AUTHOR INFORMATION

Section 1 of 11

Authored by Paul S Gerstein, MD, Chief, Department of Emergency Medicine, Holyoke Medical Center

Paul S Gerstein, MD, is a member of the following medical societies: American Academy of Emergency Medicine, and Massachusetts Medical Society

Edited by Eric Kardon, MD, FACEP, Consulting Staff, Department of Emergency Medicine, Athens Regional Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; J Stephen Huff, MD, Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health System; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Pamela Dyne, MD, Program Director, Associate Professor, Department of Medicine, Division of Emergency Medicine, University of California at Los Angeles School of Medicine

Author's Email:	Paul S Gerstein, MD
Editor's Email:	Eric Kardon, MD, FACEP

eMedicine Journal, January 23 2007, VOLUME 8, Number 1

INTRODUCTION

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Background: Delirium, dementia, amnesia, and certain other alterations in cognition are subsumed under more general terms such as mental status change (MSC), acute confusional state (ACS), or organic brain syndrome (OBS). Acute alterations in brain function are commonly referred to as MSC or ACS; chronic alterations and any MSC specifically due to nonpsychiatric causes are generally referred to as OBS.

In this article, OBS is used to distinguish changes in cognitive/behavioral functions due to physical (organic) causes from those due to psychiatric (functional) causes. However, with the growing recognition of the organic bases of many psychiatric disorders, the distinction between organic and functional has become blurred. As a result, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), no longer recognizes OBS as a diagnostic entity.

Nevertheless, the term OBS is useful to the practicing ED physician by highlighting a sizable list of diagnoses to be considered before a patient with abnormal mentation and behavior is presumed to have a psychiatric illness. If a more precise diagnosis of a change in mental status can be determined, the nebulous term OBS should be abandoned.

Pathophysiology: OBS can be divided into 2 major subgroups: acute (delirium or ACSs) and chronic (dementia). A third entity, encephalopathy (subacute OBS), denotes a gray zone between delirium and dementia; its early course may fluctuate, but it is often persistent and progressive.

The final common pathway of all forms of OBS is an alteration in cortical brain function. This condition results from (1) an exogenous insult or an intrinsic process that affects cerebral neurochemical functioning or (2) physical or structural damage to the cortex. Some of the etiologies include trauma, mass lesions, hydrocephalus, strokes (ie, multi-infarct dementia), atrophy, or dementing processes.

The end result of these disruptions of function or structure is impairment of cognition that affects some or all of the following: alertness, orientation, emotion, behavior, memory, perception, language, praxis, problem solving, judgment, and psychomotor activity. Knowledge of which areas of this spectrum are affected or spared guides both the workup and the diagnosis.

Frequency:

• In the US: Delirium accounts for 10-15% of admissions to acute care hospitals (but usually is not the primary diagnosis). The incidence of dementia increases with age, from about 2-10% of persons aged 65 years to 20-50% of those older than 85 years. Approximately 60% of nursing home beds are occupied by patients with dementia. Alzheimer disease (AD) accounts for most patients with dementia who are older than 55 years (50-90%).

• Internationally: AD is less common and has an older age of onset in Japan, China, and parts of Scandinavia. In these countries, vascular causes of dementia may outnumber AD.

Mortality/Morbidity:

• Some causes of delirium (eg, delirium tremens, severe hypoglycemia, CNS infection, heat stroke, thyroid storm) may be fatal or result in severe morbidity if unrecognized and untreated. With some exceptions, such as overdose of tricyclic antidepressants, drug intoxications generally resolve fully with supportive care. Failure to provide thiamine when administering glucose may lead to acute Wernicke syndrome (ie, ataxia, confusion, oculomotor palsies in the setting of malnutrition). If unrecognized, Wernicke syndrome may also result in chronic OBS.

• Certain withdrawal syndromes (eg, alcohol, benzodiazepines, barbiturates) can be deadly if untreated.

• Patients with primary dementias have a significantly reduced life expectancy depending upon the cause of the dementia and its severity and rapidity of progression.

Race: Delirium is seen more commonly in whites than in other races.

Sex:

• Delirium is seen more commonly in females than in males.

• AD is more prevalent among women because of their longer life expectancy. Lifetime risk in women is estimated to be 32%, while that in men is 18%. However, the age-specific risk is equal in both sexes.

Age:

• Delirium due to physical illness is more frequent among the very young and those older than 60 years.

• Delirium due to drug and alcohol intoxication or withdrawal is most frequent in persons aged mid teens to the late 30s.

• Dementia, particularly AD, is seen predominantly in elderly persons; however, certain types of dementia are seen in younger patients (eg, AIDS-related dementia, certain familial forms of AD) and some cases of Creutzfeldt-Jakob disease (ie, bovine spongiform encephalopathy). AIDS-related dementia is the most common nontraumatic dementia seen in younger persons.

CLINICAL

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History:

• Mental status changes can evolve acutely with a rapidly fluctuating course (delirium) or insidiously over months or years with a gradually worsening or stuttering course (dementia).

• Delirium presents with acute onset of impaired awareness, easy distraction, confusion, and disturbances of perception (eg, illusions, misinterpretations, visual hallucinations).

• Recent memory is usually deficient, and the patient often is disoriented to time and place.

• The patient may be agitated or obtunded, and the level of awareness may fluctuate over brief periods.

• Speech may be incoherent, pressured, nonsensical, perseverating, or rambling, which may make the taking of an accurate history from the patient impossible.

