Delirium

Delirium is a transient global disorder of cognition. The condition is a medical emergency associated with increased morbidity and mortality rates. Early diagnosis and resolution of symptoms are correlated with the most favorable outcomes. 

Delirium is not a disease but a syndrome with multiple causes that result in a similar constellation of signs and symptoms. Delirium is defined as a transient, usually reversible, cause of mental dysfunction and manifests clinically with a wide range of neuropsychiatric abnormalities. The clinical hallmarks are decreased awareness and attention span and a waxing and waning type of confusion.

Delirium is often unrecognized or misdiagnosed as dementia, depression, mania, psychotic disorders, or a typical response of the aging brain to hospitalization.  

Based on the level of psychomotor activity, delirium can be described as hyperactive, hypoactive, or mixed. Hyperactive delirium is observed in patients in a state of alcohol withdrawal or intoxication with phencyclidine (PCP), amphetamine, and lysergic acid diethylamide (LSD). These patients often exhibit agitation, restlessness, hallucinations, or delusions. Hypoactive delirium is observed in patients in states of hepatic encephalopathy and hypercapnia and may be more common in older adults. Hypoactive delirium presents with lethargy, drowsiness, apathy, decreased responsiveness, or slowed motor skills. In mixed delirium, individuals display either relatively normal levels of psychomotor activity or rapidly fluctuating levels of activity.[1, 2]

The mechanism of delirium still is not fully understood. Delirium results from a wide variety of structural or physiological insults. The neuropathogenesis of delirium has been studied in patients with hepatic encephalopathy and alcohol withdrawal. Research in these areas still is limited. The main hypothesis is reversible impairment of cerebral oxidative metabolism and multiple neurotransmitter abnormalities. The following observations support the hypothesis of multiple neurotransmitter abnormalities.[3]

Acetylcholine

Data from animal and clinical studies support the hypothesis that acetylcholine is one of the critical neurotransmitters in the pathogenesis of delirium.[4] A small prospective study among patients who have undergone elective hip replacement surgery showed reduced preoperative plasma cholinesterase activity in as many as one quarter of patients. In addition, reduced preoperative cholinesterase levels were significantly correlated with postoperative delirium.[5]

Clinically, good reasons support this hypothesis. Anticholinergic medications are a well-known cause of acute confusional states, and patients with impaired cholinergic transmission, such those with Alzheimer disease, are particularly susceptible. In patients with postoperative delirium, serum anticholinergic activity may be increased.[6]

Dopamine

In the brain, a reciprocal relationship exists between cholinergic and dopaminergic activities. In delirium, an excess of dopaminergic activity occurs. Symptomatic relief occurs with antipsychotic medications such as haloperidol and other neuroleptic dopamine blockers.

Other neurotransmitters

Serotonin: Human and animal studies have found that serotonin is increased in patients with hepatic encephalopathy and septic delirium. Hallucinogens such as LSD act as agonists at the site of serotonin receptors. Serotonergic agents also can cause delirium.

Gamma-aminobutyric acid (GABA): In patients with hepatic encephalopathy, increased inhibitory GABA levels also are observed. An increase in ammonia levels occurs in patients with hepatic encephalopathy, which causes an increase in the amino acids glutamate and glutamine, which are precursors to GABA. Decreases in CNS GABA levels are observed in patients with delirium resulting from benzodiazepine and alcohol withdrawal.

Cortisol and beta-endorphins: Delirium has been associated with the disruption of cortisol and beta-endorphin circadian rhythms. This mechanism has been suggested as a possible explanation for delirium caused by exogenous glucocorticoids.

Disturbed melatonin disturbance has been associated with sleep disturbances in delirium.[7]

Inflammatory mechanism

Recent studies have suggested a role for cytokines, such as interleukin-1 and interleukin-6, in the pathogenesis of delirium. Following a wide range of infectious, inflammatory, and toxic insults, endogenous pyrogen, such as interleukin-1, is released from the cells. Head trauma and ischemia, which frequently are associated with delirium, are characterized by brain responses that are mediated by interleukin-1 and interleukin-6.[8, 9]

Stress reaction mechanism

Studies indicate psychosocial stress and sleep deprivation facilitate the onset of delirium.

