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Table of Contents

Nicolle C.
McGowan, MD

Departments of
Psychiatry and
Psychology

Joseph A.
Locala, MD

Departments of
Psychiatry and
Psychology

Print Chapter

Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Therapy

Outcomes

References

Delirium is a syndrome characterized by the rapid onset of variable and fluctuating changes in mental status caused by physiologic consequences of a medical disturbance. According to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), "The essential feature of a delirium is a disturbance in consciousness that is accompanied by a change in cognition that cannot be better accounted for by a preexisting or evolving dementia."¹

Typically, delirium develops over a course of hours to days, and changes in mental status wax and wane over a short period of time. Because delirium is the direct result of an underlying medical condition, it typically improves fairly quickly when the causative factor is identified and corrected. The diagnosis of delirium is challenging because it has variable presentations that include disturbance in one or more of the following domains: orientation, thought process, perception, memory, mood, and behavior with or without hyperactivity. Delirium has been known by a variety of names, including acute confusional state, acute brain syndrome, metabolic encephalopathy, toxic psychosis, and acute brain failure.²

Delirium is common in hospitalized patients and is the most common clinical syndrome seen by consulting psychiatrists in general hospitals.³ It is estimated that 10-15% of patients in general surgical wards and 15-25% in general medical wards have delirium during their hospital stays. The prevalence of delirium is higher in the geriatric population; 30-40% of hospitalized patients older than 65 years have experienced an episode of delirium.^2,4 Delirium occurs in approximately 30% of patients in surgical and cardiac intensive care units, 40-50% of patients recovering from surgery for hip fracture, and 30-40% of inpatients with acquired immune deficiency syndrome (AIDS).^2,4 A high incidence of delirium is found in patients following cardiac surgery. A recent review which included fifteen relevant and valid studies of neuropsychiatric sequelae of cardiac surgery, found an average incidence of delirium of 38.5% with a range of 0-73.5%.⁷

Factors associated with a higher risk of delirium include advanced or very young age, pre-existing brain trauma (eg, dementia, cerebrovascular disease, tumor, etc.), alcohol dependence, diabetes mellitus, cancer, sensory impairment (eg, blindness or poor hearing), malnutrition, and a history of delirium.^2,4

Hospitalization is more costly when delirium is present because of associated medical morbidity and extended periods of hospitalization.⁵ Timely detection and effective treatment of delirium should help reduce hospital costs.

The signs and symptoms of delirium are manifestations of neuronal dysfunction, particularly in susceptible areas of the cortex and reticular-activating system. The cerebellum is relatively spared.³

Two mechanisms are thought to direct the way in which these susceptible neurons contribute to the development of delirium: excessive neurotransmitter release and abnormal signal conduction are believed to contribute to delirium.¹ Overactivity of muscarinic cholinergic neurons in the reticular-activating system, cortex, and hippocampus ^2,3 likely contributes to the disturbances of higher cognition (eg, disorientation, concrete thinking, and inattention) typical of an episode of delirium.

One of the most common causes of delirium is anticholinergic toxicity from prescribed medications.² Table 1 includes a list of other potential causes.

Excessive dopamine release (eg, secondary to hypoxia) may play a prominent role in delirium. Release of dopamine increases and reuptake decreases significantly under conditions of increased metabolic stress.³ Abnormally elevated dopamine can be neurotoxic via production of oxyradicals and release of glutamate, an excitatory neurotransmitter.³

Neurotransmitter perturbation is believed to cause neuronal membrane hyperpolarization that ultimately leads to spreading neuronal depression.³ Susceptible anatomic structures are affected systematically in a predictable sequence, resulting in the clinical picture of delirium.⁴

Delirium tends to develop over the course of a few hours to days, and symptoms tend to fluctuate during the course of the day.^1,2 Serial examination, therefore, is important. Recognition of fluctuating mental status helps distinguish delirium from dementia, which typically follows a more indolent course. Cognitive disturbances in delirium range from mild and easily missed to severe and global . The range of disturbances encompasses abnormalities in orientation, the sleep-wake cycle, perception, attention, concentration, memory, language, and motor function.¹

Disturbance of the sleep-wake cycle is common, and it is often the first symptom of an evolving delirium. The degree of disturbance ranges from mild insomnia or daytime sleepiness to a complete reversal of the sleep-wake cycle.¹ Nocturnal agitation and confusion are common, and typically trigger psychiatric consultation.¹

Perceptual disturbances include illusions (eg, intravenous tubing is misinterpreted as a snake) and full-blown hallucinations, where no stimulus is present.⁶ Visual hallucinations are the most common type of perceptual disturbance in the delirious patient, although hallucinations can occur in any sensory modality.^1,6 Frightening hallucinations are frequently a cause of agitated behavior.

Certain patients become frankly delusional, and paranoia is not uncommon. These patients pose a significant dilemma for medical personnel and family members, because such patients may refuse medication, medical interventions, or placement in extended care facilities.

