of the long half-life of these medications, withdrawal is smoother, and rebound withdrawal symptoms are less likely to occur. Lorazepam (Ativan) and oxazepam (Serax) are intermediate-acting medications with excellent records of efficacy. Treatment with these agents may be preferable in patients who metabolize medications less effectively, particularly the elderly and those with liver failure. Lorazepam is the only benzodiazepine with predictable intramuscular absorption (if intramuscular administration is necessary).

One randomized controlled trial (RCT)19 affirmed previous findings that carbamazepine is an effective alternative to benzodiazepines in the treatment of alcohol withdrawal syndrome in patients with mild to moderate symptoms. Patients in the study received 800 mg of carbamazepine on the first day, with the dosage tapered to 200 mg by the fifth day. Carbamazepine (Tegretol) also appears to decrease the craving for alcohol after withdrawal. It is not sedating and has little potential for abuse. Although carbamazepine is used extensively in Europe, its use in the United States has been limited by lack of sufficient evidence that it prevents seizures and delirium.

Findings of Meta-Analysis All of the benzodiazepines studied appear to have similar efficacy. Start treatment with benzodiazepines early, as indicated by the CIWA-Ar score, rather than waiting for withdrawal to advance. Use adequate doses High doses are required to counteract the tolerance that most people with alcohol dependence have to benzodiazepines. Higher doses given early, along with close monitoring using the CIWA-Ar scale, are considered safe and may avoid the late sedation that occurs with ongoing administration of lower doses.

Phenytoin has not been demonstrated to be superior to placebo in the prevention of simple withdrawal-induced seizures but may be required for multiple recurrent seizures or focal seizures or in patients with a history of epilepsy or head trauma.

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References Holbrook AM et al. Diagnosis and management of acute alcohol withdrawal. CMAJ 1999;160:675-80. Bayard et al. Alcohol Withdrawal Syndrome. Am Fam Physician. 2004 Mar 15;69(6):1443-1450.