Structural mechanism

The specific neuronal pathways that cause delirium are unknown. Imaging studies of metabolic (eg, hepatic encephalopathy) and structural (eg, traumatic brain injury, stroke) factors support the hypothesis that certain anatomical pathways may play a more important role than others. The reticular formation and its connections are the main sites of arousal and attention. The dorsal tegmental pathway projecting from the mesencephalic reticular formation to the tectum and the thalamus is involved in delirium.

Disrupted blood-brain barrier can allow neurotoxic agents and inflammatory cytokines to enter the brain and may cause delirium. Contrast-enhanced MRI can be used to assess the blood-brain barrier.[10, 11]

Visuoperceptual deficits in delirium such as hallucinations and delusions are not due to the underlying cognitive impairment.[12] Visual hallucinations during alcohol-withdrawal delirium are seen in subjects with polymorphisms of genes coding for dopamine transporter and catechol-O-methyltransferase (COMT).[13]

In patients who are admitted with delirium, mortality rates are 10-26%.[14]

Patients who develop delirium during hospitalization have a mortality rate of 22-76% and a high rate of death during the months following discharge.[15] . In a review of 28 studies of critically ill patients the rate of death for patients with delirium was more than doubled.[16]

In patients who are elderly and patients in the postoperative period, delirium may result in a prolonged hospital stay, increased complications, increased cost, and long-term disability.[17]

According to one study, delirium is associated with worse survival and greater resource consumption in those with cardiac critical illness. Among 590 patients included, the prevalence of cardiac (C)ICU delirium was 20.3%. Delirious patients were older, had greater disease severity, required longer ICU stays (5 vs 2 days; P< .001), and had higher mortality (27% vs 3%; P< .001).[18]

Frequency

Delirium is common in the United States. In a systematic review of 42 cohorts in 40 studies, 10–31% of new hospital admissions met criteria for delirium and the incidence of developing delirium during the admission ranged from 3–29%.[19]

For patients in intensive care units the prevalence of delirium may reach as high as 80%.[2]

Prevalence of postoperative delirium following general surgery is 5–10% and as high as 42% following orthopedic surgery. As many as 80% of patients develop delirium near death. Delirium is extremely common among nursing home residents.

Age

Delirium can occur at any age, but it occurs more commonly in patients who are elderly and have compromised mental status. Delirium can occur on top of an underlying dementia. This diagnosis here requires not only a careful mental status but also a thorough history from the patient's family and the staff as well as a comprehensive chart review.

The diagnosis of delirium is clinical. No laboratory test can diagnose delirium. Obtaining a thorough history is essential.

Because delirious patients often are confused and unable to provide accurate information, getting a detailed history from family, caregivers, and nursing staff is particularly important. Nursing notes can be very helpful for documentation of episodes of disorientation, abnormal behavior, and hallucinations. Learning to record accurate and specific findings in mental status as well as the particular time the finding was observed is imperative for the staff. Staff should not just report "he was confused."

Delirium always should be suspected when (a new onset) or an acute or subacute deterioration in behavior, cognition, or function occurs, especially in patients who are elderly, demented, or depressed.

Patients may have visual hallucinations or persecutory delusions as well as grandiose delusions.

Some patients with delirium also may become suicidal or homicidal. Therefore, they should not be left unattended or alone.

Delirium is mistaken for dementia or depression, especially when patients are quiet or withdrawn. However, by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5) criteria, dementia cannot be diagnosed with certainty when delirium is present. Health professionals can do Mini-Mental Status Exam (MMSE),[20] depression assessment screening using DSM-5 criteria,[1] or the Geriatric Depression Scale (GDS).[21] They can also assess for suicidal and homicidal risk if necessary. Health professionals can directly ask patients about suicidal or homicidal ideation (thoughts), intent, and plan.

Depression symptoms are commonly seen with delirium. In a recent study, patients having symptoms of dysphoric mood and hopelessness are at risk for incident delirium while in the hospital.[22] On the other hand, hypoactive delirium may be mistaken for depression. Up to 42% of patients referred to psychiatry services for suspected depressive illness in the hospital may have delirium.[23] Screening for depression in the presence of delirium is quite challenging.

Delirium is a common cause for psychotic symptoms, bizarre delusions, abnormal behavior, and thought disorders. Agitated patients are at risk for violent and abnormal behavior and in rare circumstances, agitation can lead to attempts of homicide.

The mental status is a bedside or interview assessment that dramatically fluctuates. It includes the patient's appearance, affect (mood), thoughts (especially the presence of hallucinations and delusions), inquiry into self-destructive behavior, homicidal behavior, judgment and, in this diagnosis, orientation, immediate, recent, and long-term memory.

