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Complications of Alcohol Withdrawal
Pathophysiological Insights
Louis A. Trevisan, M.D., Nashaat Boutros, M.D., Ismene L. Petrakis, M.D., and John H. Krystal, M.D.
Disease processes or events that accompany acute alcohol withdrawal (AW) can cause significant illness and death. Some patients experience seizures, which may increase in severity with subsequent AW episodes. Another potential AWcomplication is delirium tremens, characterized by hallucinations, mental confusion, and disorientation. Cognitive impairment and delirium may lead to a chronic memory disorder (i.e., Wernicke-Korsakoff syndrome). Psychiatric problems associated with withdrawal include anxiety, depression, and sleep disturbance. In addition, alterations in physiology, mood, and behavior may persist after acutewithdrawal has subsided, motivating relapse to heavy drinking. Recent advances in neurobiology may support the development of improved medications to decrease the risk of AW complications and support long-term sobriety. KEY WORDS: AOD withdrawal syndrome; disease severity; disease complication; AODR (alcohol and other drug related) seizure; delirium tremens; Wernicke Korsakoff psychosis; anxiety state;emotional and psychiatric depression; sleep disorder; mood and affect disturbance; heart disorder; acute AODE (alcohol and other drug effects); AODD (alcohol and other drug dependence) relapse; GABA receptors; glutamate receptors; sex hormones; drug therapy; AOD abstinence; literature review

brupt reduction or total cessation of long-term alcohol consumption produces a well-defined cluster ofsymptoms called acute alcohol withdrawal (AW). Although some patients experience relatively mild withdrawal symptoms, disease processes or events that accompany AW can cause significant illness and death. After acute withdrawal has subsided, a poorly defined syndrome of protracted withdrawal may ensue. The persistent alterations in physiology, mood, and behavior
Vol. 22, No. 1, 1998

Aassociated with protracted withdrawal may motivate the patient to relapse to heavy drinking. This article describes the acute withdrawal syndrome and its complications, including seizures, delirium tremens, Wernicke-Korsakoff syndrome, neuropsychiatric disturbances, and cardiovascular complications as well as the protracted withdrawal syndrome. Recent findings are discussed regarding thealcohol-induced alterations of nervous system function that underlie these

syndromes and their implications for the treatment of withdrawal.

LOUIS A. TREVISAN, M.D., is an assistant clinical professor, NASHAAT BOUTROS, M.D., is an associate professor, ISMENE L. PETRAKIS, M.D., is an assistant professor, and JOHN H. KRYSTAL, M.D., is an associate professor in psychiatry at the Department of Psychiatry,Yale University, New Haven, Connecticut.

Acute Alcohol Withdrawal Syndrome
Alcohol withdrawal is a distinctive clinical syndrome with potentially serious consequences (see table) (American Psychiatric Association 1994). Symptoms begin as early as 6 hours after the initial decline from peak intoxication. Initial symptoms include tremor, anxiety, insomnia, restlessness, and nausea.Particularly in mildly alcohol-dependent persons, these symptoms may comprise the entire syndrome and may subside without treatment after a few days. More serious withdrawal symptoms occur in approximately 10 percent of patients. These symptoms include a low-grade fever, rapid breathing, tremor, and profuse sweating. The time course of withdrawal is outlined in the figure on p. 63. Seizures may occur in morethan 5 percent of untreated patients in acute alcohol withdrawal. Another severe complication is delirium tremens (DT’s), which is characterized by hallucinations, mental confusion, and disorientation. The mortality rate among patients exhibiting DT’s is 5 to 25 percent.

alcohol detoxifications and the development of alcohol withdrawal complications, including seizures, has been ascribed to...
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