Current approaches to the diagnosis of delirium are based upon the recognition of symptoms that emerge in the pathological state. As an alternative, we propose an approach to case identification for research purposes based on the recognition of significant changes in the cognitive or cerebral state of the individual patient. Categorical change can be defined using prediction intervals calculated from repeated measures on a population of medically stable subjects. Data from subjects enrolled in a prospective study of delirium in a long-term care population were utilized to calculate prediction intervals for the Mini-Mental Status Examination and for measures of the electroencephalographic background frequency as obtained with a two-channel microprocessor-based EEG device. Preliminary findings support the validity of this quantitative approach for defining changes in brain state. Future research should evaluate both cognitive and electrophysiological techniques for monitoring vulnerable patients.

Characteristics of instruments developed by nurses for use in evaluating delirium/acute confusional states include relative emphasis on observable behavior and the need to impose low respondent burden. Two instruments that have been most used by nurse researchers are described: The Confusion Rating Scale and the NEECHAM Confusion Scale. The former is based on observable behavior; the latter incorporates vital function and oxygen saturation measurements that may serve as early warning sings of impending delirium.

The papers devoted to the subject of delirium in this issue make significant contributions toward the more precise and reliable diagnosis of the syndrome for the purposes of scientific investigation and clinical practice.

Data to demonstrate that psychosocial factors, sensory deprivation, or sleep deprivation alone can cause delirium are few. Nonetheless, these factors or conditions may contribute to the development or symptom presentation of a delirium when other metabolic or toxic etiologies are present. There is likewise little research on the appropriate treatment of the delirious patient. Clinical experience suggests that attention to the patient's psychological state through frequent orientation, emotional support, and frequent explanation can help. Low-dose neuroleptic drugs are occasionally useful and necessary.

Postoperative delirium is a common syndrome that is often mistaken for other psychiatric conditions, particularly depression. Numerous investigators have found a clear convincing association between delirium and increased morbidity and mortality. For this reason, greater attention should be focused on accurate clinical diagnosis. In this article, pre- and postoperative risk factors are reviewed. Lastly, areas demanding immediate further investigation are identified. In particular, outcome studies with particular emphasis on the role of age and prior drug exposure are urgently needed.

Delirium is the second most common psychiatric diagnosis among hospitalized elderly cancer patients. A variety of factors are known to cause delirium in cancer patients, and the most frequently observed are outlined. History, presence of an altered mental state with identification of the cognitive impairment, and a close watch of mental function will help to differentiate delirium from a normal stress reaction, an adjustment disorder to cancer diagnosis, or early dementia. As in other medically ill patients, antipsychotic drugs are the cornerstone of treatment for delirium not manageable with enviromental manipulation or causal therapy. Haloperidol is the most commonly prescribed drug for delirium in the cancer setting because of its low cardiovascular and anticholinergic effects. Cancer patients who are debilitated require a much lower starting dose than do the physically healthy.

Evaluation of the change in performance on the Blessed Memory Information Concentration Test over a one-year period was used as a probe for the prevalence of reversible cognitive disorders among patients living in a residential care facility. Of 157 patients with cognitive impairment at the initial assessment, 10 (6.4%) improved by 6 points or more, 19 (12.1%) improved by 5 points or more, and 15 (9.6%) had a reduction in the number of errors by 33% or more. Thus, using improvement over time as an indicator, we estimate that 6% to 12% of the elderly patients in our sample had a reversible component to their cognitive impairment at the initial assessment. Retrospective review of medical records identified (one or more) possible causes for impairment at baseline in each of the ten patients who showed the greatest improvement: adverse drug effects in seven patients, depression in two, and metabolic encephalopathies in three.

The etymology of delirium is highly expressive: it comes from the Latin de, meaning down or away from, and lira, a furrow or track in the fields; that is, to be off the track. The precise features of the syndrome have been specified in DSM-111-R (American Psychiatric Association, 1987) and in the Draft ICD-10 Diagnostic Criteria for Research (World Health Organization, 1990).

Delirium is often considered a global and nonspecific alteration in cerebral function. However, the recent clinical evidence for heterogeneity within the syndrome of delirium suggests that different systems of the brain may be important in different kinds of delirium. Some forms of delirium, such as anticholinergic toxicity and hepatic encephalopathy, may be caused by drugs or toxins acting on specific brain neurochemical systems. The neurophysiological bases of the control of normal arousal and attention are still relatively poorly understood. However, the recent appreciation of the existence of neurotransmitter-specific projections from the hypothalamus and brain stem directly to the cerebral cortex has spurred new research. Some of these projections may be important in particular kinds of delirium; for instance, evidence from a number of different lines of research implicates GABA systems in the brain as being important in the delirium of hepatic encephalopathy. Cholinergic neurons in the basal forebrain and pons innervate the cerebral cortex. Both of these neurons, but particularly the pontine group, may be important in the delirium of anticholinergic toxicity. Thus, more research on the physiology of these systems in normal sleep and arousal, as well as in pathophysiological states, is indicated. Little is known about changes in these systems with aging. The well-known degeneration in cholinergic systems in Alzheimer's disease, and the sensitivity of individuals with Alzheimer's disease to anticholinergic toxicity, suggest a role of central cholinergic systems in anticholinergic delirium in demented patients. Further research into the involvement of the other systems in aging and delirium apparently would be fruitful.

A wide variety of conditions lead to delirium (i.e., metabolic encephalopathies) in human beings and animals. Despite the varied etiology the clinical consequences are relatively stereotyped which suggests that the diverse insults that cause delirium may act by common metabolic and cellular “final pathways.” Related molecular and cellular mechanisms may be involved in aging and Alzheimer's disease, conditions that predispose to the development of delirium. Animal models of delirium better reflect age-related disorders such as Alzheimer's disease than those that impair a single neurotransmitter system such as the cholinergic system; the metabolic encephalopathies produce global cognitive disturbance, which is more typical of these disorders. Thus, research related to delirium has far-reaching implications for normal and abnormal brain function.

Encompassing the range from subtle cognitive impairments to frank delirium, toxicity due to benzodiazepines and to anticholinergic-containing compounds is reviewed. For benzodiazepines, an extensive literature suggests that they impair immediate and delayed memory, psychomotor performance, and subjective complaints of station. This, in several studies, results in increased patient morbidity (e.g., increasing risk of hip fractures). Anticholinergic compounds are widely utilized in managing elderly patients, particularly nursing home residents. Toxicity from anticholinergic compounds, detected by anticholinergic drug levels, is significantly correlated with the presence and severity of delirium in a number of settings including postoperative patients and elderly nursing home residents. Possible means of identifying the syndrome by prediction of dose and type of medication, as well as by quantitative EEG, are reviewed.

I have been asked to comment upon some of the themes raised by the three papers in this section, on etiologic models and their phenomenological variants. I will discuss them briefly and will also comment on some additional findings of interest.