Delirium | Diagnosis | Treatment | Prevention | Risks

Definition

Delirium is a transient, abrupt, usually reversible syndrome characterized by a disturbance that impairs consciousness, cognition (ability to think), and perception.

Description

The word delirium is derived from the Latin delirare which literally translates "to go out of the furrow." Delirium is typically an acute change in thinking with a disturbance in consciousness.Delirium is not a disease, but a syndrome that can occur as a result of many different underlying conditions. Typically, there is a broad range of accompanying symptoms. Delirium is also called acute confusional state. Delirium is a medical emergency and affects 10–30% of hospitalized patients with medical illness. It is a widespread condition that affects more than 50% of persons in certain high-risk population. Often the condition can be reversed, but delirium is associated with increased morbidity and mortality rates.

Demographics

Patients who develop delirium during hospitalization have a mortality rate of 22–76% and a high death rate months after discharge. Approximately 80% of patients develop delirium near death, and 40% of patients in the intensive care units have symptoms of delirium. The prevalence of postoperative delirium following general surgery is 5–10%, and 42% following orthopedic surgery.Delirium is very common in nursing homes. The exact incidence of delirium in emergency departments is unknown. Delirium is present in approximately 20% of medical patients at the time of hospital admission. The prevalence in hospitalized patients is approximately 10% on a general medical service, 8–12% on a psychiatric service, 35–80% on a geriatric unit, and 40% on a neurologic service. In the elderly and postoperative patients, delirium may result in long-term disability, increased complications, and prolonged hospital stay. Geriatric patients have the highest risk for developing delirium. The incidence is higher among young children, females, and Caucasians. Medications are the most common cause of delirium in the elderly, which accounts for 22–39% of cases. Medications are the most common reversible causes of delirium. Approximately 25% of hospitalized patients with cancer and 30–40% of patients with HIV (AIDS ) infection develop deliriumduring hospitalizations.

Abnormal mechanisms causing delirium

There are three types of delirium based on the state of arousal. They include hyperactive delirium, hypoactive delirium, and mixed delirium. The hyperactive delirium is associated with drug intake such as alcohol withdrawal (or intoxication), amphetamine, phencyclidine (PCP), and lysergic acid diethylamide (LSD), a psychedelic compound. Hypoactive delirium is observed in patients with hypercapnia and hepatic encephalopathy . Patients who exhibit mixed delirium often exhibit nocturnal agitation, behavioral problems, and daytime sedation. The exact pathophysiological mechanisms that elicit delirium are not fully understood. Research that primarily studied subjects with alcohol withdrawal and hepatic encephalopathy indicated that delirium is caused by a reversible impairment of cerebral oxidative metabolism and multiple neurotransmitter abnormalities.

Neurotransmitter abnormality

Acetylcholine is an excitatory chemical in the central nervous system (CNS). Anticholinergic medications, which disrupt release of acetylcholine, typically cause acute confusional states (delirium). Additionally, patients with diseases such as Alzheimer's disease with impaired cholinergic transmission and decreased acetylcholine are susceptible to delirium. Patients who develop postoperative delirium have an increase in serum anticholinergic activity.

Another neurotransmitter in the brain called dopamine causes delirium if there is an excess of dopaminergic activity. Dopaminergic and cholinergic activity in the brain exhibit a reciprocal relationship (i.e., a decrease in cholinergic activity leads to delirium, while an increase in dopaminergic activity leads to delirium). Studies have demonstrated that serotonin levels are increased in patients with septic delirium and encephalopathy. Serotoninergic agents, which are medications that may have unwanted side effects, leading to impaired serotonin release, can also cause delirium. Gama-aminobutyric acid (GABA) is an inhibitory neurochemical in the central nervous system. GABA is increased in patients with hepatic encephalopathy; this is probably caused by increases in ammonia levels.

