Alcohol Withdrawal

Etiology

Ethanol is the primary alcohol ingested by chronic users. It is a central nervous system (CNS) depressant that the body becomes reliant on with extended exposure to ethanol.  It does this by inhibiting the excitatory portion (glutamate receptors) of the CNS and enhancing the inhibitory portions (GABA receptors) of the CNS. When the depressant is stopped, the central nervous system becomes overexcited as the inhibition is taken away. Thus, the body gets an excitatory overload, which results in the symptoms of withdrawal.[3]

Epidemiology

Alcohol use disorder (AUD) per the DSM-IV is common, especially in the emergency department, where about 40% of patients have AUD.[4] In patients coming into the ED with trauma and a Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score nearly 83% were of Male gender, and 43% were older than 55 years old. Of these patients with trauma, nearly 52% of those showing AWS symptoms had a CIWA-Ar score >20, 24% progressed to delirium tremens (DT).[5] Delirium tremens is fatal in nearly 15% of cases without treatment and 1% in those who do receive treatment. 

Pathophysiology

GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous center. GABA has particular binding sites available for ethanol, thus increasing the inhibition of the central nervous system when present. Chronic ethanol exposure to GABA creates constant inhibition or depressant effects on the brain. Ethanol also binds to glutamate, which is one of the excitatory amino acids in the central nervous system. When it binds to glutamate, it inhibits the excitation of the central nervous system, thus worsening the depression of the brain. 

History and Physical

Alcohol withdrawal can range from very mild symptoms to a severe form, which is named delirium tremens. The hallmark is autonomic dysfunction resulting from the excitation of the central nervous system. Mild signs/symptoms can arise within six hours of alcohol cessation. If symptoms do not progress to more severe symptoms within 24 to 48 hours, the patient will likely recover. However, the time to presentation and range of symptoms can vary greatly depending on the patient, their duration of alcohol dependence, and the volume typically ingested. Most cases should be described by their severity of symptoms, not the time since their last drink. Noting the time of their last drink is essential in any patient with an alcohol dependence history who may be presenting with other complaints. You can help prevent withdrawal by staying on top of this! Some features that may heighten your suspicion that a patient could suffer severe withdrawal include a history of prior delirium tremens as well as a history of low platelets (thrombocytopenia) or low potassium levels (hypokalemia).[6][7]

Mild symptoms can be elevated blood pressure, insomnia, tremulousness, hyperreflexia, anxiety, gastrointestinal upset, headache, palpitations.

Moderate symptoms include hallucinations and alcohol withdrawal seizures (rum fits) that can occur 12 to 24 hours after cessation of alcohol and are typically generalized in nature. There is a 3% incidence of status epilepticus in these patients. About 50% of patients who have had a withdrawal seizure will progress to delirium tremens.

Delirium tremens is the most severe form of alcohol withdrawal, and its hallmark is that of an altered sensorium with significant autonomic dysfunction and vital sign abnormalities. It includes visual hallucinations, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis. Symptoms of delirium tremens can last up to seven days after alcohol cessation and may last even longer.

These symptoms mimic those of withdrawal from long-term benzodiazepine or barbiturate use, so important historical features to note when a patient presents with autonomic dysfunction suspicious for a withdrawal syndrome should always include a medication list and social history. Also, consider these risk factors for any patient presenting with seizures of unknown etiology.

Evaluation

The diagnosis of alcohol withdrawal can be made by taking an excellent history and performing a thorough physical examination. It is a clinical diagnosis based on mild, moderate, or severe symptoms. Patients with suspicion for alcohol withdrawal should be evaluated for other underlying disease processes such as dehydration, infection, cardiac issues, electrolyte abnormalities, gastrointestinal bleeding, and traumatic injury. Laboratory studies (electrolytes, blood counts) may be drawn but will likely be nondiagnostic. Many chronic alcoholics will have baseline ketoacidosis due to their poor nutritional status, and labs may show acidemia with ketone production similar to a diabetic but with euglycemia or hypoglycemia due to lack of glycogen stores in their liver.[8][9][10]