• For patients with delirium, attempt to obtain a current and past history from other sources, including prehospital workers, family or friends, and past medical records.

• Look specifically for street drug, alcohol, and medication use; preexisting endocrine disorders; and recent activities that may have resulted in exposure to toxins or environmental injury.

• Ask about prior psychiatric illness and similar episodes of confusion in the past.

• Dementia presents with a history of chronic, steady decline in short- and long-term memory and is associated with difficulties in social relationships, work, and activities of daily life.

• In contrast to delirium, the sensorium is clear. However, delirium can be superimposed on an underlying dementing process.

• The diagnosis usually is known previously in a patient who presents to the ED with moderate-to-severe symptoms.

• Earlier stages of dementia may present subtly, and patients may minimize or attempt to hide their impairments. Patients at this stage often have an associated depression.

• Dementia of relatively recent onset has a higher likelihood of a potentially reversible etiology (5-47%).

• Take a careful history, looking for past or present drug or alcohol abuse, current medications, and chronic or acute medical illnesses and psychiatric disorders to uncover a treatable or modifiable cause for the cognitive impairment.

• Elderly patients with depressed mood, hopelessness, and suicidality may be suffering from pseudodementia (ie, major depression). When the depression is alleviated with treatment, the dementia fully resolves.

• A history of a stuttering course may point to multi-infarct dementia, which is caused by repeated lacunar strokes. Treatment aimed at preventing future strokes may arrest further progression of the dementia. However, recent research suggests that small strokes in specific areas of the brain may trigger the onset of Alzheimer-type dementia.

Physical: Any patient who presents with altered mental status needs a complete physical examination, with particular attention to general appearance, vital signs, hydration status, evidence of physical trauma, and neurologic signs. The delirious or obtunded patient should be evaluated for pupillary, funduscopic, and extraocular abnormalities; nuchal rigidity; thyroid enlargement; and heart murmurs or rhythm disturbances. Other clues to the etiology on general examination may come from a pulmonary examination that reveals wheezing, rales, or absent breath sounds; an abdominal examination that reveals hepatic or splenic enlargement; or a cutaneous examination that shows rashes, icterus, petechiae, ecchymoses, track marks, or cellulitis. Cellulitis in elderly persons often is hidden under clothing, particularly pants and socks. Checking these areas in patients with diabetes is critical. Any serious infection can lead to mental status changes.

• General appearance (eg, unkempt, tattooed, and/or malnourished) may suggest the possibility of drug or alcohol abuse.

• Look for track marks.

• Smell for alcohol, the musty odor of fetor hepaticus, or the fruity smell of ketoacidosis.

• Icterus and/or asterixis point to liver failure with an elevation of the serum ammonia level.

• Agitation and tremulousness suggest sedative drug or alcohol withdrawal.

• Close attention to vital signs is essential and easy to overlook in the setting of extreme behavioral difficulties in a delirious patient.

• Fever may point to infection, heat illness, thyroid storm, aspirin toxicity, or the extreme adrenergic overflow of certain drug overdoses and withdrawal syndromes (in particular, delirium tremens).

• Extreme hyperthermia (with pinpoint pupils) may be seen in pontine strokes.

• In patients with a rapid respiratory rate, consider diabetic ketoacidosis (ie, Kussmaul respiration), sepsis, stimulant drug intoxication, and aspirin overdose.

• In patients with a slow respiratory rate, consider narcotic overdose, CNS insult, or various sedative intoxications.

• A rapid pulse rate is seen in patients with fever, sepsis, dehydration, thyroid storm, and various cardiac dysrhythmias and in overdoses of stimulants, anticholinergics, quinidine, theophylline, tricyclic antidepressants, or aspirin.

• Patients with a slow pulse rate may have elevated intracranial pressure, asphyxia, or complete heart block. Calcium channel blockers, digoxin, and beta-blockers also may produce OBS and bradycardia.

• Blood pressure elevation is common in delirium because of resulting adrenergic overload.

• In patients with acute OBS and severely elevated blood pressure, check the ocular fundi for arteriolar spasm, disc pallor, papilledema, flame hemorrhages, and exudates. These are all signs of malignant hypertension. Even with these changes, the patient may be alert and minimally symptomatic.

• In pregnant patients with a diastolic pressure greater than 75 mm Hg in the second trimester or greater than 85 mm Hg in the third trimester, consider preeclampsia (ie, hyperreflexia, edema, proteinuria).

• In patients with hypertension and bradycardia, consider an elevated intracranial pressure (Cushing reflex).

• With delirium and hypotension, the differential diagnosis includes dehydration, diabetic coma, hemorrhage due to trauma, aneurysmal rupture, or GI bleeding. Also, consider adrenergic depletion secondary to cocaine; amphetamine; or tricyclic overdose, which usually responds only to norepinephrine, not dopamine. Addisonian crisis, particularly in those who are steroid dependent, should be considered.

• A brief bedside neurologic examination, to include mental status testing, is an essential part of the workup of OBS when a rapidly treatable cause, such as hypoglycemia or narcotic overdose, is not immediately apparent.

• The Mini-Mental Status Examination (MMSE) is a formalized way of documenting the severity and nature of mental status changes. The MMSE, as modified from Folstein, is outlined here. The maximum score per item is indicated in parentheses.
  • Orientation (5): What are the year, season, date, day, and month?

  • Orientation (5): Where are we: state, county, town, hospital, and floor?

  • Registration (3): Name 3 objects; ask the patient to repeat these 3 objects.