Delirium develops in a short period of time (within hours), and an acute change in consciousness or difficulty focusing on what was being said could occur during the interview. Disturbance of the sleep-wake cycle with insomnia, daytime drowsiness, or disturbing dreams or nightmares can also occur. Patients are often unable to remember why they are in the hospital or the events that occurred during the delirious period (for most patients, it is like a blackout period).

Patients may have false beliefs or thinking (misinterpreting intravenous lines as ropes or snakes) or see or hear things that are not present (picking up things in the air or seeing bugs in the bedclothes). Patients may also misjudge their level of wellness and try to elope from the hospital. Emotional disturbances leading to depression, anxiety, fear, and irritability may be seen in some patients. Delirium in hospitalized seniors may result in the self-removal of catheters or intravenous tubing or attempts to get out of bed, resulting in a fall or injury.

The main symptoms of delirium include the following:

• Clouding of consciousness

• Difficulty maintaining or shifting attention

• Disorientation

• Illusions

• Hallucinations

• Fluctuating levels of consciousness

• Symptoms tend to fluctuate over the course of the day, with some improvement in the daytime and maximum disturbance at night. Reversal of the sleep-wake cycle is common.

Neurological symptoms may include the following:

• Dysphasia

• Dysarthria

• Tremor

• Asterixis in hepatic encephalopathy and uremia

• Motor abnormalities

Patients with delirium who are hyperactive have an increased state of arousal, psychomotor abnormalities, and hypervigilance. In contrast, patients with delirium who are hypoactive are withdrawn, less active, and sleepy.

Hypoactive delirium sometimes is misdiagnosed as dementia or depression.

In patients who are elderly, delirium often is the presenting symptom of an underlying illness.

Subsyndromal delirium has been defined as the presence of some core diagnostic symptoms that do not meet the criteria for diagnostic threshold. Prevalence rates of 30-50% have been reported in intensive care units.[24, 25]

A prodromal phase lasting for hours to days can occur before full syndromal delirium becomes evident. This includes sleep disturbances, vivid dreams, frequent calls for assistance, and anxiety.[24, 25]

A careful and complete physical examination including a mental status examination is necessary. Testing vital signs such as temperature, pulse, blood pressure, and respiration is mandatory.

Patients have difficulty sustaining attention, problems in orientation and short-term memory, poor insight, and impaired judgment. Key elements here are fluctuating levels of consciousness.

Impaired attention can be assessed with bedside tests that require sustained attention to a task that has not been memorized, such as reciting the days of the week or months of the year backwards, counting backwards from 20, or doing serial subtraction.

DSM-5 diagnostic criteria for delirium[1] is as follows:

• Disturbance of consciousness (ie, reduced clarity of awareness of the environment) occurs, with reduced ability to focus, sustain, or shift attention.

• Change in cognition (eg, memory deficit, disorientation, language disturbance, perceptual disturbance) occurs that is not better accounted for by a preexisting, established, or evolving dementia.

• The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day.

• Evidence from the history, physical examination, or laboratory findings is present that indicates the disturbance is caused by a direct physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more than one cause.

Other diagnostic instruments are the Delirium Symptom Interview (DSI) and the Confusion Assessment Method (CAM).[26]

Delirium symptom severity can be assessed by the Delirium Rating Scale (DRS) and the Memorial Delirium Assessment Scale (MDAS).

Table 1. Differentiating Features of Delirium and Dementia (Open Table in a new window)

To make an accurate diagnosis, periodic application of diagnostic criteria such as CAM or DSM5 criteria and knowledge of the patient's baseline mental status is imperative.

Gaps in the medical record such as once daily cognitive assessment or no formal assessments on the hallmarks of delirium (attention span and fluctuation) may make diagnosing the condition more difficult.  The physicians depend on health records (nursing notes) to identify a fluctuating course. The type of information might also be less than adequate for developing a timely diagnosis. So the recognition of delirium can be delayed by infrequent observation or documentation.[27]

A simple cognitive test like the Mini-Cog can be a predictor of inhospital delirium. At the time of admission to the hospital, if the elderly patient does not have a history of dementia or cognitive impairment, the Mini-Cog can be used to identify patients at high risk for inhospital delirium.

The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) offers the clinician the opportunity to identify delirium in critical care patients, especially patients on mechanical ventilation. The CAM-ICU makes use of nonverbal assessments to evaluate the important features of delirium.

