Delirium causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vishal Khurana, M.B.B.S., M.D. [2];Pratik Bahekar, MBBS [3]

Overview

Delirium may be caused by severe physical or mental illness, or any process which interferes with the normal metabolism or function of the brain e.g., fever, pain, poisons (including toxic drug reactions), brain injury, surgery, traumatic shock, severe lack of food or water or sleep, and even withdrawal symptoms of certain drug and alcohol dependent states, are all known to cause delirium. In addition, there is an interaction between acute and chronic symptoms of brain dysfunction; delirious states are more easily produced in people already suffering with underlying chronic brain dysfunction.

A very common cause of delirium in elderly people is a urinary tract infection, which is easily treatable with antibiotics, reversing the delirium. Delirium, like mental confusion, is a very general and nonspecific symptom of organ dysfunction, where the organ in question is the brain. In addition to many organic causes relating to a structural defect or a metabolic problem in the brain (analogous to hardware problems in a computer), there are also some psychiatric causes, which may also include a component of mental or emotional stress, mental disease, or other "programming" problems (analogous to software problems in a computer).

Causes

Too many to list by specific pathology, general categories of cause of delirium include:

Gross Structural Brain Disorders

• Head trauma (i.e., concussion, traumatic bleeding, penetrating injury, etc.),
• Gross structural damage from brain disease (stroke, spontaneous bleeding, tumor, etc.).

Neurological Disorders

• Various neurological disorders,
• Lack of sleep.

Circulatory

• Intracranial Hypertension.

Lack of Essential Metabolic Fuels, Nutrients, etc.

• Hypoxia,
• Hypoglycemia,
• Electrolyte imbalance (dehydration, water intoxication).

Toxication

• Intoxication various drugs, alcohol, anesthetics,
• Sudden withdrawal of chronic drug use ("de-tox") in a person with certain types of drug addiction (e.g. alcohol, see delirium tremens, and many other sedating drugs),
• Poisons (including carbon monoxide and metabolic blockade),
• Medications including psychotropic medications.

Mental Illness per se is not a cause, as a matter of definition

Some mental illnesses, such as mania, or some types of acute psychosis, may cause a rapidly fluctuating impairment of cognitive function and ability to focus. However, they are not technically causes of delirium, since any fluctuating cognitive symptoms that occur as a result of these mental disorders areconsideredby definition to be due to the mental disorder itself, and to be a part of it. Thus, physical disorders can be said to produce delirium as a mental side-effect or symptom; however primary mental disorders which produce the symptom cannot be put into this category, once identified. However, such symptoms may be impossible to distinguish clinically from delirium resulting from physical disorders, if a diagnosis of an underlying mental disorder has yet to be made.

Common Causes of Delirium

A mnemonic for the myriad causes of Delirium: IWATCHDEATH

• Infections (Pneumonia, Urinary Tract Infections),
• Withdrawal (Ethanol,opiate),
• Acute Metabolic (acidosis, renal failure, imbalances, alkalosis),
• Trauma (acute severe pain),
• Central nervous system pathology (epilepsy, cerebral haemorrhage),
• Hypoxia,
• Deficiencies (vitamin B12, thiamine),
• Endocriopathies (thyroid, parathyroid, hypopituitarism, hyper/hypoglycemia, Cushing's),
• Acute vascular (Stroke, MI, PE, heart failure),
• Heavy metals,
• Toxins/drugs (prescribed - Tramadol, recreational).

List of Commonly Prescribed Medicines Attributing to Delirium

• Antiarrhythmic,
• Antihistamine,
• Antiparkinsonian drugs such as benzatropine,
• Antispasmodic,
• Benzodiazepine,
• Diuretic e.g. Furosemide,
• Incontinence Oxybutynin,
• Opioid Analgesics,
• Tricyclic antidepressant.

