CHAPTER 27 DELIRIUM
Practice of Geriatrics
CHAPTER 27 DELIRIUM
Joseph Francis, Jr., M.D., M.P.H.
Evaluation and Management
Acute confusional states are common in older patients. The phenomenon of delirium is particularly challenging for clinicians because its outward manifestations vary greatly. As a result, delirium is hard to recognize. Additionally, many complex medical conditions underlie the problem. This creates management problems that test the skill of even the most expert clinicians. There is no easy, formulaic approach to delirium. However, this chapter attempts to provide a basic framework for understanding delirium and practical guidelines for recognizing and managing it in older persons.
The fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV) lists four key features that characterize delirium (Table 27-1).1 First, patients with delirium have a disturbance of consciousness that involves an altered level of awareness of their environment and impaired ability to focus, sustain, or shift their attention. In older persons, this disturbance usually appears as drowsiness, lethargy, or stupor but may present as hypervigilance (e.g., alcohol withdrawal delirium) or as subtle deficits of attention (e.g., inability to follow complex commands or maintain a train of thought owing to distractibility).
TABLE 27-1 DIAGNOSTIC CRITERIA FOR DELIRIUM
The second feature of delirium is the presence of cognitive deficits beyond what one would expect from a preexisting or evolving dementia. Again, a wide range of manifestations is possible, from obvious memory loss, disorientation, and hallucinations at one extreme to milder disturbances of language and perception at the other. In patients with delirium, speech is often rambling and incoherent, comprehension is faulty, and writing ability is severely impaired. Frank delusions or hallucinations are uncommon; more typical are misperceptions and faults in recognition (e.g., the nurse entering the room is mistaken for a hostile intruder).
Third, delirium is acute and fluctuating. It develops over hours to days, an aspect of chronology that is critical in differentiating it from dementia. Additionally, its features are unstable and typically are most severe in the evening and at night. Sometimes this fluctuation can lead clinicians to believe that delirium is resolving when in fact the relative lucidity is only temporary.
The final feature of delirium is the presence of one or more medical causes, such as acute illness or drug toxicity. In older persons the precipitating cause of delirium usually resides outside the central nervous system, and multiple contributing factors can be identified. A challenge for clinicians faced with delirium is that, other than the cognitive change, patients often do not look “sick.” This can be true even in patients with life-threatening illness, such as acute myocardial infarction or sepsis. Additionally, there is little correlation between the underlying cause of delirium and its clinical manifestations.
The DSM-IV definition for delirium omits a number of manifestations that may be seen in some individuals but lack sufficient sensitivity or specificity to confer a diagnosis. Such features include sleep disturbances, agitation, and changes in mood and affect. For example, patients with delirium may have insomnia and other sleep problems, including a frank reversal of the normal diurnal sleep-wake cycle. However, other medical illnesses can produce similar findings. Mood and behavior changes, such as depression or combativeness, can occur in people with delirium but may also be a manifestation of dementia.2
In lay speech, the term delirium connotes a hyperactive, flagrantly psychotic state, but this, too, is an uncommon manifestation in older patients. Delirium is typically a “quiet” disturbance, which makes it more easily overlooked.3
Finally, reversibility is not a necessary feature of delirium. Although the disturbance in consciousness and cognition is potentially correctable when delirium is promptly recognized and its underlying cause effectively treated, a complete return to baseline mental functioning may take weeks or months and often fails to occur.4
Prevalence and Impact
Delirium is common. Between 10% and 15% of older patients admitted to hospitals with acute medical illness have evidence of delirium. An additional 5% to 30% develop delirium later in their hospital stay, often as an iatrogenic complication. Among very frail patients, such as those experiencing hip fracture, the prevalence may exceed 50%. These startling figures indicate that delirium is one of the most common functional consequences of acute illness in geriatric populations.5
Delirium has been less studied outside of acute care hospitals. It is assumed (but has not been proved) that delirium is less common in ambulatory and long-term care settings. In one study of older patients presenting to emergency rooms, investigators identified cognitive impairment in 40%, of which one quarter met the criteria for delirium; such patients were more likely to require admission to the hospital.6
Delirium is harder to recognize in nursing home patients because it is commonly superimposed on a preexisting dementia. Pilot studies using assessment tools from the Minimum Data Set estimated that 9% of all nursing home residents and 16% of residents in special care units for the demented met criteria for delirium.7
Delirium has an enormous impact on the well-being of older persons and should be viewed as a sentinel event identifying a high-risk population needing careful attention. Reported mortality rates vary widely depending on the population studied and the diagnostic criteria employed, but pooled data from several recent cohort studies demonstrate a 1-month mortality of approximately 15% and a 6-month mortality that exceeds 20%, which is twice the rate for patients of similar age without delirium.8 Among the survivors of an episode of delirium, functional and cognitive decline often persists for months and can lead to institutionalization.9 Hospital stays are prolonged, and other complications (aspiration pneumonia, pressure ulcers, falls) occur more frequently in patients with delirium.