Another instrument that can be used in ICU settings is the Intensive Care Delirium Screening Checklist (ICDSC). The severity of delirium in the ICU can be estimated by the Delirium Detection Scale (DDS).

A 2012 meta-analysis showed a sensitivity of 75.5% and specificity of 95.8% for CAM-ICU, whereas sensitivity and specificity for the ICDSC were 80.1% and 74.6%, respectively. These results suggest the CAM-ICU is one of the most specific bedside tests that can be used to diagnose delirium in ICU patients.[28]

The CAM-S was developed for measuring the severity of delirium in hospitalized patients (short form) and those in research settings (long form).[29, 30]  Developers reported good psychometric properties, high interrater reliability, and strong associations with important clinical outcomes with this tool, which is based on the standardized and validated Confusion Assessment Method (CAM) that screens for the presence—but not the severity—of delirium. The CAM-S was tested in 2 independent cohorts at 3 academic centers comprising 300 patients scheduled for major surgery and 919 medical patients (all patients aged ≥70 y).[29, 30]

Almost any medical illness, intoxication, or medication can cause delirium. Often, delirium is multifactorial in etiology, and the physician treating the delirium should investigate each cause contributing to it. Medications are the most common reversible cause of delirium.

Some of the other common reversible causes include the following:

• Hypoxia

• Hypoglycemia

• Hyperthermia

• Anticholinergic delirium

• Alcohol or sedative withdrawal

Other causes of delirium include the following:

• Infections

• Metabolic abnormalities

• Structural lesions of the brain

• Postoperative states

• Miscellaneous causes, such as sensory deprivation, sleep deprivation, fecal impaction, urinary retention, and change of environment

• In persons who are elderly, medications at therapeutic doses and levels can cause delirium.

Although numerous risk factors have been described, a recent study identified 5 important independent risk factors.

• Use of physical restraints

• Malnutrition

• Use of a bladder catheter

• Any iatrogenic event

• Use of 3 or more medications

Dementia is one of the strongest most consistent risk factors. Underlying dementia is observed in 25-50% of patients. The presence of dementia increases the risk of delirium 2-3 times. Low educational level, which may be an indicator of low cognitive reserve, is associated with increased vulnerability to delirium.

Dysphoric mood and hopelessness are also risk factors for incident delirium.

Structural changes that may contribute to delirium include the following:

• Closed head injury or cerebral hemorrhage

• Cerebrovascular accidents, such as cerebral infarction, subarachnoid hemorrhage, and hypertensive encephalopathy

• Primary or metastatic brain tumors

• Brain abscess

Metabolic causes may include the following:

• Fluid and electrolyte abnormalities, acid-base disturbances, and hypoxia

• Hypoglycemia

• Hepatic or renal failure

• Vitamin deficiency states (especially thiamine and cyanocobalamin)

• Endocrinopathies associated with the thyroid and parathyroid

Hypoperfusion states such as shock congestive heart failure, cardiac arrhythmias, and anemias may contribute to delirium.

Infectious causes may include the following:

• CNS infections such as meningitis

• Encephalitis

• HIV-related brain infections

• Septicemia

• Pneumonia

• Urinary tract infections

Substance intoxication  with alcohol, heroin, cannabis, PCP, and LSD may cause symptoms of delirium. Withdrawal from these substances may also contribute.

Medication-induced delirium can be caused by any of the following agents:

• Anticholinergics (Benadryl, tricyclic antidepressants)

• Narcotics (meperidine)

• Sedative hypnotics (benzodiazepines)

• Histamine-2 (H2) blockers (cimetidine)

• Corticosteroids

• Centrally acting antihypertensives (methyldopa, reserpine)

• Anti-Parkinson drugs (levodopa)

Other causes may include postictal state and unfamiliar environment.

Delirium may come about as a result of surgery or operation.

• Preoperative (dementia, polypharmacy, fluid and electrolyte imbalance)

• Intraoperative (meperidine, long-acting benzodiazepines, anticholinergics such as atropine; however, medications such as glycopyrrolate can be used because, in contrast to atropine, they do not cross the blood brain barrier)

• Postoperative (hypoxia, hypotension, drug withdrawal)

Mild cognitive impairment and vascular risk factors can be independent risk factors for postoperative delirium.[31]

Drugs are a common risk factor for delirium, and drug-induced delirium is commonly seen in medical practice, especially in hospital settings. The risk of anticholinergic toxicity is greater in elderly persons, and the risk of inducing delirium by medications is high in frail, elderly persons and in those with dementia.