  • Attention and calculation (5): The serial 7 test; 1 point for each correct answer. Stop after 5 answers. Optional: Spell “world” backwards.

  • Recall (3): Ask for the 3 objects (from Registration) to be repeated. One point is scored for each correctly recalled object.

  • Language (2): Name a pencil and a watch.

  • Repetition (1): Repeat the following: “No ifs, ands, or buts.”

  • Complex commands (6): Follow a 3-stage command: “Take a paper in your right hand, fold it in half, and put it on the floor.” (3 points) Then, read and follow these printed commands: “Close your eyes.” (1 point); "Write a sentence." (1 point); and "Copy design." (1 point)

• Instructions for administering the MMSE are as follows:
  • Orientation: Ask for the date. Specifically, ask for any omitted information. Give 1 point for each correct response.

  • Registration: Ask permission to test memory. Name 3 unrelated objects clearly and slowly about 1 second apart. After all 3 objects have been named, ask the patient to repeat them. The first repetition determines the score. Keep repeating the items, up to 6 times, until the patient can repeat all 3 of them. (This step also is required for the Recall test.)

  • Attention and calculation: Ask the patient to begin with 100 and count backwards by 7s. Stop after 5 subtractions and score correct answers. If the patient cannot calculate, ask him or her to spell “world” backwards. The score is the number of letters in correct order.

  • Recall: Ask the patient to recall the 3 objects previously asked to remember (from Registration). Zero to 3 points may be scored.

  • Language: To test skills in naming objects, show a wristwatch and a pencil to the patient, and ask the patient to name each item. Zero to 2 points may be scored.

  • Repetition: Ask the patient to repeat a sentence. Allow 1 trial. Zero to 1 point may be scored.

  • Complex 3-stage command: Give the patient a piece of paper and repeat the command. Score 1 point for each portion of the command that is performed correctly.

  • Reading: Print clearly on a piece of paper in large letters the command: “Close your eyes.” Ask the patient to read and perform the command. Score 1 point if the eyes are closed.

  • Writing: Provide a blank piece of paper and ask the patient to write a sentence of his/her own choosing. It must contain a subject and a verb to be scored 1 point. Punctuation does not matter for the purpose of scoring.

  • Copying: On a clean piece of paper, draw intersecting pentagons, each side measuring 1 inch, and ask the patient to copy the figures exactly. All 10 angles must be present, and the 2 figures must intersect to score 1 point. Any rotation of the figures or tremor is ignored.

• Overall scoring: A score of less than 24 suggests the presence of delirium, dementia, or another problem affecting the patient's mental status, and it may indicate the need for further evaluation.

• In addition, or as an alternative to the MMSE, correctly drawing the face of a clock (to include the circle, numbers, and hands) is a sensitive test of cognitive function.
  • To perform this test, ask the patient to draw a clock with the hands at 8:20.

  • Two or more errors correlate significantly with dementia. No errors rule against dementia.

• Other simple screening tests include asking the patient to spell "world" backwards or performing "serial 7's," which involves starting at the number 100 and subtracting 7 repeatedly in series (ie, 100…93…86…79…).

• Pupillary dilation may be secondary to intoxication with a hallucinogen, amphetamine, cocaine, or anticholinergic medication.

• Pupillary constriction may be secondary to narcotic intoxication.

• Serious head trauma is usually obvious. However, occult trauma may be discovered by findings of basilar skull fracture, such as hemotympanum, Battle sign (ie, mastoid area ecchymoses), raccoon eyes, or otorhinorrhea. The latter condition may be tested for by placing a drop of the draining blood on filter paper and then looking for a clear ring of cerebrospinal fluid (CSF).

• A funduscopic examination may show loss of venous pulsations in cases of early intracranial pressure (ICP) elevation or papilledema in severe ICP elevation.

• Pupillary inequality may be a late sign of uncal herniation.

Causes:

• Delirium or ACSs may be caused by the following:

• Intoxication with a substance (eg, hallucinogens, alcohol, medications, toxins)

• Occult infection (eg, meningitis, encephalitis, neurosyphilis, sepsis)

• Head trauma

• Seizure disorder

• Acute mania or other psychiatric etiology

• Endocrine crisis (eg, thyroid, adrenal, diabetic)

• Renal failure

• Liver failure

• Neoplasia

• Inflammation (eg, systemic lupus erythematosus)

• Cerebral vascular accident (CVA)

• Respiratory dysfunction (eg, hypoxia, hypercarbia)

• Shock

• In the elderly, the combined effects of visual and auditory impairments; dementia or other chronic brain dysfunction; medication side effects, particularly polypharmacy; and/or unfamiliar environment or nighttime darkness can lead to acute confusion or psychosis, which is known as sundowning. As the name implies, this condition usually occurs in the evening hours. Vitamin B-12 deficiency is a potential cause of sundowning and progressive, reversible dementia.

• Amnesia: Head trauma, Korsakoff syndrome, transient global amnesia, and various dementing processes can cause amnesia.

• Head trauma can lead to transient amnesia with retrograde (events prior to injury) and anterograde (events following injury) features.

• Postconcussive syndrome is a constellation of mental dullness, poor memory, depressed mood, and headaches that may follow head trauma, often lasting days to weeks, with full resolution in most cases.

