Delirium in the hospitalized patient

I. Delirium

Delirium is a disturbance of attention (a reduced ability to direct, focus, sustain, or shift attention) and awareness (reduced orientation to the environment). In the fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, delirium is in the category of “neurocognitive disorders”.

The disturbance of attention and awareness develops over a short period of time (hours to days), represents an acute change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. The individual with delirium has an additional disturbance in cognition (memory deficit, disorientation, language, visuospatial ability or perception) that is not better accounted for by a pre-existing, established, or evolving neurocognitive disorder. It does not occur in the context of a severely reduced level of arousal such as a coma.

There is also evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal, or exposure to a toxin. Often, there are multiple etiologies that can explain a patient’s delirium.

Delirium is common in the inpatient setting, affecting up to 30% of hospitalized patients who are medically ill; this number can be over 50% in the frail elderly undergoing surgery. The most common risk factor for developing delirium while hospitalized is an underlying CNS condition such as dementia, stroke, or Parkinson’s disease. Other risk factors include age >65 (among nursing home residents over 75 years of age, up to 60% may have delirium at any given time), a diagnosis of cancer, human immunodeficiency virus (HIV) infection, sleep deprivation, sensory impairment (decreased vision, hearing), malnutrition, post-surgical status, multiple comorbidities, polypharmacy, and admission to an intensive care unit.

Delirium is often divided into three categories:

Hyperactive: increased psychomotor agitation, often associated with alcohol or benzodiazepine withdrawal, phencyclidine (PCP), lysergic acid diethylamide (LSD) or amphetamine intoxication
Hypoactive: hepatic encephalopathy, hypercapnia
Mixed: daytime sedation with nocturnal agitation and behavioral problems

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The differential diagnosis of the causes of delirium is broad. It is best to approach the problem in a stepwise, systems-based approach.

METABOLIC DISORDERS

Endocrine causes

Hypoglycemia
Hyperglycemia, diabetic ketoacidosis (DKA), hyperosmolar non-ketotic state
Severe hypothyroidism
Apathetic hyperthyroidism

Renal/electrolyte disturbances

Dehydration
Acute and chronic renal insufficiency

(Renal disease can cause delirium in two different ways: uremia as well as decreased renal clearing of drugs)
Hyponatremia/hypoosmolar states
Hyper/hypocalcemia
Hyper/hypomagnesemia
Hyper/hypophosphatemia
Urinary catheter
Acute urinary retention

Hepatic causes

Hepatic encephalopathy with elevated ammonia levels from end stage liver disease (ESLD)
Acute hepatitis

Pulmonary causes

Hypoxemia
Hypercarbia
Carbon monoxide poisoning

Infectious causes

Sepsis from any cause
Pneumonia
Urinary tract infection
Central nervous system infections, such as cerebritis and meningoencephalitis
Fever itself

Neurologic causes

Cerebral ischemia: stroke, transient ischemic attack (TIA) (reverses within 24 hours)
Seizure, especially nonconvulsive status epilepticus
Postictal state
Head Injury
Hypertensive encephalopathy
Sleep deprivation
Pain

Cardiovascular causes

Hypotension, decreased cardiac output from myocardial infarction (MI), arrhythmia, congestive heart failure (CHF)
Myocardial ischemia
Anemia

Nutritional causes

Wernicke’s encephalopathy
Vitamin B12 deficiency
Folate deficiency
Niacin deficiency

DRUGS

Prescription/over-the-counter drugs

Anticholinergics
Antihistamines (diphenhydramine, chlorpheniramine)
Antipsychotics
Benzodiazepines
Histamine H2 blockers (cimetidine, ranitidine)
Muscle relaxers
Opioids

Drugs of abuse

Ethanol
Opioids, including heroin and abuse of prescription drugs such as oxycodone, hydrocodone, et al.
Hallucinogens, including PCP, psilocybin (hallucinogenic mushrooms), peyote, and LSD

Drug withdrawal states

Ethanol
Benzodiazepines

Drug side effects

Valproic Acid: hyperammonemia
Quinalone antibiotics: confusion
Serotonin syndrome (especially drug-drug interactions with selective serotonin re-uptake inhibitors (SSRIs), tramadol, linezolid/fentanyl)

It should be noted that in a patient who is at high risk for developing delirium, any drug could be a precipitant.

