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Time of appearance after cessation Symptoms 6–12 hours Minor withdrawal symptoms: insomnia, tremulousness, mild anxiety, gastrointestinal upset, headache, diaphoresis, palpitations, anorexia 12–24 hoursa Alcoholic hallucinosis: visual, auditory, or tactile hallucinations 24–48 hoursb Withdrawal seizures: generalized tonic-clonic seizures 48–72 hoursc Alcohol withdrawal delirium (delirium tremens): hallucinations (mainly visual), disorientation, tachycardia, hypertension, low-grade fever, agitation, diaphoresis ↵a Symptoms generally resolve within 48 hours.
↵b Symptoms reported as early as 2 hours after cessation.
↵c Symptoms as late as 5 days.
From Bayard M, McIntyre J, Hill KR, Woodside J, Jr. Alcohol withdrawal syndrome. Am Fam Physician 2004; 69:1443–1450. Reproduced with permission from the American Academy of Family Physicians.
Symptom Observation Points Nausea and vomitinga
(Ask “Do you feel sick to your stomach? Have you vomited?”)No nausea and vomiting 0 Intermittent nausea with dry heaves 4 Constant nausea, frequent dry heaves, vomiting 7 Tremora
(Observe with arms extended and apart.)No tremor 0 No tremor visible, but can be felt, fingertip to fingertip 1 Moderate tremor with arms extended 4 Severe tremor, even with arms not extended 7 Paroxysmal sweatsa No sweat visible 0 Beads of sweat obvious on forehead 4 Drenching sweats 7 Anxietya
(“Do you feel nervous?”)No anxiety (at ease) 0 Mildly anxious 1 Moderately anxious or guarded, so anxiety is inferred 4 Equivalent to acute panic states that occur in severe delirium or acute schizophrenic reactions 7 Agitationa Normal activity 0 Somewhat more than normal activity 1 Moderately fidgety and restless 4 Paces back and forth during most of interview or constantly thrashes about 7 Tactile disturbances
(“Do you have any itching, pins-and-needles sensations, burning, or numbness, or do you feel like bugs are crawling on or under your skin?”)None 0 Very mild itching, pins-and-needles sensation, burning, or numbness 1 Mild itching, pins-and-needles sensation, burning, or numbness 2 Moderate itching, pins-and-needles sensation, burning, or numbness 3 Moderately severe hallucinations 4 Severe hallucinations 5 Extremely severe hallucinations 6 Continuous hallucinations 7 Auditory disturbances
(“Are you more aware of sounds around you? Are they harsh? Do they frighten you? Are you hearing anything that is disturbing to you? Are you hearing things you know are not there?”)Not present 0 Very mild harshness or ability to frighten 1 Mild harshness or ability to frighten 2 Moderate harshness or ability to frighten 3 Moderately severe hallucinations 4 Severe hallucinations 5 Extremely severe hallucinations 6 Continuous hallucinations 7 Visual disturbances
(“Does the light appear to be too bright? Is its color different? Does it hurt your eyes? Are you seeing anything that is disturbing to you? Are you seeing things you know are not there?”)Not present 0 Very mild sensitivity 1 Mild sensitivity 2 Moderate sensitivity 3 Moderately severe hallucinations 4 Severe hallucinations 5 Extremely severe hallucinations 6 Continuous hallucinations 7 Headache, fullness in head
(“Does your head feel different? Do you feel like there is a band around your head?”)
Do not rate for dizziness or lightheaded-ness. Otherwise, rate severity.Not present 0 Very mild 1 Mild 2 Moderate 3 Moderately severe 4 Severe 5 Very severe 6 Extremely severe 7 Orientation and clouding of sensorium
(“What day is this? Where are you? Who am I?”)Oriented and can do serial additions 0 Cannot do serial additions or is uncertain about date 1 Date disorientation by no more than 2 calendar days 2 Date disorientation by more than 2 calendar days 3 Disoriented to place or person, or both 4 Total CIWA-Ar score Maximum possible: 67 ↵a If symptoms lie between the point categories listed, it is acceptable to rate as a whole number in between. CIWA-Ar = revised Clinical Institute Withdrawal Assessment for Alcohol15
Based on Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for alcohol scale (CIWA-Ar). Br J Addict 1989; 84:1353–1357.
