Delirium: Etiology

By | July 7, 2012

Delirium has a wide variety of etiologies, which may occur alone or in combination (). These include primary cerebral disorders, systemic disturbances that affect cerebral function, drug and toxin exposure (including intoxication and withdrawal), and a range of factors that can contribute to delirium but have an uncertain role as etiological factors by themselves (psychological and environmental factors). To be considered causal, an etiology should be a recognized possible cause of delirium and be temporally related in onset and course to delirium presentation; also, the delirium should not be better accounted for by other factors. No clear cause is found in approximately 10% of patients, and these cases are categorized as delirium not otherwise specified in DSM-IV-TR.

In those studies in which the possibility of multiple etiologies has been considered, between two and six possible causes are typically identified, with a single etiology identified in fewer than 50% of cases. Delirium with multiple etiologies is more frequent in the elderly and those with terminal illness. For example, delirium in cancer patients can be due to the direct effect of the primary tumor or the indirect effects of metastases, metabolic problems (organ failure or electrolyte disturbance), chemotherapy, radiation and other treatments, infections, vascular complications, nutritional deficits, and paraneo-plastic syndromes. This multifactorial nature has been underemphasized in research — etiological attribution typically is based on clinical impressions that are not standardized (e.g., the most likely cause identified by referring physician) or that are oversimplified by documenting a single etiology for each case. That delirium due to a single etiology is the exception rather than the rule highlights the importance of multidisciplinary approaches to management and the need for continued vigilance to the possibility of further etiological inputs even when a cause has been identified.

Some causes are more frequently encountered in particular populations. Delirium in children and adolescents involves the same categories of etiologies as in adults, although specific causes may differ. Delirium related to illicit drugs is more common in younger populations, whereas delirium due to prescribed drugs and polypharmacy is more common in older populations. Cerebral hypoxia is common at age extremes — chronic obstructive airway disease, myocardial infarction, and stroke are common in older patients, and hypoxia due to foreign-body inhalation, drowning, and asthma are more frequent in younger patients. Poisonings are also more common in children than in adults, whereas young adults have the highest rates of head trauma.

Once delirium is diagnosed, a careful and thorough, but prioritized, search for causes must be conducted. Ameliorations of specific underlying causes are important in resolving delirium; however, this should not preclude treatment of the delirium itself, which can reduce symptoms even before underlying medical causes are rectified.

TABLE Selected etiologies of delirium

Drug intoxication
Alcohol
Sedative-hypnotics
Opiates
Psychostimulants
Hallucinogens
Inhalants
Drug withdrawal
Alcohol
Sedative-hypnotics
Metabolic and endocrine disturbance
Volume depletion or volume overload
Acidosis or alkalosis
Hypoxia
Uremia
Anemia
Hepatic failure
Hypoglycemia or hyperglycemia
Hypoalbuminemia
Bilirubinemia
Hypocalcemia or hypercalcemia
Hypokalemia or hyperkalemia
Hyponatremia or hypernatremia
Hypomagnesemia or hypermagnesemia
Hypophosphatemia
Thyroid storm
Hypopituitarism
Other metabolic disorders (e.g., porphyria, carcinoid syndrome)
Traumatic
Traumatic brain injury
Subdural hematoma
Fat emboli
Hypoxic
Pulmonary insufficiency
Pulmonary emboli
Neoplastic disease
Intracranial primary/metastasis/meningeal carcinomatosis
Paraneoplastic syndrome
Intracranial infection
Meningitis
Encephalitis
Abscess
Neurosyphilis
Human immunodeficiency virus
Systemic infection
Bacteremi a/sepsis
Fungal
Protozoal
Viral
Cerebrovascular
Stroke, transient ischemic attack
Subarachnoid hemorrhage
Other central nervous system disorders
Cerebral edema
Seizures
Hypertensive encephalopathy
Eclampsia
Autoimmune
Central nervous system vasculitis
Systemic lupus erythematosus
Acute graft rejection
Acute graft vs. host disease
Cardiac
Heart failure
Endocarditis
Other systemic etiologies
Postoperative state
Hyperthermia: heatstroke, neuroleptic malignant syndrome,
malignant hyperthermia
Hypothermia
Disseminated intravascular coagulation and other
hypercoagulable states
Radiation
Electrocution

TABLE Selected drugs causing delirium

Analgesics
Opiates (especially meperidine, pentazocine)
Salicylates
Antimicrobials
Acyclovir, ganciclovir
Aminoglycosides
Amphotericin B
Antimalarials
Cephalosporins
Chloramphenicol
Ethambutol
Interferon
Isoniazid
Metronidazole
Rifampin
Sulfonamides
Vancomycin
Anticholinergic drugs
Antihistamines, H; (e.g., diphenhydramine)
Antispasmodics
Atropine and atropine-like drugs (e.g., scopolamine)
Benztropine
Biperiden
Phenothiazines (especially thioridazine)
Tricyclics (especially amitriptyline)
Trihexyphenidyl
Anticonvulsants
Phenobarbital
Phenytoin
Valproic acid
Anti-inflammatory drugs
Corticosteroids
Nonsteroidal anti-inflammatory drugs
Antineoplastic drugs
Aminoglutethimide
Asparaginase
Dacarbazine (DTIC)
5-Fluorouracil
Hexamethylenamine
Methotrexate (intrathecal)
Procarbazine
Tamoxifen
Vinblastine
Vincristine
Antiparkinsonian drugs
Amantadine
Bromocriptine
Levodopa
Cardiac drugs
Beta-blockers
Captopril
Clonidine
Digitalis
Disopyramide
Lidocaine
Methyldopa
Mexiletine
Procain amide
Quinidine
Tbcainide
Sedative-hypnotics
Barbiturates
Benzodiazepines
Stimulants
Amphetamines
Cocaine
Ephedrine, epinephrine, phenylephrine
Theophylline
Miscellaneous drugs
Antihistamines, H2 (e.g., cimetidine, ranitidine)
Baclofen
Bromides
Chlorpropamide
Disulfiram
Ergotamines
Lithium
Metrizamide (intrathecal)
Podophyllin (by absorption)
Propylthiouracil
Quinacrine
Timolol ophthalmic