Clinical Vignette

A 62-year-old college professor was admitted to the hospital for elective hip replacement. Surgery was uncomplicated, but on the second postoperative day he was anxious, diaphoretic, and had a low-grade fever. A broad-spectrum antibiotic regimen was begun. That night, he began to hallucinate, insisting that strangers had come into his room. He hardly slept. The next morning he had a generalized convulsive seizure. A neurologic consultant noted agitation, disorientation, impaired recall, visual hallucinations, tremor, and tachycardia. The patient described his alcohol intake as “two per day,” but his wife described his two drinks as tumblers of scotch and estimated his intake at a pint of whiskey daily. He had no history of liver disease, gastrointestinal bleeds, blackouts, withdrawal symptoms, solitary drinking, or occupational impairment.

He was treated with high-dose benzodiazepines, intravenous thiamine, intravenous fluids, and electrolyte replacement. His autonomic signs rapidly stabilized and no further seizures occurred. However he remained confused and agitated during the ensuing 2 weeks. Although he was carefully counseled about his alcohol abuse, and its inherent risks, he rejected the diagnosis of alcoholism, and refused follow-up treatment subsequent to his discharge.

Comment: This is a typical example of the understated abuser of alcoholic beverages. “Two a day” is a classic patient euphemism used to subconsciously or deliberately cover up their daily habit. The physician must always explore the precise meaning of such a statement vis-à-vis the actual amount of wine, beer, or spirits consumed. As in this instance, an observant and often concerned spouse is more frequently able to objectively report the actual degree of alcoholic consumption. A forewarned physician is much better able to critically observe the patient’s in-hospital demeanor. At the slightest hint of cerebral and autonomic decompensation, so classic for early delirium tremens, appropriate therapies can be expeditiously initiated and a potentially fatal outcome prevented.

Delirium is a common, acquired neuropsychiatric disorder frequently encountered in clinical practice. Marked by cognitive and behavioral symptoms and a fluctuating course, delirium presents doctors and families with a host of challenges, from initial diagnosis and management, to ethical dilemmas surrounding informed consent, personal autonomy, and patient safety (Fig. 17.1). There is a lack of consensus regarding the definition and terminology pertaining to delirium. Terms such as “acute confusional state,” “encephalopathy,” and “change in mental status” are often used arbitrarily. As delirium often presents within the context of myriad medical and/or surgical conditions, it is often not appreciated to be a clinically independent entity. Nevertheless, delirium is associated with considerable morbidity and mortality, delaying or interfering with proper care as well as promoting great distress for nursing staff, physicians, and families.

Figure 17-1 Delirium.

Definition

There are no universally accepted criteria for a diagnosis of delirium. The most often cited criteria are found in the DSM IV and include the following core features:

Some clinicians reserve the term “delirium” to confusional states associated with agitated behavior, hallucinations, and delusions. The term “confusional state” might be applied preferentially to describe cases where cognitive disturbance predominates over psychiatric features. Although this distinction is academically enticing, it has no proven clinical utility. For the purposes of this text, the term delirium encompasses all variations of acute change in mental status.

Epidemiology

Nearly 30% of all patients aged 65 years or older will experience some degree of delirium during hospitalization. The risk varies from 10% to >50% depending on comorbidities, severity of illness, and hospital setting. For example, as much as 70% of intensive care patients experience delirium. Delirium prolongs hospitalization, rehabilitation, and promotes functional decline and risk of institutionalization. Mortality associated with delirium is high according to pooled data from several studies.

The prevalence of delirium in the nonacute setting is quite elusive. The Canadian Study of Health and Aging estimates a prevalence of <0.5% in a cohort of Canadians aged 65 years or older residing outside of the acute care setting. However, when nondemented subjects developed delirium, their 5-year survival was quite low. This suggests that the appearance of delirium per se may be a harbinger of serious illness in this cohort.

