Withdrawal Syndromes

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The manifestations of alcohol withdrawal occur when a person decreases or stops a high level of alcohol intake, either after a binge lasting a matter of days or after the regular ingestion of alcohol sustained over many months. Although the exact mechanisms are not known, most symptoms appear related to overactivity of various portions of the nervous system resembling a "rebound" phenomenon after profound suppression, and its basis may relate to alterations in the function of GABA or NMDA receptor systems. The earliest findings of alcohol withdrawal typically occur within 6 to 8 hours of alcohol cessation. y Tremulousness is the earliest and most common complaint, and many alcoholics view their so-called shakes as an indication that it is time to resume drinking in order to avoid more severe complications of withdrawal. Tremor appears within hours of cessation of alcohol ingestion and gradually increases to a peak within 1 or 2 days. y The tremor is postural and appears to be irregular due to its variable but large amplitude. The amplitude may increase at the end points of an action, and the typical frequency varies from 6 to 11 Hz. y This movement abnormality mainly involves the hands yet can cause titubation. The tremor remits during relaxation and sleep but often persists for weeks after discontinuation of alcohol consumption. The pathophysiological mechanisms of the tremor are not known, but it probably represents an exaggerated physiological tremor^ The tremulousness is associated with hyperacuity of all sensory modalities, hyperreflexia, hypervigilance, anxiety, tachycardia, hypertension, and insomnia. The severity of these signs and symptoms vary with the intensity and duration of the previous alcohol exposure. In mild forms of withdrawal, the signs and symptoms usually resolve after 48 hours.

In severe reactions, patients may experience additional symptoms including auditory hallucinations, which usually take the form of identifiable voices saying critical or threatening things to the patient. When they occur, hallucinations generally appear within 24 hours of withdrawal. At first, patients tend to accept the voices as real and react accordingly, but as the intensity of the hallucinations wanes, they recognize their true origin. The hallucinosis may be accompanied by global confusion, and the autonomic hyperactivity continues and may become more pronounced.

Between 6 and 48 hours following alcohol discontinuation, seizures occur in approximately 3 to 4 percent of untreated patients. y , y Although the seizures are almost always multiple with short interictal intervals over a few hours, there may be only a single seizure. y The seizures are generalized tonic-clonic, and focal seizures should suggest the presence of a focal lesion in addition to the effects of the alcohol. Alcoholics may also develop seizure disorders as a result of acute head trauma, the presence of a subdural hematoma, or other causes seen in nonalcoholics. Alcohol withdrawal itself may also potentially aggravate any pre-existing seizure disorder unrelated to the alcohol abuse. Thirty to forty percent of patients with seizures progress to delirium tremens if they are left untreated. y , y One quarter of these individuals do so without an interceding lucid period. The remaining individuals have a period of improvement ranging between 12 hours and 5

Delirium tremens comprises a combination of psychic and autonomic hyperactivity, occurring usually after 3 to 5 days of alcohol abstinence but may be seen as late as 14 days. Only 5 to 6 percent of untreated patients withdrawing from alcohol develop this syndrome. y Patients with delirium tremens are agitated, hallucinating, and confused. The hallucinations are frequently of a visual nature, but other types occur. In addition, fever, tachycardia, diaphoresis, hypertension and confusion are typical. Seizures are uncommon during this phase of withdrawal. Once it is present, the delirium typically lasts for 3 days.

Often by the time patients reach the hospital, alcohol is no longer detectable in the blood. Therefore the diagnosis depends on the history and documentation of other clinical signs that are suggestive of chronic alcoholism (e.g., liver disease). Those patients with seizures or delirium tremens require laboratory screening for superimposed metabolic disorders which may contribute to the clinical picture. Additionally, individuals with clinically uncharacteristic seizures should undergo CT of the brain to rule out focal trauma, stroke, or hemorrhage. The electroencephalogram (EEG) may also be helpful in this setting because it may demonstrate focal slowing or epileptiform activity. Generally, the EEG shows a sequence of changes induced by alcohol beginning with a decrease in the frequency during chronic intoxication, followed by a return to normal with alcohol cessation. During the awake EEG, withdrawal seizures may be precipitated by photic stimulation.

Febrile, delirious patients should have close monitoring of their vital signs, preferably in an intensive care unit, while a search is conducted for possible sources of infection

that may cause or contribute to the clinical presentation. Volume repletion is often necessary due to excessive perspiration. Owing to possible nutritional deficiencies, 100 mg IV and 100 mg of intramuscular thiamine should be provided before the administration of glucose in order to prevent the acute precipitation of WKS. Intravenous fluids should also be supplemented by daily B-complex vitamins. Benzodiazepines are helpful in reducing anxiety and tremulousness, and may be useful in the prevention of seizure activity during withdrawal. y Chlordiazepoxide and diazepam are long-acting drugs with pharmacologically active metabolites and repeated daily dosages can result in accumulation of these agents. Oxazepam, in contrast, is rapidly converted to an inactive compound and does not accumulate and contribute to excessive CNS depression.

Beta blockers or clonidine can be used to treat the associated tachycardia and hypertension. y , y Because withdrawal seizures are typically self-limited, treatment is generally not required. Furthermore, the value of phenytoin in uncomplicated withdrawal seizures has not been demonstrated, and the long-term administration of anticonvulsants is usually ineffective in preventing recurrences. Some studies have reported better control of seizures in patients with a previous history of seizures when phenytoin is added to benzodiazepine administration. Evidence from other reports has conflicted with this finding. Status epilepticus is rare in alcohol withdrawal but should be treated in a manner similar to the one used when it is found in other clinical settings.

As a group, the alcohol withdrawal syndromes represent self-limited episodes that resolve with no residual effects. However, delirium tremens carries a measurable mortality rate (perhaps 10 to 20 percent) due to autonomic dysfunction. The obvious means of preventing these disorders is drinking alcohol only in moderation. For those who are abusing alcohol already, the only sure way to prevent withdrawal syndromes is to continue the alcohol, which is rarely practical in a hospital setting.

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