eMedicine Specialties > Psychiatry > Emergency

Delirium

Kannayiram Alagiakrishnan, MD, MBBS, Associate Professor, Department of Medicine, Division of Geriatric Medicine, University of Alberta
Patricia Blanchette, MD, Department Chair and Director, Geriatric Medicine Fellowship Program, Professor of Geriatric Medicine, Geriatric Medicine, John A Burns School of Medicine, University of Hawaii

Updated: Aug 3, 2009

Introduction

Background

Delirium or acute confusional state 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. Therefore, it must be treated as a medical emergency.

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

Delirium often is unrecognized or misdiagnosed and commonly is mistaken for dementia, depression, mania, an acute schizophrenic reaction, or part of old age (patients who are elderly are expected to become confused in the hospital).

The word delirium is derived from the Latin term meaning "off the track." This syndrome was reported during Hippocrates' time, and, in 1813, Sutton described delirium tremens. Later, Wernicke described the encephalopathy that bears his name.

Pathophysiology

Based on the state of arousal, 3 types of delirium are described. Hyperactive delirium is observed in patients in a state of alcohol withdrawal or intoxication with  phencyclidine (PCP), amphetamine, and lysergic acid diethylamide (LSD). Hypoactive delirium is observed in patients in states of hepatic encephalopathy and hypercapnia. In mixed delirium, individuals display daytime sedation with nocturnal agitation and behavioral problems.

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.

Acetylcholine

Data from animal and clinical studies support the hypothesis that acetylcholine is one of the critical neurotransmitters in the pathogenesis of delirium.¹ 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 is increased.

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. Serotoninergic 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.²

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.^3,4

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.^5,6

Visuoperceptual deficits in delirium such as hallucinations and delusions are not due to the underlying cognitive impairment.⁷ Visual hallucinations during alcohol-withdrawal delirium are seen in subjects with polymorphisms of genes coding for dopamine transporter and catechol-O-methyltransferase (COMT).⁸

Frequency

United States

Delirium is common in the United States. It has been found in 14-56% of elderly patients who are hospitalized. Delirium is present in 10-22% of elderly patients at the time of admission, with an additional 10-30% of cases developing after admission. Delirium has been found in 40% of patients admitted to intensive care units. 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.

Mortality/Morbidity

• In patients who are admitted with delirium, mortality rates are 10-26%.⁹
• Patients who develop delirium during hospitalization have a mortality rate of 22-76% and a high rate of death during the months following discharge.¹⁰
• 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.¹¹

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.

Clinical

History

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, Fourth Edition, Text Revision (DSM-IV-TR) criteria, dementia cannot be diagnosed with certainty when delirium is present. Health professionals can do Mini-Mental Status Exam (MMSE),¹² depression assessment screening using DSM-IV-TR criteria,¹³ or the Geriatric Depression Scale (GDS).¹⁴ 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.¹⁵ 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.¹⁶ 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.
• Main symptoms
  • 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
  • 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.^17,18
• 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.^17,18

Physical

• 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-IV-TR diagnostic criteria for delirium¹³
  • 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).¹⁹
• 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

  Features	Delirium	Dementia
  Onset	Acute	Insidious
  Course	Fluctuating	Progressive
  Duration	Days to weeks	Months to years
  Consciousness	Altered	Clear
  Attention	Impaired	Normal, except in severe dementia
  Psychomotor changes	Increased or decreased	Often normal
  Reversibility	Usually	Rarely

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

Causes

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.