As with other geriatric syndromes, delirium is multifactorial. It is helpful to classify risk factors into two categories: those that increase baseline vulnerability (e.g., advanced age, underlying dementia) and those that precipitate the disturbance (Table 27-2).10 These risk factors can interact in complex ways. For example, patients with high baseline vulnerability may develop delirium with relatively trivial insults, and combinations of risk factors may confer more than an additive effect.
TABLE 27-2 RISK FACTORS FOR DELIRIUM
The most consistent risk factor for delirium in recent studies has been the presence of underlying brain disease, particularly dementia, cerebrovascular disease, and Parkinson’s disease. Twenty-five to fifty percent of delirious patients have evidence of preexisting dementia. The presence of dementia increases the risk of delirium by nearly threefold. Other chronic brain lesions, such as infarctions, are frequently found on brain imaging studies of delirious patients. Finally, Parkinson’s disease can increase the risk of delirium following surgery or electroconvulsive therapy, although the drugs used to treat this disorder may also play a role.
Many different drugs have been implicated in individual cases of delirium, but only a few are regularly associated with delirium in prospective studies. These include narcotics, sedative-hypnotics, and anticholinergic agents. Some members of a drug class have a particular propensity for causing delirium. For example, long-acting benzodiazepines and meperidine are more strongly associated with delirium in the perioperative setting than other sedatives or narcotics. This reflects their pharmacologic properties; for example, meperidine’s metabolite, normeperidine, accumulates in older persons with impaired renal function and has anticholinergic and central nervous system (CNS)-excitatory properties.11
The pathophysiology of delirium is poorly understood. This should not surprise the clinician who is familiar with delirious patients. The severity of the illness, lack of cooperation, and complicating features (e.g., multiple drugs, underlying dementia) make even the most basic investigations challenging.
Additionally, electrophysiologic studies, positron-emission tomography (PET), and other techniques for studying brain function are hard to employ in patients with so transient and fluctuating a disturbance. Animal models of delirium, which examine maze running, locomotion, electroencephalographic (EEG) changes, and subjective changes in behavior following a stressor known to induce delirium in humans, have been proposed but are still in their infancy. Finally, we lack a good conceptual model, since our knowledge of the normal mechanisms of consciousness and arousal remains fragmentary.
Despite these limitations, some important facts are known. Romano and Engel performed seminal work in the 1940s using electroencephalography in acutely ill patients.12 They established that delirium was a disturbance of global cortical function. EEG changes of delirium (slowing of the dominant posterior alpha rhythm and appearance of abnormal slow-wave activity) correlated with the level of consciousness and other observed behaviors. Additionally, a variety of causes induced similar EEG changes, suggesting a final common neural pathway. The major exception appeared to be that of delirium accompanying alcohol and sedative-drug withdrawal, in which low voltage, fast-wave activity predominated.
EEG measures primarily cortical activity, but recent investigations using evoked potential studies support an important role for subcortical structures (e.g., thalamus, basal ganglia, and pontine reticular formation) in the pathogenesis of delirium. Such findings correlate with clinical reports that patients with structural abnormalities of the basal ganglia have a higher susceptibility to delirium.