• Transient global amnesia (TGA) is seen in previously well, usually middle-aged patients who present with a sudden onset of confusion, amnesia, and anxious perseveration. TGA can occur spontaneously or following minor trauma, exertion, or emotional stress. The amnesia usually lasts a few hours, with full recovery and rare recurrence. Various causes have been proposed for TGA—most recently, TIA-like ischemia or perhaps ministrokes in the hippocampal or thalamic memory areas of the brain. Although the incidence of cerebrovascular risk factors in TGA is low, those patients with such risk factors (eg, hypertension, smoking, DM, hypercholesterolemia) should be considered for antiplatelet therapy.

• Traveler amnesia typically is seen following a nap on an airplane after taking a short-acting hypnotic, such as alprazolam, triazolam, or zolpidem.

• Korsakoff syndrome is caused by neuronal damage that results from thiamine deficiency in association with chronic alcohol abuse.
  • It usually is preceded by an episode of Wernicke encephalitis (eg, ataxia, confusion, oculomotor palsy), typically precipitated by administration of glucose to a malnourished alcoholic without concomitant parenteral thiamine.

  • Confabulation is a hallmark finding of Korsakoff syndrome (also called Korsakoff psychosis).

• Dementia or chronic OBS can occur primarily or can be secondary to cerebrovascular disease, chronic CNS infection, CNS trauma, increased ICP (eg, neoplasia, mass effect, hydrocephalus), toxins, avitaminosis, autoimmune disease, and psychiatric illness.

• Primary causes include AD and frontotemporal dementia (FTD). AD accounts for up to 90% of all primary dementias and more than 50% of all dementing illnesses.
  • FTD is highly familial; presents at a younger age than AD; and is associated with profound personality changes, social incompetence, and stereotypical behaviors, yet with preserved visuospatial skills. Pick disease is a subtype of FTD. The brain invariably shows a severe and asymmetric atrophy of the frontal and temporal lobes with only rare involvement of the parietal or occipital lobes associated with sparing of the posterior two thirds of the superior temporal gyrus. A thin, knife-edge appearance of the gyri is often seen secondary to the severe atrophy present in Pick disease. The typical pattern of atrophy is often prominent enough to distinguish Pick disease from AD macroscopically.

  • Some forms of AD are thought to have a genetic or familial basis. This is particularly true of AD that begins at a relatively young age and follows a fulminant course.

  • Alzheimerlike dementia is seen in 40% of patients with Parkinson disease and in a very high percentage of patients with Down syndrome who live long enough to develop AD.

• Cerebrovascular causes include lacunar stroke syndrome (multi-infarct dementia), thalamic stroke, and vasculitides as seen in systemic lupus erythematosus (SLE) and other rheumatologic disorders.

• Infectious causes of dementia include HIV, Creutzfeldt-Jakob disease, neurosyphilis, and the end stages of some cases of meningitis and encephalitis.

• Traumatic causes of dementia include anoxia, diffuse axonal injury (following a severe blow to the head), and dementia pugilistica (punch drunk). A chronic subdural hematoma may present with a dementialike syndrome.

• Toxins causing chronic OBS include heavy metals (eg, lead in solder, ceramic glazes), organic chemical exposures, severe carbon monoxide poisoning, and chronic substance abuse. (However, one study disputes the common assumption that chronic alcohol abuse leads to OBS. The researchers failed to find any evidence linking heavy alcohol intake with any form of cognitive decline or with atrophy of the brain regions involved in cognitive functions.)

• Avitaminoses, including deficiencies of vitamin B-12 and folate, can cause OBS.

• Autoimmune causes include SLE, giant cell arteritis, and sarcoidosis.

• Psychiatric illnesses mimicking dementia include the pseudodementia of major depression in elderly persons and chronic schizophrenia.

• Other causes to consider include chronic endocrinopathies, Wilson disease (copper storage disease), and lipid storage diseases.

DIFFERENTIALS

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Brain Abscess
Delirium Tremens
Diabetic Ketoacidosis
Encephalitis
Epidural and Subdural Infections
HIV Infection and AIDS
Heat Exhaustion and Heatstroke
Herpes Simplex
Herpes Simplex Encephalitis
Hypercalcemia
Hypernatremia
Hyperosmolar Hyperglycemic Nonketotic Coma
Hypertensive Emergencies
Hypoglycemia
Hypothyroidism and Myxedema Coma
Neoplasms, Brain
Neuroleptic Malignant Syndrome
Panic Disorders
Schizophrenia
Subarachnoid Hemorrhage
Subdural Hematoma
Toxicity, Amphetamine
Toxicity, Anticholinergic
Toxicity, Antidepressant
Toxicity, Antihistamine
Toxicity, Cocaine
Toxicity, Cyclic Antidepressants
Toxicity, Hallucinogen
Toxicity, Lead
Toxicity, Mushroom - Hallucinogens
Wernicke Encephalopathy
Withdrawal Syndromes

WORKUP

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Lab Studies:

• Laboratory studies may be helpful for ruling in or ruling out specific diagnoses that cause delirium or a dementialike presentation. Many of these tests may not be immediately available to the ED physician, such as vitamin B-12 levels, Venereal Disease Research Laboratory (VDRL) test, and thyroid function studies.

• Oxygen saturation and, in some cases, arterial blood gases (ABG) with a carbon monoxide level are helpful.

• Complete blood count, electrolytes level, blood glucose level, BUN level, and creatinine level should be checked.

• In older patients, consider vitamin B-12 and folate levels.

• Consider calcium level, magnesium level, and liver function tests (LFTs), including serum ammonia, prothrombin time (PT), and activated partial thromboplastin time (aPTT).

