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AUTHOR: DR. SHAHUL AMEEN, M.D.

2. Cognitive disorders

2.1 DELIRIUM

The term ‘delirium’ was coined by Celsus in 1 AD (Lindesay, 1999). Delirium is a complex neuropsychiatric syndrome that typically involves a plethora of cognitive and non-cognitive symptoms, resulting in a broad differential diagnosis dominated by mental disorders. Psychiatrists' skills in assessing cognitive function and psychopathology, coupled with their knowledge of psychotropic agents, make them well suited to improving detection, coordinating management and facilitating research into this understudied disorder (Meagher, 2001).

Epidemiology

Delirium is a common problem in all health care settings, with a prevalence of 0.4% in general population, 1.1% in general population aged >55 years, 9–30% in general hospital admissions and 5–55% in elderly general hospital admissions (Meagher, 2001). Approximately 10% of consultation–liaison referrals have delirium and only around 10% of delirious general hospital patients receive a psychiatric consultation (Sirois, 1988; Francis et al, 1990), with the involvement of psychiatrists reserved for more complex cases.

Risk Factors and Etiology

Risk factors for delirium can be categorized as predisposing factors and precipitating factors. Predisposing factors of delirium include older age, male sex, visual impairment, presence of dementia, severity of dementia, depression, functional dependence, immobility, hip fracture, dehydration, alcoholism, severity of physical illness, stroke and metabolic abnormalities; while the precipitating factors include narcotics, severe acute illness, urinary tract infection, hyponatremia, hypoxemia, shock, anemia, pain, physical restraint, bladder catheter use, surgery, intensive care unit admission and a high number of hospital procedures (Rolfson, 2002).

The etiology of delirium is usually multifactorial, and it has been reported that between two and six factors may be present in any single case (Rudberg et al., 1997). In a typical case, predisposing and precipitating factors interact with multiple aggravating or perpetuating factors which influence the course. It is therefore vital to be aware of risk factors and, having identified an explanation for delirium, remain vigilant as to the possibility of additional factors. The causes of delirium have been divided into patient factors, pharmacological factors, and environmental factors. Patient factors could be individual (like severe comorbidity, previous episode of delirium, and personality before illness), perioperative (like course of postoperative period, and type and duration of operation) and specific conditions (like depression and alcoholism). Pharmacological factors include treatment with many drugs, dependence on drugs or alcohol, use of psychoactive drugs or alcohol and specific drugs that may cause problems (like  benzodiazepines, anticholinergic agents and narcotics); while environmental factors include extremes in sensory experience (for e.g., hypothermia), deficits in vision or hearing, immobility or decreased activity, social isolation and novel environment.

Pathophysiology

There is widespread disruption of higher cortical function in delirium, and there is evidence of dysfunction in brain areas like subcortical structures, brain stem, thalamus, non-dominant parietal lobe, fusiform and pre-frontal cortices, and the primary motor cortex (Filley, 2002). Right-sided lesions have been suggested as important in the final common pathway for delirium (Trzepacz, 2000).

Cholinergic deficiency has been suggested to be present in delirium based on the following facts: metabolic and structural brain abnormalities associated with decreased acetylcholine activity are risk factors for delirium, high serum anticholinergic activity has been associated with severity of delirium (Trzepacz, 2000), and there is anecdotal evidence to suggest that anticholinesterase drugs used in the treatment of Alzheimer's Disease (AD) may also be of benefit in treating the symptoms of delirium (Wengel et al., 1998).

Clinical features

The onset of delirium is usually rapid and the course lasts less than six months. Clinical features of delirium include impairments of consciousness, thinking, memory, psychomotor behaviour, perception and emotion (Lishman, 1997).

Impairment of consciousness

Consciousness characteristically fluctuates diurnally, with deterioration in the evening when environmental stimulation is the least. Very minor degrees of impaired consciousness can occur, such as difficulty in estimating the passage of time (tested by asking the patient to estimate how long the interview has lasted). Disordered attention and concentration is another key clinical feature of delirium. Simple tests of concentration include: serial 7s where the patient counts backwards in sevens from 100; saying the months of the year backwards, or counting down from 20 to 1. The interpretation of these assessments should take into account the patient’s age and educational attainment.

