Epidemiology

Altered mental status affects 5% to 10% of patients seen in the emergency department (ED) and in up to 30% of the older population.¹ Delirium and dementia account for a significant proportion of the altered mental status. Hustey and Meldon reported that of 78 ED patients with changes in mental status, 62% had cognitive impairment without delirium and the remaining 38% had delirium.² In a study at a single tertiary care center, it was found that emergency physicians (EPs) missed the diagnosis of delirium in up to 75% of patients older than 65 years; either the condition was misdiagnosed or the patients were discharged home.³ Some studies suggest a mortality rate as high as 9% in patients who are admitted to the hospital because of altered mental status. One study found that patients who were discharged home with unrecognized delirium had a mortality of 30.8% at 6 months.⁴ The challenge for the EP, who has not generally seen the patient previously, is recognizing delirium—an acute process—when it is superimposed on dementia—a chronic process. Therefore, a systematic approach to ED evaluation is necessary.

Alzheimer dementia is the most common form of dementia in adults (occurring in 50% to 60% of patients), followed by vascular dementia (15% to 25%), Lewy body dementia (5%), and Parkinson dementia (5%).^5,6

Delirium

Presenting Signs and Symptoms

Delirium is a syndrome and not a specific disease; therefore, identifying the underlying cause requires a comprehensive approach that includes a medical and family history, physical examination, bedside cognitive assessment, and diagnostic testing. The confusion assessment method is a useful tool to screen for delirium in the medical setting.⁸ In an uncooperative or severely confused patient, information obtained from emergency medical service personnel and the patient’s family, personal items brought in with the patient, and a detailed physical examination with close attention to vital signs are important. Figure 104.1 provides a structured approach to assessing cognition at the bedside; patients who are oriented with immediate recall and the ability to sustain attention and recite months or digits in reverse but no delayed recall are unlikely to have delirium and should be suspected of having dementia.⁸ The EP should consider all possible reversible medical causes of delirium so that treatment can be initiated as soon as possible (Box 104.1).

Fig. 104.1 Bedside assessment of cognition.

MMSE, Mini-Mental State Examination; R/O, rule out.

Box 104.1 Causes of Delirium

Infections

Systemic

• Urinary tract infection, pneumonia

Central nervous system

• Meningitis, seizures, encephalitis, abscess, mass

Human immunodeficiency virus

• Toxoplasmosis, cytomegalovirus, Cryptococcus

Metabolic and Fluid Disorders

Electrolyte

• Hypoglycemia, hyperglycemia, hyponatremia, hypercalcemia

Hypovolemia

• Dehydration, bleeding

Other

• Uremia, hepatic encephalopathy

Drugs

Withdrawal

• Alcohol, benzodiazepines

Illicit and abuse

• Sympathomimetics, hallucinogens, alcohol

Prescription medications (see Box 104.2)

Cerebrovascular

Medical

• Hypertensive emergency, stroke

Traumatic

Hypoxia and Hypercapnia

Pulmonary

• Asthma, chronic obstructive pulmonary disease, pulmonary embolism

Hematologic

• Carbon monoxide, methemoglobinemia

Endocrine

• Hyperthyroidism, hypothyroidism, Cushing syndrome, hyperparathyroidism

Environment and Toxicity

Toxic exposure

• Pesticides, cyanide, carbon monoxide, methemoglobinemia, lead, mercury

Temperature

• Heat stroke, hypothermia

Other

• Bites, stings, plants (see Box 104.4)

Vitamin Deficiency

• Vitamin B₁, vitamin B₁₂

Infection

One of the most common causes of delirium in the elderly is infection. A simple urinary tract infection or pneumonia, which is easily handled by the immune system of a healthy adult, can have deleterious effects on the mental balance of an elderly patient who has little physiologic reserve. Progression to sepsis often worsens the delirium and can lead to coma. A history of recent coughing, fever, or urinary symptoms can help establish the diagnosis of delirium in elderly patients. Central nervous system infections range from localized abscess, meningitis, and encephalitis to late manifestations of syphilis. All these disease forms may be accompanied by symptoms of delirium ranging from minimal changes in mental status to severe confusion.