Inflammatory mechanisms

Recent research indicates that there is a role for specific chemical mediators such as interleukin-1 (IL-1) and interleukin-6 (IL-6). These chemical mediators are released from cells after a broad range of infectious and toxic insults. Head trauma and ischemia, which are frequently associated withdelirium, cause brain responses that are mediated by IL-1 and IL-6. Abnormal release can cause damage to nerve cells.

Structural mechanisms

Specific objective nerve pathways in the brain that induce delirium are unknown. Neuroimaging studies in patients with traumatic brain injury (TBI), stroke , and hepatic encephalopathy indicate that certain anatomical nerve pathways may contribute to a delirious state more than others. A specific pathway called the dorsal tegmental is also involved in delirium.

Summary of causes

In general, the causes of delirium fall within 11 categories: infectious, withdrawal, acute metabolic, trauma, CNS disease, hypoxic, deficiencies, environmental, acute vascular, toxins/drugs, and heavy metals. Examples of diseases or disorders in each category include:

·         infectious: sepsis (infections that spread in blood and cause infections in the brain), encephalitis, meningitis, syphilis, CNS abscess

·         withdrawal: as a result of drug withdrawal from alcohol or sedatives

·         acute metabolic: acidosis, electrolyte disturbance, liver and kidney failure, other metabolic disturbances (glucose, Mg++, Ca++, conditions that affect the body's regulation of acid and electrolyte balance)

·         trauma: head trauma, burns (delirium can occur secondary to traumatic events or severe burns)

·         CNS disease such as stroke, bleeding in the brain, or seizures

·         hypoxia : as a result of hypoxia (lack of oxygen), chronic obstructive lung disease (e.g., emphysema, bronchitis), or low blood pressure

·         deficiencies of vitamins, especially B-complex vitamins

·         environmental: severe changes in body temperature, either a decrease (hypothermia) or an increase (hyperthermia); hormonal imbalance (diabetes and thyroid problems)

·         acute vascular: conditions affecting blood vessels in the brain, such as hemorrhage or blockage of a blood vessel from a clot

·         toxins/drugs: chemical toxins such as street drugs, alcohol, pesticides, industrial poisons, carbon monoxide, cyanide, and solvents

·         heavy metals: exposure to certain metals such as lead or mercury Other common causes of delirium include hypoglycemia and hyperthermia.

Diagnostic criteria for delirium

The diagnosis of delirium is clinical, requiring physical examination and the analysis of symptoms because there is no single test that can successfully measure this condition. A careful history is essential to establish the diagnosis. Delirium is clinically characterized by an acutely transient alteration in mental status. Patients can have problems in orientation and short-term memory, difficulty sustaining attention, poor insight, and impaired judgment. In the hyperactive subtype ofdelirium, patients have an increased state of arousal, hypervigilance, and psychomotor abnormalities. Conversely, patients with the hypoactive subtype are typically withdrawn, less active, and sleepy. The mixed subtype category often presents with delirium as the primary symptom of an underlying illness. Mental status can be checked quickly and should include assessment of memory, attention, concentration, orientation, constructional tasks, spatial discrimination, writing, and arithmetic ability. Two of the most sensitive indicators for delirium are dysgraphia (impaired writing ability) and dysnomia (inability to name objects correctly).

Psychological deficit

The psychological diagnostic criteria for delirium include:

·         change in cognition (i.e., disorientation, language disturbance, perceptual disturbance): this alteration cannot be accounted for by a preexisting, established, or evolving dementia

·         disturbance of consciousness (i.e., reduced clarity of awareness of the environment) occurs with a reduction in ability to focus, maintain, or shift (change) attention

·         the alterations develop over a short period (hours to days) and exhibit fluctuation during the day

·         evidence exists from history, medical and/or laboratory findings, which indicates that the delirium is caused by a general medical condition, substance intoxication, substance withdrawal, medication use, or more than one cause (multiple etiologies)

Diagnostic instruments

There are several instruments that help establish the diagnosis of delirium. They include the Confusion Assessment Method (CAM), the Delirium Symptom Interview (DSI), and the Folstein Mini-Mental State Examination (MMSE). Delirium symptom severity can be assessed utilizing the Memorial Delirium Assessment Scale (MDAS) and the Delirium Rating Scale (DRS).

