Delirium

Definition and Overview

Image courtesy of UConn Today Opens in new window Delirium (or sudden, acute confusion) is the behavioral response to widespread disturbances in cerebral metabolism. The term delirium is derived from the Latin for “off the track,” and some have labeled the condition reversible madness.

Like dementia Opens in new window, delirium is not a disease but a syndrome with many possible causes (the diagnostic criteria for the syndrome of delirium are listed as Criteria A, B, and C).

According to DSM-IV-TR Opens in new window (see Table X1 Opens in new window), the primary feature of delirium is a diminished clarity of awareness of the environment. Symptoms of delirium are characteristically global, of acute onset, fluctuating, and of relatively brief duration.

In most cases of delirium, an often overlooked prodome of altered sleep patterns, unexplained fatigue, fluctuating mood, sleep phobia, restlessness, anxiety, and nightmares occurs. A review of nursing notes for the days before the recognized onset of delirium often illustrates early-warning signs of the condition.

The clinical features of delirium can be divided into abnormalities of :

• arousal,
• language and cognition,
• perception,
• orientation,
• mood,
• sleep and wakefulness, and
• neurological functioning.

1. Arousal

The state of arousal in delirious patients may be increased or decreased. Some patients exhibit marked restlessness, heightened startle, hypervigilance, and increased alertness. This pattern is often seen in states of withdrawal from depressive substances (e.g. alcohol) or intoxication by stimulants (phencyclidine, amphetamine, lysergic acid diethylamide).

Patients with increased arousal often have such concomitant autonomic signs as pallor, sweating, tachycardia, mydriasis, hyperthermia, piloerection, and gastrointestinal distress. These patients often require sedation with neuroleptics or benzodiazepines.

Hypoactive arousal states such as those occasionally seen in hepatic encephalopathy and hypercapnia are often initially perceived as depressed or demented states. The clinical course of delirium in any particular patient may include both increased and decreased arousal states. Many such individuals display daytime sedation with nocturnal agitation and behavioral problems (sundowning).

2. Language and Cognition

Patients with delirium frequently have abnormal production and comprehension of speech. Nonsensical rambling and incoherent speech may occur. Other patients may be completely mute.

Memory Opens in new window may be impaired, especially primary and secondary memory. Remote memory may be preserved, although the patient have difficulty distinguishing the present from the distant past.

3. Perception

Perception abnormalities in delirium represent an inability to discriminate sensory stimuli and to integrate current perceptions with past experiences. Consequently, patients tend to personalize events, conversations, and so forth that do not directly pertain to them, become obsessed with irrelevant stimuli, and misinterpret objects in their environment.

The misinterpretations generally take the form of auditory and visual illusions. Patients with auditory illusions, for example, might hear the sound of leaves rustling and perceive it as someone whispering about them.

Paranoia and sleep phobia may result. Typical visual illustrations are that intravenous tubing is a snake or worm crawling into the skin or that a respirator is a truck or farm vehicle about to collide with the patient. The former auditory illusion may lead to tactile hallucinations, but the most common hallucinations in delirium are visual and auditory.

4. Orientation

Orientation is often abnormal in delirium. Disorientation in particular seems to follow a fluctuating course, with patients unable to answer question about orientation in the morning, and yet be fully oriented by the afternoon.

Orientation to time, place, person, and situation should be evaluated in the delirious patient. Generally, orientation to time is the sphere most likely to be impaired, with orientation to the person usually preserved.

Orientation to significant people (parents, children) should also be tested. Disorientation to the self is rare and indicates significant impairment. The examiner should always reorient patients who do not perform well on this parameter of the Mental Status Examination Opens in new window, and serial testing of orientation on subsequent days is important.

5. Mood

Patients with delirium are susceptible to rapid fluctuations in mood. Unprovoked anger and rage reactions occasionally occur and may lead to attacks on hospital staff.

Fear is a common emotion and may lead to increased vigilance and unwillingness to sleep because of increased vulnerability during somnolence Opens in new window.

Apathy—such as that seen in hepatic encephalopathy, depression, use of certain medications (e.g. sulfamethoxazole), and frontal lobe syndromes—is common, as is euphoria secondary to medications (e.g. corticosteroids, DDC, zidovudine) and drugs of abuse (phencyclidine, inhalants).

6. Sleep and Wakefulness

Sleeping patterns of delirious patients are usually abnormal. During the day they can be hypersomnolent, often falling asleep in midsentence, whereas at night they are combative and restless.