Neurotransmitter and Humoral Mechanisms
Drugs that are agonists or antagonists of a number of neurotransmitters can produce delirium-like effects, but the precise role of such neurotransmitter systems is difficult to determine. Additionally, measurements of cerebrospinal fluid (CSF) levels of neuropeptides (e.g., somatostatin), endorphins, serotonin, norepinephrine, and gamma-aminobutyric acid (GABA) reveal multiple alterations in patients with delirium, but it is difficult to exclude the potential confounding effects of underlying illness or dementia in such studies.
Of all the neurotransmitters studied to date, acetylcholine appears to play the most important role in delirium. Anticholinergic drugs produce delirium when given to healthy volunteers and are even more likely to produce acute confusion in frail older persons. This effect can be reversed with cholinesterase inhibitors such as physostigmine. Medical conditions that precipitate delirium such as hypoxia, hypoglycemia, and thiamine deficiency have been shown to decrease acetylcholine synthesis in the CNS. Serum anticholinergic activity, measured with binding assays employing purified preparations of brain muscarinic receptors, correlates with the severity of delirium in postoperative and medical patients. Finally, Alzheimer’s disease, itself characterized by a loss of cholinergic neurons, increases the risk of delirium due to anticholinergic medication.
It is very important for clinicians to keep in mind the anticholinergic mechanism because so many agents (including many not traditionally viewed as having “anticholinergic” effects) show muscarinic binding. Some older patients with delirium show elevated serum anticholinergic activity even in the absence of anticholinergic drug use, raising the possibility that endogenous anticholinergic substances may play a role in delirium.13
Recent investigations have also uncovered an emerging role of inflammatory mediators. Cytokines such as interleukins have strong CNS effects when they are injected into the ventricles of experimental animals. Endogenous cytokine activity may be responsible for delirium in such situations as sepsis (in which mental changes may actually precede fever) and cardiopulmonary bypass.14,15 When cytokines are used therapeutically (e.g., interferons in patients with chronic hepatitis or cancer), cognitive and behavioral effects frequently occur, especially in patients who are more susceptible to delirium due to underlying organic brain disease.
Failure to Recognize Delirium
Prompt recognition of delirium and identification of its underlying causes are essential for proper treatment. Unfortunately, clinicians fail to recognize delirium in up to 70% of cases. Usually this is not because behavioral problems or cognitive impairment are inapparent. Rather, clinicians wrongly attribute acute confusion to the patient’s age, to his or her dementia, or to other mental disorders. In one study, for instance, over 40% of patients referred to a consulting liaison psychiatrist for evaluation or treatment of depression were ultimately found to have delirium.16
Assessing the Presence of Delirium
DSM-IV criteria form a practical framework for the assessment of delirium. Level of consciousness is often the first observable clue. Clinicians must not “normalize” lethargy or somnolence by assuming that illness, sleep loss, fatigue, or anxiety are causing the changes. When the patient appears to be awake, the ability to focus, sustain, or shift attention can be assessed during attempts to obtain a history. A global assessment of the patient’s “accessibility” during conversation or the performance of a mental status examination has been shown to be a sensitive indicator of delirium.17 Conversation with the patient may also elicit memory deficits, disorientation, or speech that is tangential, disorganized, or incoherent. Beware, however, of superficially appropriate conversation that follows social norms but is poor in content. When in doubt, clinicians should perform formal mental status testing, such as the mini-mental state examination or brief bedside tests of attention (e.g., forward digit span; vigilance A test). It is important to emphasize that no single test can substitute for an astute observer with knowledge of the criteria for delirium.18
A determination that cognitive impairment or perceptual problems are not due to a prior or progressing dementia can be challenging and requires knowledge of the patient’s baseline functioning. If a clinician has not previously assessed the cognitive abilities of an older patient who is presenting with confusion, capable informants must be immediately sought to establish a chronology. Formal and informal caregivers also are important sources for establishing fluctuations. Not infrequently, the patient who was combative or confused the night before is found to be completely lucid during morning rounds. Clinicians should not rely on a single assessment of mental state but must actively solicit evidence of behavioral change from all available caregivers, especially those caring for the patient during evenings and nights.
