Dementia Special: Delirium, Alzheimer's, Dementia Care, and Supporting CaregiversPage 5 of 51

2. Causes of Delirium

That’s the key to success—a healthy colon.

Eddie Murphy, 1983
Delirious: An HBO Special

One of the difficulties in adequately recognizing delirium is that so many conditions can cause it. Some of the major causes leading to delirium include neurologic issues, medications, infection, dehydration, metabolic changes, fecal impaction, and urinary retention (Maneeton & Maneeton, 2013; Cavallazzi et al., 2012).

Physical Causes

Urinary retention and fecal impaction are commonly cited causes delirium (Gower et al., 2012). Although the connection is not quite clear, cases of cystocerebral syndrome have been referenced in literature since the term was first coined in 1990 by Timothy Blackburn and Marvin Dunn to describe acute urinary retention presenting as delirium (Blackburn et al., 1990; Ble et al., 2001).

Neurologic Causes

Issues with the central nervous system (CNS) can cause delirium. This might seem obvious because delirium is, in fact, a CNS manifestation. While head trauma or even stroke may first come to mind as causes, other conditions such as hypertensive encephalopathy, intracranial neoplasm, and epilepsy can also cause delirium (Maneeton & Maneeton, 2013). Deficits in cholinergic function and the synthesis of acetylcholine, a type of neurotransmitter, are also thought to cause delirium and cognitive decline (Sonneville et al., 2013; Cavallazzi et al., 2012).

Medications

A wide variety of medications can trigger delirium, and can include everything from antibiotics, antidepressants, antipsychotics, lithium, to sedatives and many more. Studies have shown that taking three or more medications can be a risk factor, putting elders—who often take more than one prescription—at particular risk (Maneeton & Maneeton, 2013). Other prescribed medications can cause delirium, especially in older patients. These can include anticholinergic agents, benzodiazepines, and opiates (Cavallazzi et al., 2012).

Commonly prescribed drugs and over-the-counter (OTC) medications have also been implicated in causing delirium. These can include digoxin, diphenhydramine (Benedryl), beta blockers, antibiotics (primarily penicillins, cephalosporins, and quinolones), heartburn controllers like histamine receptor blockers (also called H2 receptor antagonists, eg, Pepcid, Zantac), corticosteroids, and lidocaine (von Moltke et al., 2001; Fujii et al., 2012).

Many illegal drugs can cause delirium. Methamphetamines, cocaine, hallucinogens, inhalants, opioids, and so-called bath salts (synthetic cathinones related to amphetamines) are noted culprits (Maneeton & Maneeton, 2013; National Institute on Drug Abuse, 2012).

Infection

Infections, especially widespread illness like sepsis, can cause delirium (Sonneville et al., 2013). In fact, infection is a leading cause of delirium in pediatric patients (Maneeton & Maneeton, 2013). Other infections such as urinary tract infections, meningitis, encephalitis, and pneumonia can also make patients susceptible to delirium (Maneeton & Maneeton, 2013; NIH, MedLine Plus, 2014a; Grover et al., 2009).

Metabolic Issues

A number of metabolic conditions can cause delirium. Too little or too much of some electrolytes has been implicated in delirium, specifically sodium, calcium, and magnesium. Liver impairment causing elevated liver enzymes or the more serious hepatic encephalopathy, has been implicated in delirium (Nordstrom et al., 2012). Other metabolic disorders contributing to delirium include metabolic acidosis (decreased blood pH due to metabolic processes), hypoxia (low blood oxygen levels), and uremia (elevated blood urea nitrogen, or BUN) (Maneeton & Maneeton, 2013; Aldemir et al., 2001; Gower et al., 2012).