• DSM-IV-TR classification of delirium
  • Delirium due to general medical condition
  • Substance intoxication delirium
  • Substance withdrawal delirium
  • Delirium due to multiple etiologies
  • Delirium not otherwise specified
• 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
  • 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
  • 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
  • Shock
  • Congestive heart failure
  • Cardiac arrhythmias
  • Anemias
• Infectious causes
  • CNS infections such as meningitis
  • Encephalitis
  • HIV-related brain infections
  • Septicemia
  • Pneumonia
  • Urinary tract infections
• Toxic causes
  • Substance intoxication - Alcohol, heroin, cannabis, PCP, and LSD
  • Medication-induced delirium
    • Anticholinergics (Benadryl, tricyclic antidepressants)
    • Narcotics (meperidine)
    • Sedative hypnotics (benzodiazepines)
    • Histamine-2 (H2) blockers (cimetidine)
    • Corticosteroids
    • Centrally acting antihypertensives (methyldopa, reserpine)
    • Anti-Parkinson drugs (levodopa)
  • Substance withdrawal from alcohol, opioids, and benzodiazepines
• Other causes
  • Postictal state
  • Unfamiliar environment
• Operation-related delirium
  • 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.²⁰
  • 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.

Differential Diagnoses

Depression

Other Problems to Be Considered

Dementia
AIDS-related complex
Psychosis

Dementia is one of the most important risk factors for delirium. It often coexists in patients who are hospitalized. Delirium may be a risk factor or marker for the development of dementia. The safest rule is to consider delirium when recent changes in an elderly patient's level of consciousness and cognition have occurred in an acute care setting.

Patients with hypoactive withdrawn delirium may be misdiagnosed as depressed. Depressed patients also may have cognitive symptoms, but the patient's level of consciousness is normal.

Delirium may have to be differentiated from psychosis because both have psychotic features. In delirium, the patient usually does not have a previous history of serious psychiatric illness. The onset of symptoms of delirium is acute or subacute, the hallucinations predominantly are visual and fluctuate, and the patient has impaired memory and orientation and clouding of consciousness.

Workup

Laboratory Studies

• 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 - To diagnose infection
• 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.²¹ )

Imaging Studies

• 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 x-ray is used to diagnose pneumonia or congestive heart failure.

Other Tests

• 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.

Treatment

Medical Care

When delirium is diagnosed or suspected, the underlying causes should be sought. 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
  • These 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.
• Environmental modifications
  • 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. Support from a familiar nurse and family should be encouraged.
  • Family members and staff should explain proceedings at every opportunity, reinforce orientation, and reassure the patient.
  • Sensory deficits should be corrected, if necessary, with eyeglasses and hearing aids.
  • 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.

Consultations

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

Medication

Delirium that causes injury to the patient or others should be treated with medications. The most common medications used are neuroleptics. Benzodiazepines often are used for withdrawal states. 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.²²

Neuroleptics

The medication of choice in the treatment of psychotic symptoms. Older neuroleptics such as haloperidol, a high-potency antipsychotic, are useful but have many 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. Neuroleptics can be associated with adverse neurological effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, and tardive dyskinesia. 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.

Dosing

Adult

Moderate symptomatology: 0.5-2 mg PO bid/tid
Severe symptomatology: 3-5 mg PO bid/tid
Geriatric and debilitated: 0.5-2 mg PO bid/tid; 1-2 mg IM q4-6h

Pediatric

<3 years: Not established
3-12 years: 0.05 mg/kg/d or 0.25-0.5 mg/d PO bid/tid initially and increase by 0.25-0.5 mg q5-7d
Maintenance dose: 0.05-0.15 mg/kg/d PO in 2-3 divided doses; not to exceed 0.15 mg/kg/d
6-12 years: 1-3 mg/dose IM q4-8h, not to exceed 0.15 mg/kg/d; change to PO therapy as soon as possible
>12 years: Administer as in adults

Interactions

May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; rifampin, phenobarbital, and carbamazepine may decrease effects; coadministration with anticholinergics may increase intraocular pressure; encephalopathiclike syndrome is associated with concurrent administration with lithium; Haldol can potentiate CNS depressant effects of alcohol, opiates, and anesthetics

Contraindications

Documented hypersensitivity, Parkinson disease, severe depression, comatose states

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for extrapyramidal symptoms (reduce dose if these occur); avoid anticholinergics; severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, watch for hypotension; caution in diagnosed CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue if it occurs)

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.

