Delirium - Information Overview

Delirium is an acute, transient, usually reversible, fluctuating disturbance of attention, perception, and level of consciousness. Delirium can be caused by virtually any disease, intoxication, or pharmacological effects. Diagnosis is made clinically, using clinical, laboratory, and imaging studies to determine the cause of delirium. Treatment involves correcting the cause of delirium and supportive therapy.

Delirium can develop at any age, but is more common in older people. At least 10% of older patients admitted to hospitals have delirium; 15% to 50% have had delirium during previous hospitalizations. Delirium also commonly occurs in patients cared for at home by medical staff. When delirium develops in younger people, it is usually the result of medication use or a manifestation of some systemic life-threatening condition.

The DSM-IV defines delirium as "a disturbance of consciousness and changes in cognitive processes that develop over a short period of time" (American Psychiatric Association, DSM-IV). Delirium is characterized by easy distractibility of patients, impaired concentration, memory impairment, disorientation, and speech impairment. These cognitive disorders can be difficult to assess due to the inability of patients to concentrate attention and rapid fluctuations in symptoms. Associated symptoms include affective disorders, psychomotor agitation or retardation, and perceptual disorders such as illusions and hallucinations. Affective disorders during delirium are extremely variable and can be represented by anxiety, fear, apathy, anger, euphoria, dysphoria, irritability, which often replace each other within a short time. Perceptual disorders are especially often represented by visual hallucinations and illusions, less often they are auditory, tactile, or olfactory in nature. Illusions and hallucinations are often distressing to patients and are usually described as fragmentary, vague, dreamlike, or nightmarish images. Confusion may be accompanied by behavioral manifestations such as pulling out intravenous lines and catheters.

Delirium is classified depending on the level of wakefulness and psychomotor activity. The hyperactive type is characterized by pronounced psychomotor activity, anxiety, alertness, rapid excitability, loud and insistent speech. The hypoactive type is characterized by psychomotor slowness, calmness, detachment, weakening of reactivity and speech production. In a "violent" patient who attracts the attention of others, delirium is easier to diagnose than in a "quiet" patient who does not bother other patients or medical personnel. Since delirium carries an increased risk of serious complications and death, it is difficult to overestimate the importance of timely recognition and adequate treatment of "quiet" delirium. On the other hand, in violent patients, treatment may be limited to suppression of excitement using pharmacological agents or mechanical fixation of the patient, while an appropriate examination is not carried out that can establish the cause of delirium.

The cause of delirium cannot be determined with certainty by the level of activity. The patient's activity level during one episode may vary or may not fall into any of the above categories. However, hyperactivity is more often observed in intoxication with anticholinergic drugs, alcohol withdrawal syndrome, thyrotoxicosis, while hypoactivity is more typical of hepatic encephalopathy. These types are distinguished on the basis of phenomenology and do not correspond to any specific changes in the EEG, cerebral blood flow, or level of consciousness. Delirium is further divided into acute and chronic, cortical and subcortical, anterior and posterior cortical, right and left cortical, psychotic and non-psychotic. DSM-IV classifies delirium by etiology.

The importance of the problem of delirium

Delirium is a pressing health issue because this very common syndrome can cause serious complications and death. Patients with delirium stay in hospital longer and are more often transferred to mental health facilities. Behavioral disorders can interfere with treatment. In this condition, patients often refuse to consult a psychiatrist.

Delirium and forensic psychiatry

This is a state of impaired consciousness, with confusion, disorientation, possibly with delirium, vivid hallucinations or delusions. It may have many organic causes. However, the medical defence is based on the state of mind, not on what caused it. It is extremely rare for someone to commit a crime while in a state of organic delirium. The court's decision to commit such an offender to appropriate services will depend on the clinical needs of the person. The choice of defence will also depend on the individual's situation. It may be appropriate to plead not guilty by reason of lack of intent, or to seek an order for hospitalisation (or some other form of treatment) on the grounds of mental illness, or (in very severe cases) to plead insanity under the McNaughten Rules.