Laboratory tests that may be helpful for diagnosis include the following:

• Complete blood cell count with differential - Helpful to diagnose infection and anemia

• Electrolytes - To diagnose low or high levels

• Glucose - To diagnose hypoglycemia, diabetic ketoacidosis, and hyperosmolar nonketotic states

• Renal and liver function tests - To diagnose liver and renal failure

• Thyroid function studies - To diagnose hypothyroidism

• Urine analysis - Used to diagnose urinary tract infection

• Urine and blood drug screen - Used to diagnose toxicological causes

• Thiamine and vitamin B-12 levels - Used to detect deficiency states of these vitamins

• Tests for bacteriological and viral etiologies including syphilis

• Sedimentation rate

• Drug screen including alcohol level

• HIV tests

• Tests for other infectious causes if necessary or clinically indicated (These tests are not performed routinely, even though 30-40% of hospitalized patients with HIV infection develop delirium during hospitalization.[32] )

• Serum marker for delirium: The calcium-binding protein S-100 B could be a serum marker of delirium. Higher levels are seen in patients with delirium when compared to patients without delirium.[33]

See the list below:

• Neuroimaging

  • Perform CT scan of the head.

  • Magnetic resonance imaging (MRI) of the head may be helpful in the diagnosis of stroke, hemorrhage, and structural lesions.

• Electroencephalogram

  • In delirium, generally, slowing of the posterior dominant rhythm and increased generalized slow-wave activity are observed on electroencephalogram (EEG) recordings.

  • In delirium resulting from alcohol/sedative withdrawal, increased EEG fast-wave activity occurs.

  • In patients with hepatic encephalopathy, diffuse EEG slowing occurs.

  • The type of patterns observed includes triphasic waves in toxicity or metabolic derangement, continuous discharges in nonconvulsive status epilepticus, and localized delta activity in focal lesions.

• Chest radiograph is used to diagnose pneumonia or congestive heart failure.

Lumbar puncture is indicated when CNS infection is suspected as a cause of delirium or when the source for the systemic infection cannot be determined.

Pulse oximetry is used to diagnose hypoxia as a cause of delirium.

Electrocardiogram is used to diagnose ischemic and arrhythmic causes.

When delirium is diagnosed or suspected, the underlying causes should be sought and treated. Despite every effort, no cause for delirium can be found in a small percentage of patients. Components of delirium management include supportive therapy and pharmacological management.

Fluid and nutrition should be given carefully because the patient may be unwilling or physically unable to maintain a balanced intake. For the patient suspected of having alcohol toxicity or alcohol withdrawal, therapy should include multivitamins, especially thiamine.

Reorientation techniques or memory cues such as a calendar, clocks, and family photos may be helpful. The environment should be stable, quiet, and well-lighted. One study showed a reduction of sound during the night by using earplugs in the ICU setting decreased the risk of delirium by 53%, and improved the self-reported sleep perception of the patient for 48 hours.[34] Sensory deficits should be corrected, if necessary, with eyeglasses and hearing aids. Family members and staff should explain proceedings at every opportunity, reinforce orientation, and reassure the patient. Support from a familiar nurse and family should be encouraged. A meta-analysis of 7 studies that focused on the usefulness of interventions such as physical or occupational therapy, daily reorientation, and the avoidance of sensorial deprivation found a significant reduction in the development of delirium among elderly inpatients.[35]

Physical restraints should be avoided. Delirious patients may pull out intravenous lines, climb out of bed, and may not be compliant. Perceptual problems lead to agitation, fear, combative behavior, and wandering. Severely delirious patients benefit from constant observation (sitters), which may be cost effective for these patients and help avoid the use of physical restraints. These patients should never be left alone or unattended.

Psychiatric consultation may be indicated for management of behavioral problems such as agitation or aggressive behavior.

Scottish Intercollegiate Guidelines Network

Guidelines for risk reduction and management of delirium were published by the Scottish Intercollegiate Guidelines Network (SIGN) in March 2019.[74]

Detecting delirium

Use the 4 As Test (Arousal, Attention, Abbreviated Mental Test 4 [AMT4], Acute change) for identifying patients with probable delirium in emergency and acute hospital settings. This tool may also be used in community or other settings.