Clinicians must also remember the factors that are not required in the definition of delirium. Agitated behaviors are infrequent among older persons with delirium despite the popular connotations of the term. “Quiet” delirium, including withdrawal, subtle misperceptions, or passive compliance, is more likely than dramatic outbursts, which makes the disturbance all too easy to mistake for depression or dementia.
Many authors place great emphasis on differentiating delirium from dementia and other psychiatric disorders. In practice, careful attention to the key features of acute onset, fluctuating course, altered consciousness, and cognitive decline readily distinguish delirium from depression, psychotic illness, and dementia. When in doubt, the most useful rule-of-thumb is to assume delirium and attempt to rule out common medical causes. This is true even for patients with known psychiatric illnesses, since they, too, are susceptible to delirium when acutely ill.
A common and particularly challenging clinical situation is the patient with known dementia who experiences a sudden change in behavior. Not all behavioral changes in demented patients are due to delirium. Patients with dementia resulting from diffuse Lewy body disease may, for instance, manifest fluctuating confusion, hallucinations, and delusions with no identifiable medical cause. Other psychiatric illnesses (e.g., depression) as well as catastrophic reactions to stressful situations (loss of spouse, accident, unfamiliar environment) can cause patients with Alzheimer’s-type dementia to deteriorate. Differentiating these possibilities is difficult when the patient is unable to give a coherent history or cooperate with the examination. However, it is well known that dementia increases the older patient’s susceptibility to delirium, so a wise course is again to assume the latter and evaluate the patient for common medical or drug precipitants.
Finally, delirium should also be distinguished from “sundowning,” a frequently seen but poorly understood phenomenon of behavioral deterioration seen in the evening hours, typically in demented, institutionalized patients.19 Sundowning should be presumed to be delirium when it is a new pattern. However, in patients with established sundowning and no obvious medical illness, impaired sleep regulation, circadian disturbances, or nocturnal factors in the institutional environment (e.g., shift changes, noise, reduced staffing) may contribute to this phenomenon.
EVALUATION AND MANAGEMENT
Patients with delirium are sick, so a search for the underlying causes must not be delayed. Although virtually any medical illness can precipitate delirium in the predisposed individual, certain ones are found so frequently that an initial evaluation should consider them in every delirious patient (Table 27-3).
TABLE 27-3 MEDICAL CONDITIONS COMMONLY CAUSING DELIRIUM
Review of medications heads the list, since drug toxicity accounts for approximately 30% of all cases of delirium.20 The most common offending drugs are listed in Table 27-4. Clinicians should be careful not to neglect over-the-counter agents, drugs prescribed by other physicians, or drugs belonging to other household members. A simple but high-yield diagnostic procedure is to ask a family member to clean out the medicine cabinet and bring the contents in for review.
TABLE 27-4 DRUGS COMMONLY CAUSING DELIRIUM
Performing a comprehensive history and physical examination is often difficult or impossible in the confused or uncooperative patient. Clinicians should instead perform a focused assessment, concentrating on vital signs, state of hydration, skin condition, potential infectious foci, and neurologic findings. Pitfalls must be kept in mind: the temperature may be under 101°F even in patients with serious infections; auscultatory and radiographic findings of pneumonia may be subtle or absent; abdominal catastrophes may present without peritoneal signs in frail older patients. False-positive findings occur as well—for example, nuchal rigidity may not signify meningitis.