TOXINS

Atypical alcohols (methanol, ethylene glycol)
Inhaled toxins (cyanide, carbon monoxide, hydrogen sulfide)
Plant-derived (Jimson weed, salvia)
Heavy metal poisoning

B. Describe a diagnostic approach/method to the patient with this problem

The diagnostic approach to a patient with delirium involves evaluating and treating the underlying cause while also treating the patient’s symptoms. Patients with delirium can put themselves and others at risk from pulling out intravenous lines, catheters, and endotracheal tubes. A patient who is acutely confused is at risk from injury from falls as well.

1. Historical information important in the diagnosis of this problem.

One of the most important components of the patient’s history is determining what the patient’s baseline mental status was before the delirium began. As delirium is often superimposed on dementia or other psychiatric illnesses, it is difficult to determine the extent of the patient’s delirium without this information. Generally, the history is obtained from caregivers rather than the patient directly. Family caregivers and nursing staff are often the most helpful in this regard.

There are several key components to the history:

The temporal nature of the delirium: often, significant clues can be obtained by simply determining when the delirium began and if there were any complaints prior to the change in mental status, such as symptoms of dysuria, cough, fever, and the time of day (i.e., sundowning or symptoms that develop shortly after taking medications).

A complete medication history: if the patient presents to the hospital with delirium, a thorough medication history must be obtained from caregivers, including use of over-the-counter (OTC) medications. Does the patient have access to his or her medications at home? Are they generally self-administered? If the delirium has developed while in the hospital, it is important to review all medications given, not necessarily just new ones. Sleep deprivation is a major cause of delirium, so obtaining a history of the patient’s sleep habits from nursing staff is critical.

A complete past medical history, including any history of substance abuse, a recent illness, depression or other psychiatric illness, or a history of organ failure. Particular attention should be paid to any sensory deficits the patient may have, as these will often contribute to confusion and exacerbate the delirium.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

A complete, detailed physical examination is often difficult in a patient who is confused or uncooperative. A focused assessment is often needed, with particular attention paid to vital signs (hypo/hypertension, fever/hypothermia, tachycardia, tachypnea), the state of hydration (mucus membranes, skin turgor), skin condition (decubiti, cellulitis) and potential foci of infection (such as pneumonia).

The physical examination components that are important to assess in any patient with delirium are:

General appearance: dusky, cyanotic, jaundiced
Head, ears, eyes, nose and throat (HEENT): dilated or constricted pupils, bitten tongue
Skin: spider angiomata, caput medusa, cherry-red lips, diaphoresis
Lungs: rales, rhonchi, localized lung findings of decreased air movement/absent breath sounds
Heart: tachycardia, new murmur with or without fever
Abdomen: taut, absent bowel sounds, liver enlargement
Neurologic: diminished or accentuated deep tendon reflexes

The Confusion Assessment Method (CAM) is a well-validated tool for making a diagnosis of delirium and in allowing the clinician to follow the patient’s response to treatment. It is based on the following criteria for the diagnosis of delirium:

Acute change in mental status (observation by family member, caregiver, or primary care physician) and
Symptoms that fluctuate over minutes or hours (observation by nursing staff or caregiver) and
Inattention (patient history, poor digit recall, inability to recite months of year backwards)

plus

Altered level of consciousness (hyperalertness, drowsiness, stupor, or coma) or
Disorganized thinking (rambling or incoherent speech)

The CAM-ICU is a modified form of the confusion assessment method for patients in the intensive care unit who are on mechanical ventilation. It can be administered by physicians and nurses and is useful for diagnosing and following the course of the delirium.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

In ordering ancillary studies to find the cause of delirium, there are no tests that have been shown to be better than a good history. Targeted testing is the most useful.

Complete blood count (CBC) with differential, serum electrolytes, creatinine, glucose, urinalysis (UA) and urine culture
Drug levels when appropriate
Urine/serum toxicity screens—more useful when the cause is not immediately obvious
Arterial blood gas (ABG), chest x-ray (CXR)
Liver function tests (LFTs), ammonia, thyroid function, B12/folate

Neuroimaging should be used selectively rather than on all patients with delirium. If no cause can be found after the initial assessment, however, a computed tomography (CT) scan of the head is indicated. It is also indicated if the presumed cause of the delirium is corrected and the patient does not return to his or her baseline level of functioning.

Lumbar puncture is indicated if all the above history and testing still does not find a cause for the delirium. Older patients with bacterial meningitis will often present with delirium rather than fever, altered mental status and meningismus.

Electroencephalography (EEG) is not generally indicated, but it can be useful in identifying a patient with an underlying seizure disorder. It is the only way to diagnose non-convulsive status epilepticus.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

The standard mini-mental state exam is often too cumbersome and inexact to be helpful in evaluating a patient with delirium.