In the ICU setting, use the Confusion Assessment Method for the ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC) to identify patients with probable delirium.

Use CT brain scan in those patients presenting with delirium in the presence of the following:

• New focal neurological signs
• Reduced level of consciousness
• A history of falls
• Head injury
• Anticoagulation therapy

Consider an electroencephalogram when there is suspicion of epileptic activity or non-convulsive status epilepticus.

Reducing risk of delirium

Consider all of the following as part of a package of care for patients at risk for delirium:

• Ensuring patients have their glasses and hearing aids, if applicable
• Promoting sleep hygiene
• Early mobilization
• Pain control
• Prevention, early identification, and treatment of post-operative complications
• Maintaining optimal hydration and nutrition
• Regulation of bladder and bowel function
• Provisions of supplementary oxygen, if appropriate

Monitor depth of anesthesia in patients 60 years of age and over undergoing surgery that is expected to last more than 1 hr.

Treating delirium

Consider acute, life-threatening causes of delirium. These may include low oxygen level, low blood pressure, low glucose level, and drug intoxication or withdrawal.

Identify and treat potential causes such as medications and acute illness. Multiple causes are common.

Optimize physiology, environment, and medications to promote brain recovery.

Detect and treat agitation or distress with non-pharmacologic means, if possible.

Communicate diagnosis to patients and caregivers and provide ongoing support.

Attempt to prevent delirium complications such as immobility, falls, pressure sores, dehydration, malnourishment, and isolation.

Monitor patient recovery and refer to a specialist if necessary.

Delirium that causes injury to the patient or others should be treated with medications. The most common medications used are antipsychotic medications. While this is a common and seemingly useful strategy, the literature is still mixed. A 2015 meta-analysis of 15 studies found that second-generation antipsychotics (SGAs) may treat delirium better than placebo, usual care, or haloperidol.[36]  A 2016 meta-analysis of 19 studies found that antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU length of stay.[37]

Benzodiazepines often are used for alcohol and benzodiazepine withdrawal states.

Since decreased anticholinergic activity may be associated with delirium, anticholinesterase inhibitors have been tried. Even though case reports showed evidence that cholinesterase inhibitors may play a role in the management of delirium, larger trials and systematic review did not support this use.[38]  A randomized, double-blinded, placebo-controlled, multicenter trial in intensive care unit patients showed rivastigmine did not decrease duration of delirium and increased mortality in these patients. In this trial, the study group had more sicker patients with emergency admissions to the ICU, and this trial had used IV haloperidol, lorazepam, or propofol, in addition to rivastigmine, which might also have contributed to the delirium and increased mortality.[39]  A review of 7 trials of anticholinesterase inhibitors found that in 5 of the studies there was no benefit from the medications in either the prevention or management of delirium.[40]

Recent clinical trials showed that the melatonin supplement and its receptor agonist ramelteon may be useful in the prevention and management of delirium. Melatonin levels were found to be altered in delirium subjects.[41] Melatonin is available over the counter in North America. Ramelteon has been approved by the FDA for the treatment of insomnia.[42]

Class Summary

This class of drugs are the medication of choice in the treatment of psychotic symptoms of delirium. Older antipsychotics such as haloperidol, a high-potency antipsychotic, are useful but have adverse neurological effects. Newer neuroleptics such as risperidone, olanzapine, and quetiapine relieve symptoms while minimizing adverse effects. Initial doses may need to be higher than maintenance doses. Use lower doses in patients who are elderly. Discontinue these medications as soon as possible. Attempt a trial of tapering the medication once symptoms are in control. Antipsychotics can be associated with adverse neurological effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, and tardive dyskinesia. Longer term use is also associated with metabolic syndrome. Doses should be kept as low as possible to minimize adverse effects. Paradoxical and hypersensitivity reactions may occur.

Haloperidol (Haldol)

A butyrophenone high-potency antipsychotic. One of most effective antipsychotics for delirium. High-potency antipsychotic medications also cause less sedation than phenothiazines and reduce risks of exacerbating delirium.

Risperidone (Risperdal)

A newer antipsychotic with fewer extrapyramidal adverse effects than Haldol. Binds to dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor. Improves negative symptoms of psychoses and reduces incidence of adverse extrapyramidal effects.