Causes by Organ System

Cardiovascular	Malignant hypertension , Heart failure
Chemical/Poisoning	Withdrawal states from ethanol, benzodiazepines , Water hemlock poisoning , Toxic mushrooms -- Monomethylhydrazine , Toluene , Texas Mescalbean poisoning , Poison hemlock , Organic solvent , Methanol , Marijuana , Lead , Jimson weed, , Hyperbaric sickness , Hydrogen sulfide , Heroin , Hallucinogens , Ethylene glycol , Ethanol , Daphne poisoning , Cyanide , Carbon tetrachloride , Carbon monoxide toxicity , Alcohol withdrawal , Thallium Sulfate poisoning , Phencyclidine poisoning , Nickel Carbonyl poisoning
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Valproic acid , Skeletal muscle relaxers , Serotonin syndrome , Quinolones , Lithium , Drug withdrawal , Drug overdose , Cabergoline , Antipsychotics, Antihistamines
Ear Nose Throat	No underlying causes
Endocrine	Pituitary apoplexy , Phaeochromocytoma , Hypothyroidism , Hypopituitarism , Hypoglycemia , Hyperthyroidism , Hyperosmolar non-ketotic diabetic coma , Hyperglycemia , Hyperthyroidism , Elevated or depressed pituitary function , Elevated or depressed adrenal function , Diabetic ketoacidosis , Diabetic hypoglycemia , Cushing syndrome , Adrenal cortex insufficiency
Environmental	Hypothermia , Hyperthermia , Heat stroke , Electric shock , Decompression sickness , Acute Altitude sickness
Gastroenterologic	Elevated or depressed pancreas function , Chronic Liver failure , Acute Liver failure
Genetic	No underlying causes
Hematologic	Thrombocytosis , Polycythemia , Leukemic blast cell crisis , Hypereosinophilia
Iatrogenic	Postoperative stress
Infectious Disease	Viral Hemorrhagic Fevers , Vancomycin resistant enterococcal bacteremia , Urinary tract infection , Typhoid fever , systemic inflammatory response syndrome , Systemic infections , Surgical wound infection , Subdural empyema , Sleeping sickness (West African) , Sleeping sickness (East African) , Sepsis , Rickettsiae , Rabies , Pyelonephritis, acute , Plague , Neurocysticercosis , Malaria , Intraspinal abscess / granuloma , Intracranial abscess / granuloma , Infections , Gangrene , Chest infection , Cerebral malaria , Brain or epidural abscess , Brain infection
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	Venous sinus thrombosis , Raised intracranial pressure , Post-ictal states , Nonconvulsive status epilepticus , Meningoencephalitis , Meningitis , Intracranial bleeding , Hypertensive encephalopathy , Epileptic seizures , Epidural haemorrhage , Encephalitis , Encephalitis , Cerebrovascular accident , Cerebral oedema , Cerebral infarction , Brain tumor , Brain bleeding , Brain abscess
Nutritional/Metabolic	Wilson's disease , Wernicke's encephalopathy , Vitamin B12 deficiency , Thiamine (Vitamin B1) deficiency , Niacin deficiencies , Folate deficiency , Acute intermittent porphyria
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	Schizoaffective disorder , Mental stress , Mental exhaustion
Pulmonary	Respiratory failure , Hypoxemia , Hypercarbia
Renal/Electrolyte	Hypophosphatemia , hypoosmolar states , Hyponatremia , Hypocalcemia , Hyperosmolar states , Hypernatremia , Hypermagnesemia , Hypercalcemia , Hypomagnesemia , Hyperphosphatemia , Chronic Renal failure , Acute Renal failure
Rheumatology/Immunology/Allergy	Vasculitis
Sexual	No underlying causes
Trauma	Trauma , Skull fracture , Head injury
Urologic	No underlying causes
Miscellaneous	Coproporphyria , Burns

Causes in Alphabetical Order

Acute intermittent porphyria Acute Liver failure Acute Renal failure Adrenal cortex insufficiency Alcohol withdrawal Altitude sickness, acute Antihistamines Antipsychotics Brain abscess Brain bleeding Brain infection Brain or epidural abscess Brain tumor Burns Cabergoline Carbon monoxide toxicity Carbon tetrachloride Cardiac failure Cerebral infarction Cerebral malaria Cerebral oedema Cerebrovascular accident Chest infection Chronic Liver failure Chronic Renal failure Coproporphyria, hereditary Cushing syndrome Cyanide Daphne poisoning Decompression sickness Diabetic hypoglycemia Diabetic ketoacidosis Drug overdose Drug withdrawal Electric shock Elevated or depressed adrenal function Elevated or depressed pancreas function Elevated or depressed pituitary function Encephalitis Encephalitis Epidural haemorrhage Epileptic seizures Ethanol Ethylene glycol Fat embolism Folate deficiency Gangrene Hallucinogens Head injury Heart failure