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Epidemiology of delirium

Among hospitalized patients, the incidence of delirium is 4-10% of patients per year, and the prevalence is from 11 to 16%.

According to one study, postoperative delirium most often occurs in patients with a hip fracture (28-44%), less often in patients who have undergone hip replacement surgery (26%) and myocardial revascularization (6.8%). The prevalence of delirium largely depends on the characteristics of the patient and the hospital. For example, delirium is more often observed in hospitals where complex surgical interventions are performed or in specialized centers where especially severe patients are referred. In regions with a higher prevalence of HIV infection, delirium caused by complications of HIV infection or its treatment is more common. The prevalence of substance abuse, another common cause of delirium, varies greatly in different communities, which, along with the properties of the substances themselves and the age of the patients, significantly affects the frequency of delirium. Delirium was noted in 38.5% of patients over 65 years of age admitted to a psychiatric hospital. At the same time, delirium was detected in 1.1% of people over 55 years old registered with the East Baltimore Mental Health Service.

Delirium is more common in patients admitted to a psychiatric hospital from nursing homes (64.9%) than in patients who lived in the general population before admission (24.2%). This is not surprising, since patients admitted to nursing homes are usually older and have more serious illnesses. Age-related changes in the pharmacokinetics and pharmacodynamics of drugs may partly explain the high incidence of delirium in the elderly.

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What causes delirium?

A variety of conditions and medications (especially anticholinergics, psychotropics, and opioids) can cause delirium. In 10-20% of patients, the cause of delirium cannot be determined.

The mechanisms of delirium development have not been fully elucidated, but may be accompanied by reversible disorders of the cerebral redox metabolism, various changes in the exchange of neurotransmitters and the production of cytokines. Stress and any circumstances leading to the activation of the sympathetic nervous system, a decrease in parasympathetic influences, and a violation of cholinergic function contribute to the development of delirium. In elderly people, who are especially sensitive to a decrease in cholinergic transmission, the risk of developing delirium increases. It is also impossible, of course, not to take into account the violation of the functional activity of the cerebral hemispheres and thalamus and a decrease in the influence of the brainstem activating reticular formation.

Differential diagnosis of delirium and dementia

Sign	Delirium	Dementia
Development	Sudden, with the ability to determine the time of onset of symptoms	Gradual and gradual, with an uncertain time of onset of symptoms
Duration	Days or weeks, but it can be longer.	Usually constant
Cause	Usually, it is always possible to identify a causal relationship (including infection, dehydration, use or withdrawal of medications)	Usually there is a chronic brain disease (Alzheimer's disease, dementia with Lewy bodies, vascular dementia)
Flow	Usually reversible	Slowly progressive
Severity of symptoms at night	Almost always more pronounced	Often more pronounced
Attention function	Significantly impaired	Does not change until dementia becomes severe
Severity of disturbances in the level of consciousness	Varies from slow to normal	Does not change until dementia becomes severe
Orientation in time and place	It can be different	Violated
Speech	Slow, often disconnected and inappropriate to the situation	Sometimes there are difficulties in choosing words
Memory	Hesitates	Violated, especially in light of recent events
Need for medical care	Immediate	Required, but less urgent

The differences are usually significant and help establish the diagnosis, but there are exceptions. For example, traumatic brain injury occurs suddenly but can lead to severe, irreversible dementia; hypothyroidism can lead to slowly progressive dementia that is completely reversible with treatment.