Class Summary

Reserved for delirium resulting from seizures or withdrawal from alcohol or sedative hypnotics. Coadministration with antipsychotics is considered only in patients who tolerate lower doses of either medication or have prominent anxiety or agitation. Benzodiazepines are preferred over neuroleptics for treatment of delirium resulting from alcohol or sedative hypnotic withdrawal. They also may be used when unknown substances may have been ingested and may be helpful in delirium from hallucinogen, cocaine, stimulant, or PCP toxicity. Use special precaution when using benzodiazepines because they may cause respiratory depression, especially in patients who are elderly, those with pulmonary problems, or debilitated patients.

Lorazepam (Ativan)

Preferable because it is short acting and has no active metabolites. In addition, can be used in both IM and IV forms. When patient needs to be sedated for longer than 24 h, this medication is excellent. Commonly used prophylactically to prevent delirium tremens.

Class Summary

Patients with alcoholism and patients with malnutrition are prone to thiamine and vitamin B-12 deficiency, which can cause delirium.

Thiamine

For alcohol withdrawal and in cases of Wernicke encephalopathy.

Cyanocobalamin (Physicians EZ Use B-12, Nascobal)

Vitamin B-12 deficiency can cause confusion or delirium in patients who are elderly. Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B-12 in humans. Vitamin B-12 is synthesized by microbes but not by humans or plants. Vitamin B-12 deficiency may result from intrinsic factor deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum.

Class Summary

Agents in this class may be useful in the prevention and management of delirium.

Melatonin

Melatonin is a naturally occurring hormone secreted by the pineal gland. The concentration of melatonin is highest in the blood during normal times of sleep and lowest during normal times of wakefulness. The general consensus is that melatonin given during normal waking hours has hypnotic properties.

Ramelteon (Rozerem)

Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintaining circadian rhythm and a normal sleep-wake cycle. Ramelteon does not cause rebound insomnia or withdrawal symptoms at discontinuation. It is approved for prolonged use. It is indicated for insomnia characterized by difficulty with sleep onset.

Following recovery, patient's memories of events of the delirium are variable. Be sure to educate the patient, family, and primary caregivers about future risk factors.

It is not unusual for patients who are elderly to require 6-8 weeks or longer for full recovery. In particular, elderly patients with postacute care complications are at risk for prolonged and persistent delirium.[43]

Carefully assess patients to determine their level of care needs. Assessment should include behavior (24 h), daily mental status, potential for injury, and underlying medical and metabolic status.

Prevention should be the goal because delirium is associated with adverse outcomes and high health care costs.

A multicomponent intervention study that targeted cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration showed significant reduction in the number and duration of episodes of delirium in older patients who were hospitalized.

Patients who are at high risk for delirium should be monitored closely as outpatients, during hospitalization, and throughout surgical procedures.

Physicians should become familiar with prescribing practices for patients who are elderly, keeping dosages low and avoiding medications that cause delirium.

Monitoring the patient's mental status as a vital sign helps to diagnose delirium early.

Complications of delirium may include the following:

• Malnutrition, fluid and electrolyte abnormalities

• Aspiration pneumonia

• Pressure ulcers

• Weakness, decreased mobility, and decreased function

• Falls and combative behavior leading to injuries and fractures

• Wandering and getting lost

• Long-term cognitive impairment: Accumulating evidence shows that delirium is not only a transient, reversible acute confusion, but also can give rise to a persistent long-term cognitive impairment.[44]

Delirium significantly worsens prognosis and is associated with increased mortality at discharge and at 12 months. A significant proportion of patients with delirium during their hospital admission continued to demonstrate symptoms of delirium at discharge, 6-month, and 12-month follow-up.[19]

Resolution of symptoms may take longer in patients with poor premorbid cognitive function, incorrect or incomplete diagnosis of contributing factors, and structural brain diseases treated with large doses of psychoactive medications prior to the onset of acute medical illness.

For some patients, the cognitive effects of delirium may resolve slowly or not at all.

Patient and family education

See the list below:

• Educating families and patients regarding the etiology and course of disease is an important role for physicians.

• Educate the patient, family, and primary caregivers about future risk factors.

• Families may worry that the patient has brain damage or a permanent psychiatric illness. Providing reassurance that delirium often is temporary and is the result of a medical condition may be beneficial to both patients and their families.

• Suggest that family members or friends visit the patient, usually one at a time, and provide a calm and structured environment. Encourage them to furnish some familiar objects, such as photos or a favorite blanket, to help reorient the patient and make the patient feel more secure.

• Patient and family education materials are available here:

  • MedlinePlus: Delirium

  • Merck: Delirium