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Diagnosis and management of delirium
PSYCHIATRYUPDATE
DIAGNOSIS AND MANAGEMENT OF DELIRIUM Michael
W. Weinbefger, MD,*t
Delirium is a transient, usually reversible, disorder characterized by impaired cognitive function and reduced level of consciousness. The incidence of delirum in patients hospitalized on medical wards ranges from l&50%, and up to 15% of patients over age 60 develop delirium following surgery. Delirium occasionally occurs during the puerperium. Patients who develop delirium have more complications, longer hospital stays, less improvement in functional status, and higher mortality rates than controls. Although many risk factors have been identified for delirium, medications are a predominant cause. Drugs commonly used in obstetrics and gynecology that may induce delirium in the susceptible individual include narcotic analgesics, antibiotics, uterotonic and anticholinergic agents, and dopamine receptor agonists. This article reviews the risk factors, assessment, outcomes, and clinical management of the delirious patient. (Prim Care Update OblGyns 1997;4:80-86. 0 1997 Elsevier Science Inc. All rights reserved.)
The physician caring for older women must be able to’ diagnose and treat delirium because it is a common condition; the reported incidence in patients hospitalized on acute medical and surgical wards ranges from 10-50%.~ Patients who develop delirium have longer hosFrom the Departments of *Obstetrics and Gynecology and tInterna1 Medicine, University of Wisconsin, and the *Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
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pitalizations and are at increased risk of nursing home placement and death. Despite the important consequences of delirium, nonpsychiatric physicians recognize cognitive impairment less than 50% of the time compared with standard mental status screening tests.’ This article reviews the risk factors, assessment, outcomes, and clinical management of delirium in hospitalized patients.
Terminology Delirium was one of the first mental disorders described in medicine and more than 30 diagnostic terms have been used to describe this clinical syndrome.3 Delirium is defined as a transient, usually reversible, dysfunction in cerebral metabolism of acute or subacute onset that manifests itself by disturbance of consciousness and change in cognition. Delirium is diagnosed clinically, and criteria for making this diagnosis have been established by the American Psychiatric Association in the Diagnostic and Statistical Manual for Mental Disorders, Fourth edition (DSM-IV)4 (Table 1).
Clinical Features One of the cardinal features of delirium is a reduction in the ability to focus, maintain, and shift attention. Delirious patients are easily distracted by activities in the environment. If one were interviewing a delirious patient and someone walked by, the patient might attend to the distraction, then turn to the examiner and say, “Did you ask me Inc.,
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a question?” The delirious patient may perseverate when answering questions, have difficulty completing a thought, or even fall asleep during the interview. The attention disturbance typically fluctuates and may recede altogether for minutes or hours (so called lucid intervals). Delirium impairs the brain’s major functions: perception, memory, and thought. Perceptual abnormalities may involve illusions or hallucinations. Misinterpretation of actual sensory stimuli (illusions) may cause the delirious patient to believe, for example, that an intravenous tubing is a snake. False perceptions that the patient believes to be real (hallucinations) may be visual or both auditory and visual. Visual hallucinations are most common and range in complexity from simple shapes, lights, or colors to complex inanimate objects, animals, or ghost-like forms. Auditory hallucinations have been reported to occur in up to 40% of delirious patients and are represented by simple sounds, music, or voices. Olfactory and tactile hallucinations are rare. Delirious patients interpret their illusions and hallucinations as real; some may reach out to them, cry out, converse with them, or attempt to flee. Although these behaviors may disturb others, they may prove life threatening to the patient herself. Agitated, confused, and fearful, she may try to “escape;” sustaining a fracture or other injury. She may tear open her sutures and pull out intravenous lines or Foley catheters. Delirium impairs the key aspects of memory: registration, retention, and recall. Whether due to attention
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DELIRIUM Table 1. DSM-IV Diagnostic for Delirium
Criteria
A.
