Delirium

Delirium is defined as a transient disorder characterized by impaired attention, memory impairment, disorientation or language and perceptual disturbances. This is the manifestation of an underlying medical condition such as infection, coronary ischemia, hypoxemia, or metabolic derangement. Delirium usually has a rapid onset (hours to days) and is episodic within this time range. Incidence

• Delirium is one of the most common mental disorders found in both the ED and in-patient populations. In medically ill hospitalized patients approximately 10-30% of patients experience delirium.
• Delirium is particularly common among elderly individuals, especially those with preexisting cognitive impairments such as dementia. Approximately 40% of hospitalized demented patients are delirious.
• Risk factors include: low serum albumin, multiple medical problems, dementia or cognitive impairment, polypharmacy, metabolic disturbances, few social interactions, advanced age, infection, fractures, visual impairment, fever or hypothermia, psychoactive drug use.
• Delirium has been associated with increased mortality, though specific mortality risk depends on a variety of factors.

Clinical Presentation

Diagnostic Methods

• If delirium is suspected, the priority should be to identify contributory medical problems.
  Table: Medical conditions that can cause delirium

  CNS Disorders	Metabolic Disorders	Cardiopulmonary Disorders	Systemic Illness
  Head trauma Seizures Postictal state Vascular disease Degenerative disease	Renal failure Hepatic failure Anemia Hypoxia Hypoglycemia Thiamine deficiency Endocrinopathy Fluid or electrolyte imbalance Acid-base imbalance Low serum albumin	Myocardial infarction Congestive heart failure Cardiac arrhythmia Shock Respiratory failure	Sub intoxication/withdrawal Infection Neoplasm Severe trauma Sensory deprivation Temperature dysregulation Postoperative state Cancer

• Evaluation should include a comprehensive physical examination incorporating medical history, neurological examination, vital signs, and anesthesia record (if postoperative).
• Mental status should be assessed periodically. Cognitive tests such as clock face, digit span, and trailmaking tests, may be useful in identifying symptoms of delirium.
• The patient’s medications should be reviewed, as delirium is frequently associated with medication initiation or withdrawal (some of the substances that have been associated with delirium are listed in Table 17.5).
• Routine laboratory tests may be helpful in determining the etiology of delirium and may include: complete blood count, blood chemistries (electrolytes, BUN and serum creatinine, thyroid, glucose, calcium, albumin, liver function studies [SGOT, SGPT, bilirubin], alkaline phosphatase, magnesium, PO4) urinalysis, electrocardiography, chest X-ray, and measurement of arterial blood gases or oxygen saturation.
• Other laboratory tests may be indicated depending on the patient’s clinical condition. These tests may include urine culture and sensitivity, urine drug screen, blood tests (venereal disease research laboratory (VDRL), heavy metal screen, B12 and folate
  Table: Drugs that can cause delirium

  Drugs of Abuse	Medications	Toxins
  Alcohol Amphetamines Cannabis Cocaine Hallucinogens Inhalants Opioids Phencyclidine Sedatives Hypnotics Other	Anesthetics Analgesics Antiasthmatic agents Anticholinergics Anticonvulsants Antihistamines Antihypertensive and cardiovascular medications Antimicrobials Antiparkinsonian medications Corticosteroids Diuretics Gastrointestinal medications Muscle relaxants Immunosuppressive agents Lithium and psychotropic medications with anticholinergic properties	Anticholinesterase Organophosphate insecticides Carbon monoxide Carbon dioxide Volatile substances such as fuel or organic solvents

  levels, lupus erythematosus (LE) prep, antinuclear antibody (ANA), urinary porphyrins, ammonia, human immunodeficiency virus (HIV)), blood cultures, measurement of serum levels of medications, lumbar puncture, brain computerized tomography (CT), or magnetic resonance imaging (MRI), or electroencephalogram.