Metabolic, Fluid, and Electrolyte Disturbances

Hypoglycemia is a common cause of delirium seen in the ED and one that is readily treatable. Patients can have symptoms ranging from mild agitation to coma. As a note of caution, delirium from hypoglycemia may not be suspected in patients with a hypoglycemia-induced focal neurologic deficit or seizure. A history of diabetes, medications, and the time of the last meal are important; documentation of the administration of dextrose and other medications by the emergency medical service should be obtained.

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma can both be manifested as an acute confusional state. Hyperosmolar hyperglycemic nonketotic coma is seen more commonly in elderly patients with no history of diabetes or in patients with adult-onset diabetes and an underlying stressor such as infection.

Hyponatremia can cause delirium, but it is related to the rate of sodium reduction and not the absolute quantity. A patient with a slight, sudden decrease in serum sodium can have delirium, whereas a larger, more gradual reduction (over days) is well tolerated by many patients. Hyponatremia has many causes, from underlying medical conditions such as the syndrome of inappropriate secretion of antidiuretic hormone to intentional and unintentional water ingestion.

Hypercalcemia may be associated with delirium. The normal range of total serum calcium is between 8.5 and 10.5 mg/dL. Patients with calcium elevated above this range can exhibit confusion, depending on the rate of increase.

Patients with end-stage kidney and liver disease can also have delirium. The patient’s medical history or family members may document dialysis or a history of encephalopathy. The underlying process causing the encephalopathy, such as infection or lack of compliance with treatment, should be investigated.

Drug Withdrawal

Alcohol withdrawal in its severe form can cause delirium, which is known as delirium tremens. These patients will be seen in the ED with agitation and possible confusion. Visual or auditory hallucinations (or both) and delusions can also be part of the clinical findings and can contribute to misdiagnosis in these patients with a primary psychiatric disorder. Diagnosis of delirium tremens is based on a history of chronic alcohol abuse and symptoms of acute confusion and sympathetic hyperactivity. Typically, the last drink of alcohol was more than 48 hours before arrival at the ED. Vital signs may show severe hypertension, hyperthermia, and tachycardia. On physical examination, the patient often exhibits postural tremor and hyperreflexia.

Withdrawal from chronic benzodiazepine abuse can have a similar manifestation, although the onset of the symptoms varies, depending on the time of the last dose and the half-life of the drug.

Drug Toxicity

Alcohol intoxication is a common finding in the ED. The patient is often agitated, confused, and combative. This patient population is more susceptible to other causes of delirium, including infection, trauma, and concomitant ingestion of drugs; a thorough, unbiased evaluation is therefore important.

Common classes of abused drugs causing delirium include sympathomimetics such as cocaine and amphetamine and hallucinogens such as lysergic acid diethylamide (LSD) and ketamine. Close attention to vital signs and identification of a toxic syndrome (toxidrome) are essential in making the diagnosis. Patients with sympathomimetic toxicity may have significant increases in heart rate, blood pressure, and temperature with associated hyperactivity, agitation, and diaphoresis. Clinical findings associated with ketamine abuse include vertical and rotatory nystagmus, midpositioned pupils, hallucinations, labile affect, hyperthermia, and muscle rigidity. Mild tachycardia and hypertension may be seen. Investigation of personal belongings for pills and interview with family members may augment the diagnosis. Anticholinergic medications are also commonly used in the ED and outpatient settings. Delirium associated with mydriasis, hyperthermia, anhydrosis, and hyperemia is seen in this toxidrome.

Many commonly prescribed medications can cause delirium as a result of improper dosing, change in metabolism, intentional overdose, and drug-drug interactions (Box 104.2).⁹ Family members or the patient’s personal physician may be able to provide valuable information about recent changes in medication dosages or the addition of new medications.

Box 104.2 Medications Associated with Delirium

Anticholinergics

H₁ receptor blockers (diphenhydramine, meclizine, hydroxyzine)

Antiparkinson drugs (benztropine)

Phenothiazine (promethazine)

Antidepressants

Tricyclics (amitriptyline, nortriptyline)

Selective serotonin reuptake inhibitors (fluoxetine, sertraline)

Sedatives

Benzodiazepine (alprazolam, diazepam)

Analgesics

Opioids (codeine, morphine)

Antiinflammatory Agents

Nonsteroidal antiinflammatory drugs (aspirin, ibuprofen)

Corticosteroids (hydrocortisone, prednisone)

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