Disturbance of consciousness (ie, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention. B. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. C. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. D. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by one of the following: 1. A general medical condition 2. Substance intoxication or withdrawal (including medications) 3. Multiple etiologies 4. Delirium not otherwise specified DSM-IV, Diagnostic and Statistical Mental Disorders, Fourth edition.
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deficits or perceptual disturbances, the delirious patient is unable to transfer events into memory. As a result, tests of immediate recall and recent memory are abnormal. Following recovery from the delirium, some patients are amnestic for the entire episode; others are able to recall isolated events. Abnormalities in the flow, form,
and content of thought are prominent in delirium. Attention deficits impair the acquisition, organization, and utilization of information. As a result, thinking becomes illogical, undirected, and incoherent. The delirious patient is unable to make appropriate decisions, perform simple tasks, or maintain self-care. As bizarre thoughts, iminto ages, and fantasies intrude consciousness, the delirious patient may develop delusions. Unlike schizophrenic delusions, those in delirium are vague, transient, Volume
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poorly systematized, and highly influenced by the environment. Language functions are always abnormal in delirium. Speech may be slurred, rambling, tangential, irrelevant, or incoherent. Fluency may be reduced and word-finding difficulties or paraphasias often develop. Writing ability is commonly disturbed in delirium. Chedru and Geschwind” found that dysgraphia, characterized by poorly drawn letters, spatially misaligned letters and lines, and syntactical and spelling errors, is a highly sensitive indicator of delirium. Although dysgraphia is not specific to delirium, occurring in dementia and acute psychiatric disorders, delirious patients tend to be more severely impaired. The delirious patient is usually disoriented to time, often disoriented to place, but very rarely to person. She typically mistakes unfamiliar surroundings and people for familiar ones. The extent of the patient’s disorientation will fluctuate with the severity of the delirium. Delirium is characterized by a rapid onset (hours to days) and may be heralded by nocturnal episodes of cognitive disorganization. Levkoff and colleagues7 found that almost 70% of patients who developed delirium had a prodromal period of at least 1 day before fullblown delirium occurred. During this prodrome, patients may wake from vivid dreams or nightmares grossly disoriented and agitated. Sleep disruption, anxiety, or restlessness may cause reversal of the sleep-wake cycle. Ultimately, patients become unable to judge the passage of time and have difficulty distinguishing dreams from valid perceptions. Patients have described their delirium as a “dreamlike” state that hovers between full wakefulness and sleep. Symptoms tend to fluctuate during the course of the day, and are often most severe at night. Psychomotor activity may be ei-
Table 2. Risk Factors for Development of Delirium While Hospitalized Age over 80 years Preexisting dementia Admission from a nursing home Severe illness, particularly end-stage cancer Symptomatic infection Postoperative state, particularly following cardiotomy and repair of femoral neck fracture Use of psychoactive drugs or narcotic analgesics Visual impairment Azotemia Dehydration Fever or hypothermia
ther reduced, with decreased wakefulness and alertness (hypoactive variant) or increased, with heightened vigilance and an increased response to stimuli [hyperactive variant). Hyperactive
delirium,
ex-
emplified by drug-withdrawal or delirium tremens, is characterized by marked autonomic arousal including diaphoresis, tachycardia, dilated pupils, flushing, hyperpyrexia, and tremor. Hyperactive patients, with their disruptive behavior, typically come to the attention of medical staff, hypoactive patients are more likely to be labeled as depressed, uncooperative, or as having a character disorder. Four categories of delirium are recognized based on whether the etiology is a general medical condition, substance intoxication or withdrawal, multiple etiologies, or not otherwise specified (Table 1). Because the clinical manifestations of delirium are similar regardless of the underlying cause, the diagnostic criteria are the same for each catePY*
Causes of Delirium Many risk factors have been identified for the occurrence of delirium (Table 2). In most studies, medications are the predominant cause of 81