Dosing

Adult

0.5-2 mg PO qd or bid
0.5 mg PO bid for elderly debilitated patients with severe renal or hepatic failure or predisposed to hypotension

Pediatric

Not established

Interactions

Coadministration with carbamazepine may decrease effects; may inhibit effects of levodopa; SSRIs and clozapine may increase levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Can cause orthostatic hypotension, seizures, hyperprolactinemia, and body temperature regulation abnormalities; has potential for proarrhythmic effects by prolonging QT interval; > 2 mg/d may increase adverse extrapyramidal effects in elderly patients. (Some studies have shown a possible increased risk of stroke.)

Short-acting sedatives

Reserved for delirium resulting from seizures or withdrawal from alcohol or sedative hypnotics. Coadministration with neuroleptics 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.

Dosing

Adult

0.5-2 mg PO/IV/IM; frequent repeat dosing (q2-4h) may be needed in cases of delirium tremens

Pediatric

Not established

Interactions

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Contraindications

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma; sleep apnea syndrome; severe respiratory insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in limited pulmonary reserve, patients who are elderly, and very ill patients; can cause hypoxic cardiac arrest; caution also needed in patients with myasthenia gravis, organic brain syndrome, or Parkinson disease

Vitamins

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

Thiamine hydrochloride (Thiamilate)

For alcohol withdrawal and in cases of Wernicke encephalopathy.

Dosing

Adult

100 mg IV initially, followed by 50-100 mg/d IV/IM

Pediatric

50 mg IV initially, followed by 10-25 mg/d IV/IM

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy may occur following glucose administration in patients who are thiamine-deficient; administer before or together with dextrose-containing fluids in suspected thiamine deficiency

Cyanocobalamin (Crystamine, Cyomin, 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.

Dosing

Adult

Maintenance dose: 1000 mcg IM monthly or 500 mcg/wk intranasally or 100 mcg/d PO
Load initially if deficient (100 mcg IM injections for 1 wk, then every wk for 6 mo)

Pediatric

10-50 mcg/d IM for 5-10 d, followed by 100-250 mcg/dose IM q2-4wk

Interactions

None reported

Contraindications

Documented hypersensitivity; hereditary optic nerve atrophy

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Intradermal test dose recommended before parenteral administration (anaphylactic shock and death reported with parenteral administration); hypokalemia and thrombocytosis can occur upon conversion from severe megaloblastic anemia to normal erythropoiesis after cyanocobalamin therapy; monitor serum potassium levels and platelet count; vitamin B-12 therapy can unmask polycythemia vera

Follow-up

Further Inpatient Care

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.

Further Outpatient Care

• Following recovery, patient's memories of events of the delirium are variable.
• 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.

Deterrence/Prevention

• 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

• 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

Prognosis

• 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 Education

Patient and family education

• 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

Miscellaneous

Medicolegal Pitfalls

• With altered mental status, determining whether the patient has the capacity to make informed health care decisions is advisable. Ascertain the existence of a legal surrogate.
  • Assessments of capacity are best made by an objective experienced consultant who is familiar with the surrogate decision-making laws in the state.
  • Physicians who understand the patient's medical illness and have skills in determining the patient's capacity may include psychiatrists, geriatric psychiatrists, and geriatricians.
  • The consultant makes a recommendation with regard to capacity. Competence is a legal term, and the final authority rests with the court.
  • Capacity usually is not globally impaired unless delirium or depression is severe or dementia is advanced. Ordinarily, the issue is one of determining specific capacity, such as the capacity to make or withhold informed consent for health care or the capacity to designate a surrogate health care decision-maker. For example, a patient may be unable to understand health care options but may be quite clear and consistent on appointing a specific family member as their surrogate.
  • Surrogate decision-making laws differ from state to state. Advice is best obtained from a practitioner familiar with the laws in the patient's state. This person should be familiar with advance directives, such as durable power of attorney (DPOA) for health care decisions and living wills, and their differing contents. Physicians should request social work assistance and consultation with hospital administrators when decision-making authority is in question.
• Patients with altered mental status are at high risk for elopement. Precautions must be taken to prevent them from leaving the facility and becoming lost or injured.
• Patients with clouded sensorium may attempt to leave the hospital against medical advice (AMA). Immediate consultation should be sought to determine whether the patient has the capacity to understand the consequences of leaving. If they do not, the AMA document would likely be declared invalid, and significant liability could ensue if the patient were to leave and have an adverse outcome. Urgent legal assistance should be obtained to hold the patient against his or her will. Again, hospitals and nursing homes often have administrators on call and legal consultants to help with these difficult cases.
• Explain to the family the patient's condition and the possible causes. This is especially key because of the rapidly fluctuating mental status, which is very hard for families to appreciate and comprehend.