Causes of delirium

Category	Examples
Medicines	Alcohol, anticholinergics, antihistamines (including diphenhydramine), antihypertensives, antiparkinsonian drugs (levodopa), antipsychotics, antispasmodics, benzodiazepines, cimetidine, glucocorticoids, digoxin, hypnogenic drugs, muscle relaxants, opioids, sedatives, tricyclic antidepressants, general tonics
Endocrine disorders	Hyperparathyroidism, hyperthyroidism, hypothyroidism
Infections	Colds, encephalitis, meningitis, pneumonia, sepsis, systemic infections, urinary tract infections (UTIs)
Metabolic disorders	Acid-base imbalance, changes in water-electrolyte balance, hepatic or uremic encephalopathy, hyperthermia, hypoglycemia, hypoxia, Wernicke's encephalopathy
Neurological diseases	Post-concussion syndrome, condition after epileptic seizure, transient ischemia
Organic diseases of the nervous system	Brain abscesses, cerebral hemorrhage, cerebral infarction, primary or metastatic brain tumors, subarachnoid hemorrhage, subdural hematoma, vascular occlusion
Vascular/circulatory disorders (circulatory disorders)	Anemia, cardiac arrhythmia, heart failure, volemia, shock
Vitamin deficiency	Thiamine, vitamin B 12
Withdrawal syndromes	Alcohol, barbiturates, benzodiazepines, opioids
Other reasons	Environmental changes, prolonged constipation, prolonged stay in the intensive care unit (ICU), postoperative conditions, sensory deprivation, sleep deprivation, urinary retention

Predisposing factors include CNS disease (eg, dementia, stroke, Parkinson's disease), older age, decreased perception of the environment, and multiple comorbidities. Precipitating factors include use of ≥3 new medications, infection, dehydration, immobility, malnutrition, and use of a urinary catheter. Recent use of anesthesia also increases the risk, especially if the anesthesia was prolonged and anticholinergics were used during surgery. Decreased sensory stimulation at night may be a trigger for delirium in at-risk patients. Elderly patients in intensive care units are at particularly high risk for delirium (ICU psychosis).

Delirium - Causes and Pathogenesis

Diagnosis of delirium

Diagnosis is clinical. All patients with any cognitive impairment require a formal mental status assessment. Attention should be assessed first. Simple tests include repeating the names of 3 objects, digit span (ability to repeat 7 digits forward and 5 digits backward), and naming the days of the week forward and backward. Inattention (patient does not perceive commands or other information) must be distinguished from short-term memory impairment (i.e., when the patient perceives information but quickly forgets it). Further cognitive testing is useless in patients who do not retain information.

After a preliminary assessment, standard diagnostic criteria are used, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the Confusion Assessment Method (CAM). The diagnostic criteria are an acutely developing thought disorder with daytime and nighttime fluctuations, attentional disturbances (impaired focus and stability of attention), plus additional features: according to the DSM - impaired consciousness; according to the CAM - either changes in the level of consciousness (i.e., agitation, drowsiness, stupor, coma), or disorganized thinking (i.e., jumping from one thought to another, irrelevant conversations, illogical flow of thoughts).

Interviewing family members, caregivers, and friends can determine whether mental status changes are recent or have occurred previously. History taking helps to differentiate psychiatric disorders from delirium. Psychiatric disorders, unlike delirium, almost never cause inattention or fluctuations in consciousness, and their onset is usually subacute. History should also include information about alcohol and illicit drug use, OTC use, prescription medications, particular attention to medications that affect the central nervous system, drug interactions, discontinuation of medications, and changes in dosage, including overdose.

Physical examination should be alert for signs of CNS injury or infection (including fever, meningismus, Kernig's and Brudzinski's signs). Tremor and myoclonus suggest uremia, liver failure, or drug intoxication. Ophthalmoplegia and ataxia suggest Wernicke-Korsakoff syndrome. Focal neurologic symptoms (including cranial nerve palsies, motor or sensory deficits) or papilledema suggest organic (structural) CNS damage.

The work-up should include blood glucose measurement, thyroid function assessment, toxicology screening, plasma electrolyte assessment, urinalysis, microbial culture (especially urine), and cardiovascular and pulmonary examination (ECG, pulse oximetry, chest X-ray).

