Clinical Features

Key Points

Delirium is an acute disorder of global cognitive function involving attention, consciousness, orientation, memory, sensory perception, executive function, and behavior. Misperceptions of any of the senses may occur, but auditory and visual disturbances manifesting as suggestible hallucinations or illusions are common. For example, the delirious patient may interpret spots on the floor tiles as bugs or the sound of the wind as whispering. Delirious patients have abnormal visual perception compared to cognitively normal and demented patients that is independent of the severity of cognitive impairment (Brown et al., 2009).

Delirium cases can be grouped into hyperactive, hypoactive, and mixed subtypes on the basis of psychomotor behavior (Meagher et al., 2008). It has been suggested that the hypoactive subtype is more often seen in elderly persons and with delirium caused by hypoxia, metabolic abnormality, and anticholinergic drugs, whereas the hyperactive subtype is more common in substance intoxication and withdrawal states. Cognitive impairment and generalized slowing of the electroencephalogram (EEG) are similar in hypoactive and hyperactive subtypes.

Delirium can occur at any age, although advanced age is an independent risk factor. Rather than considering chronologic age in assessing risk, a family physician may best consider biologic age and frailty.

Delirium is often overlooked or misdiagnosed. This lack of diagnostic clarity is concerning given that, independent of other variables, delirium worsens prognosis (Fong et al., 2009; McAvay et al., 2006), often leading to chronic decreased function and cognition. Only 15% of delirious hospitalized patients will regain their baseline function by discharge, and less than half will return to prior function at 6 months (Khan et al., 2009). Delirium increases hospital length of stay by 5 to 10 days (Siddiqi et al., 2006), as well as the likelihood of nursing home placement (Inouye et al., 1998). Finally, mortality increases by 10% to 37% in hospitalized elderly patients (McCusker et al., 2002; Siddiqi et al., 2006). Approximately 40% of patients with delirium during hospitalization who survive to discharge will die within 1 year (Inouye, 2006).

Delirium prevalence and incidence vary greatly across settings of care and populations served. From 10% to 15% of hospitalized elderly patients have delirium on admission, and another 5% to 10% develop it during their stay. More than half of long-term care residents will exhibit delirium on hospital admission. Postsurgical patients (e.g., hip fracture, cardiac surgery) and elderly patients cared for in an intensive care unit (ICU) are at particularly high risk (Khan et al., 2009).

Etiology

Key Points

A stress-diathesis model has been proposed to explain the risk of delirium, depending on the severity of an insult to brain function and the vulnerability of the brain because of immaturity in children and central nervous system (CNS) disease or degenerative disorders most common in elderly persons. This helps explain the highest risk of delirium in the elderly population and more frequent occurrence in children than in young and middle-aged adults.

Although the phenomenology of delirium in adults and in elderly persons differs only in the severity of cognitive symptoms and resilience in recovery, the course and symptomatology in childhood are different. Childhood delirium is often associated with febrile illness and from CNS-toxic medications (anticholinergics) (Lenntjens et al., 2008). Delirium in a child is more likely to have a very acute onset, but a less fluctuating course with less disruption of the sleep-wake cycle, than in adults. Cognitive deficits may be less pronounced in children, whereas hallucinations, delusional thinking, and labile mood may be more pronounced. The different array of causes of delirium in children and adults might explain these differences. In both children and elderly patients with dementia, problematic behaviors caused by delirium are often falsely attributed to irritability associated with illness or oppositional behavior toward caregivers. When a child cannot be comforted by a parent, delirium should be suspected.

The remainder of this discussion focuses on delirium in the elderly patient.

Neurochemical Hypothesis

Cholinergic transmission in the CNS has a major role in cognition and attention, and an acute cholinergic deficit exists in delirium. Dopaminergic transmission is increased in delirium, and this or the imbalance between cholinergic and dopaminergic systems may be etiologic. Disturbances in other neurotransmitters are hypothesized, perhaps explaining subtypes or variations in presentations of delirium. Serotonin may be increased in delirium associated with serotonin syndrome and in hepatic encephalopathy, but decreased in delirium from other causes. Glutamate and γ-aminobutyric acid (GABA) are believed to be increased in alcohol withdrawal and hepatic encephalopathy. Melatonin may be increased or decreased in delirium, which may explain hypoactive and hyperactive subtypes. Norepinephrine may be increased in delirium associated with anoxia and in hepatic encephalopathy. Inflammation may also play a role in causing delirium, either by a direct neurotoxic effect or by causing disturbances in the neurotransmitters. Figure 48-1 depicts a theoretic explanation for the etiology of delirium.

Figure 48-1 Theoretic etiologic hypothesis for delirium.

Diagnostic Process

Key Points

Diagnostic criteria for delirium are adapted from the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM IV-TR, 2000) (Box 48-1). Given the high prevalence of delirium in certain health care settings and clinical circumstances, diagnosis should not depend solely on a high index of suspicion. Formal evaluation of mental status to detect delirium or dementia should become part of routine assessment of elderly patients presenting with a change of condition. This not only fosters appropriate preventive and therapeutic interventions, but also alerts the interdisciplinary team (IDT) to plan care to ensure patient and staff safety, specific patient and family education, carefully considering cognition and function at discharge planning.