Special Concerns

• Subsyndromal delirium: A condition where a patient has some symptoms of delirium but does not meet the full criteria for the diagnosis of delirium. It is also associated with longer hospital stays and require institutionalization at discharge .
• Delirium may be the only presenting symptom of an underlying medical problem, especially in people who are elderly.
  • Patients with infections may present without fever, patients with myocardial infarction may present without chest pain, and patients with acute stroke may present without hemiparesis.
  • Hypoxemia from pulmonary edema or pulmonary embolus should be considered.
  • Rare causes of delirium, such as carbon monoxide poisoning, should be considered. 
• Obtaining a detailed drug history is imperative because patients may be taking over-the-counter cold and sleep medications, which are frequent causes of delirium. Sometimes, drugs may be the sole cause of delirium. Clinicians should be aware of medications with a significant anticholinergic effect. In patients who develop delirium, a record of all medications and supplements given within the past few weeks should be carefully obtained. In some cases, the drug that is responsible for an episode of delirium is clear because of a temporal relationship. If not, the clinician should carefully analyze the patient's history and look for a characteristic constellation of drug-related findings. Any recent addition of a new medication or increase in dose should be verified.
• The use of complementary medicine is increasing in North America. While these products are considered to be "natural," they may contain ingredients or contaminants that can contribute to delirium. Some examples of herbal products that have anticholinergic effects are henbane, jimson weed, and mandrake. Unfortunately, research on the adverse cognitive effects of complementary and alternative medicine products is limited, so the clinical effects may be greater than perceived.
• Both the cause and symptoms of delirium should be treated. The approach to delirium has been shifted to prevention and early diagnosis and management.

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Keywords

acute confusional state, acute cognitive dysfunction, toxic metabolic encephalopathy, hyperactive delirium, hypoactive delirium, mixed delirium

Contributor Information and Disclosures

Author

Kannayiram Alagiakrishnan, MD, MBBS, Associate Professor, Department of Medicine, Division of Geriatric Medicine, University of Alberta
Kannayiram Alagiakrishnan, MD, MBBS is a member of the following medical societies: American College of Physicians, American Geriatrics Society, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Patricia Blanchette, MD, Department Chair and Director, Geriatric Medicine Fellowship Program, Professor of Geriatric Medicine, Geriatric Medicine, John A Burns School of Medicine, University of Hawaii
Patricia Blanchette, MD is a member of the following medical societies: American College of Physicians, American Geriatrics Society, American Medical Association, American Medical Directors Association, Gerontological Society of America, and Hawaii Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Mohammed A Memon, MD, Medical Director of Geriatric Psychiatry, Department of Psychiatry, Spartanburg Regional Hospital System
Mohammed A Memon, MD is a member of the following medical societies: American Association for Geriatric Psychiatry, American Medical Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Iqbal Ahmed, MBBS, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii
Iqbal Ahmed, MBBS is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

CME Editor

Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin
Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: lilly Honoraria Speaking and teaching; Forest Labs Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; Pfizer Grant/research funds Speaking and teaching; Northstar Grant/research funds Research; Novartis Grant/research funds research; Pfizer  Speaking and teaching; Sanofi-avetis Grant/research funds research; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research

Chief Editor

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Stephen Soreff, MD is a member of the following medical societies: American College of Mental Health Administration and American Psychosomatic Society
Disclosure: Nothing to disclose.

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