• Consider VDRL and/or fluorescent treponemal antibody absorption (FTA-ABS) test to help rule out neurosyphilis (see CSF studies below).

• Urinalysis

• When alcohol, drugs, and/or toxins are suspected, consider the following:

• Serum ethanol, salicylate, acetaminophen, carbon monoxide, and other specific drug or toxin levels as indicated

• Comprehensive drug analyses of blood and urine

• Such toxic screens are generally not helpful in the acute setting unless turnaround time is rapid.

• In a suspected endocrine emergency, the following are required:

• A bedside fingerstick blood glucose determination followed by serum glucose and serum acetone

• Thyroid-stimulation hormone (TSH), possibly thyroid panel

• Serum cortisol

• Serum calcium, phosphorus, and parathyroid levels

• In suspected CNS infection, the following may be ordered:

• Lumbar puncture may be done for CSF studies, including cryptococcal antigen or India ink prep, and VDRL.

• CT scan of head should be done before lumbar puncture to rule out toxoplasmosis or abscess, especially in patients with HIV who present with headache.

Imaging Studies:

• A head CT scan with and without contrast should be obtained if CNS infection, trauma, or a CVA is suspected. A CT scan is excellent for detecting acute hematomas and most subarachnoid hemorrhages (SAH) but is most accurate early in the course. Follow-up lumbar puncture may be needed to rule out SAH.

• Though not typically part of the workup in the ED, an MRI may be considered.

• Plain abdominal radiographs may reveal swallowed bags that contain drugs of abuse ("body packing") or radiodense substances such as iron tablets.

Other Tests:

• An ECG may be performed to search for myocardial infarction or atrial fibrillation with rapid ventricular response. Low voltages, as seen in hypothyroidism and pericardial effusion, may give a clue to the etiology. Look for tachycardia, widened QRS, or prolonged QT interval, which suggest tricyclic overdose.

• A postmortem examination of the brain is currently the only way to positively diagnose the various dementing illnesses.

• A blood test for apolipoprotein E (ApoE) subtype e4 is still under study, but it promises to greatly enhance diagnostic accuracy for AD.

Procedures:

• CSF evaluation is indicated to rule out SAH not seen on a CT scan. Approximately 5-10% are missed on CT scan, particularly 12 hours or more from the time of symptom onset.

TREATMENT

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Prehospital Care:

• Prehospital care workers involved in the transport of an acutely confused, combative, or delirious patient must ensure the safety of the patient and staff.

• Prior to transport, consider sedation with a benzodiazepine with or without a neuroleptic if unable to control a dangerous patient. Keep in mind that excess sedation may obscure the MMSE in the ED.

• Use physical restraints as needed.

• Provide supplemental oxygen.

• Intubate when the airway is at risk or when the patient is comatose or has a poor gag reflex. Protect the cervical spine in the setting of trauma.

Emergency Department Care: ED physicians caring for the patient with agitation, confusion, delirium, combativeness, or obtundation must ensure the safety of both the patient and the staff while attending to issues of airway protection and immediate recognition and treatment of rapidly reversible problems (eg, hypoxia, hypoglycemia, narcotic overdose).

• Provide supplemental oxygen unless oxygen saturation is above 93% on room air.

• When carbon monoxide poisoning is suspected, ignore the oxygen saturation, obtain a carboxyhemoglobin level, and provide 100% oxygen.

• In cases of airway compromise, coma, or poor gag reflex, the ED physician should have a low threshold for intubation.

• Use rapid sequence intubation (RSI) in the settings of possible head trauma, elevated ICP, or a combative patient. RSI may be necessary to facilitate imaging studies.

• Some patients with life-threatening overdoses as the cause of their delirium who are uncooperative may require paralysis and intubation prior to gastric lavage. However, the practice of gastric lavage is controversial and is only indicated in recent (less than 1 hour or so) and potentially severe or fatal ingestions for which less invasive therapy (eg, activated charcoal or specific antidote) is unavailable or unlikely to help. As a result, gastric lavage should be rarely indicated.

• Behavioral control of a patient with delirium who is agitated and combative should be primarily medication-based with physical restraining kept at a minimum for protection of the patient and staff (see Medication).

Consultations: Specific cases may require consultation with neurosurgery, neurology, or internal medicine subspecialists (eg, infectious disease, endocrinology, nephrology, gastroenterology, toxicology, psychiatry).

• In the setting of trauma or neurosurgical emergency, notify surgeons early in the workup. When available, a neurosurgeon should be consulted before using mannitol or high-dose steroid therapy.

• The patient's private physician and/or family members are often the best sources of information regarding baseline functioning, prior medical history, and current medications.

• Consult social services for home evaluation and placement issues for patients with dementia.

MEDICATION

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Medications typically used in the ED treatment of delirium or acute mental status changes include sedatives, neuroleptics, and antidotes. Other drugs may be useful in treating specific etiologies uncovered in the workup. The medications outlined here are used for acute behavioral changes.

Drug Category: Sedatives -- These agents are used to calm acute agitation, to control the behavior of combative patients, and to facilitate procedures.