Several standardized instruments have been developed to assess for delirium and monitor severity. The Confusion Assessment Method (CAM) is based on DSM IV-R criteria and has 94% to 100% sensitivity and 90% to 95% specificity, with good interrater reliability when used with formal cognitive testing and administered by trained interviewers (Inyoue et al., 1990). Once diagnosed, the 10-item Memorial Delirium Assessment Scale is useful to monitor severity (Breibart et al., 1997). Other scales are used in specific settings (e.g., ICU). Given the fluctuating course of delirium, it is essential to perform monitoring frequently.

Prevention

Key Point

An evaluation of risk allows caregivers to apply preventive strategies to avoid development of delirium in high-risk individuals (Box 48-5). However, given the high prevalence in hospitalized elderly patients and in long-term care patients, and the benign nature of many of the strategies for prevention, a standardized facility-wide prevention program may be more appropriate and effective. Prevention involving nonpharmacologic strategies attempts to maintain or normalize sleep patterns, stimulate physical and mental activity consistent with the elderly person’s function, maintain or restore orientation to time/person/place, avoid or correct fluid and electrolyte disturbances, maximize the accuracy of sensory perceptions, and minimize the use of catheters and physical restraints.

Benzodiazepines and anticholinergic medications are best avoided when possible. Appropriate pain relief must be balanced with the risk of narcotic-induced delirium. Meperidine creates high risk from short analgesic effect but prolonged elimination of a nonanalgesic but CNS-toxic metabolite. Trials of proactive geriatrics consultation (Marcantonia et al., 2001), nurse-led IDT protocol-based interventions (Milsen et al., 2001), and preemptive low-dose haloperidol (Kalisvaart et al., 2005) have demonstrated decreases in delirium severity in elderly patients hospitalized for repair of hip fractures.

Treatment

Key Points

Treatment of delirium begins with maximized effort to apply strategies outlined in Box 48-5. Identifying and treating one or more potential causes of delirium are equally important (e.g., correcting fluid and electrolyte imbalance, treating an infection and discontinuing medications conferring risk). Many delirium-induced behaviors respond well to nonpharmacologic interventions. For example, a delirious elderly patient with repetitive vocalizations disturbing others should be managed by protecting others from the noise, not by sedating the delirious patient. Having a family member or sitter stay with a restless patient is better than use of physical or chemical restraints.

Pharmacologic treatment becomes necessary when patients have delirium-induced behavior that makes them a danger to self or others, or that interferes with needed medical care (e.g., maintaining bed rest after major surgery, maintaining catheter integrity). Hypoactive delirium might warrant treatment to improve oral intake of food, fluids, and medication or to avoid the medical consequences of inactivity. Additionally, some patients will require treatment for the confusion or hallucinations causing anxiety and fear. Both agitation in hyperactive delirium and lethargy in hypoactive delirium increase the risk for malnutrition and dehydration, aspiration, pressure ulcerations, and deep venous thrombosis or pulmonary embolism. The goal of pharmacologic management should be correction of neurochemical abnormalities, not simply sedation.

No medications are approved by the U.S. Food and Drug Administration (FDA) for treatment of delirium. Benzodiazepines are first-line therapy in patients with delirium induced by alcohol and sedative withdrawal. Antipsychotics are generally considered the drugs of choice in patients with most other types of delirium requiring pharmacologic management. The mode of action for antipsychotics in delirium is probably antagonism of dopamine and the resultant increase in acetylcholine. The choice of antipsychotic should be individualized based on suspected etiology, target symptoms, and patient susceptibility to adverse drug reactions (ADRs) because of age and comorbid conditions. The profile of antipsychotics regarding risk of cardiovascular events and death, QT_c prolongation, anticholinergic effects, sedation, hypotension, and resulting glucose intolerance and movement disorders must be considered when choosing a drug. Higher doses and longer duration of therapy increase the risk of ADRs, as do age, female gender, and preexisting mood disorders or dementia.

Delirious patients, particularly the elderly, often respond to fairly brief courses of low doses of antipsychotics, which decreases the chance of adverse side effects. Benzodiazepines are not recommended, but if used, low doses of short–half-life products (loratzepam, oxazepam) are preferred in elderly patients. Occasionally, methylphenidate is tried in hypoactive delirium. Delivery of medication to a delirious patient can be difficult; rapidly dissolving oral formulations are useful when cooperation with tablets or capsules is problematic. Depot injections of antipsychotics have no role in the treatment of delirium.

The fluctuating course of delirium makes evaluation of drug therapy difficult. Monitoring of mental status and behavior throughout the day using objective measures is required. The use of any of the recognized pharmacologic treatments for delirium risks further impairment of cognitive function, thereby confounding monitoring because the observer has little to differentiate an inadequate response to therapy (and need for uptitration), worsening of the delirium per se, or worsening of cognition from an adverse drug effect, compounding the original delirium.

When treating delirium, the family physician should employ nonpharmacologic strategies, medicate only when necessary, and use monotherapy. Adjust dose to age/body weight/composition and renal/hepatic function; avoid as-needed dosing; and titrate dose based on repeated objective assessments of delirium severity at intervals consistent with the time necessary for the drug to reach steady state. Treatment for 7 to 10 days after symptoms resolve is usual.

Natural History of Delirium

Delirium is usually of acute onset and transient duration. Delirium often resolves a few days to a few weeks after etiologic insults are corrected. In some patients, however, delirium may persist. When chronic, delirium may result in permanent cognitive deficits, meeting the criteria for dementia (Fong et al., 2009). Hastening the progression of an existing dementia might explain this clinical observation. Delirium is persistent at hospital discharge in almost one third of patients, with almost as many still having symptoms and signs of delirium 6 months after discharge (McAvay et al., 2006; McCusker et al., 2003).