Alcohol withdrawal syndrome

Alcohol withdrawal syndrome encompasses the clinical manifestations that occur due to the reduction or abrupt cessation of alcohol consumption in a chronic alcoholic. This condition is common and is considered a relative medical emergency.

Epidemiological and Pathophysiological Elements

Unlike smoking, which includes any tobacco consumption, there is no consensus on the definition of chronic alcoholism. Some definitions are based on daily consumption, others on weekly consumption levels, physical or psychological dependence, or the presence of harmful physical or psychosocial consequences.

As a result, there is also no consensus on the prevalence of chronic alcoholism. In any case, it is common, with a prevalence of 10 to 30% in the general population in Europe and the USA, depending on the definitions used. It is higher among hospitalized patients (30 to 40%), as chronic alcohol use is a major factor in morbidity and mortality.

The symptoms of alcohol withdrawal result from alcohol being a depressant of the central nervous system, with a positive action on inhibitory pathways (modulation of GABA activity) and a negative action on excitatory pathways (modulation of glutamate activity).

About 20% of alcohol withdrawal cases present with "severe" symptoms. There is a genetic predisposition. Risk factors for severe symptoms include:

• The extent of chronic alcohol consumption
• The amount of alcohol consumed in the 48 hours preceding withdrawal
• A history of seizures or delirium tremens during a previous withdrawal
• Age over 30 years
• Presence of intercurrent illnesses (++ infections)

The mortality rate for untreated delirium tremens is 30 to 40%. With appropriate treatment, it drops to 5%.

Clinical Presentation

Clinical manifestations appear within 6 to 96 hours after the last consumption and vary in severity:

• "Mild" manifestations:
  • Fine tremors of the extremities, irritability, sleep disturbances, anxiety, headaches
  • Loss of appetite, nausea, vomiting
  • Hypertension, tachycardia, palpitations, excessive sweating
• "Moderate to severe" manifestations (present in 20% of withdrawal syndromes):
  • Visual, tactile, or auditory hallucinations
  • Repeated seizures (often between 12 to 24 hours from the onset of withdrawal)
  • Cardiac arrhythmias
  • Delirium tremens: the "ultimate stage"
    • Generally appears between the 2nd and 4th days of withdrawal
    • "Confuso-onirique": confusion, severe psychomotor agitation, tachypnea, insomnia, hallucinations, tremors, dysarthria, balance and coordination disorders, mydriasis, fever, tachycardia, sweating, dehydration
    • Can progress to altered consciousness up to an alcoholic coma
    • Often preceded and accompanied by seizures

In the case of seizures, altered consciousness, or a history of falls, always rule out another cause or complication of withdrawal (e.g., post-fall intracranial hemorrhage).

Diagnostic Criteria

In practice, the diagnosis of alcohol withdrawal syndrome is based on a combination of clinical and anamnestic evidence. However, the DSM-V sets the following criteria:

1. Cessation or reduction of "heavy and prolonged" alcohol consumption
2. At least two of the following criteria:
   • Autonomic hyperactivity
   • Increased hand tremor
   • Insomnia
   • Nausea or vomiting
   • Transient auditory, visual, or tactile hallucinations
   • Psychomotor agitation
   • Anxiety
   • Generalized tonic-clonic seizures
3. The symptoms cause significant dysfunction (psychological distress, social consequences, etc.)
4. The symptoms are not attributable to another cause

Differential Diagnosis and Complications

The differential diagnoses are numerous and should be considered based on the clinical presentation: causes of confusion, tremors, seizures, etc. Special attention should be given to Wernicke's syndrome (classic triad: confusion, balance disorders, oculomotor disorders) and metabolic disorders, particularly in chronic alcoholics. In practice, however, appropriate vitamin prophylaxis (the only treatment and prevention for Wernicke's syndrome) should be systematically initiated in any alcohol withdrawal syndrome.

Potential complications are also numerous. The most common are post-traumatic intracranial hemorrhages (falls due to confusion, balance disorders, or seizures), cardiac arrhythmias, aspiration pneumonia, and iatrogenic complications (nosocomial infections, Wernicke's syndrome triggered by the administration of glucose or mixed infusions without associated vitamin supplementation, etc.).

Additional Examinations

The diagnosis is purely clinical and requires no specific tests. However, to rule out differential diagnoses and/or complications, the following are systematically performed:

• Biology
• Electrocardiogram (ECG)

Non-systematic but frequently performed tests include:

• CT scan of the brain — systematic in case of a fall or lack of information on the circumstances of onset
• Electroencephalogram (EEG)
• Arterial blood gas
• Chest X-ray

Other tests (lumbar puncture, additional biological tests, etc.) are only justified on a case-by-case basis.

Treatment and Management

Outpatient management after medical evaluation can be chosen in the absence of severe clinical criteria and if the patient is adequately supported socially:

• Vitamin B1-B6 supplementation (Befact 1 to 3 tablets/day), maintain adequate vitamin supplementation at a distance
• Diazepam (Valium) 10 mg 4 to 6 times/day, maximum 60 mg/day on an outpatient basis
• Daily clinical monitoring for at least 3 days

The occurrence of seizures, cardiac arrhythmias, altered consciousness, hallucinations, fever, balance disorders, or unusual signs requires evaluation and hospital management. In the absence of severity signs but in cases of patient social isolation, hospitalization should also be considered. Management in the vegetative withdrawal or pre-delirium tremens phase:

• Diazepam (Valium) 10 mg 4 to 6 times/day (maximum 120 mg/day), preferably oral
• Vitamin B1 (200 - 500 mg/day IV for the first 5 days, followed by Befact PO for at least 3 months) - B6 - PP + Omeprazole 20 mg/day
• Usual prevention of stress ulcers and thromboembolism: Omeprazole 20 mg/day and Clexane 40 mg/day SC
• Hyperhydration up to 3 to 6 liters/day, preferably with NaCl (0.9%) or mixed
• Symptomatic management according to clinical presentation (oxygen therapy, intubation, mechanical ventilation, IV benzodiazepines and anticonvulsants, antiarrhythmics, haloperidol, antibiotics, etc.)

It should be noted that medications such as antiarrhythmics or antiepileptics should generally be discontinued once withdrawal is complete. In particular, the recurrence of withdrawal or intoxication-related seizures in the absence of epileptic disease or epileptogenic lesions should be managed with benzodiazepine coverage rather than antiepileptics (in practice, however, it is often difficult to determine the best approach, as alcoholic patients often have post-traumatic brain lesions that may be potentially epileptogenic).

Bibliography

EMC, Traité de médecine AKOS, Elsevier, 2018

Hoffman, Management of moderate and severe alcohol withdrawal syndromes, Uptodate, 2022

Holt SR, Ambulatory management of alcohol withdrawal, Uptodate, 2022

Pace C, Alcohol withdrawal: Epidemiology, clinical manifestations, course, assessment, and diagnosis, Uptodate, 2022