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).
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).
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).
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).
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).
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 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).
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).
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.
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.
DELIRIUM: Mnemonic for Reversible Causes of Delirium
Lack of drugs
Reduced sensory input
Rare: consider only if new focal neurologic findings, suggestive history, or work-up are otherwise negative
I WATCH DEATH: Mnemonic for Differential Diagnosis of Delirium
HIV, sepsis, pneumonia
Alcohol, barbiturate, sedative-hypnotic
Acidosis, alkalosis, electrolyte disturbance, hepatic failure, renal failure
Closed-head injury, heat stroke, postoperative, severe burns
Abscess, hemorrhage, hydrocephalus, subdural hematoma, infection, seizures, stroke, tumors, metastases, vasculitis, encephalitis, meningitis, syphilis
Anemia, carbon monoxide poisoning, hypotension, pulmonary or cardiac failure
Vitamin B12, folate, niacin, thiamine
Hyper/hypoadrenocorticism, hyper/hypoglycemia, myxedema, hyperparathyroidism
Hypertensive encephalopathy, stroke, arrhythmia, shock
Toxins or drugs
Prescription drugs, illicit drugs, pesticides, solvents
Lead, manganese, mercury
Dr. DRE: Mnemonic for Conditions to Consider
Diseases (Sepsis, COPD, CHF)
Drug removal (SATs and stopping benzodiazepines/narcotics)
Environment (Immobilization, sleep and day/night, hearing aids, glasses)
THINK: Mnemonic for What to “Think” About
Infection/sepsis (nosocomial); Immobilization
K+ (potassium) or electrolyte problems
DELIRIOUS: Mnemonic of Delirium Causes
Drugs (continuous drips, Na+, Ca+, BUN/Cr, NH3+)
Environmental factors (hearing aids, eye glasses, sleep/wake cycle)
Labs (including Na+, K+, Ca+, BUN/Cr, NH3+)
Respiratory status (ABGs-PaO2 and PCO2)
Organ failure (renal failure, liver failure, heart failure)
Shock (sepsis, cardiogenic)/steroid