The neurologic examination is often discounted because many items have poor interrater reliability (e.g., plantar and deep-tendon reflex testing) or are difficult in uncooperative patients (e.g., sensory testing). However, a basic assessment emphasizing level of consciousness, unambiguous cranial nerve and motor deficits, and, if possible, visual fields, is useful for identifying individuals with a higher likelihood of intracranial disease. For instance, posterior cortical stroke can present as delirium and has few findings other than hemianopsia.21
Just as the potential causes of delirium are legion, so also are the laboratory tests that might be considered. Unfortunately, a desire for diagnostic completeness not only increases costs, it can also delay prompt treatment of more obvious disorders. Authorities have therefore stressed the importance of targeted testing. Serum electrolytes, creatinine, glucose, and calcium levels, complete blood count, and urinalysis are reasonable tests for most patients with delirium when a cause is not immediately obvious. Drug levels should be ordered when appropriate, but the results should not lull one into complacency because delirium can occur even in the presence of “therapeutic” levels of such agents as digoxin, lithium, or quinidine. Further testing should be based on the history and clinical examination; a report of slow cognitive decline over several months, for instance, increases the importance of evaluating thyroid function and vitamin B12 level.
Although older patients with bacterial meningitis are more likely to present with delirium than with the classic triad of fever, headache, and meningismus, this is still an uncommon disorder. In febrile older patients with delirium, routine evaluation of the CSF is usually not necessary as long as other infectious foci are obvious.22
Finally, neuroimaging should be performed immediately if a new focal neurologic finding is present or recent head trauma has occurred. In all other patients, selective use is advised. Computed tomographic (CT) abnormalities of the head are commonly seen in patients with delirium but usually represent chronic conditions that may predispose the patient to delirium but less often represent acute, treatable causes. If the initial clinical evaluation discloses an obvious disturbance and the patient improves with treatment, neuroimaging is probably not warranted.
The only specific therapy with the potential to reverse delirium is successful treatment of the medical condition or conditions that have caused the disturbance. Because more than one condition is typically present, several lines of treatment are started simultaneously. However, correction of sepsis, dehydration, or drug toxicity may take days. During that period, the patient with delirium is susceptible to intercurrent illness, iatrogenic complications, and further drug exposures that can maintain the delirious state.
Additionally, the uncooperative and disruptive behaviors that characterize delirium in many older patients can threaten the success of therapies directed at specific medical causes. The patient who refuses to eat or drink because of fear of staff or who pulls out his or her intravenous line, nasogastric tube, or oxygen cannula thwarts the therapeutic process and may cause further injury. Most of the pharmacologic therapies (Table 27-5) described for delirium are means of controlling these disruptive behaviors and are themselves nonspecific. One notable exception is physostigmine, which can reverse the effects of anticholinergic intoxication. Because physostigmine has a short duration of action and side effects of its own, most cases of known anticholinergic toxicity are best treated by stopping the offending agent and providing supportive care.
TABLE 27-5 PHARMACOLOGIC TREATMENT OF DELIRIUM
Maintaining this distinction between specific and nonspecific therapy (or “cure” and “control”) is important, since there is no ideal drug for managing the behavioral complications, and nearly all the agents used to treat delirium can themselves cause adverse behavioral effects. Benzodiazepines such as lorazepam, for instance, may be useful as short-acting sedatives but can worsen delirium; they are best reserved for patients with delirium due to sedative drug or alcohol withdrawal. Haloperidol has been favored for the treatment of delirium because of its absence of anticholinergic effects and its low potential for cardiac toxicity (even in critically ill patients), although prolongation of the QT interval and torsades de pointes have been reported after administration of high doses.23 Haloperidol can produce serious adverse effects such as rigidity, akathisia (which sometimes is mistaken for worsening delirium and can lead to escalating doses of the medication), and life-threatening neuroleptic malignant syndrome.
An aspect often neglected in the treatment of delirium is the provision of a safe supportive environment; some suggested modalities for achieving this goal are listed in Table 27-6. Modern hospitals are often characterized by pandemonium, and the needs of frail, confused patients for reassurance, gentle stimulation, and orienting stimuli can be lost in the quest for cost-efficiency. Environmental measures have proved helpful in managing disruptive behaviors among demented institutionalized patients and may be useful for delirious patients as well. Simple measures may be the most effective. For instance, a window with a view to the outside may reduce the risk of delirium by half,24 and bedside sitters (preferably family members and others familiar to the patient) can obviate the application of restraints.
TABLE 27-6 ENVIRONMENTAL MEASURES THAT REDUCE AGITATION IN CONFUSED PATIENTS
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