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Alcohol withdrawal represents a major cause of morbidity in the alcoholic population and a substantial resource burden on certain medical centers and communities. Complicating management is that there is no diagnostic test for this clinical syndrome, and the diagnosis is established on the basis of the patient history and clinical findings. The impact on patient outcome and resource utilization can be enhanced through early recognition of risk factors and insight into the expected clinical course of these patients. This will allow for empiric initiation of therapy and targeted management. The underlying pathophysiology provides insight into the potential complications associated with alcohol withdrawal and the choice of therapy. It is important to seek alternative diagnoses and inciting factors for withdrawal, which may indeed be the same entity.

The medical problems associated with alcoholism and alcohol withdrawal were first described by Pliny the Elder in the 1st century B.C. In his work Naturalis Historia, the alcoholic and alcohol withdrawal were described as follows: "…drunkenness brings pallor and sagging cheeks, sore eyes, and trembling hands that spill a full cup, of which the immediate punishment is a haunted sleep and unrestful nights. …"80 Initial treatments as described by Osler were focused on supportive care, including confinement to bed, cold baths to reduce fever, and judicious use of potassium bromide, chloral hydrate, hyoscine, and possibly opium.79

Some of the initial large series of alcohol related complications in the early 20th century describe the alcohol withdrawal syndrome (AWS) as a major public health concern. At Bellevue Hospital in New York City, Jolliffe described 7000–10,000 admissions per year for alcohol-related problems from 1902–1935, with an estimated rate of 2.5–5 admissions per 1000 New York City residents.54 Moore et al.75 described similar numbers of admissions to Boston City Hospital, with up to 10% of alcoholics admitted with evidence of delirium tremens (DTs). The mortality at the beginning of their study among patients with DTs was 52% (1912), and DTs was the leading cause of death among admitted alcoholics. Over the ensuing 20 years, the mortality rate declined to approximately 10%–12%, a decrease believed to be secondary to improved supportive care and nursing.75

Though alcoholics were widely recognized to have a high incidence of delirium and psychomotor agitation, the etiology of these signs and symptoms was controversial and attributed to ethanol use, ethanol abstinence, or coexisting psychological disorders. Isbell and colleagues, in 1955, proved that abstinence from alcohol was the cause of this syndrome when they subjected nine male prisoners to chronic alcohol ingestion for a period of 6–12 weeks followed by 2 weeks of abstinence.52 While they were ingesting alcohol daily none of these prisoners developed signs and symptoms of DTs but during the abstinence phase six of the nine men developed tremor, elevations in blood pressure and heart rate, diaphoresis, and varying degrees of either auditory or visual hallucinations, consistent with the diagnosis of DTs.52 In ...

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