In contrast, the incidence of delirium within the hospitalized patient population ranges from 10% to 20% overall, and increases in direct relationship to increasing age. About 25% of hospitalized senior citizens, more than age 70 years, experience some degree of delirium. This age-related increased prevalence of delirium is more common in the setting wherein an underlying brain disease is present. In some instances, this may not have been previously identified, such as in the individual with occult Alzheimer disease. Sensory impairment (including poor hearing and vision) heightens the potential for delirium to develop in our senior citizens.

Despite such a potential prevalence, some studies suggest that delirium is neither detected nor documented in up to 66% of these patients. Precipitants of delirium include polypharmacy, infection, metabolic disturbance, malnutrition, and dehydration. Other inciting clinical settings often include intensive care setting, immobility (particularly when using restraints), frequent room changes, absence of a clock or a watch, and lack of reading glasses.

Another very high risk group for developing delirium is the patient who is in palliative care settings wherein close to half of these patients will be witnessed to have these mental status changes. Delirium is also common as a postoperative complication, occurring in up to 52% of these patients, and again preferentially in elderly individuals. Certain procedures are associated with a greater risk, such as coronary bypass and emergency hip surgery. The specific type of anesthesia does not influence risk. However, a low preoperative hematocrit (<30%) may increase the risk of postoperative delirium. Severe postoperative pain also increases the propensity for delirium. However, proper pain management may provide an excellent reduction in severity and duration of the delirium per se. Paradoxically, the initiation of opioid therapy may also precipitate delirium. Thus, it is essential to attempt to find a balance between pain control and opioid intoxication.

Diagnosis

Neuroanatomic Considerations

The anatomic substrate of delirium is not well understood; it most likely is composed of an interaction within multiple cortical and subcortical neuronal networks. Certain neuronal systems likely contribute to the overall presentation of delirium in various combinations and permutations. The subcortical reticular activating system and thalamic nuclei may contribute to the various fluctuations in level of consciousness, whereas the cortical and limbic system involvement most likely contributes to the specific cognitive and behavioral features at presentation.

Various focal cerebral lesions may produce differing states of delirium that are particularly noteworthy. These include the nondominant parietal lobe, associated with misidentification syndromes; posterior circulation territories, including thalamus and mesial temporal lobes, notable for various amnestic syndromes; and frontal lobe syndromes, characterized by differing attention disorders, executive dysfunction, or akinetic mutism. The delirious patient may exhibit a variety of these symptoms at once, likely fluctuating in severity over the course of a single episode of delirium.

Neurochemical Foundations

It is important to appreciate the important neurochemistry attributes that often accompany the delirious state. Acute administration of benzodiazepines may lead to not only sedation but also a disoriented and inattentive state. Chronically, these medications may produce short-term memory impairment as well. Dopaminergic pharmacotherapeutic agents may produce acute confusional states characterized by visual hallucinations and agitation. Anticholinergic therapies typically lead to a delirious state with prominent amnestic features. These various neuropharmacologic agents, each having a potential to lead to delirium, also offer a possible means to elucidate some of the neuroanatomic localizations responsible for the various features of delirium. Of particular importance is the observation that senior citizens are much more prone to experiencing these various neurotoxic side effects. Whenever one evaluates a delirious older individual, it is important to carefully review the patient’s medication list for not only valid prescriptions per se but over-the-counter drugs and various dietary supplements.

Evaluation

The bedside assessment of a delirious patient must include evaluation of a multiplicity of mental functions, including attention, orientation, short-term memory, abstract thinking, cognitive speed, and perception. Use of the digit span test, serial three subtractions, or listing months of the year backwards, provide very useful means for evaluation. When assessing patients’ attention and concentration abilities at the bedside, their orientation to time and place must be assessed. Patients need to be able to estimate how long they’ve been in the hospital and the reason for their hospitalization, as well maintain their ability to readily identify familiar people. Healthy individuals are able to register three words and recall them spontaneously after 5 minutes. Normal persons are able to provide definitions of common words and interpret common proverbs. Asking about the similarities and differences between various items is another useful way to assess abstract reasoning. A mentally alert and healthy patient is able to easily produce a list of 12 animals within a 1-minute time frame. And, lastly, normal individuals are able to easily describe their immediate surroundings or look at a photograph in an organized fashion and then recall the details to their examiner.