Vitamin Deficiencies

Vitamin deficiencies have been known to cause delirium. Wernicke’s encephalopathy, a severe form of thiamine (Vitamin B1) deficiency often seen in chronic alcohol abuse, is a noted cause of delirium (Oudman et al., 2014). Vitamin B12 and niacin (Vitamin B3) deficiencies are associated with delirium, especially among those with alcoholism (Kibirige & Mwebaze, 2013); Briani et al., 2013; Oldham & Ivkovic, 2012).

Endocrine Disorders

Perhaps one of the most common causes of reversible delirium is abnormal blood sugar. Delirium can occur with hypoglycemia or diabetic ketoacidosis as a result of hyperglycemia (Maneeton & Maneeton, 2013). Although both conditions can be caused by factors other than diabetes, diabetes and/or a side effect of its treatment are the most common causes of blood sugar abnormalities, which can lead to delirium (Sonneville et al., 2013; Sanford & Flaherty, 2014; National Diabetes Information Clearinghouse, 2012; Virtual Labs Media Library, Stanford University, 2005).

A thyroid hormone imbalance can also be the culprit behind the disorder, and is one that is often missed (Medline Plus, 2014a; National Institute of Neurological Disorders & Stroke, 2015).

A more serious form of hypothyroidism, known as myxedema, and a rare condition called Hashimoto’s encephalopathy, wherein autoimmune antibodies attack brain tissue, can also present with delirium (Heinrich & Grahm, 2003; Ma & Leung, 2008; Jain et al., 2015).

While hypothyroidism can result in the hypoactive form of delirium, agitated, or hyperactive delirium can be caused by hyperthyroidism (NIH, Medline Plus, 2015).

Withdrawal Syndrome

Delirium tremens isa form of delirium that occurs during withdrawal, most notably of alcohol, but also with some drugs, such as benzodiazepines, barbiturates, other sedatives, and hypnotics (NIH, MedLine Plus, 2015; Maneeton & Maneeton, 2013). In fact, many of the causes for delirium mentioned previously are related to alcoholism and withdrawal. ICD-10 defines delirium tremens as

a short-lived, but occasionally life-threatening, toxic-confusional state with accompanying somatic disturbances. It is usually a consequence of absolute or relative withdrawal of alcohol in severely dependent users with a long history of use. Onset usually occurs after withdrawal of alcohol. (World Health Organization, 2010)

Heavy Metal Toxicity

Heavy metal toxicity is a rare but noted cause of delirium (Maneeton & Maneeton, 2013). Lead poisoning from exposure to leaded gasoline, industrial processes, paint, battery recycling, and other sources can manifest as symptoms of delirium (Flora et al., 2012).

Exposure to high or prolonged levels of mercury—primarily caused by outgassing of mercury from dental amalgam, ingestion of contaminated fish, or occupational exposure—can result in delirium (Bernhoft, 2012).

Symptoms of severe confusion and hallucinations have been reported with bismuth intoxication caused by overdosing on common preparations (eg, Pepto-Bismol) used to treat upset stomach and peptic ulcers (Tripathi & Vibha, 2009).

Other metal toxicities that are known to cause delirium include aluminum, lithium, manganese, and arsenic, which is used in creating chromated copper arsenate for pressure-treated wood to make it more resistant to water damage (Tripathi & Vibha, 2009).

Mnemonics for the Causes of Delirium

Polonius: Though this be madness, yet there is method in’t.

William Shakespeare
Hamlet, Act 2, Scene 2

The list of potential causes of delirium can confuse even the most experienced clinician. Luckily there are several mnemonic devices that can help. While they vary somewhat in their grouping of causes, they can serve as helpful tools in making a differential diagnosis. See tables below.

Source: Anderson & McDonald, 2009. Adapted from: Saint Louis University Geriatrics Evaluation Mnemonics Screening Tools (SLU GEMS). Developed or compiled by: Faculty from Saint Louis University Geriatrics Division and St. Louis Veterans Affairs GRECC.