The spectrum of psychomotor disturbances ranges from somnolence and lethargy to restlessness, agitation, and belligerence.¹ Agitation can be dangerous when it manifests in belligerent behavior (eg, punching, scratching, kicking), attempts to disrupt continuity of medical care (eg, self-extubation, pulling out catheters, tubes, and/or intravascular lines) or attempts to leave "against medical advice." A sitter or companion may be necessary to provide continuous monitoring, reassurance, and calming measures. Restraints may be required when these less restrictive measures are inadequate to ensure safety.

Attention and concentration are impaired in the delirious patient. This is evidenced by distractibility and poor focus on conversation or other activities. These disturbances are easily identified during bedside interview. Specific tests of attention include serial sevens, digit-span testing, spelling the word "world" backwards, and repeating the months of the year in reverse order.

Memory impairment is usually limited to the period of the delirium for which many patients are amnestic. Long-term memory is relatively preserved during an episode of delirium.⁶

Other disturbances associated with delirium include anomia, dysarthria, dysgraphia, perseveration, loosened associations, and inappropriate or uncharacteristic speech.⁶ "Soft" neurologic signs (eg, frontal release signs) occur frequently as well.

Delirium is a clinical diagnosis. Diagnosis is based on observed changes in mental status that are related to some underlying medical disturbance. According to DSM-IV, "The disorders in the "Delirium" section share a common symptom presentation of a disturbance in consciousness and cognition, but are differentiated based on etiology: Delirium Due to a General Medical Condition, Substance-Induced Delirium (including medication side effects), and Delirium Due to Multiple Etiologies."¹ The DSM-IV criteria for the different types of delirium are listed in Table 2.

Several formal instruments have been developed to help diagnose and monitor the clinical course of delirium: the Clinical Assessment of Confusion; the Delirium Symptom Inventory; and the Delirium Rating Scale. These instruments are generally used for research. Standard psychiatric and medical examinations are usually sufficient to diagnose and evaluate delirium.⁶

Routine electroencephalogram (EEG) reveals slowing in most cases of delirium.⁶ Generalized slowing of the EEG in delirium, however, is nonspecific . Its absence does not rule out the diagnosis.⁶ Delirium tremens and benzodiazepine-withdrawal delirium for example are characterized by low-voltage fast activity.⁶ The differential diagnosis of delirium includes dementia, depression, psychotic disorders (eg, schizophrenia), and substance intoxication.²

Identifying and Correcting the
Underlying Etiology:

Medical management of the delirious patient entails identification and correction of the underlying etiologic conditions. Careful medical, neurologic, and psychiatric examinations should be performed. This should include the Folstein Mini-Mental Status Examination (MMSE). The patient's vital signs and overall medical condition must be monitored carefully until the underlying disturbance (eg, infection, change in respiratory status, drug toxity, fluid/electrolyte imbalance) has been corrected or stabilized.

A thorough review of recent medication usage is mandatory. Attention should be given to type, dosage and recent addition or discontinuation of medication(s) with special emphasis on psychoactive medications (eg, sedative-hypnotic agents, narcotics, antidepressants).

It is also essential to gather and review pertinent laboratory and radiographic studies . Special testing (eg, for human immunodeficiency virus [HIV]) should be performed on a case-by-case basis. Collateral information from family members and caregivers can help identify baseline behavior and mental status as well as potentially provide clues to the etiology of delirium (Table 3).⁶

Drug Therapy:

Identification and correction of the etiologic condition may be sufficient to reverse delirium. However, some cases of delirium, especially in the elderly, are protracted and may take weeks to clear. Subclinical delirium lasting months has been associated with hepatic encephalopathy. Specific pharmacologic intervention may become necessary to help to reduce the intensity and duration of delirium. The medication of choice is a low-dose, high-potency neuroleptic. Multiple studies have demonstrated the safety and efficacy of antipsychotics in treating agitation and psychotic symptoms in the medically ill.⁶ Although there has been an increase in the use of novel, atypical antipsychotics (eg, risperidone and olanzapine) in the treatment of delirium, there are no well-controlled studies of these medications.⁶

Haloperidol
Of the antipsychotics, haloperidol is the best studied and most frequently used medication. It is relatively safe in this population; it has few or no anticholinergic side effects, minimal cardiovascular effects, and no active metabolites.⁶ No optimum dose of haloperidol has yet been established for the treatment of delirium. In general, scheduled low doses are preferable to larger doses that are administered on an as-needed basis. Several studies have recommended doses as low as 0.25 and 0.5 mg every 4 hours for elderly patients, but the average dose is in the range of 1 to 2 mg every 4 hours.⁶ Severely agitated patients may require higher doses; in such cases, special attention must be paid to potential adverse cardiac effects, especially QTc prolongation.⁶ Prolongation of the QTc interval to greater than 450 msec or to greater than 25% of that seen on previous ECGs may warrant discontinuation of the medication.⁶ Although the use of haloperidol is certainly associated with neurologic effects, especially extrapyramidal signs, these effects are rarely observed when the medication is administered intravenously.⁶ However, the clinician should bear in mind that the IV form of haloperidol is twice as potent as the oral form.