Impairment of thinking

Delirium is characterized by a progressive disturbance of thinking. Initially the speech is slowed or speeded up, judgment and abstract thinking becomes more obviously impaired as the deliriums proceeds, and with further progression of the illness incoherent and disorganized thoughts supervene. The patient may seem to be cut off from the external world and increasingly occupied with inner thoughts and experiences.

Impairment of memory

Memory disturbances include short-term memory and working memory. Impairment of immediate short-term memory manifests as disorientation in time and place.

Disturbances of psychomotor behaviour

The patient might show little spontaneous activity when the disturbance is mild, although inner experiences such as hallucinations or delusions may result in quick reactions, as in delirium tremens. Purposeless behaviour, such as groping or picking, can occur, with complex stereotyped movements and rarely, the mimicking of a work pattern—occupational delirium (Byrne, 1994). Lipowski (1990) described the hypoactive and hyperactive syndromes.

Psychiatric Symptoms

Webster and Holroyd (2000) found the prevalence of psychotic symptoms in delirium to be 42.7%. Wolff and Curran (1935) noted visual hallucinations in 67.9% of subjects, auditory hallucinations in 41.5%, followed in frequency by tactile, olfactory, and gustatory hallucinations. Nicholas and Lindsay (1995) estimated that approximately 7% of delirious patients attempt some form of deliberate self-harm.

Other symptoms

The sleep/wake cycle is almost always disturbed, with marked periods of drowsiness and sleep in the day, and insomnia at night. Excessive dreaming with persistence of the experience into wakefulness is common.

Investigations

The clinical picture is so characteristic that a confident diagnosis of delirium can be made even if the underlying cause is not firmly established. In addition to a history of an underlying physical or brain disease, evidence of cerebral dysfunction (such as an abnormal electroencephalogram, usually but not invariably showing a slowing of the background activity) may be required if the diagnosis is in doubt.

Suggested evaluation of delirium (Casey et al., 1996)

• Detailed history

  Special attention to risk factors, medications, drug side effects and interactions

• Cognitive testing

  Short-term memory and orientation are most commonly disturbed

• Precise physical examination

  Special attention to infectious diseases, focal neurologic deficits (especially in elderly patients); signs of metabolic disease, substance abuse or withdrawal, infection (especially in younger patients); signs of trauma in all age-groups

• Empirical testing

  Complete blood cell count, blood chemistry profile, chest radiograph in all cases if no apparent cause

• Search for occult infection

  Urinalysis, blood cultures

• Toxicologic drug screening

  Consider drug screens, measurement of blood alcohol levels (especially in younger patients)

• Further targeted testing

  When no cause discovered despite the above evaluation, further testing depending on the index of suspicion: ammonia level, arterial blood gases, electrocardiogram, brain imaging, electroencephalogram, thyroid function tests

Diagnosis

Delirium is underidentified in clinical practice, with reported non-detection rates of 33-66% (Inouye, 1994). Failure to diagnose the disorder does not merely reflect preferences in terminology but represents an actual failure to recognize and treat the disorder appropriately and is associated with a poorer outcome (Rockwood et al., 1995). The agitated, disturbed image of delirium tremens is an inaccurate and damaging stereotype because it represents the minority of cases, and the existence of this stereotype is linked to the underdetection of somnolent or hypoactive cases. It would be preferable for all patients to be screened for risk factors at admission to hospital. Once patients are admitted, minor episodes of confusion, behavioural disturbance, or increasing agitation should be taken seriously and investigated appropriately.

Detection of delirium can be improved by putting greater emphasis on routine cognitive testing and the use of screening instruments. The Mini-Mental State Examination (MMSE – Folstein et al., 1975) screens for deficits in orientation, attention, memory, language, and visuoconstruction abilities. Administering the MMSE several times during the course of delirium can be a way to assess improvement. The Confusion Assessment Method is also widely used because it is reliable, brief, and applicable to a variety of settings (Inouye, 1994).