Drug Name	Lorazepam (Ativan) -- Benzodiazepine of choice in ED. Can be given PO/SL(for rapid effect in panic attack)/IV/IM and can be mixed in syringe with neuroleptic agent. Sedative hypnotic with short onset of effects and relatively long duration of action. By increasing action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. When patient needs to be sedated for longer than 24-h period, this medication is excellent. Has longer CNS effect than diazepam and is preferred for seizure control. Easily titrated for acute withdrawal syndromes (eg, alcohol, benzodiazepines, barbiturates) and status seizures when given IV (10 mg or more may be needed in status epilepticus). Two mg of lorazepam approximately equivalent to 5 mg of diazepam. Preferred over neuroleptics for treating toxic effects of hallucinogens, cocaine, stimulants, or PCP.
Adult Dose	0.5-2 mg PO/SL or 2-4 mg IM or 1-2 mg IV Status epilepticus: 2-10 mg/dose IV, repeat q10-20min; alternative: 2 mg IV initial dose; double dose q10-20min until adequate sedation Delirium tremens: 10-20 mg IV initial dose, repeat prn; severe cases may need >100 mg in first few hours
Pediatric Dose	0.02-0.05 mg/kg PO/IV/IM; not to exceed 4 mg/dose
Contraindications	Documented hypersensitivity, preexisting CNS depression, hypotension, narrow-angle glaucoma
Interactions	Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, or MAOIs; alcohol cross-tolerant (alcoholics may require large doses for sedation)
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease

Drug Category: Neuroleptics -- These agents have more robust calming effects than benzodiazepines in acutely agitated patients. They act fast when given IV. They can be mixed in the same syringe with lorazepam for rapid chemical restraint (IM/IV). They are easily titrated and long acting.
Haloperidol and droperidol are of the butyrophenone class, which is noted for high potency and low potential for orthostasis. However, they have great potential for extrapyramidal symptoms (EPS)/dystonia.
Caveat: Neuroleptics can mask the signs of withdrawal from alcohol, benzodiazepines, and barbiturates while failing to treat adrenergic and GABA-nergic dysregulation. They do not prevent seizures.

Drug Name	Haloperidol (Haldol) -- DOC for severe agitation, acute psychosis, and severe delirium when no contraindications exist. Parenteral dosage form may be admixed in same syringe with 2 mg lorazepam for better anxiolytic effects.
Adult Dose	1-5 mg PO; may be given as liquid for faster onset of action 2-5 mg (5 mg is standard) IV/IM Elderly or debilitated patients: 0.5-2 mg IV/IM
Pediatric Dose	Severe behavioral disturbance/psychosis: 0.05-0.15 mg/kg/d PO/IV/IM; higher doses may be necessary
Contraindications	Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage; neuroleptic malignant syndrome
Interactions	May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; coadministration with anticholinergics may increase intraocular pressure; encephalopathylike syndrome associated with concurrent lithium
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Severe neurotoxicity that manifests as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, watch for hypotension; caution in CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue it occurs); use with caution in settings in which seizures may occur (eg, DT, cocaine OD)—neuroleptics can lower seizure threshold

Drug Name	Droperidol (Inapsine) -- Some clinicians believe droperidol is DOC for control of severely disturbed and/or violent patient. Somewhat faster acting and more sedating than haloperidol, but more likely to cause hypotension. May exert antipsychotic activity through dopaminergic system. May alter dopamine action in CNS. Parenteral dosage form may be admixed in same syringe with 2 mg lorazepam for better anxiolytic effects. Now has black-box warning regarding life-threatening torsade de pointes (TdP) (a rhythmic pattern of sinusoidal ventricular complexes that lead to ventricular fibrillation and cardiac arrest), especially in the setting of prolonged QT syndrome. Assessing QT interval via ECG or rhythm strip advised before administering droperidol.
Adult Dose	0.625-5 mg IM/IV (5 mg standard adult dose for chemical restraint)
Pediatric Dose	<2 years: Not established >2 years: 0.03-0.07 mg/kg IV/IM; may need 0.1-0.15 mg/kg/dose; not to exceed 2.5 mg/dose over 2 min
Contraindications	Documented hypersensitivity; neuroleptic malignant syndrome; suspected pheochromocytoma; hypotension; may cause life-threatening torsade de pointes in those with prolonged QT interval
Interactions	May increase toxicity of CNS depressants and has additive effects with benzodiazepines
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hypovolemic patients may experience hypotension; may decrease pulmonary arterial pressure; 40% of patients develop tardive dyskinesia; elderly may experience high rate of EPS May cause QT prolongation (delayed recharging of heart between beats) within minutes following injection at doses at or below recommended levels; prolonged QT can cause potentially fatal heart arrhythmia known as torsade de pointes; all patients should undergo a 12-lead ECG prior to administration of drug to determine if QT interval is prolonged (ie, QTc >440 msec for males or 450 msec for females); if QT interval is prolonged, droperidol should not be administered; for patients in whom potential benefit of droperidol treatment is felt to outweigh risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2-3 h after completing treatment to monitor for arrhythmias

Drug Category: Atypical antipsychotics -- These are newer neuroleptics with a lowered risk of extrapyramidal syndrome (EPS) and improved efficacy for the negative symptoms (eg, withdrawal, apathy) of psychosis because of their enhanced serotonergic activity as compared to older-style neuroleptics. These medications have largely supplanted older neuroleptics for sedation and treatment of psychosis in elderly patients with dementia.

