Delirium

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Delirium
ICD-10	F05
ICD-9	293.0
DiseasesDB	29284
MedlinePlus	000740
MeSH	D003693

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Editor(s)-in-Chief: C. Michael Gibson, M.S.,M.D. [1] Phone:617-632-7753; Vishal Khurana, M.B.B.S., M.D. [2]

Overview

Delirium is an acute and relatively sudden (developing over hours to days) decline in attention-focus, perception, and cognition. In medical usage it is not synonymous with drowsiness, and may occur without it. It is commonly associated with a disturbance of consciousness (eg, reduced clarity of awareness of the environment). The change in cognition (memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance, must be one that is not better accounted for by a preexisting, established, or evolving dementia. Usually the rapidly fluctuating time course of delirium is used to help in the latter distinction.

Because it represents a change in cognitive function, the diagnosis cannot be made without knowledge of the affected person's baseline level of cognitive function.

Without careful assessment, delirium can easily be confused with a number of psychiatric disorders because many of the signs and symptoms are conditions present in dementia, depression, and psychosis. Delirium is probably the single most common acute disorder affecting adults in general hospitals. It affects 10-20% of all hospitalized adults, and 30-40% of elderly hospitalized patients.

Delirium itself is not a disease, but rather a clinical syndrome (a set of symptoms), which result from an underlying disease or new problem with mentation. Like its components (inability to focus attention and various impairments in awareness and temporal and spacial orientation), delirium is simply the common symptomatic manifestation of early brain or mental dysfunction (for any reason).

Distressing symptoms of delirium are sometimes treated with antipsychotics, preferably those with minimal anticholinergic activity, such as haloperidol or risperidone, or else with benzodiazepines, which decrease the anxiety felt by a person who may also be disoriented, and has difficulty completing tasks. However, since these drug treatments do not address the underlying cause of delirium, and may mask changes in delirium which themselves may be helpful in assessing the patient's underlying changes in health, their use is difficult. Because delirium is a mere symptom of another problem which may be very subtle, the wisdom of treatment of the delirious patient with drugs must overcome natural skepticism, and requires a high degree of skill.

Epidemiology and Demographics

• 30% of older patients who are hospitalized experience delirium

  • Therefore have a prolonged hospital stay, at a higher risk for institutionalization and have functional decline

Common usage of the term versus standard medical usage

In common usage, delirium is often used to refer to drowsiness and disorientation. In broader medical terminology, however, a number of other symptoms, including sudden inability of focus attention, and even (occasionally) sleeplessness and severe agitation and irritability, are also defined as "delirium."

There are several medical definitions of delirium (including those in the DSM-IV and ICD-10). However, all include some core features.

The core features are:

• Disturbance of consciousness (that is, reduced clarity of awareness of the environment, with reduced ability to focus, sustain, or shift attention)
• Change in cognition (e.g., problem-solving impairment or memory impairment) or a perceptual disturbance
• Onset of hours to days, and tendency to fluctuate.

Common features also tend to include:

• Intrusive abnormalities of awareness and affect, such as hallucinations or inappropriate emotional states.

Differential Diagnoses

Differential points from other processes and syndromes that cause cognitive dysfunction:

• Delirium may be distinguished from psychosis, in which consciousness and cognition may not be impaired (however, there may be overlap, as some acute psychosis, especially with mania, is capable of producing delirium-like states).
• Delirium is distinguished from dementia (chronic organic brain syndrome) which describes an "acquired" (non-congenital) and usually irreversible cognitive and psychosocial decline in function. Dementia usually results from an identifiable degenerative brain disease (for example Alzheimer disease or Huntington's disease). Once again dementia is not associated with a change in level of consciousness.
• Delirium is distinguished from depression.
• Delirium is distinguished by time-course from the confusion and lack of attention which result from long term learning disorders and varieties of congenital brain dysfunction. Delirium has also been referred to as 'acute confusional state' or 'acute brain syndrome'. The key word in both of these descriptions is "acute" (meaning: of recent onset), since delirium may share many of the clinical (i.e., symptomatic) features of dementia, developmental disability, or attention-deficit hyperactivity disorder, with the important exception of symptom duration.

