Alcohol withdrawal syndrome can occur when heavy drinkers reduce or stop alcohol consumption. It is caused by changes in brain neurotransmitter systems due to chronic alcohol use and abrupt cessation. Symptoms range from mild anxiety and insomnia to severe autonomic arousal and life-threatening seizures. It is diagnosed using scales like CIWA-AR which assess autonomic signs and symptoms. Benzodiazepines are the standard treatment.

1. ALCOHOL WITHDRAWAL
SYNDROME
ADE WIJAYA, MD – FEBRUARY 2019

2. INTRODUCTION
• ALCOHOL USE DISORDER (AUD) WAS ESTIMATED TO AFFECT APPROXIMATELY
18% OF THE GENERAL POPULATION LIFETIME AND 5% ANNUALLY
• UP TO 50% OF AUD PATIENTS EXPERIENCE WITHDRAWAL SYMPTOMS
• A MINORITY REQUIRES MEDICAL TREATMENT
Whiteman PJ, Hoffman RS, Goldfrank LR. Alcoholism in the emergency department: an epidemiologic study. Acad Emerg Med. 2000;7:14–20.
Saitz R. Clinical practice. Unhealthy alcohol use. N Engl J Med. 2005;352:596–607.
Hall W, Zador D. The alcohol withdrawal syndrome. Lancet. 1997;349:1897–1900.

3. PATHOPHYSIOLOGY
• ACUTE ALCOHOL INGESTION PRODUCES CNS DEPRESSION SECONDARY TO AN
ENHANCED GABAERGIC NEUROTRANSMISSION AND TO A REDUCED
GLUTAMATERGIC ACTIVITY.
• THE STIMULATION OF GABAA RECEPTORS AND THE INHIBITION OF N-METHYL-
D-ASPARTATE (NMDA) RECEPTORS REPRESENTS THE MOST KNOWN
MECHANISMS
• CHRONIC CNS EXPOSURE TO ALCOHOL PRODUCES ADAPTIVE CHANGES IN
SEVERAL NEUROTRANSMITTER SYSTEMS  TOLERANCE
• GABA RECEPTORS DOWN REGULATION & NMDA RECEPTORS UP REGULATION
Mirijello A, D’Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F, Leggio L, Gasbarrini A, Addolorato G. Identification and management of alcohol withdrawal syndrome. Drugs. 2015 Mar 1;75(4):353-65.

4. PATHOPHYSIOLOGY
• UP-REGULATION OF GLUTAMATE RECEPTORS Α-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-
4-PROPIONIC ACID (AMPA) AND KAINATE HAS BEEN DESCRIBED DURING AWS
• THE ABRUPT REDUCTION OR CESSATION OF ALCOHOL INTAKE PRODUCES AN ACUTE
UNBALANCE DUE BOTH TO THE ACUTE REDUCTION OF GABA ACTIVITY AND THE INCREASE OF
GLUTAMATERGIC ACTION, WITH CONSEQUENT HYPER EXCITABILITY AND DEVELOPMENT OF
AWS SYMPTOMS WHICH MAY START AS EARLY AS A FEW HOURS AFTER THE LAST ALCOHOL
INTAKE
• THE UP-REGULATION OF DOPAMINERGIC AND NORADRENERGIC PATHWAYS COULD BE
RESPONSIBLE FOR THE DEVELOPMENT, RESPECTIVELY, OF HALLUCINATIONS AND OF
AUTONOMIC HYPERACTIVITY DURING AWS
• “KINDLING” IS REPRESENTED BY AN INCREASED NEURONAL EXCITABILITY AND SENSITIVITY
AFTER REPEATED EPISODES OF AWS. “KINDLING” HAS BEEN PROPOSED TO EXPLAIN THE RISK OF
PROGRESSION OF SOME PATIENTS FROM MILDER TO MORE SEVERE FORMS OF AWS.
Mirijello A, D’Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F, Leggio L, Gasbarrini A, Addolorato G. Identification and management of alcohol withdrawal syndrome. Drugs. 2015 Mar 1;75(4):353-65.

5. SYMPTOMS
Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28:401–410.
Bayard M, McIntyre J, Hill KR, et al. Alcohol withdrawal syndrome. Am Fam Physician.2004;69:1443–1450.

6. RISK FACTORS FOR
SEVERE ALCOHOL WITHDRAWAL SYNDROME
Maldonado JR, Sher Y, Ashouri JF, et al. The “Prediction of Alcohol Withdrawal Severity Scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48:375–390.
Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28:401–410

7. DIAGNOSIS
DSM-5 REQUIRES THE OBSERVATION OF AT LEAST TWO OF THE FOLLOWING SYMPTOMS:
• AUTONOMIC HYPERACTIVITY (SWEATING OR TACHYCARDIA)
• INCREASED HAND TREMOR
• INSOMNIA
• NAUSEA OR VOMITING
• TRANSIENT VISUAL, TACTILE OR AUDITORY HALLUCINATIONS OR ILLUSIONS
• PSYCHOMOTOR AGITATION
• ANXIETY
• TONIC–CLONIC SEIZURES

8. DIAGNOSIS
• < 8 : MILD WITHDRAWAL
• 8–15 : MODERATE WITHDRAWAL
(MARKED AUTONOMIC AROUSAL)
• >15 : SEVERE WITHDRAWAL;
PREDICTIVE OF THE DEVELOPMENT
OF SEIZURES AND DELIRIUM
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;84:1353–7.

9. DIAGNOSIS
• < 6: MILD AWS
• 6-9: MODERATE AWS
• > 9: SEVERE AWS
Wetterling T, Kanitz RD, Besters B, et al. A new rating scale for the assessment of the alcohol-withdrawal syndrome (AWS
scale). Alcohol Alcohol. 1997;32:753–60

10. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med.2003;348:1786–1795.

12. SUMMARY
• LIFE THREATENING
• AUTONOMIC HYPERACTIVITY
• CIWA-AR OR ALCOHOL WITHDRAWAL SCALE
• TREATMENT: BENZODIAZEPINES