Qu L, Ma XP, Simayi A, Wang XL, Xu GP. Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: a systematic review and network meta-analysis. Int Clin Psychopharmacol. 2024 May 1;39(3):148-162. doi: 10.1097/YIC.0000000000000526. Epub 2023 Dec 27. PMID: 38170803.
Lee CM, Dillon DG, Tahir PM, Murphy CE 4th. Phenobarbital treatment of alcohol withdrawal in the emergency department: A systematic review and meta-analysis. Acad Emerg Med. 2024 May;31(5):515-524. doi: 10.1111/acem.14825. Epub 2024 Jan 8. PMID: 37923363; PMCID: PMC11065966.
The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020 May/Jun;14(3S Suppl 1):1-72. doi: 10.1097/ADM.0000000000000668. Erratum in: J Addict Med. 2020 Sep/Oct;14(5):e280. doi: 10.1097/ADM.0000000000000731. PMID: 32511109.
Holleck JL, Merchant N, Gunderson CG. Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials. J Gen Intern Med. 2019 Jun;34(6):1018-1024. doi: 10.1007/s11606-019-04899-7. Epub 2019 Apr 1. PMID: 30937668; PMCID: PMC6544709.
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DefinitionTop
Alcohol use disorder (AUD) is estimated to affect >400 million people aged ≥15 years, is directly responsible for >7% of all premature deaths, and is the third leading risk factor for death or disability globally. In 2015 in Canada, the number of hospitalizations directly related to alcohol-induced harm, including withdrawal, exceeded those due to myocardial infarction. Since AUD in North America and Europe has an estimated lifetime prevalence of 20% to 30%, a significant percentage of adults admitted to the hospital are at risk of acute alcohol withdrawal, routine screening for the risk of alcohol withdrawal is recommended.
Clinical Features and DiagnosisTop
Acute alcohol withdrawal is defined by a constellation of clinical signs and symptoms associated with abrupt discontinuation or reduction of alcohol use after a period of heavy drinking. These symptoms and signs include:
1) Tremors, sweating, tachycardia, headache, light sensitivity, nausea, anxiety, and fidgeting.
2) In the case of more severe alcohol withdrawal, seizures, hallucinations (visual, auditory, or tactile), and delirium.
As other conditions can cause similar manifestations, it is important to consider, among others, sepsis, other drug intoxication, other psychiatric diagnoses, and hyperthyroidism.
According to the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), which is based on 8 history questions, blood alcohol level, and evidence of autonomic activity (available at mdcalc.com), the odds of developing severe alcohol withdrawal syndrome (AWS) increase by >100 times if the score is ≥4.
TreatmentTop
The Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) is one of the best-known monitoring scales to diagnose AWS and to measure the severity of alcohol withdrawal (available at mdcalc.com; Table 1). Once its interrater reliability was optimized, the scale has become an essential tool for gauging the need for treatment and for deciding which treatment to use. We have found that a structured order set has been highly effective at improving the management of AWS. The set includes:
1) Screening for AUD by asking how much alcohol the patient consumes.
2) History (time and date) of the patient’s last drink.
3) Recommendations for blood and/or urine alcohol measurement.
4) CIWA-Ar monitoring as frequent as hourly.
5) Thiamine administration for all patients.
6) High-dose benzodiazepine therapy in patients with a CIWA-Ar score ≥9.
This approach can reduce the incidence of delirium tremens and seizures by ~5 and ~8 cases per 100 patients managed for withdrawal, respectively, in comparison with placebo or other drugs.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997 Jul 9;278(2):144-51. PMID: 9214531.
Mild, Uncomplicated AWS (CIWA-Ar <9)
Treatment is aimed at reducing symptoms of alcohol withdrawal, so that the patient can focus on detoxification and addressing their AUD.
1. Usually it is sufficient to place the patient in dimly lit, peaceful surroundings. Pharmacologic treatment is not necessary.