It is a corollary of the above differential criteria that a diagnosis of delirium cannot be made without a previous assessment or knowledge of the affected person's baseline level of cognitive function.

Pathogenesis

The pathophysiology of delirium that is associated with critical illness remains largely uncharacterized and may vary depending on the cause. The GABAa agonists and anticholinergic drugs are highly associated with the development of delirium. The hypothesis that GABAergic and cholinergic neurotransmitter systems play a contributory role still has not be proven, therefore the pharmacological management strategies are still largely empirical.

Causes

Delirium may be caused by severe physical or mental illness, or any process which interferes with the normal metabolism or function of the brain. For example, 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.

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)
• Toxins/drugs (prescribed - Tramadol, recreational)
• Heavy metals

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 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

Complete List of Differential Diagnoses

• Acidosis
• After hypoxia
• Alcohol/drug withdrawal
• Bacterial Meningitis
• Cerebral contusion
• Cerebral ischemia
• Cerebral masses
• Congestive Heart Failure (CHF)
• Dementia
• Depression
• Drug intoxication
• Hepatic encephalopathy
• HIV
• Hypoglycemia
• Pneumonia
• Postoperative and postconcussive states
• Psychotic illness
• Rheumatic Fever
• Septicemia
• Stroke
• Subarachnoid hemorrhage
• Sundowning
• Thiamine deficiency
• Thyrotoxicosis
• Toxins
• Tuberculosis
• Typhoid Fever
• Viral encephalitis

Commonly co-occurring mental symptoms, with a note on severity

Since delirium may occur in very many grades of severity, all symptoms may occur with varying degrees of intensity. A mild disability to focus attention may result in only a disability in solving the most complex problems. As an extreme example, a mathematician with the flu may be unable to perform creative work, but otherwise may have no difficulty with basic activities of daily living. However, as delirium becomes more severe, it disrupts other mental functions, and may be so severe that it borders on unconsciousness or a vegetative state. In the latter state, a person may be awake and immediately aware and responsive to many stimuli, and capable of coordinated movements, but unable to perform any meaningful mental processing task at all.

Inability to focus attention, confusion and disorientation

The delirium-sufferer loses the capacity for clear and coherent thought. This may be apparent in disorganised or incoherent speech, the inability to concentrate (focus attention), or in a lack of any goal-directed thinking.

Disorientation (another symptom of confusion, and usually a more severe one) describes the loss of awareness of the surroundings, environment and context in which the person exists. It may also appear with delirium, but it is not required, as noted below. Disorientation may occur in time (not knowing what time of day, day of week, month, season or year it is), place (not knowing where one is) or person (not knowing who one is).

Cognitive function may be impaired enough to make medical criteria for delirium, even if orientation is preserved. Thus, a patient who is fully aware of where they are and who they are, but cannot think because they cannot concentrate, may be medically delirious. The state of delirium most familiar to the average person is that which occurs from extremes in pain, lack of sleep, or emotional shock.

Because most high level mental skills are required for problem solving, including ability to focus attention, this ability also suffers in delirium. However, this is a secondary phenomenon, since problem-solving involves many sub-skills and basic mental abilities, any of which may be impaired in a delirious patient.

Memory formation disturbance

Impairments to cognition may include temporary reduction in the ability to form short-term or long-term memory. Difficult short-term memory tasks like ability to repeat a phone number may be continuously disrupted during a delirium, but easier short-term memory tasks like repeating single words, or remembering simple questions long enough to give an answer, may not be impaired. Reduction in formation of new long-term memory (which by definition survive withdrawal of attention), is common in delirium, because initial formation of (new) long-term memories generally requires an even higher degree of attention, than do short-term memory tasks. Since older memories are retained without need of concentration, previously formed long-term memories (i.e., those formed before the period of delirium) are usually preserved in all but the most severe cases of delirium (and when destroyed, are destroyed by the underlying brain pathology, not the delirious state per se).