Drug Name	Risperidone (Risperdal) -- Now considered DOC for sundowning in elderly patients. Binds to dopamine D2 receptor with 20 times lower affinity than for serotonin 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of EPS. Also may have antidepressant effects, probably because of its serotonin activity.
Adult Dose	1-8 mg/d PO Initial dosing for delirium or sundowning in elderly persons: 0.25-0.5 mg/d, titrated upwards
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration with carbamazepine may decrease effects; may inhibit effects of levodopa; clozapine may increase risperidone levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause EPS, orthostatic hypotension, tachycardia, and arrhythmias; increased risk for EPS with doses higher than 10 mg/d

Drug Category: Antidotes -- These agents are used when the toxic agent is known and has an antidote or as a coma cocktail in patients who are stuporous or comatose. Includes oxygen, thiamine (100 mg IV/IM), glucose (50 mL of D50W IV push), and naloxone (Narcan; 2-10 mg SC/IM/IV or via ETT). The use of flumazenil (Romazicon) for suspected or known benzodiazepine overdose is controversial. Flumazenil may precipitate refractory seizures in the setting of long-term use or mixed overdose with seizure-inducing agents (eg, TCAs). It may be useful in diagnosis and in avoiding the need for intubation.

Drug Name	Naloxone (Narcan) -- Prevents or reverses opioid effects (hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors.
Adult Dose	0.4-2 mg IV/IM/SC q2-3 min prn; use increments of 0.1-0.2 mg in patients who are opioid dependent; may be given via ETT; may need to repeat dose q20-60min If no response after administering 10 mg, question diagnosis Alternatively, when sedation recurs in patients who ingested long-acting narcotics, may be given as a drip; mix 10 mg in 100 mL of diluent, start at 10-20 mL/h, and titrate to effect
Pediatric Dose	0.1 mg/kg IV/IM/SC; repeat q2-3min prn
Contraindications	Documented hypersensitivity
Interactions	Decreases analgesic effects of narcotics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in cardiovascular disease; may precipitate withdrawal symptoms in patients addicted to opiates; in setting of opioid dependence, naloxone can exacerbate delirium

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• Most patients with delirium require admission and often require telemetry or ICU care.

Further Outpatient Care:

• Most cases of newly recognized dementia can be worked up in an outpatient setting. In some cases, admission is needed until an appropriate living situation or a nursing home placement is arranged.

In/Out Patient Meds:

• Outpatient medications for primary dementia are coordinated best by health care providers who have continuing contact with the patient. Medications may include the following:

• Anticholinesterase inhibitors, such as tacrine (Cognex) and donepezil (Aricept): Donepezil has the advantages of once daily dosing and the absence of liver toxicity. These medications are useful early in the disease course, but they lose their effectiveness or may worsen mental status in advanced stages of the disease.

• Antidepressants, especially the selective serotonin reuptake inhibitors or bupropion (Wellbutrin): Avoid tricyclic antidepressants because of their anticholinergic properties, which can worsen dementia.

• Benzodiazepines for sedation or sleep: These drugs may worsen cognitive deficits and increase the risk of falls.

• Neuroleptics for psychotic ideation or behavior: High-potency agents are preferred. Risperidone (Risperdal), a newer atypical antipsychotic, is well tolerated and useful for sundowning. Thioridazine (Mellaril), an older agent used for sundowning, is considered second-line because of its toxic effects (eg, cardiac effects, orthostatic hypotension, anticholinergic effects).

Deterrence/Prevention:

• Various substances are thought to prevent or retard the onset of dementia, perhaps via preservation of CNS supporting cells, prevention of CNS inflammation, or free-radical inhibition.

• Estrogen: In women, use of estrogen at any time in life may decrease the risk of AD by greater than 50%. This may be because of the preservation of CNS supporting cells. This is controversial.

• Nonsteroidal anti-inflammatory drugs (NSAIDs): The mechanism of action is thought to involve prevention of CNS inflammation. The newer COX-2 inhibitors, such as celecoxib (Celebrex), are being investigated for their effectiveness for prevention of dementia. This is controversial.

• Vitamin E: The dose for prevention is 200-400 IU/d; higher doses are sometimes given for treatment. The mechanism of action may be free-radical inhibition.

• Vitamin B-6, vitamin B-12, and folate: These reduce levels of homocysteine, a potential brain neurotoxin.

• Statin cholesterol-lowering medications: Recent reports suggest that these drugs substantially protect against dementia via an effect not related directly to blood levels of cholesterol. This finding has not yet been verified by clinical trials but appears promising (see Bibliography).

• A high intake of dietary fats and calories is associated with an increased risk of AD.

• Undertreated depression, hypertension, diabetes mellitus, hypercholesterolemia, and obesity have all been associated with higher risk of AD.

• Excessive amounts of alcohol act as a neurotoxin and can increase AD risk. In moderate doses, alcohol inhibits cerebrovascular disease while it may still enhance brain atrophy. Antioxidants in wine (bioflavonoids) may be additionally beneficial (over spirits and beer). Red wines grown in more grape-stressful climates (eg, upstate New York) contain the highest concentrations of these nutrients.

Complications:

• Delirium is a true medical emergency. Failure to recognize and aggressively treat the underlying cause can be catastrophic.

Prognosis:

• Delirium is fully reversible in most cases with proper recognition and treatment of the etiology.

• Dementia is usually insidious and relentlessly progressive. However, about 20-30% of cases are due to reversible causes. On average, patients with AD die within 8 years of onset, with a range of 2-15 years. Younger patients usually have a more fulminant course. Pick disease has a similar course.

• Subacute OBS (encephalopathy) may be reversible, persistent, or progressive.

Patient Education:

• For excellent patient education resources, visit eMedicine's Dementia Center. Also, see eMedicine's patient education articles Dementia Overview, Dementia Medication Overview, and Possible Early Dementia.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• The major pitfall is failing to exclude organic causes for mental status change when evaluating a patient presumed to have an acute psychiatric illness. In addition, significant organic illness may coexist with, but be masked by, psychobehavioral disturbances.