Lab studies

Glucose levels can help diagnose delirium causes by hypoglycemia or uncontrolled diabetes. A complete blood count with differential cell analysis can help to diagnose infection and anemia. Electrolyte analysis can diagnose high or low levels. Renal (kidney) and liver function test (LFTs) can diagnose liver and/or kidney failure. Other tests that can assist with identifying the underlying cause of delirium include urine analysis (urinary tract infections), urine/blood drug screen (to diagnose the presence of toxic substance), thyroid function tests (to diagnose an underfunctioning thyroid gland, a condition called hypothyroidism), and special tests to diagnose bacterial and viral causes of infection.

Neuroimaging studies such as computerized axial tomography (CAT) and magnetic resonance imaging (MRI) can be helpful to establish a diagnosis due to structural lesions or hemorrhage. Electroencephalogram (EEG), a special test that records brain activity in waves can be helpful to establish a diagnosis, especially in patients with hepatic encephalopathy (diffuse slow waves) and alcohol/sedative withdrawal (faster wave pattern).

Treatment

Clinicians must be vigilant to aggressively identify the underlying etiology of delirium, since the condition is a medical emergency. Symptomatic treatment for delirium may include the use of antipsychotic drugs. These medications help to control hallucinations, agitation, and help to improve the level of orientation and attention abilities (sensorium). Haloperidol (Haldol) is a highly researched medication and is often administered in the symptomatic management of delirium. The typical dose for patients with delirium of moderate severity is 1–2 mg twice daily and repeated every four hours as needed. Haldol can be administered orally, intravenously, or by intramuscular injection. Elderly patients should start with lower doses of Haldol, typically 0.25–1.0 mg twice daily and repeated every four hours as needed.

Environmental interventions

Treatment of delirium can be worsened by over stimulation or under stimulation in the environment. It is important to provide support and orientation to the patient. Additionally, providing the patients an environment with few distractions such as removing unnecessary objects in the room, use of clear language when talking to them, and avoidance of sensory extremes can be conducive to treatment planning.

Clinical trials

Information concerning clinical trials and research on delirium can be obtained from the National Institutes of Health (NIH). Research related to delirium is active at the Mayo Clinic Foundation, including research on Alzhiemer's disease, postoperative delirium in orthopedic surgical patients, and pharmacological treatment of Parkinson's disease .

Resources

BOOKS

Marx, John A., et al. (eds). Rosen's Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby, Inc., 2002.

PERIODICALS

Chan, D., and N. Brennan. "Delirium: Making the Diagnosis, Improving the Prognosis." Geriatrics 54, no. 3 (March 1999).

Francis, J. "Three Millennia of Delirium Research: Moving Beyond Echoes of the Past." Journal of the American Geriatrics Society 47, no. 11 (1999).

Gleason, O. "Delirium." American Family Physician (March 2003).

Samuels, S., and M. M. Evers. "Delirium: Pragmatic Guidance for Managing a Common, Confounding, and Sometimes Lethal Condition." Geriatrics 57, no. 6 (June 2002).

WEBSITES

Delirium. (May 20, 2004) <http://omni.ac.uk>.

National Cancer Institute. (May 20, 2004) <http://www.cancer.gov>.

Association of Cancer Online Resources. (May 20, 2004) <http://www.acor.org>.

ORGANIZATIONS

National Institute of Neurological Disorders and Stroke (NINDS) Neurological Institute. P.O. Box 5801, Bethesda, MD 20824.

Laith Farid Gulli, MD

Nicole Mallory, MS, PA-C

Robert Ramirez, DO