Confusion Assessment Method

Delirium diagnosed if (a) + (b) + one of either (c) or (d):

1. Acute onset and fluctuating course: Evidence of an acute change in mental status from the patient's baseline that changes in severity during the day

2. Inattention: Patient has difficulty focusing attention, e.g. is easily distractible or has difficulty keeping track of conversation

3. Disorganized thinking: Patient's thinking is disorganized or incoherent, as evidenced by rambling or irrelevant conversation and unclear or illogical flow of ideas

4. Altered consciousness: A rating of a patient's level of consciousness as other than alert (normal) i.e. vigilant or hyperalert, lethargic or drowsy, stuporose or comatose

Management

Four key steps in management of delirium are - addressing the underlying causes, maintaining behavioural control, preventing complications, and supporting functional needs (Marcantonio, 2002). Delirium is par excellence a disorder requiring a multifaceted biopsychosocial approach to assessment and treatment, and the management strategies include both nonpharmacologic and pharmacologic interventions.

Nonpharmacologic Interventions

Physical Interventions: Initial interventions include general measures to support cerebral function, such as intravenous hydration and appropriate nourishment. Supplemental oxygen has been found to be highly effective in patients who develop delirium following thoracotomy for pulmonary malignancy (Aakerlund et al., 1994). This intervention may also facilitate recovery in other patients whose oxygenation is not optimal, such as those with pneumonia. Physical restraints, once a mainstay in the treatment of delirium, are now used only when all pharmacologic and nonpharmacologic interventions have failed. Hard restraints (i.e., restraints made of leather instead of cloth) are used only to maintain safety in an emergency situation and should never be the sole intervention (Jacobson and Schreibman, 1997).

Environmental Interventions: The hospital environment is a significant factor in the management of delirium. Environmental manipulations are directed toward providing the right amount of stimulation for the patient, encouraging sleep, maximizing the patient's ability to perceive the environment accurately, maintaining safety, and achieving familiarity and consistency for the patient. Overstimulation should be avoided, because it contributes to both confusion and insomnia. Some specialists recommend that the patient with delirium have a private room or at least not share a room with another delirious patient (Lipowski, 1990).

Understimulation is probably a more common problem and is perhaps equally injurious. Delirious patients who are left alone without stimulation often withdraw and begin to respond more to internal stimuli than external stimuli. In such situations, regular interaction with hospital staff can be helpful. It is often appropriate to place the delirious patient in a room close to the nursing station or other workstation (Trockman, 1978). Sundowning, a transient worsening of delirium that occurs in the evening hours, is presumably related, at least in part, to decreased stimulation. Sundowning can be lessened by leaving a radio on in the patient's room (Trockman, 1978). It has long been recognized that, in certain cases, the hallucinations of delirium can be specifically treated: visual hallucinations by controlled visual stimuli, auditory hallucinations by music and other meaningful external sounds, and olfactory hallucinations by the introduction of odors or scents (Wolff and Curran, 1935).

To help the patient perceive the environment accurately, adequate daytime lighting and a night light should be provided (Lesko and Fleishman, 1991). Hearing aids, eyeglasses and other devices that assist sensory perception should be used whenever possible and should not be put away during a delirious episode (Trockman, 1978).

One of the most helpful interventions is having family members stay with the patient. Family members should also be encouraged to bring personal effects from home, because some patients with delirium are greatly comforted by the presence of familiar photographs or objects.

Cognitive Interventions: Reorientation is one of the most easily accomplished cognitive interventions. The first step is to place a clock and a calendar where the patient can see them easily. The patient should then be verbally reoriented to time and place several times over the course of the day. Experienced staff can integrate orientation information into conversations in such a way that patients do not experience the process as patronizing. Verification is recognition of the patient's fears. Rather than dismissing the patient's fears as groundless, the physician or hospital staff member says, "I can understand why this may be frightening, but I assure you we will do what needs to be done to keep you safe here." In explanation, the patient is told (and then regularly reminded) why he or she is in the hospital, what the medical problem is and what specific symptoms may be related to this problem. To allay anxiety, hallucinations and delusions should be explained to the patient (even a patient who denies having such experiences) and should be related to the delirium, which is a transient condition. Repetition is recommended to compensate for memory impairment in the delirious patient. The importance of repetition must be emphasized to busy hospital staff, since these individuals are primarily responsible for the patient's daily care (Richeimer, 1987).