• Difficulty obtaining a reliable history and poor patient cooperation with physical examination may complicate the workup. Therefore, a high index of suspicion and a diligent examination are required to avoid missing a critical diagnosis.

• "Medical clearance" examinations are risky. Typically brief, these evaluations are rarely sufficient to rule out organic etiologies. Do not document: "Patient is medically cleared." If necessary, state: "No clear-cut organic etiology is evident at this time. Further evaluation may be needed depending on the clinical setting."

• Vital signs often are overlooked in the setting of acute behavioral disturbance.

• Be sure to obtain a temperature at some point in the evaluation.

• Be certain that abnormal vital signs are rechecked before transfer out of the ED.

• Know ED and hospital regulations and regional statutes regarding the use of physical restraints and involuntary psychiatric commitment.

• Document reasons for restraining a patient, mentioning patient and staff safety and protection. Document reasons for involuntary commitment and be sure to follow all COBRA regulations when transferring.

• Do not order: "Restrain prn." Give specific reasons for applying and removing restraints. Have restrained patient continuously observed. Personally ensure that restraints are applied in a safe manner.

• In most cases, chemical restraint is preferable to physical restraint when prolonged behavioral control is necessary or when the patient is severely combative. Serious injury or death can result from intense or prolonged struggling against restraints.

Special Concerns:

• Do not assume that dementia in an elderly person is irreversible, particularly when of recent onset. Search diligently for a reversible or modifiable cause.

• Workup may be initiated in the ED and continued in an outpatient setting.

• Admission may be required for the safety of the patient, even when inpatient workup or treatment is unnecessary.

• Be wary of occult causes for changes in mental status.

• Hypoxia (eg, pulmonary embolism), hypercarbia, carbon monoxide poisoning, hypoglycemia, hypothyroidism, hyperthyroidism, hypercalcemia, hyponatremia, temporal lobe seizure, and postictal states may cause changes in mental status.

• Myocardial infarction in elderly persons can cause delirium.

• Infection may cause changes in mental status, and fever can be absent. Check the skin carefully for cellulitis, rash, and petechiae. Have a low threshold for lumbar puncture.

• Signs may be subtle in CNS trauma. For example, only a CT scan can diagnose shaken baby syndrome. Be sure to look carefully for other signs of abuse.

TEST QUESTIONS

Section 10 of 11

CME Question 1: A 22-year-old woman presents with delirium, dry mucus membranes, red skin, rapid pulse, and widened QRS on rhythm strip. What is the most likely diagnosis?

A: Toxic shock syndrome
B: Heat stroke
C: Sepsis and dehydration
D: Tricyclic antidepressant overdose
E: Acute psychosis

The correct answer is D: The anticholinergic effects of tricyclic antidepressants account for the patient’s symptoms, which sometimes are described as follows: “Mad as a hatter, dry as a bone, red as a beet, blind as a bat, hot as Hades.” The quinidinelike effects cause tachycardia, a widened QRS complex, and lengthening of the QT interval.

CME Question 2: A previously well 82-year-old man presents with memory loss, confusion, social withdrawal, and poor self-care of several weeks’ duration. What is the least likely cause of his symptoms?

A: Alzheimer disease
B: Depression
C: Head trauma
D: Hyperthyroidism
E: Medication for allergies

The correct answer is A: This patient’s previously good functioning and relatively rapid change point to a reversible cause of his dementialike symptoms. Conversely, symptoms of Alzheimer disease manifest insidiously over many months’ duration. Depression and chronic subdural hematoma may present with dementia signs and symptoms. Hyperthyroidism can present as apathy in elderly persons. Medications with anticholinergic effects can cause a dementialike reaction.

Pearl Question 1 (T/F): The ED physician should avoid documenting "Patient is medically cleared" when performing a psychiatric clearance examination.

The correct answer is True: Even a thorough ED evaluation is insufficient to make this blanket assurance.

Pearl Question 2 (T/F): In the treatment of delirium tremens, neuroleptics adequately control the patient's behavior and agitation.

The correct answer is False: While these medications (eg, haloperidol, droperidol) may be necessary to control extreme agitation, benzodiazepines must be provided in sufficient doses to reverse the adrenergic hyperactivity. Neuroleptics can lower seizure threshold.

Pearl Question 3 (T/F): Major depression is a common cause of dementialike symptoms in elderly persons and should be considered in the setting of intact language skills.

The correct answer is True: Major depression can cause pseudodementia in elderly persons.

Pearl Question 4 (T/F): Nontraumatic dementia in a young person is most commonly due to Alzheimer disease.

The correct answer is False: The most common nontraumatic dementia in a young person is AIDS-related dementia, present in about 60% of HIV-infected patients at some point in the disease course. It is caused by a direct infection of neurons with HIV, often occurring within weeks of the initial exposure. Consider this condition at any age when risk factors are present.

BIBLIOGRAPHY

Section 11 of 11

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• American Psychiatric Association: Delirium, dementia, and amnestic and other cognitive disorders. In: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 4th ed. Washington, DC: American Psychiatric Association; 1994:123-63.
• American Psychiatric Association: Mental disorders due to a general medical condition. In: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 4th ed. Washington, DC: American Psychiatric Association; 1994:165-74.
• Bair BD: Frequently missed diagnosis in geriatric psychiatry. Psychiatr Clin North Am 1998 Dec; 21(4): 941-71, viii[Medline].
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