Various disorders need to be considered in the differential diagnosis of the delirious patient. In order to differentiate delirium from dementia, there are some very simple means (Table 17-1). These include the following:

Table 17-1 Clinical Differences Between Delirium and Dementia

Delirium also needs to be differentiated from an acute psychosis where, in contrast to the delirious individual, the psychotic patient maintains his or her:

However, manic patients may mimic delirium as they often present with insomnia, agitation, delusions, even confusion. In such instances, ancillary studies such as electroencephalography (EEG) may prove useful. The psychotic patient typically has a normal EEG, whereas the delirious patient often has widespread slowing of brainwave activity.

Treatment

Management of delirium may be divided into two major categories. This includes (1) treatment of the precipitating mechanism leading to the delirium and (2) management of the problem behaviors associated with delirium.

The underlying cause of delirium is often readily identified; specific treatment is directed at the predisposing medical condition. Once this is defined, and therapy initiated, the delirium gradually resolves; however, it is not uncommon for the delirium to have an incomplete resolution during the initial treatment of the primary inciting mechanism. Thus, it may take days or weeks before patients return to their baseline mental status, well after they are discharged from hospital. Very specific interventions are required in some individuals presenting with delirium, as illustrated below.

In most cases of delirium, the specific treatment largely addresses the underlying medical precipitants of delirium. Sedative medications are largely used to address problem behaviors that disrupt the delivery of care and place patient and staff at risk. Neuroleptics and atypical neuroleptics are often used for this purpose. These medications must be prescribed judiciously to avoid side effects, which paradoxically may include toxic delirium and increased risk of falls. One also needs to be careful to gain a history of the patient’s predelirious state to ascertain whether there were earlier signs of a dementing illness. If such is not recognized, these interventions are particularly worrisome. For example, those patients with previously unrecognized dementia with Lewy bodies (DLB) may be predisposed to a medication hypersensitivity. This is particularly the case with neuroleptics.

The various mental fluctuations found in DLB patients often mimic delirium as manifested by agitation and psychotic features. Even very low doses of neuroleptic medication in these patients can induce a severe parkinsonian syndrome or neuroleptic malignant syndrome.

Benzodiazepines may be used for their sedating and anxiolytic effects.

A paradoxical delirium and agitation may occur in many otherwise nonneurologically impaired, elderly patients. In some settings, benzodiazepines may exacerbate an underlying cognitive impairment with its increased risk of patient falling. Trazodone is sometimes helpful in reducing anxiety and helping to induce sleep. Any use of chemical restraints, to overcome problematic behavior, must be discontinued as quickly as possible.

Nonpharmacologic interventions are very important. The patient’s eyeglasses and hearing aids need to be readily available. The hospital room must include a prominent clock in the patient’s room, an easily readable calendar, consistent care providers with limited changes in personnel, and proper lighting. Frequent reorientation, one-to-one monitoring, and a structured environment to avoid environmental triggers of agitation may reduce the need for chemical and physical restraint in many cases.

Summary

Delirium is a serious complication for many hospitalized patients; its presence must be identified early on, as well as its associated systemic precipitants, in order to provide a timely therapy that will reduce the patient’s morbidity and mortality. EEG is a useful ancillary diagnostic study, especially in cases where acute psychiatric illness is a possibility. Here the EEG is typically normal. Nonpharmacologic interventions provide a safe means of reducing problem behaviors. The use of medications to reduce agitation must be done with specific goals in mind and in a limited fashion. In every instance, the patient’s dignity must be respected as well as his family counseled and guided throughout the course of delirium. This helps to facilitate proper decision making on the patient’s behalf.