III. Management while the Diagnostic Process is Proceeding

A. Management of delirium.

A diagnosis of delirium carries a significant risk of morbidity and mortality. The management of delirium is unique in that it involves not only treating the symptom of delirium, but also treating the underlying cause. Pharmacologic treatment should be instituted only when behavioral and environmental treatments have been ineffective and patients pose a risk to themselves or others. No pharmacologic therapy has U.S. Food and Drug Administration (FDA) approval for this setting. The management of delirium is based primarily on expert consensus and observational studies, as there are few controlled clinical studies.

ENVIRONMENTAL RECOMMENDATIONS

Keeping a (40-60 watt) light on in the patient’s room at night
Have family stay with the patient
Have consistency in nursing staff from day to day
Maintain normal sleep-wake cycles—limit unnecessary nighttime blood draws, vital signs
Give repeated verbal reminders of the day, the time, and identity of persons on the care team
Keep a clock, calendar, and the day’s schedule in the patient’s room
Keep some familiar items from the patient’s home in the room
Correct the patient’s sensory deficits—eyeglasses, hearing aids, dentures

PHARMACOLOGIC RECOMMENDATIONS

Haloperidol

Haloperidol 0.5-2 mg twice a day and every 4 hours as needed

Haloperidol has been the most studied of the antipsychotics in the treatment of delirium. It should not be used in patients with Parkinson’s or neuroleptic malignant syndrome. It prolongs the QT interval and may have extrapyramidal effects, with incidence increasing with more than three doses in 24 hours. When possible, oral dosing is preferred as IV dosing has a relatively short duration of action and increases QTc. IM dosing is also acceptable if the oral route is unavailable.

Atypical antipsychotics

Risperidone 0.5 mg twice a day
Olanzepine 2.5-5 mg/day
Quetiapine 25 mg twice a day

Needs hematologic monitoring

Better in patients with Parkinson’s

These are all associated with increased mortality in the elderly. Monitor the QTc interval.

Benzodiazepines

Lorazepam 0.5-1 mg PO/IV with additional doses every 4 hours as needed

Benzodiazepines are second-line agents. These are best in patients with delirium from sedative/alcohol withdrawal, Parkinson’s, and neuroleptic malignant syndrome. They may cause paradoxical excitation, respiratory depression, and over sedation.

RESTRAINTS

The use of restraints is to be avoided if at all possible. These should be reserved for patients who, despite using environmental and pharmacologic treatments, are still a risk to themselves (by pulling out lines, catheters, or tubes, or not permitting needed care to be given) or a risk to others (combative). Another indication for restraint use would be respiratory depression with further increases in doses of drugs used to treat the delirium. Restraints should be used only for a specified period of time (usually hours) and the need for the restraints should be reassessed frequently. Family and caregivers should be made aware of the use of restraints as soon as possible. Hospitals often have written policies about restraints, giving specific duration, monitoring, and discontinuation guidelines for their use. Restraints can often worsen the delirium.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

By definition, the onset of delirium is rapid and has a fluctuating course. The duration of the symptoms is highly variable and may persist for months. Treatment should be continued until the patient has returned to his or her baseline level of functioning. This can take months. A frequent reassessment of the patient is needed to determine when therapy can be discontinued. Delirium is often very stressful for the family and caregivers and every effort should be made to keep them up to date with the patient’s progress and the expected course of the illness. Delirium in the hospital setting increases the risk of placement in a skilled nursing facility or long-term care.

IV. What's the evidence?

Diagnostic and statistical manual of mental disorders. 2013.

“Practice guidelines for the treatment of patients with delirium”. Am J Psychiatry. vol. 156. 1999. pp. 1-20.

Ely, EW, Inouye, SK. “Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU)”. JAMA. vol. 286. Dec 5, 2001. pp. 2703-10.

Fann, JR. “The epidemiology of delirium: a review of studies and methodological issues”. Semin Clin Neuropsychiatry. vol. 5. 2000. pp. 64-74.

Inouye, S. “Clarifying confusion: the confusion assessment method. A new method for detection of delirium”. Ann Intern Med. vol. 113. 1990. pp. 941-948.

O’Mahoney, R, Murthy, L. “Synopsis of the National Institute for Health and Clinical Excellence guideline for the prevention of delirium”. Ann Intern Med. vol. 154. Jun 7, 2011. pp. 746-751.

Schrijver, EJ. “Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence”. Eur J Intern Med.. vol. 27. 2016 Jan. pp. 14-23.

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Delirium in the hospitalized patient