• Electroencephalograms (EEG) of patients experiencing delirium commonly reflect generalized slowing and in some types of delirium may show low-voltage fast-activity (e.g., alcohol or sedative withdrawal). This escalated activity is often associated with agitated behavior.
• Various nursing scales may have clinical utility in detecting symptoms of delirium: NEECHAM Confusion Scale, Confusion Rating Scale (CRS), Clinical Assessment of Confusion (CAC-A), and the MCV Nursing Delirium Rating Scale (MCV-NDRS).
• The Delirium Symptoms Interview (DSI) is an interview schedule used to guide the diagnosis of delirium.
• Checklist, analog, and algorithm methods used to detect symptoms of delirium include: Confusion Assessment Method (CAM), Delirium Scale (D-Scale), Global Assessment Rating Scale (GARS), Organic Brain Syndrome Scale (OBS), and Saskatoon Delirium Checklist (SDC).
• Other scales are useful for assessing symptom severity among patients already diagnosed with delirium including the Delirium Rating Scale and the Memorial Delirium Assessment Scale (MDAS).

• DSM-IV describes general classifications of delirium
  • Delirium due to a general medical condition
  • Substance-induced delirium
  • Delirium due to multiple etiologies
  • Not otherwise specified
• Cognitive/neurological symptoms may be the result of diffuse cerebral dysfunction and can include: impaired recall and short-term memory, abnormalities of thought process, language alterations (dysgraphia [considered to be a sensitive indicator of delirium] dysarthria, dysnomia, aphasia) visuoconstructional deficits.
• Physical symptoms include autonomic changes (tachycardia, dilated pupils, and sweating).
• Perceptual symptoms include: illusions, visual (most common), auditory, gustatory, olfactory, and tactile hallucinations.
• Behavioral / psychiatric symptoms include: anxiety, irritability and agitation, increased or decreased psychomotor behavior, delusions (often persecutory), sleep-wake cycle disturbances, altered or labile affect, depression, euphoria, apathy, hallucinations (visual and/or auditory).
• Before developing overt delirium the patient may display symptoms such as restlessness, anxiety, irritability, drowsiness, and insomnia.
• Two subtypes of delirium have been described based on psychomotor activity.
  • Hyperactive subtype: patient is agitated, hyperalert
  • Hypoactive subtype: patient is lethargic, hypoalert (may result from an effort to reduce stimulus overload)
• Mental status impairment tends to fluctuate during the 24 h period, between periods of quiet reserve and overt agitation) with increased impairment usually seen in the evening hours. This is referred to as "sundowning".

Differential Diagnosis

• Special attention should be taken as to the sudden versus progressive onset of symptoms, as rapid onset is associated with delirium, while gradual onset may signify dementia.
• Cognitive disturbances associated with delirium tend to be reversible, while those associated with dementia generally are not.