Sleep is generally fragmented, and vivid nightmares are common. Some patients may become hypervigilant and develop a sleep phobia because of concern that something untoward may occur while they sleep.

7. Neurological Functioning

Neurological symptoms often occur in delirium. These include dysphagia as seen after a cerebrovascular accident (CVA), tremor, asterixis (hepatic encephalopathy, hypoxia, uremia), poor coordination, gait apraxia, frontal release signs (grasp, suck), choreiform movements, seizures Opens in new window, Babinski’s sign, and dysarthria. Focal neurological signs occur less frequently.

An appropriate work-up of delirious patients includes a complete physical, mental status, and neurological examination. History-taking from the patient, any available family, previous physicians, the old chart, and the patient’s current nurse is essential. Previous delirious states, etiologies identified in the past, and interventions that proved effective should be elucidated.

Course

After elimination of the cause of the delirium, the symptoms gradually recede during 3–7 days. Some symptoms in certain populations may take weeks to resolve. The age of the patient and the period of time the patient was delirious affect symptom resolution time.

In general, the patient has a spotty memory for events that occurred during delirium. Comments from the staff (“You’re not as confused today”) or the presence of a sitter or use of wrist restraints may cause patients to wonder why they required these interventions.

Patients who wake up in restraints are often quite distraught, wondering what behavior they have engaged in that required them to be tied down. Patients should be reassured that they were not responsible for their behavior while delirious and that no one hates or resents them for the behavior they may have exhibited.

As mentioned earlier, delirious patients have an increased risk of mortality in the next year. Patients with underlying dementia show residual cognitive impairment after the resolution of a delirium, and it has been suggested that a delirium may merge into a dementia.

Predisposing factors in the development of delirium include old age, young age (children), previous brain damage, prior episodes of delirium, malnutrition, sensory impairment (especially vision), sleep deprivation, and alcohol dependence.

Other risk factors include use of physical restraints, sensory deprivation, use of a Foley catheter, and frequent room changes. In general, the mortality and morbidity of any serious disease are doubled if delirium ensues.

The risk of dying is greatest in the first two years after the illness, with a higher risk of death from heart disease and cancer in women and from pneumonia in men. Overall, the three-month mortality rate for persons who have an episode of delirium is about 28%, and the one-year mortality rate for such patients may be as high as 50%.

Differential Diagnosis

Delirium must be differentiated from dementia Opens in new window, because the two conditions may have different prognoses. In contrast to the changes in dementia, those in delirium have an acute onset.

The symptoms in dementia tend to be relatively stable over time, whereas clinical features of delirium display wide fluctuation with periods of relative lucidity. Clouding of consciousness is common in delirium, but demented patients are usually alert.

Attention and orientation are more commonly disturbed in delirium, although the latter can become impaired in advanced dementia. Perception abnormalities, alterations in the sleep-wakefulness cycle, and abnormalities of speech are more common in delirium. Most important, a delirium is more likely to be reversible than is dementia.

Delirium and dementia can occur simultaneously; in fact, the presence of dementia is a risk factor of delirium. Some studies suggest that about 30% of hospitalized patients with dementia have a superimposed delirium.

Delirium must often be differentiated from psychotic states related to such conditions as Schizophrenia or mania and Factitious Disorders with psychological symptoms. Generally, the psychotic features of Schizophrenia are more constant and better organized than are those in delirium, and patients with Schizophrenia seldom have the clouding of consciousness seen in delirium.

The psychosis of patients with Factitious Disorder is inconsistent, and these persons do not exhibit many of the associated features of delirium.

Apathetic and lethargic patients with delirium may occasionally resemble depressed individuals, but tests such as EEG distinguish between the two. The EEG demonstrates diffuse slowing in most delirious states, except for the low-amplitude, fast-activity EEG pattern seen in alcohol withdrawal. The EEG in a functional depression or psychosis is normal.

Causes of Delirium

The cause of delirium may lie in intracranial processes, extracranial ones, or a combination of both. The most common etiological factors are briefly discussed as follows.

1. Infection Induced

Infection is a common cause of delirium in hospitalized patients. The usual abnormalities in hematology, serology, and vital signs are abnormal except in persons (elderly, chronic alcohol abusers, chemotherapy patients, those with HIV spectrum disease) who may not be able to mount the typical response.