Abnormalities of awareness and affect

Hallucinations (perceived sensory experience with the lack of an external source) or distortions of reality may occur in delirium. Commonly these are visual distortions, and can take the form of masses of small crawling creatures (particularly common in delirium tremens, caused by severe alcohol withdrawal) or distortions in size or intensity of the surrounding environment.

Strange beliefs may also be held during a delirious state, but these are not considered fixed delusions in the clinical sense as they are considered too short-lived (i.e., they are temporary delusions). Interestingly, in some cases sufferers may be left with false or delusional memories after delirium, basing their memories on the confused thinking or sensory distortion which occurred during the episode of delirium. Other instances would be inability to distinguish reality from dreams.

Abnormalities of affect which may attend the state of delirium may include many distortions to perceived or communicated emotional states. Emotional states may also fluctuate, so that a delirious person may rapidly change between, for example, terror, sadness and jocularity.

Duration

The duration of delirium is typically affected by the underlying cause. If caused by a fever, the delirious state often subsides as the severity of the fever subsides. However, it has long been suspected that in some cases delirium persists for months and that it may even be associated with permanent decrements in cognitive function. Barrough said in 1583 that if delirium resolves, it may be followed by a "loss of memory and reasoning power." Recent studies bear this out, with cognitively normal patients who suffer an episode of delirium carrying an increased risk of dementia in the years that follow. In many such cases, however, delirium undoubtedly does not have a causal nature, but merely functions as a temporary unmasking with stress, of a previously unsuspected (but well-compensated) state of minimal brain dysfunction (early dementia).

Causation

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).

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 are considered by 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.

History and Symptoms

• Thorough history including:

  • Incoherent speech
  • Memory difficulties
  • Disorientation
  • Level of attention
  • Conversations with family and/or caregivers of patient

• Performance of abbreviated mental exam

Risk Factors

• Age
• Cognitive impairments
• Psychiatric conditions
• Severe chronic medical illness

References

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Physical Examination

• Vitals
• Infectious foci
• Hydration state
• Thorough investigation into underlying disease etiologies

Laboratory Findings

• Complete blood count (CBC)
• Glucose
• Calcium
• Urinalysis
• Magnesium
• Blood urea nitrogen (BUN) / creatinine
• Arterial blood gases
• Pulse oximetry
• Vitamin B12
• Folate levels
• Thyroid function tests
• Urine cultures
• Blood cultures

Chest X Ray

• Possible chest X-ray may be indicated

MRI and CT

• Possible head CT scan may be indicated

Other Imaging Findings

• Electroencephalogram (EEG) may be indicated for those patients suspected of having seizure disorders

Other Diagnostic Studies

• Possible lumbar puncture

Accounts of delirium

Sims (1995, p.31) points out a "superb detailed and lengthy description" of delirium in The Stroller's Tale from Charles Dickens' The Pickwick Papers.

Type of Delirium

Phenomenological findings of different motoric subtypes of delirium reveal that purely hypoactive (somnolent) or hyperactive (agitated) patients appear to be monority of cases, with more than 50% of patients experiencing a mixed profile during the course of their illness.

• Hyperactive delirium
• Hypoactive delirium
• Mixed delirium

Treatment of Delirium

Delirium is not a disease, but a syndrome (i.e. collection of symptoms) indicating dysfunction of the brain, in the same way shortness of breath describes dysfunction of the respiratory system, but does not identify the disorder. Treatment of delirium is achieved by treating the underlying dysfunction cause, or in many cases, the causes (plural), as delirium is often multi-factorial.

Antipsychotics are the treatment of choice for distressing symptoms although ones with minimal anticholinergic activity, such as haloperidol or risperidone are preferable. Benzodiazepines are usually used in alcohol withdrawal.

• Treatment of underlying etiology important, as delirium can be reversible if diagnosed and treated correctly
• Surrounding environment supports to help with orientation
• Psychosocial support
• Safety of environment

Pharmacotherapy

Acute Pharmacotherapies

• Antipsychotics
• Benzodiazepines

References

See also

• Deliriant