Psychologic Interventions: The delusions expressed by a patient should not be directly disputed. Instead, alternative explanations of events should be offered, and frequent reassurance should be given. Patients with delirium fare best when caregivers behave as if their symptoms are a "normal" part of an illness or a postoperative course. Some patients do not readily accept reassurance and, after discharge, may still feel humiliated by their lack of control in the hospital. They may continue to be fearful that their delirium is a harbinger of future mental illness. For these patients, consultation with an experienced psychotherapist is recommended (Jacobson and Schreibman, 1997).

Educational Interventions: Staff education on the recognition and treatment of delirium is essential to good delirium management. Staff members who are unfamiliar with the signs and symptoms of delirium may miss the onset of the syndrome, while staff and family members who are not knowledgeable about the biologic basis of delirium and its prognostic implications may assume that the delirious patient's behaviors represent personally directed insults or the onset of rapidly progressive dementia.

Pharmacologic Interventions

Drug treatment of delirium requires careful consideration of the balance between the effective management of symptoms and potential adverse effects. The use of psychotropic drugs complicates the ongoing assessment of mental status, can impair the patient's ability to understand or cooperate with treatment, and is associated with a greater incidence of falls. Sedative compounds can improve agitation but may worsen cognitive impairment.

Antipsychotics: Antipsychotics ameliorate a range of symptoms, are effective both in patients with a hyperactive or hypoactive clinical profile, and generally improve cognition. The improvement is usually evident within hours or days and thus occurs before underlying causes are treated. Neuroleptics are superior to benzodiazepines in treating delirium that has been caused by factors other than alcohol withdrawal or sedative hypnotics. The dose of an antipsychotic drug is determined by the route of administration, the patient's age, the amount of agitation, the patient's risk of developing side effects, and the therapeutic setting. Chlorpromazine and haloperidol have similar efficacy, but haloperidol is preferred because it has fewer active metabolites, limited anticholinergic effects, less sedative and hypotensive effects, and can be administered by different routes (American Psychiatric Association, 1999). Moreover, intravenous administration of haloperidol seems to be less likely to cause extrapyramidal side effects in patients with delirium (Menza et al., 1987). Low dose oral haloperidol (1 mg to 10 mg/day) improves symptoms in most patients (Platt et al., 1994). Pimozide is a potent calcium antagonist and may be more appropriate for treating delirium that is accompanied by hypercalcaemia (Mark et al., 1993). Olanzapine (5-10 mg) and risperidone (1.5-4 mg) have been used successfully in uncontrolled case series (Sipahimalani and Masand, 1998; Sipahimalani et al., 1997).

Benzodiazepines: Benzodiazepines are first line treatment for delirium associated with seizures or withdrawal from alcohol or sedatives (Mayo-Smith, 1997). They are also a useful adjunctive treatment for patients who cannot tolerate antipsychotic drugs because lower doses can be used (Menza et al., 1988) and their effects can be rapidly reversed with flumazenil. The therapeutic aims of drug treatment should be explicit since anxiolytic, sedative, and hypnotic effects occur as doses are increased. Benzodiazepines can both protect against delirium and be a risk factor for it, and this highlights the need for judicious use in patients dependent on alcohol or benzodiazepines. Lorazepam has several advantages owing to its sedative properties, rapid onset, and short duration of action. Lower doses are necessary in elderly patients, those with hepatic disease, or those receiving compounds that undergo extensive hepatic oxidative metabolism (for example, cimetidine and isoniazid). The recommended upper limits for intravenous lorazepam are 2 mg every four hours.  Giving adequate initial doses reduce the risk of paradoxical excitement (Sanders and Cassem, 1993).

A treatment regimen for severe cases requiring prompt, aggressive control of symptoms is outlined below (Meagher, 2001).

Managing the patients after discharge

Many patients with delirium are discharged before their symptoms are fully resolved, and this factor must be accounted for in planning their post-discharge care. The continuing need for rehabilitation must be explicitly documented. Problems with attention and orientation are especially persistent (Levkoff et al., 1994). Further episodes may be prevented by addressing risk factors such as medication and sensory impairment. Most patients dismiss the episode of delirium once it has passed, but a significant minority has lingering concerns that an episode of delirium may represent the first step towards loss of mental faculties and independence (Schofield, 1997). Other patients experience "silent delirium" and are ashamed or afraid to admit to symptoms. A post-hospital visit to the treatment environment can facilitate adjustment and clarify the transient nature of delirium symptoms (Easton and MacKenzie, 1988).

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