Treatment

• The first priority in delirium management is to address any underlying physical causes. Consequently, medical clearance guidelines should be followed to ensure all possible contributory medical conditions are addressed.
• Environmental regulation is important in the management of a patient experiencing delirium.
  • Patient should be provided with a safe quiet environment.
  • Family members may be of help to keep the patient calm and secure.
  • Sensory impairments should be reduced.
  • Environmental cues should be used to facilitate orientation (e.g., clocks, calendars, lighting cues).
• Cognitive-emotional support can be helpful in strengthening any retained adaptive cognitive functioning.
• The use of restraints should be avoided as this could increase agitation and carry risks for injury.
• Pharmacological intervention is indicated for behavioral control and subjective distress. Neuroleptics of the butyrophenone class (haloperidol and droperidol) are favored over phenothiazines, which cause more sedation and which may exacerbate delirium.
  1. Historically traditional neuroleptics have been the treatment of choice for delirium.
     • Haloperidol (doses of 1-2 mg every 2-4 h as needed) either orally or parenterally, may be repeated until agitation is controlled. Haloperidol is the treatment of choice for patients in whom oral administration is impractical. For patients experiencing severe delirium, intravenous administration may be helpful. An initial haloperidol bolus of 10 mg IV followed by continuous intravenous infusion of 5-10 mg/h) offers rapid onset and continued efficacy. Elderly patients should initially receive low doses (0.25-0.5 mg orally or 0.125-0.25 mg parenterally). The use of haloperidol is associated with side effects including extrapyramidal symptoms and hypotension.
  2. Atypical antipsychotic agents have shown efficacy in treating delirium.
     • Risperidone is regarded as the preferred atypical antipsychotic for the treatment of delirium. Risperidone can be started at 0.25-0.5 mg twice daily, and increased to 4 mg/day if symptoms initially fail to clear. Maintenance doses of 0.25-0.5 mg may be given every 4 h for persistent agitation or decreased delirium. In rare cases risperidone has been associated with the onset of delirium, but this has not occurred in the absence of other risk factors (e.g., coprescribed medications, old age, or medical conditions).
     • Initial findings indicate that olanzapine (5-15 mg/day) has comparable efficacy to haloperidol (1.5-10 mg/day) in treating delirium without substantial risk of EPS. An initial dose of 2.5-5 mg at bedtime is a reasonable starting dose, and may be increased to 20 mg/day if symptoms fail to respond. Supplemental doses may be given, but this practice has not consistently produced greater efficacy. The side effect most commonly associated with olanzapine has been sedation.
     • Initial findings indicate that quetiapine (25-750 mg/day) is equally efficacious as haloperidol (1-10 mg/day) in treating delirium. The effective dose of quetiapine is somewhat variable, but the initial dose should be in the range of 25-50 mg twice daily. If it is well tolerated, it can be increased every 1-2 days to 100 mg twice daily. Additional doses of 25-50 mg may be given every 4 h for agitated or delirium symptoms. One case report indicated that quetiapine use was temporally related to the onset of delirium, though the mechanism of this was not understood.
     • A case report indicated that ziprasidone 40-100 mg/day may be effective in treating delirium. In a case of extreme overdose (4020 mg) ziprasidone was associated with the onset of delirium.
  3. Benzodiazepine monotherapy is usually ineffective for most types of delirium.
     • Benzodiazepines are generally reserved for cases of suspected alcohol, suicide or other substance withdrawal.
     • When benzodiazepines are used, a relatively short-acting medication with no active metabolites (e.g., lorazepam) should be selected.
     • Combined haloperidol and lorazepam therapy can be started with 3 mg IV of haloperidol followed immediately by 0.5-1.0 mg IV of lorazepam and then modified according to the patient’s degree of improvement.
     • The use of lorazepam for treatment of delirium has been associated with ataxia, oversedation, disinhibition, and increased confusion.
• Delirium associated with specific etiologies requires specific pharmacological interventions:
  • For delirium caused by anticholinergics, cholinergic drugs may be helpful. Within this class of drugs, physostigmine, a cholinesterase inhibitor has been used most commonly. Physostigmine may be used in intramusuclar or intravenous doses of 0.16 to 2.00 mg, or as 3 mg/h continuous intravenous infusions. Side effects associated with cholinesterase inhibitors include bradycardia, nausea, vomiting, salivation, and increased gastrointestinal acid.
  • For delirium associated with hypercatabolic conditions, paralytic sedation and mechanical ventilation may be required.
  • For delirium related with alcohol withdrawal, folate and thiamine should be administered.
  • Palliative treatment, involving morphine or other opiates, may be effective for patients in whom pain is an aggravating factor. However, opiates are known to have anticholinergic effects which can exacerbate delirium.
  • Multivitamins might be helpful for malnourished patients who might be experiencing delirium as a result of B vitamin deficiencies.
• The prognosis for delirious patients is generally positive.
  • Elderly patients, however, often do not recover fully, and persistent cognitive deficits are common.