Bacteremia septicemia (especially that caused by gram-negative bacteria), pneumonia, encephalitis, and meningitis are common offenders. The elderly are particularly susceptible to delirium secondary to urinary tract infections.

2. Metabolic and Endocrine Disturbances

Metabolic causes of delirium include hypoglycemia, electrolyte disturbances, and vitamin deficiency states. The most common endocrine causes are hyperfunction and hypofunction of the thyroid, adrenal, pancreas, pituitary, and parathyroid.

Metabolic causes may involve consequences of diseases of particular organs, such as hepatic encephalopathy resulting from liver disease, uremic encephalopathy, and post-dialysis delirium resulting from kidney dysfunction, and carbon dioxide narcosis and hypoxia resulting from lung disease.

The metabolic disturbance or endocrinopathy must be known to induce changes in mental status and must be confirmed by laboratory determinations or physical examination, and the temporal course of the confusion should coincide with the disturbance. In some individuals, particularly the elderly, brain injured, and demented, there may be a significant lag time between correction of metabolic parameters and improvement in mental state.

3. Low-Perfusion States

Any condition that decreases effective cerebral perfusion can cause delirium. Common offenders are hypovolemia, congestive heart failure, and other causes of decreased stroke volume such as arrhythmias, and anemia, which decreases oxygen binding. Maintenance of fluid balance and strict measuring of intake and output are essential in the overall management of delirious states.

4. Intracranial Causes

Intracranial causes of delirium include head trauma, especially involving loss of consciousness, postconcussive states, and hemorrhage; brain infections; neoplasms; and such vascular abnormalities as CVAs, subarachnoid hemorrhage, transient ischemic attacks, and hypertensive encephalopathy.

5. Postoperative States

Postoperative causes of delirium may include infection, atelectasis, lingering effects of anesthesia, thrombotic and embolic phenomena, and adverse reactions to postoperative analgesia.

Patients who have undergone open heart surgery are particularly at risk for microemboli and subsequent confusion. General surgery in an elderly patient has been reported to be followed by delirium in 10–14% of cases and may reach 50% after surgery for hip fracture.

6. Sensory and Environmental Changes

Many clinicians underestimate the disorienting potential of an unfamiliar environment. The elderly are especially prone to develop environment-related confusion in the hospital. Individuals with preexisting dementia, who may have learned to compensate for cognitive deficits at home, often become delirious once hospitalized.

In addition, the nature of the intensive care unit often lends itself to periods of high sensory stimulation (as during a “code”) or low sensory input, as occurs at night.

Often, patients use such external events as dispensing medication, mealtimes, presence of housekeeping staff, and physicians’ rounds to mark the passage of time. These parameters are often absent at night, leading to increased rates of confusion during nighttime hours. Often, manipulating the patient’s environment or removing the patient from the intensive care unit can be therapeutic.

7. Substance Intoxication Delirium

The list of drugs of abuse that can produce delirium is extensive. Some such agents have enjoyed a resurgence after years of declining usage. These include lysergic acid diethylamide, psilocybin (hallucinogenic mushrooms), heroin, and amphetamines.

Other agents include barbiturates, cannabis (especially dependent on setting, experience of the user, and whether is it laced with phenycyclidine (superweed) or heroin), jimsonweed (highly anticholingeric), and mescaline. In cases in which the intravenous use of drugs is suspected, HIV spectrum illness must be ruled out as an etiological agent for delirium.

The physical examination of a patient with suspected illicit drug-induced delirium may reveal sclerosed veins, “pop” scars caused by the subcutaneous injection of agents, pale and atrophic nasal mucosa resulting from intranasal use of cocaine, injected conjunctiva, and papillary changes.

Toxicological screens are helpful but may not be available on an emergency basis. Some agents such as cannabis have long half lives so both qualitative and quantitate assays are recommended.

8. Substance Withdrawal Delirium

Alcohol and certain sedating drugs can produce a withdrawal delirium when their use is abruptly discontinued or significantly reduced.

Withdrawal delirium requires a history of use of a potentially addicting agent for a sufficient amount of time to produce dependence. It is associated with such typical physical findings as abnormal vital signs, papillary changes, tremor, diaphoresis, nausea and vomiting, and diarrhea. Patients generally complain of abdominal and leg cramps, insomnia, nightmares, chillds, hallucinations (especially visual), and a general feeling of “wanting to jump out of my skin.”

Some varieties of drug withdrawal, although uncomfortable, are not life threatening (e.g. opioid withdrawal). Others such as alcohol withdrawal delirium are potentially fatal.