Heat stroke Heroin Hperthyroidism Hpherphosphatemia Hydrogen sulfide Hyomagnesemia Hyperbaric sickness Hypercalcemia Hypercarbia Hypereosinophilia Hyperglycemia Hypermagnesemia Hypernatremia Hyperosmolar non-ketotic diabetic coma Hyperosmolar states Hypertensive encephalopathy Hyperthermia Hyperthyroidism Hypocalcemia Hypoglycemia Hyponatremia hypoosmolar states Hypophosphatemia Hypopituitarism Hypothermia Hypothyroidism Hypoxemia Hypoxia Infections Intracranial abscess / granuloma Intracranial bleeding Intraspinal abscess / granuloma Jimson weed Lead Leukemic blast cell crisis Lithium Liver failure Malaria Malignant hypertension Marijuana Meningitis Meningoencephalitis Mental exhaustion Mental stress Methanol Neurocysticercosis Niacin deficiencies Nickel Carbonyl poisoning Nonconvulsive status epilepticus

Organic solvent Phaeochromocytoma Phencyclidine poisoning Pituitary apoplexy Plague Poison hemlock Polycythemia Porphyria Post-ictal states Postoperative stress Pyelonephritis, acute Quinolones Rabies Raised intracranial pressure Renal failure, acute Renal failure, chronic Respiratory failure Rickettsiae Schizoaffective disorder Sepsis Serotonin syndrome Skeletal muscle relaxers Skull fracture Sleeping sickness (East African) Sleeping sickness (West African) Subdural empyema Surgical wound infection Systemic infections systemic inflammatory response syndrome Systemic organ failure Texas Mescalbean poisoning Thiamine (Vitamin B1) deficiency Thallium Sulfate poisoning Thrombocytosis Toluene Toxic mushrooms -- Monomethylhydrazine Trauma Typhoid fever Urinary tract infection Valproic acid Vancomycin resistant enterococcal bacteremia Vasculitis Venous sinus thrombosis Viral Hemorrhagic Fevers Vitamin B12 deficiency Water hemlock poisoning Wernicke's encephalopathy Wilson's disease Withdrawal states from ethanol, benzodiazepines

Risk Factors

• Older age,
• Cognitive impairment / dementia,
• Physical comorbidity (biventricular failure, cancer, cerebrovascular disease),
• Psychiatric comorbidity (e.g. depression),
• Sensory impairment (vision, hearing),
• Functional dependence (e.g. requiring assistance for self-care and/or mobility),
• Dehydration / Malnutrition,
• Drugs and drug-dependence,
• Alcohol dependence.

Precipitating factors

Any acute factors that affect neurotransmitter, neuroendocrine or neuroinflammatory pathways can precipitate an episode of delirium in a vulnerable brain. Clinical environments can also precipitate delirium, and optimal nursing and medical care are key component of delirium prevention. Some of the most common precipitating factors are listed below:

• Metabolic
• Malnutrition,
• Dehydration,
• Electrolyte imbalance,
• Anaemia,
• Hypoxia,
• Hypercapnoea,
• Hypoglycaemia,
• Endocrine disorders (e.g. SIADH, Addison’s disease, hyperthyroidism, hypercalcaemia),
• Infection,

• Especially respiratory and urinary tract infections,

• Medication,

• Anticholinergics, dopaminergics, opioids, steroids, recent polypharmacy,

• Vascular,

• Stroke/Transient ischaemic attack,
• Myocardial infarction, arrhythmias, decompensated heart failure,

• Physical/psychological stress,
• Pain,
• Iatrogenic event, esp. post-operative, mechanical ventilation in ICU,
• Chronic/terminal illness, esp. cancer,
• Post-traumatic event, e.g. fall, fracture.
• Immobilisation/restraint,
• Substance withdrawal, esp. alcohol, benzodiazepines,
• Substance intoxication,
• Traumatic head injury.

Due to unspecified etiology

• Unrecognized medication use or substance abuse is the cause of an intoxication or withdrawal delirium,
• A rare cause may surface later, such as disseminated intravascular coagulation,
• Environmental factors.

References