Alcohol withdrawal syndrome

Learning objectives

Recognize signs and symptoms of alcohol withdrawal syndrome and delirium tremens
Manage and treat alcohol withdrawal syndrome and delirium tremens

Alcohol withdrawal syndrome (AWS) is a set of symptoms that occur following a reduction in alcohol use after a period of excessive use
Symptoms can be suppressed by alcohol intake and are more common in the postoperative period
AWS starts typically after 6-24 hours without alcohol and is most pronounced at 24-36 hours, however, can be delayed for up to 5 days
AWS results from neurological changes after long-term alcohol use:
- Ethanol binds to postsynaptic GABAA receptors, thereby enhancing their inhibitory effect
- The resulting chronic excitatory suppression leads to an increased brain synthesis of excitatory neurotransmitters such as norepinephrine, 5-hydroxytryptamine, and dopamine
- The brain is flooded with increased levels of excitatory neurotransmitters when the inhibitory effects of ethanol are withdrawn
Delirium tremens is a rapid onset of confusion due to alcohol withdrawal
Delirium tremens occurs in 5% of patients experiencing withdrawal
Mortality rate of delirium tremens is 10% (due to hypotension, dysrhythmias or seizures)

AWS	Delirium tremens
Tremors Nightmares Hallucinations Gastric upset Nausea Vomiting Hyperreflexia Anxiety Agitation Mild confusion Insomnia Autonomic nervous system hyperactivity (tachycardia, Hypertension, cardiac dysrhythmia)	Shaking Shivering Tachycardia Sweating Hallucinations Hyperthermia Nausea Vomiting Seizures Agitation Aggression Tachycardia Hypertension or Hypotension Grand mal seizures

CNS	Wernicke–Korsakoff syndrome Peripheral neuropathy Autonomic dysfunction
CVS	Cardiomyopathy Heart failure Hypertension Arrhythmias (e.g. AF, SVT, VT)
GI	Alcoholic liver disease Pancreatitis Gastritis Oesophageal and bowel carcinoma
Metabolic	Hyperlipidemia Obesity Hypoglycemia Hypokalemia Hypomagnesemia Hyperuricemia
Hematological	Macrocytosis Thrombocytopenia Leucopenia
Musculoskeletal	Myopathy Osteoporosis Osteomalacia

Prophylactic treatment before the onset of AWS symptoms

Benzodiazepines are the first-line treatment for AWS and delirium tremens

Class	Example	Duration of action	Route of administration	Dose
Benzodiazepines	Chlordiazepoxide	Long	p.o.	Prophylaxis: 5-25 mg Treatment: 50 -100 mg
	Lorazepam	Short	p.o./IV	Prophylaxis: 0.5-2 mg Treatment: 1-8 mg
Other agents	Diazepam	Long	p.o./IV	Prophylaxis: 2.5-10 mg Treatment: 10-40 mg
	Clomethiazole		p.o.	Prophylaxis: 9-12 capsules in 24h
	Haloperidol		p.o./IV/IM	Treatment: 0.5-20 mg
	Clonidine		IV	Treatment: 0.1-1 mg bolus/0.1-4 µg/kg/h

Be aware that the required doses for severe AWS can vary substantially within the first 24h
Clomethiazole is not advised in critically ill patients due to bronchial secretion and a elevated risk of pneumonia
Non-benzodiazepine agents should be used in conjunction with benzodiazepines
Beta-adrenergic blockers and centrally acting alpha-adrenergic agonists (clonidine, dexmedetomidine) achieve symptomatic control but they do not reduce the incidence of delirium or seizures
Haloperidol (for severe agitation or hallucinations) may increase the risk of seizures
Consider anticonvulsant agents such as carbamazepine, sodium valproate, and topiramate

General treatment

Correct metabolic (potassium, magnesium, and thiamine) and hemodynamic derangements
Correct fluid and blood product deficits
General supportive care (early nutrition)
Severe cases will need ICU admission & propofol infusion/dexmedetomidine & possible intubation
Offer psychosocial support: counseling and detoxification/rehab

As the severity of withdrawal symptoms can vary greatly, a scale such as the CIWA-Ar is useful for:

Monitoring the effectiveness of prophylactic treatment or fixed-schedule treatment regimens
Guiding administration in symptom-triggered treatment regimens