2. Correct water and electrolyte disturbances, if present (see Electrolyte, Fluid, and Acid-Base Balance Disorders).
3. Administer thiamine 100 mg IV (preferred route) or orally for 3 days. There are no high-quality data to dictate dosing and duration. This dose is appropriate to prevent Wernicke encephalopathy. Higher doses (up to 500 mg tid for 5 days) have been suggested for the treatment of Wernicke encephalopathy.
4. Provide psychologic support and frequent reorientation to the patient’s surroundings and circumstances.
5. As AWS resolves, patients should be referred for psychologic therapy, such as cognitive behavioral therapy or other, and offered pharmacologic management for their harmful drinking.
Moderate to Severe AWS (CIWA-Ar ≥9)
Although mortality from severe alcohol withdrawal is low, there is a risk of seizures, myocardial ischemia, aspiration, and delirium—morbid events that prolong hospitalization and have long-term health consequences. Aside from the components of the CIWA-Ar, the risk of AWS becoming severe may be increased by a history of delirium tremens, elevated gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST) levels, or low platelet counts.
1. Frequently monitor the patient’s clinical condition using the CIWA-Ar.
2. Correct water and electrolyte disturbances (see Electrolyte, Fluid, and Acid-Base Balance Disorders). Patients often present with considerable dehydration, hypokalemia, and hypomagnesemia. In the case of tachyarrhythmias, treatment with a beta-blocker may be indicated.
3. Administer thiamine 100 mg IV (preferred route) or orally. There are no high-quality data to dictate dosing and duration.
4. Use symptom-triggered replacement doses of a benzodiazepine (either diazepam 20 mg or lorazepam 4 mg orally) every hour up to 3 consecutive doses if the hourly CIWA-Ar score remains ≥9. After these 3 doses, the patient should be reassessed to make sure that the diagnosis of AWS is correct. Many patients with severe AWS will require >3 high doses of a benzodiazepine. The symptom-triggered approach with full alcohol-replacing doses has been shown to be superior to fixed-schedule doses, causing resolution of AWS faster and with lower total drug doses administered.
5. Treatments that are specifically not recommended include alcohol (difficult to titrate, more adverse effects, psychologically inappropriate for AUD), antipsychotics (lower seizure threshold, inferior outcomes), most nonbenzodiazepine anticonvulsants including phenobarbital (nonsuperior to benzodiazepines with no established dosing regimens), and beta-blockers or baclofen (no evidence that they prevent seizures). Combination therapies have not been adequately evaluated.
6. Brief interventions aimed to identify and counsel patients with a harmful drinking problem on the health effects of drinking have been shown to be effective. There is new evidence that when started during AWS, cognitive bias modification training, which attempts to disrupt patients’ automatic action tendency to approach alcohol-related cues, increases early abstinence rates.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to generalizability. Manning V, Garfield JBB, Staiger PK, et al. Effect of Cognitive Bias Modification on Early Relapse Among Adults Undergoing Inpatient Alcohol Withdrawal Treatment: A Randomized Clinical Trial. JAMA Psychiatry. 2021 Feb 1;78(2):133-140. doi: 10.1001/jamapsychiatry.2020.3446. PMID: 33146693; PMCID: PMC7643044.
7. Once AWS symptoms have resolved, patients should be referred for psychologic therapies to ameliorate harmful drinking and offered drugs like naltrexone or acamprosate. Do not prescribe ongoing benzodiazepines, as the risk of addiction is high.