DELIRIUM: Mnemonic for Reversible Causes of Delirium

Drugs

  • Any new additions, increased doses, or interactions
  • Consider over-the-counter drugs and alcohol
  • Consider esp. high-risk drugs (anticholinergics, tricyclic antidepressants, some opioids

Electrolyte disturbances

  • Especially dehydration, sodium imbalance
  • Thyroid abnormalities

Lack of drugs

  • Withdrawals from chronically used sedatives, including alcohol and sleeping pills
  • Poorly controlled pain (lack of analgesia)

Infection

  • Especially urinary and respiratory tract infections

Reduced sensory input

  • Poor vision
  • Poor hearing

Intracranial

  • Infection
  • Hemorrhage, stroke, tumor

Rare: consider only if new focal neurologic findings, suggestive history, or work-up are otherwise negative

Urinary, fecal

  • Urinary retention; “cystocerebral syndrome”
  • Fecal impaction

Myocardial, pulmonary

  • Myocardial infarction, arrhythmia, exacerbation of heart failure
  • Exacerbation of chronic obstructive pulmonary disease
  • Hypoxia
Source: ICU Delirium & Cognitive Impairment Study Group, Vanderbilt University, 2013. Permission pending.

I WATCH DEATH: Mnemonic for Differential Diagnosis of Delirium

Infection

HIV, sepsis, pneumonia

Withdrawal

Alcohol, barbiturate, sedative-hypnotic

Acute metabolic

Acidosis, alkalosis, electrolyte disturbance, hepatic failure, renal failure

Trauma

Closed-head injury, heat stroke, postoperative, severe burns

CNS pathology

Abscess, hemorrhage, hydrocephalus, subdural hematoma, infection, seizures, stroke, tumors, metastases, vasculitis, encephalitis, meningitis, syphilis

Hypoxia

Anemia, carbon monoxide poisoning, hypotension, pulmonary or cardiac failure

Deficiencies

Vitamin B12, folate, niacin, thiamine

Endocrinopathies

Hyper/hypoadrenocorticism, hyper/hypoglycemia, myxedema, hyperparathyroidism

Acute vascular

Hypertensive encephalopathy, stroke, arrhythmia, shock

Toxins or drugs

Prescription drugs, illicit drugs, pesticides, solvents

Heavy Metals

Lead, manganese, mercury

Source: ICU Delirium & Cognitive Impairment Study Group, Vanderbilt University, 2013. Permission pending.

Dr. DRE: Mnemonic for Conditions to Consider
When Delirium is Present

D

Diseases (Sepsis, COPD, CHF)

DR

Drug removal (SATs and stopping benzodiazepines/narcotics)

E

Environment (Immobilization, sleep and day/night, hearing aids, glasses)

Source: ICU Delirium & Cognitive Impairment Study Group, Vanderbilt University, 2013. Permission pending.

THINK: Mnemonic for What to “Think” About
When Delirium Is Present

T

Toxic situations:

  • CHF, shock, dehydration
  • Deliriogenic meds (tight titration)
  • New organ failure (eg, liver, kidney)

H

Hypoxemia

I

Infection/sepsis (nosocomial); Immobilization

N

Nonpharmacologic Interventions:

  • Hearing aids
  • Glasses
  • Reorient
  • Sleep protocols
  • Music
  • Noise control
  • Ambulation

K

K+ (potassium) or electrolyte problems

Source: ICU Delirium & Cognitive Impairment Study Group, Vanderbilt University, 2013. Permission pending.

DELIRIOUS: Mnemonic of Delirium Causes

D

Drugs (continuous drips, Na+, Ca+, BUN/Cr, NH3+)

E

Environmental factors (hearing aids, eye glasses, sleep/wake cycle)

L

Labs (including Na+, K+, Ca+, BUN/Cr, NH3+)

I

Infection

R

Respiratory status (ABGs-PaO2 and PCO2)

I

Immobility

O

Organ failure (renal failure, liver failure, heart failure)

U

Unrecognized dementia

S

Shock (sepsis, cardiogenic)/steroid