Benzodiazepines
With few exceptions, the role of benzodiazepines in the treatment of delirium should be limited to use as an adjunct to neuroleptic therapy. Benzodiazepines have not been shown to be an effective monotherapy for delirium except in alcohol- and sedative hypnotic-withdrawal delirium. The addition of a benzodiazepine to a neuroleptic might reduce the amount of neuroleptic required to control agitation and thus reduce the likelihood of neuroleptic side effects.⁶ Benzodiazepines, especially long-acting formulations, may be quite harmful in patients whose delirium is a result of hepatic encephalopathy or respiratory insufficiency.⁶ Possible side effects of benzodiazepines include sedation, behavioral disinhibition, amnesia, ataxia, respiratory depression, and delirium; children and geriatric patients may be more susceptible to these effects than are young or middle-aged adults.⁶ When a benzodiazepine is indicated, a short-acting agent without active metabolites is preferred; the most frequently used agent is lorazepam. Again, no optimum dose has yet been established for the benzodiazepines, but lower, fixed dosing is preferable to higher, as-needed dosing. To ensure proper dosing frequency, it is necessary to take into consideration the half-life of the particular benzodiazepine that is prescribed.

Environmental Interventions:

Environmental interventions are very useful in treating the symptoms of delirium. According to the American Psychiatric Association's practice guideline, "The general goals are to reduce environmental factors that exacerbate delirium, confusion, and misperception while providing familiarity and an optimal level of environmental stimulation."⁶ For example, "timelessness" in the hospital, a situation in which there are often no indicators to distinguish day from night, can contribute to disorientation, sleep disturbance, and nighttime agitation.⁶ Simple interventions-such as turning lights off and on at appropriate times and opening and closing curtains and blinds-may help keep the delirious patient oriented as to the correct time of day. Wall calendars that are kept up to date and analog clocks can also assist with orientation. Patients may also benefit from repeated, gentle reorientation by nurses, companions, or family members several times throughout the course of the day; reorientation should be practiced in a nonconfrontational manner and should include reminders that the patient's symptoms are temporary and reversible.⁶

The confused patient can also be overstimulated by excessive noise from IV pumps, beepers, overhead pages, alarms, etc. Excessive noise can be minimized by tuning the television to a relaxing program and turning it off when no one is watching. Some patients may need to be placed in a room without a roommate or in a room that is distant from a noisy nurses' station. Delirium can also be exacerbated by sensory impairments, such as poor vision or hearing.⁶ Every effort should be made to make sure the patient has appropriate access to glasses or hearing aids. Restraints, while occasionally necessary for safety reasons, should be avoided if at all possible in delirious patients, who usually will not comprehend the reasons for being restrained. This lack of comprehension can contribute to fear, paranoia, and agitation, especially in patients who are already agitated. The bedside presence of family members or familiar items from the patient's home may be very helpful in calming and reassuring the delirious patient.⁶

Psychiatric Care:

Consultation from the psychiatric specialist may be indicated if the previously mentioned treatment measures have failed, if the delirium has no clear etiology, if more aggressive symptom management is necessary, or if further education of family and support staff is appropriate.

The presence of delirium is associated with significant morbidity and mortality. Estimated 3-month mortality among hospitalized patients with delirium ranges from 23% to 33%, and the 1-year mortality may be as high as 50%.² Moreover, patients who experience delirium have significantly longer and costlier hospital stays than do nondelirious patients.⁵ Aggressive treatment of delirium can reduce the length and cost of hospital stay as well as the risk of iatrogenic complications.⁵

The American Psychiatric Association has published Practice Guideline for the Treatment of Patients with Delirium. Copies may be obtained from the American Psychiatric Press Inc, 1400 K St NW, Washington, DC 20005. Orders can also be placed by telephone (800-368-5777) or online.

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1. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:124-133.
   
   
2. Kaplan HI, Sadock BJ. Kaplan and Sadock's Synopsis of Psychiatry. 8th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 1998:320-327.
   
   
3. Brown TM. Basic mechanisms in the pathogenesis of delirium. In: Stoudemire A, Fogel BS, Greenberg DB, eds. Psychiatric Care of the Medical Patient. 2nd ed. New York, NY: Oxford University Press; 2000:571-580.
   
   
4. Litaker D, Locala J, Franco K, Bronson DL, Tannous Z. Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry. 2001;23:84-89.
   
   
5. Franco K, Litaker D, Locala J, Bronson D. The cost of delirium in the surgical patient. Psychosomatics. 2001;42:68-73.
   
   
6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Delirium. Am J Psychiatry. 1999;156(5 Suppl):1-20.
   
   
7. Dyer CB, Ashton CM, Teasdale TA. Postoperative delirium: A review of 80 primary data-collection studies. Archives of Internal Medicine. 1995;155:461-465.

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