TablesTop
Patient: Date: Time: Heart rate: Blood pressure: |
|
Nausea and vomiting (observation) |
0 None |
1 Mild nausea and no vomiting |
|
2 More severe symptoms |
|
3 More severe symptoms |
|
4 Intermittent nausea with dry heaves |
|
5 More severe symptoms |
|
6 More severe symptoms |
|
7 Constant nausea, frequent dry heaves and vomiting |
|
Tremor (observation; arms extended and fingers spread apart) |
0 No tremor |
1 Not visible but can be felt fingertip to fingertip |
|
2 More severe symptoms |
|
3 More severe symptoms |
|
4 Moderate, with patient’s arms extended |
|
5 More severe symptoms |
|
6 More severe symptoms |
|
7 Severe, even with arms not extended |
|
Paroxysmal sweats (observation) |
0 No sweat visible |
1 Barely perceptible sweating, palms moist |
|
2 More severe symptoms |
|
3 More severe symptoms |
|
4 Beads of sweat obvious on forehead |
|
5 More severe symptoms |
|
6 More severe symptoms |
|
7 Drenching sweats |
|
Anxiety (observation; ask the patient: “Do you feel nervous?”) |
0 No anxiety, at ease |
1 Mildly anxious |
|
2 More severe symptoms |
|
3 More severe symptoms |
|
4 Moderately anxious, or guarded, so anxiety is inferred |
|
5 More severe symptoms |
|
6 More severe symptoms |
|
7 Equivalent to acute panic states as seen in severe delirium or acute schizophrenic reactions |
|
Agitation (observation) |
0 Normal activity |
1 Somewhat more than normal activity |
|
2 More severe symptoms |
|
3 More severe symptoms |
|
4 Moderately fidgety and restless |
|
5 More severe symptoms |
|
6 More severe symptoms |
|
7 Paces back and forth during most of the interview or constantly thrashes about |
|
Tactile disturbances (observation; ask the patient: “Do you have any itching, pins and needles sensations, any burning, any numbness? Do you feel bugs crawling on or under your skin?”) |
0 None |
1 Very mild itching, pins and needles, burning, or numbness |
|
2 Mild itching, pins and needles, burning, or numbness |
|
3 Moderate itching, pins and needles, burning, or numbness |
|
4 Moderately severe hallucinations |
|
5 Severe hallucinations |
|
6 Extremely severe hallucinations |
|
7 Continuous hallucinations |
|
Auditory disturbances (observation; ask the patient: “Are you more aware of sounds around you? Are they harsh? Do they frighten you? Do you hear anything that is disturbing you? Can you hear things you know are not there?”) |
0 Not present |
1 Very mild harshness or ability to frighten |
|
2 Mild harshness or ability to frighten |
|
3 Moderate harshness or ability to frighten |
|
4 Moderately severe hallucinations |
|
5 Severe hallucinations |
|
6 Extremely severe hallucinations |
|
7 Continuous hallucinations |
|
Visual disturbances (observation; ask the patient: “Does the light appear to be too bright? Is its color different? Does it hurt your eyes? Can you see anything that is disturbing to you? Are you seeing things that you know are not there?) |
0 Not present |
1 Very mild sensitivity |
|
2 Mild sensitivity |
|
3 Moderate sensitivity |
|
4 Moderately severe hallucinations |
|
5 Severe hallucinations |
|
6 Extremely severe visual hallucinations |
|
7 Continuous hallucinations |
|
Headache, fullness in head (observation; ask the patient: “Does your head feel different? Does it feel like there is a band around your head?”; do not rate for dizziness or light-headedness; otherwise, rate severity) |
0 Not present |
1 Very mild |
|
2 Mild |
|
3 Moderate |
|
4 Moderately severe |
|
5 Severe |
|
6 Very severe |
|
7 Extremely severe |
|
Orientation and clouding of sensorium (observation; ask the patient: “What day is this? Where are you? Who am I?”) |
0 Oriented and can do serial additions |
1 Cannot do serial additions or is uncertain about date |
|
2 Disoriented for date by ≤2 calendar days |
|
3 Disoriented for date by >2 calendar days |
|
4 Disoriented for place and/or person |
|
The maximum possible score is 67 points. |
|
Total CIWA-Ar score: Rater’s initials: |
|
Source: Br J Addict. 1989;84(11):1353-7. |