Withdrawal delirium is much more common in hospitalized patients than in patients living in the community. The incidence of delirium tremens, for example, is 1% of all those with alcoholism, but 5% of hospitalized alcohol abusers. Improvements of the delirium occurs when the offending agent is reintroduced or a cross-sensitive drug (e.g. a benzodiazepine for alcohol withdrawal) is employed.

When treating patients in withdrawal with high doses of benzodiazepines, oxygen saturation levels should be monitored closely, and shorter-acting agents (e.g. lorazepam, alprazolam, oxazepam) should be used in those individuals with significant pulmonary or hepatic diseases. The causes of delirium are summarized in Table X2.

9. Delirium Duet to Multiple Etiologies

In many patients with delirium, there are often multiple simultaneous causal factors involved. In some cases, multiple general medical conditions may impact on the central nervous system (CNS) in such a way as to lead to a delirium. For example, a patient with hepatic encephalopathy who falls and hits his or her head may develop a delirium attributable to the combined effects of both general medical conditions. Similarly, the combined effects of a medical condition coupled with the effects of medications used to treat that condition may cause a delirium. In such situations, Delirium Due to Multiple Etiologies is given.

Treatment

Once delirium has been diagnosed, the etiological agent must be identified and treated. For the elderly, the first step generally involves discontinuing or reducing the dosage of potentially offending medications.

Some delirious states can be reversed with medication, as in the case of physostigmine administration for anticholinergic delirium. However, most responses are not as immediate, and attention must be directed toward protecting the patient from unintentional self-harm, managing agitated and psychotic behavior, and manipulating the environment to minimize additional impairment.

Supportive therapy should include fluid and electrolyte maintenance and the provision of adequate nutrition. Reorienting the patient is essential and is best accomplished in a well-lit room with a window, clock, and visible wall calendar. Familiar objects from such as a stuffed animal, favorite blanket, or photographs are helpful.

Patients who respond incorrectly to questions of orientation should be provided with the correct answers, and because these individuals often see many consultants, physicians should introduce themselves and state their purpose for coming at every visit.

Physicians must take into account that impairments of vision and hearing can produce confusional states, and the provision of appropriate prosthetic devices may be beneficial. Around-the-clock accompaniment by hospital-provided “sitters” or family members may be required.

Despite these conservative interventions, the delirious patient often requires pharmacological intervention. The liaison psychiatrist is the most appropriate person to recommend such treatment.

The drug of choice for the agitated, delirious patients has traditionally been haloperidol. It is particularly beneficial when given by the intravenous route and some authors have reported using dosages as high as 260 mg a day without adverse effect.

Extrapyramidal symptoms may be less common with haloperidol administered intravenously as opposed to orally and intramuscularly. In general, doses in the range of 0.5 to 5.0 mg intravenously are used, with the frequency of administration depending on a variety of factors including the patient’s age.

An electrocardiogram should be obtained before administering haloperidol. If the QT interval is greater than 450, use of intravenous haloperidol can precipitate an abnormal cardiac rhythm known as Torsades de pointes. Lorazepam has also been proven effective in doses of 0.5 to 2.0 mg intravenously.

Some authors have suggested that haloperidol and lorazepam act synergistically when given to the agitated delirious patient. If the delirium is secondary to abuse of drugs or alcohol, benzodiazepines or clonidine should be used. For patients who are mildly agitated or amenable to taking medications by mouth, oral haloperidol or lorazepam is appropriate.

Recent studies have advocated the use of newer atypical antipsychotic features in delirium. Such agents as quetiapine, olanzapine, and risperidone have been used successfully to treat delirium.

Newer agents may have lower incidences of dystonias and dyskinesias, but still carry the risk of QT interval prolongation, particularly in patients with electrolyte abnormalities.

Quetiapine and olanzapine are quite sedating and occasionally a combination of bedtime olanzapine may raise blood glucose levels and precipitate weight gain, but is available as an oral preparation which is absorbed through the oral mucosa and can therefore be given to patients who are unable to take medications by mouth.

There have been some cases of sudden death in patients simultaneously taking parenteral lorazepam and parenteral olanzapine so this combination should be avoided. Parenteral forms of ziprasidone and aripriprazole are also available.

Whatever antipsychotic is chosen, the patient should be carefully monitored for muscle rigidity, unexplained fever, tremor, and other warning signs of neuroleptic side effects, especially neuroleptic malignant syndrome.