In the past, approximately 15 percent of cases of delirium tremens ended fatally, but the figure now is closer to 5 percent. In many of the fatal cases there is an associated infectious illness or injury, but in others, no complicating illness is discernible. Many of the patients die in a state of hyperthermia; in some, death comes so suddenly that the nature of the terminal events cannot be determined. Reports of series of cases with a negligible mortality rate in delirium tremens can usually be traced to a failure to distinguish between delirium tremens and the minor forms of the withdrawal syndrome, which are far more common and practically never fatal.
We make note here of our experience with delirium following the withdrawal of barbiturates (Romero et al), which is almost identical to the DTs, including the abrupt cessation of symptoms, as discussed in the section on “Barbiturate Abstinence, or Withdrawal, Syndrome” further on.
There are also alcohol withdrawal states, closely related to delirium tremens and about as frequent, in which one facet of the delirium tremens complex assumes prominence, to the virtual exclusion of the other symptoms. The patient may simply exhibit a transient state of quiet confusion, agitation, or peculiar behavior lasting several days or weeks. Or there may be a vivid hallucinatory–delusional state and abnormal behavior consistent with the patient’s false beliefs. Unlike typical delirium tremens, the atypical states usually present as a single circumscribed episode without recurrences, are only rarely preceded by seizures, and do not end fatally.
Pathologic examination is singularly unrevealing in patients with delirium tremens. Cerebral edema been absent in the authors’ pathologic material except when shock or hypoxia had occurred terminally. There have been no significant microscopic changes in the brain, which is what one might expect in a disease that is essentially reversible. The EEG findings have been discussed in relation to withdrawal seizures.
Pathogenesis of the Tremulous-Hallucinatory-Delirious Disorders
Prior to 1950, it was the common belief that these symptoms represented the most severe forms of alcohol intoxication—an idea that fails to satisfy the simplest clinical logic. The symptoms of toxicity—consisting of slurred speech, uninhibited behavior, staggering gait, stupor, and coma—are in themselves distinctive and, in a sense, the opposite of the symptom complex of tremor, fits, and delirium. It is evident, from observations in both humans and experimental animals, that the most important and the one obligate factor in the genesis of delirium tremens and related disorders is the withdrawal of alcohol following a period of sustained chronic intoxication. Furthermore, the emergence of withdrawal symptoms depends on a rapid decline in the blood alcohol level from a previously higher level and not necessarily upon the complete disappearance of alcohol from the blood.
The mechanisms by which the withdrawal of alcohol produces symptoms are incompletely understood. In all but the mildest cases, the early phase of alcohol withdrawal is attended by a drop in serum magnesium concentration and a rise in arterial pH—the latter on the basis of respiratory alkalosis (Wolfe and Victor). Possibly the compounded effect of these two factors, both of which are associated with hyperexcitability of the nervous system, is responsible in part for seizures and for other symptoms that characterize the early phase of withdrawal. However, these factors alone are not explanatory. The molecular mechanisms that are thought to be operative in the genesis of alcohol tolerance and withdrawal have been mentioned earlier. The GABA-ergic system has been most strongly implicated, in part because the receptors for this inhibitory transmitter are downregulated by chronic alcohol use, but the situation is not nearly so simple, insofar as the excitatory glutaminergic system is also inhibited by alcohol.