Delirium tremens

Delirium tremens (DTs) is a severe manifestation of alcohol withdrawal. Pearson first described it in 1813 as an acute psychosis following abstinence from alcohol. Although it only occurs in a relatively small number of patients who undergo alcohol withdrawal, it can be fatal. DTs is a medical emergency that requires prompt recognition and treatment.

Pathophysiology
Chronic intake of alcohol affects several of the neurotransmitter systems in the brain. These effects include increased release of endogenous opiates; activation of the gamma-aminobutyric acid-A (GABA-A) receptor and a decrease in GABA-A receptor function, with resultant influx of chloride ions; inhibition of the N -methyl-D-aspartate (NMDA) type of glutamate receptor, which mediates the postsynaptic excitatory effects of glutamate, with up-regulation of this receptor; and interactions with serotonin and dopamine receptors. During withdrawal from alcohol, the loss of GABA-A receptor stimulation causes a reduction in chloride flux and is associated with tremors, diaphoresis, tachycardia, anxiety, and seizures. In addition, the lack of inhibition of the NMDA receptors may lead to seizures and delirium. Excessive nervous system excitability during periods of abstinence from alcohol is related to the effect of alcohol on the number and function of brain receptors.

Frequency
United States

Fewer than 50% of alcohol-dependent persons develop any significant withdrawal symptoms that require pharmacological treatment upon cessation of alcohol intake. DTs, the most severe manifestation of withdrawal, occurs in 5% of patients with alcohol withdrawal.
Mortality/Morbidity

Despite appropriate treatment, the current mortality for patients with DTs ranges from 5-15%. Mortality was as high as 35% prior to the era of intensive care and advanced pharmacotherapy. The most common conditions leading to death in these patients are respiratory failure and cardiac arrhythmias.

Sex
According to surveys among the US population, men have a higher prevalence of alcohol dependence than women. Research on gender differences among persons with alcohol dependence have found that women are more likely to deny that they have an alcohol problem and frequently minimize problems related to excessive alcohol use. Whether or not gender differences exist in the rates of development of severe alcohol withdrawal are not clear.

Age
According to surveys, young adult males have the highest prevalence of alcohol dependence and unsafe alcohol use. Unsafe alcohol use is also common among the elderly. According to the US 2000 National Health Interview Survey, the prevalence of heavy drinking is 10% in men over 65 years of age, but only 2% among women in this age group. Among older adults presenting to emergency departments, the prevalence of alcohol abuse and dependence is 10-15%.

Clinical
History
Alcohol withdrawal syndrome is the clinical syndrome that occurs when people who are physically dependent upon alcohol stop drinking or reduce their alcohol consumption. Alcohol withdrawal syndrome is divided into 4 categories.
Minor withdrawal (withdrawal tremulousness) occurs within 6-24 hours following the last drink and is characterized by tremor, anxiety, nausea, vomiting, and insomnia.
Major withdrawal (hallucinations) occurs 10-72 hours after the last drink. The signs and symptoms include visual and auditory hallucinations, whole body tremor, vomiting, diaphoresis, and hypertension.
Withdrawal seizures (rum fits) occur within 6-48 hours of alcohol cessation and are characterized by major motor seizures that occur during withdrawal in patients who normally have no seizures and have normal EEGs. These seizures are typically generalized and brief. In the absence of treatment, multiple seizures occur in 60% of patients, but the duration between first and last seizure is usually less than 6 hours. Only 3% of patients go on to develop status epilepticus. An alcohol withdrawal seizure is frequently the first sign of alcohol withdrawal, and no other signs of withdrawal may be present after the seizure abates. About 30-40% of patients with alcohol withdrawal seizures progress to DTs.
DTs is the most severe manifestation of alcohol withdrawal. It occurs 3-10 days following the last drink. Clinical manifestations include agitation, global confusion, disorientation, hallucinations, fever, and autonomic hyperactivity (tachycardia and hypertension).

The most objective and best validated tool to assess the severity of alcohol withdrawal is the Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar).1 This survey consists of 10 items and can be administered rapidly at the bedside.

The 10 items include nausea and vomiting, anxiety, tremor, sweating, auditory disturbances, visual disturbances, tactile disturbances, headache, agitation, and clouding of sensorium. Zero to 7 points are assigned for each item except for the last item, which is assigned 0-4 points, with a total possible score of 67.

This scale has been demonstrated to have high reliability, reproducibility, and validity based on comparisons with ratings by experienced clinicians and has been shown to be usable in detoxication units, psychiatry units, and hospital medical/surgical wards.

The CIWA-Ar scale is intended only for patients who have been drinking recently. It relies on patients’ ability to respond to questions about their symptoms. Patients must be able to communicate and have a clear enough sensorium to reply logically because many of the items require coherent answers. The CIWA-Ar scale has not been validated in complex medical patients, postsurgical patients and critically ill patients.

A score of greater than 15 is seen in patients with moderate-to-severe alcohol withdrawal. Patients with a score greater than 15 or those who have a history of alcohol withdrawal seizures should be treated with medication upon presentation. These patients need to be monitored carefully for the development of DTs. Patients with a score of 8-15, who have mild alcohol withdrawal, should probably also receive drug treatment. Careful and frequent monitoring with the CIWA-Ar is particularly helpful in patients receiving treatment with symptom-triggered drug therapy.

Routine screening for unhealthy alcohol use in patients admitted to the hospital can detect patients who are at risk for developing alcohol withdrawal. The AmericanCollege of Surgeons Committee on Trauma mandates routine screening for unhealthy alcohol use for level one and two trauma centers. *Such screening tools include AUDIT, CAGE, and AUDIT-C.

Physical
No specific findings on physical examination are diagnostic for DTs. However, DTs often presents with a coexisting illness, so a careful physical examination should be performed in order to uncover any potentially serious illness that may be present.
Physical examination findings in a patient with DTs may include fever, hypertension, tachycardia, diaphoresis, tremor, agitation, positional nystagmus, global confusion, and disorientation.

Causes
Risk factors for developing DTs include coexisting acute illness, long duration of alcohol intake, large volume of alcohol intake, severe withdrawal symptoms at presentation, prior DTs, prior seizures, prior detoxification, and intense craving for alcohol.

The signs of alcohol withdrawal in critically ill patients, especially if accompanied by delirium, may mimic those of other serious disorders, including sepsis, stroke, intracranial hemorrhage, meningitis, drug toxicity, hepatic encephalopathy, hypoxia, hypoglycemia, and other metabolic disorders. These disorders may need to be excluded before a firm diagnosis of alcohol withdrawal is made