Chlordiazepoxide Diazepam Lorazepam Oxazepam Dosage forms Oral Oral, gel, intramuscular, intravenous Oral, intramuscular, intravenous Oral Equivalent dosages 25 mg 5 mg 1 mg 15 mg Half-life 5–15 hours with active metabolites > 100 hours 30–60 hours with active metabolites >100 hours 10–20 hours 5–20 hours Active metabolites Desmethylchlordiazepoxide, desmoxepam, desmethyldiazepam Desmethyldiazepam None None Lipid solubility Less lipophilic than diazepam; slower onset of action Highly lipophilic; quick onset of action Less lipophilic than diazepam; slower onset of action Less lipophilic than diazepam; slower onset of action Effect of hepatic disease Half-life increases in patients with cirrhosis Half-life increases in patients with cirrhosis, acute viral hepatitis, chronic active hepatitis Half-life increases in patients with cirrhosis Half-life increases in patients with cirrhosis Effect of renal disease No effect Decreases protein binding Half-life increases; impaired elimination No effect Effect of older age Slower absorption; half-life increases Half-life increases; decreased protein binding No effect on half-life; decreased protein binding No effect on half-life; decreased protein binding Bird RD, Makela EH. Alcohol withdrawal: what is the benzodiazepine of choice? Ann Pharmacother 1994; 28:67–71. Copyright 1994, Annals of Pharmacotherapy; Reproduced and adapted with permission from SAGE Publications, Inc.
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Trials comparing inpatient symptom-triggered vs fixed-dosing benzodiazepine therapy in alcohol withdrawal syndrome
Saitz et al16 Jaeger et al17 Daeppen et al18 Weaver et al19 Reoux and Miller20 No. of patients 101 216 117 183 40 Type of program Alcohol withdrawal inpatient treatment program Retrospective, adult medicine patients Alcohol withdrawal inpatient treatment program Prospective, adult medicine patients Addiction unit vs medical and psychiatric services Duration and monitoring 4 days; CIWA-Ar scores every 8 hours and 1 hour after medication dose Up to 7 days; CIWA-Ar scores every 1–2 hours 3 days; CIWA-Ar scores every 30 minutes CIWA-Ar every 4 hours 2 to 8 days; CIWA-Ar scores every 8 hours Symptom-triggered protocol If CIWA-Ar ≥ 8, chlordiazepoxide 20–100 mg every hour If CIWA-Ar > 10, chlordiazepoxide 50–100 mg with repeated doses Placebo every 6 hours
If CIWA-Ar 8–15, oxazepam 15 mg
If CIWA-Ar > 15, oxazepam 30 mgIf CIWA-Ar 6–9, lorazepam 0.5 mg intravenously or orally;
If 10–19, 2 mg
If 20–29, 3 mg
if 30–39, 4 mgIf CIWA-Ar ≥ 10, oxazepam 30 mg or chlordiaz-epoxide 50 mg every hour until < 10 Fixed schedule Chlordiazepoxide 50 mg every 6 hours for 4 doses, then 25 mg every 6 hours for 8 doses Usual care: tapering, fixed-dose regimen, or sporadic dosing by medical staff Oxazepam 30 mg every 6 hours Lorazepam 2 mg every 4 hours for 48 hours, then 1 mg every 4 hours for 24 hours, then 0.5 mg every 4 hours for 24 hours As ordered by attending physician Total dosea 100 vs 425 mg
(P < .001)Benzodiazepine equivalents
20.1 vs 20.1 mg37.5 vs 231.4 mg
(P < .001)Lower with symptom-triggered protocol Benzodiazepine equivalents 82.7 vs 367.5 mg
(P < .01)Duration of therapy (hours)a 9 vs 68
(P < .001)44.9 vs 55.5 20 vs 62.7
(P < .001)— 10.7 vs 20.7
(P < .01)CIWA-Ar score differencesa Not significant Not reported P < .01 P < .01 Not reported Outcomesa Delirium tremens (DTs) 2% vs 6%
Readmission in 30 days 6% vs 8%DTs
6.9% vs 20.5%
(P < .04)No DTs
One seizure in symptom-triggered groupNo DTs or seizures in either group
Median length of stay 3 days in both groupsNo DTs, seizures, or adverse drug events in either group
Oversedation and hypotension in one patient in usual-care group↵a Symptom-triggered group vs fixed-schedule group.
CIWA-Ar = revised Clinical Institute Withdrawal Assessment for Alcohol scale (Table 1)
CIWA-Ar score Chlordiazepoxide dose (oral)a Lorazepam dose (oral or intravenous)a Reassess CIWA-Ar and vital signs, and redose 0–7 No medication necessary No medication necessary Every 2 hours 8–10 25–50 mg 1–2 mg Every 2 hours 11–15 50–75 mg 2–3 mg Every 1–2 hours 16–19 75–100 mg 3–4 mg Every 1–2 hours 20 or greater Evaluation for patient transfer to intensive care unit CIWA-Ar < 8 for three consecutive checks Reassess or redose to every 4 hours. If score remains < 8 every 4 hours on three checks, reassess or redose every 8 hours. If CIWA-Ar score is < 8 for 48 hours, discontinue monitoring. ↵a Patients with liver failure and elderly patients should be started on lower doses. CIWA-Ar = revised Clinical Institute Withdrawal Assessment for Alcohol scale (Table 1)
Based on references 15, 16, and 19.