CT or MRI should be performed if clinical examination suggests a CNS lesion or if the initial evaluation does not reveal a cause for delirium, particularly in patients over 65 years of age, since they are more likely to have a primary CNS lesion. Lumbar puncture may be indicated to exclude meningitis, encephalitis, or SAH. If nonconvulsive status epilepticus is suspected, which is rare (based on history, subtle motor twitches, automatisms, or persistent but less intense drowsiness and confusion), an EEG should be performed.

Delirium - Diagnosis

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Treatment of delirium

Treatment consists of eliminating the cause and eliminating provoking factors (i.e. stopping medications, eliminating infectious complications), providing support to patients by family members, and correcting anxiety to ensure patient safety. Adequate fluids and nutrition should be provided, and in case of nutritional deficiency, vitamin deficiency should be corrected (including thiamine and vitamin B ₁₂ ).

The environment should be stable, calm, welcoming, and include visual cues (calendar, clock, family photos). Regular patient orientation and patient reassurance from health care staff or family members may also be helpful. Sensory deficits in patients should be minimized (including regular replacement of hearing aid batteries, reassurance for patients who require glasses and hearing aids in using them).

The treatment approach should be multidisciplinary (involving a physician, occupational therapist, nurses, and social worker) and should include strategies to increase mobility and range of motion, treat pain and discomfort, prevent skin damage, alleviate urinary incontinence problems, and minimize the risk of aspiration.

Patient agitation may be dangerous to the patient, caregivers, and staff. Simplifying the medication regimen and avoiding intravenous medications, Foley catheters, and activity restrictions (especially during long-term hospital stays) may prevent patient agitation and reduce the risk of injury. However, in some circumstances, activity restrictions may prevent injury to the patient and those around the patient. Activity restrictions should be used only under the supervision of trained staff, who should be changed at least every 2 hours to prevent injury and to eliminate it as quickly as possible. Using hospital staff (nurses) as constant observers may help avoid the need for activity restrictions.

Medications, usually low-dose haloperidol (0.5 to 1.0 mg orally or intramuscularly), reduce anxiety and psychotic symptoms but do not correct the underlying cause and may prolong or exacerbate delirium. Second-generation atypical antipsychotics (including risperidone 0.5 to 3.0 mg orally every 12 hours, olanzipine 2.5 to 15 mg orally once daily) may be used instead; they have fewer extrapyramidal side effects but increase the risk of stroke when used long-term in older adults.

These drugs are not usually given intravenously or intramuscularly. Benzodiazepines (including lorazepam at a dose of 0.5-1.0 mg) have a more rapid onset of action (5 minutes after parenteral administration) than antipsychotics, but usually lead to worsening disorientation and sedation in patients with delirium.

In general, both antipsychotics and benzodiazepines are equally effective in treating anxiety in patients with delirium, but antipsychotics have fewer side effects. Benzodiazepines are preferred in patients with delirium to treat sedative withdrawal and in patients who do not tolerate antipsychotics well (including those with Parkinson's disease, dementia with Lewy bodies). Doses of these drugs should be reduced as soon as possible.

Delirium - Treatment

Prognosis of delirium

Morbidity and mortality are higher in patients who are hospitalized with delirium and in those who develop delirium during hospitalization.

Some causes of delirium (e.g. hypoglycemia, intoxication, infection, iatrogenic factors, drug intoxication, electrolyte imbalance) resolve fairly quickly during treatment. However, recovery may be delayed (by days and even weeks or months), especially in the elderly, as a result of prolonged hospitalization, due to increasing complications, increased treatment costs, and ongoing maladaptation. Some patients do not fully recover their status after developing delirium. Over the next 2 years, the risk of cognitive and functional impairment increases, transforming them into organic changes, and the risk of death increases.

Course and outcome of delirium

If delirium develops in hospital, then in about half of the cases this occurs on the third day of hospitalization, and by the time of discharge from the hospital its symptoms may persist. On average, every sixth patient has symptoms of delirium for 6 months after discharge from the hospital. During the subsequent two-year observation, such patients had a higher risk of death and lost their independence in everyday life faster.