Assessment

The Clinical Institute for Withdrawal Assessment for alcohol revised scale (CIWA-Ar) is a tool used to assess the severity of alcohol withdrawal symptoms. The tool allows clinicians to monitor for the signs and symptoms of withdrawal and determine who needs medical therapy. The features that are used for the CIWA-Ar scale include the presence of:

• Nausea and vomiting
• Headache
• Auditory disturbances
• Agitation
• Paroxysmal sweating
• Visual disturbances
• Tremor
• Clouding of sensorium
• Orientation
• Anxiety

Some literature recommends checking an alcohol level at the time of onset of symptoms as symptomatic patients while still having a positive alcohol level with symptoms of autonomic dysfunction/withdrawal will have a higher morbidity/mortality, and their short-term prognosis can be poor.

Patients with prolonged altered sensorium or significant renal abnormalities should receive an evaluation for the potential ingestion of another toxic alcohol. Patients who become financially strapped due to alcoholism could ingest other alcohols to become intoxicated. These can include isopropyl alcohol, commonly known as rubbing alcohol, which can lead to acidemia without ketosis as well as hemorrhagic gastritis. Ethylene glycol (antifreeze) ingestion can lead to an altered sensorium, seizures, and severe renal dysfunction with acidemia that may require the initiation of hemodialysis. Methanol is rarely ingested as an ethanol substitute but can result in multisystem organ failure, blindness, and seizures.

Other common household substances can also contain a significant amount of alcohol if ingested in large quantities, including mouthwash and cough syrup. Some of these items may also contain a high content of salicylates or acetaminophen, so consider checking aspirin and acetaminophen levels in patients presenting with alcohol withdrawal.

Treatment / Management

Patients should be kept calm in a controlled environment to try to reduce the risks of progression from mild symptoms to hallucinations. With mild to moderate symptoms, patients should receive supportive therapy in the form of intravenous rehydration, correction of electrolyte abnormalities, and have comorbid conditions as listed above ruled out. Due to the risk of a comorbid condition called Wernicke-Korsakoff syndrome, patients can also receive a “banana bag” or cocktail of folate, thiamine, dextrose containing fluids, and a multivitamin.[11][12][13](A1)

The hallmark of management for severe symptoms is the administration of long-acting benzodiazepines. The most commonly used benzodiazepines are intravenous diazepam or intravenous lorazepam for management. Patients with severe withdrawal symptoms may require escalating doses and intensive care level monitoring. Early consultation with a toxicologist is recommended to assist with aggressive management as these patients may require benzodiazepine doses at a level higher than the practitioner is comfortable with to manage their symptoms.

While patients with mild symptoms can be managed as outpatients, the following patients should be admitted:

• Absence of support systems
• Abnormal laboratory results
• High risk of Delirium tremens
• History of withdrawal seizures
• Concomitant psychiatric problems
• Abuse of other substances
• Suicidal ideations

Withdrawal seizures can typically be managed with benzodiazepines but may require adjunct therapy with phenytoin, barbiturates, and may even require intubation and sedation with propofol, ketamine, or in the most severe cases, dexmedetomidine.

Oral chlordiazepoxide and oxazepam are very commonly used for the prevention of withdrawal symptoms. Other drugs often used to manage symptoms include neuroleptics, anticonvulsants like carbamazepine, and valproic acid.

Propofol is used to manage refractory cases of delirium tremens, and baclofen can be used to treat muscle spasms.

Toxic alcohol co-ingestion should be managed with the assistance of a toxicologist.

Differential Diagnosis

• Thyrotoxicosis
• Stimulant drug abuse
• Status epilepticus
• CNS infection
• Withdrawal from sedative-hypnotics
• Essential tremors

Prognosis

The prognosis often depends on the severity of alcohol withdrawal syndrome. Clinical outcomes such as length of hospital length of stay, length of time in the ICU, and alcohol withdrawal syndrome complications often show significant differences based on alcohol withdrawal syndrome severity and are worse with more severe manifestations of alcohol withdrawal syndrome. Mortality is also greater in patients who progress to delirium tremens.

Complications

Complications that can accompany alcohol withdrawal syndrome include[14]:

• Delirium tremens
• Seizures
• Wernicke-Korsakoff syndrome
• Anxiety
• Depression
• Sleep disturbances
• Hallucinations
• Cardiovascular complications