WEINBERGERANDCARNES delirium. Lipowski’ states that virtually any drug is capable of inducing delirium in the susceptible individual. Narcotic analgesics, neuroleptics, benzodiazepines, medications with anticholinergic properties, cycloplegics and mydriatics, glucocorticoids, lidocaine, and digoxin are commonly used medications that may cause delirium. Advancing age increases the risk of delirium, with an age of 80 years or older usually cited as being associated with greatest risk. Among elderly patients, the incidence of delirium ranges from 15% to more than 50% depending on the population studied and the methods used to detect the syndrome.’ Patients with baseline cognitive impairment are at greatest risk of delirium. Erkinjuntti et al9 found that, whereas delirium was present in 12% of patients older than age 55 admitted to medical wards, it was present in 41% of those with underlying dementia. Other impediments to completely normal brain function, such as depression, visual impairment, and previous stroke, have been found to be associated with the development of deliriurn.l,‘O Cerebral hypoperfusion states resulting from dehydration, hypotension, low cardiac output, or stroke may cause delirium. In one retrospective study, 3% of patients with acute strokes presented with delirThe post-ictal state may ium.” mimic delirium and should be considered in any patient with a preexisting seizure disorder, or in older patients a history of stroke, which can cause the new onset of seizures. Alcohol use is associated with delirium during both acute intoxication and withdrawal. Typically, symptoms of withdrawal such as tremulousness, tachycardia, and hypertension precede the development of delirium, but these symptoms may be less prominent in older patients. It should be remembered
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that the patient who chronically abuses alcohol or is malnourished may develop Wernicke encephalopathy (characterized by confusion, nystagmus, and ataxia) due to acute thiamine deficiency caused by glucose administration. Intoxication with other substances of abuse, including amphetamines, cocaine, hallucinogens, and phencyclidine, can cause delirium also. Altered fluid and electrolyte status and symptomatic infection can cause delirium.lO~ll Metabolic abnormalities that adversely affect neurotransmission and thus cause delirium include hypo- or hypernatremia, hypo- or hyperglycemia, hypercalcemia, uremia, liver failure, and hypoxia. Infections of any kind may cause delirium, particularly in patients with underlying dementia; a high index of suspicion for a urinary tract or pulmonary infection should be maintained. No specific cause of delirium can be identified in up to 50% of cases, and multiple factors may contribute in older patients. In general, the older, sicker patient with underlying cognitive impairment and a high burden of illness is at greatest risk of developing delirium. The more risk factors a patient has, the greater the likelihood that delirium will develop*
1,ll
Postoperative
Delirium
The true incidence of postoperative delirium is unknown, but it is estimated that s-10% of patients undergoing general surgery and lo15% of those older than age 60 become delirious.2~12 Postoperative delirium is an important cause of morbidity and mortality. When compared with control subjects, patients who develop postoperative delirium have hospital stays that are 150-200% longer, a 20-fold higher mortality rate, and a threefold to fivefold increased likelihood of discharge to a nursing home.13-15 Pa-
Table 3. Risk Factors for Postoperative Delirium Age 60 years or older Addiction to alcohol and/or sedative hypnotics Personal history of delirium or functional psychosis Poor preoperative cognitive status (assessed by Mini-Mental Status Examination) Poor preoperative functional status (classified by ASA physical status) Abnormal preoperative serum chemistry results (particularly sodium, potassium, and glucose) Emergency surgery Duration of operation of more than 4 hours Iatrogenic drug intoxication (particularly agents for premeditation, anesthesia, and analgesia) Sensory deprivation or overload (?] Sleep deprivation (?) Immobilization (?) Psychologic stress (?) Psychiatric illness, including depression, paranoid personality disorder (?) ASA,
American
Society
of Anesthesiologists.
tients who develop delirium have significantly more postoperative complications and less improvement in functional status than control subjects.13,14*1” The poor outcomes associated with delirium reflect, in part, the severity of underlying illness for which delirium is a marker. In up to 50% of cases, the development of mental status changes is the initial manifestation of an undiagnosed postoperative complication.17 The appearance of delirium must, therefore, be viewed as a medical emergency that requires immediate diagnosis and treatment. Although recent research has tended to focus on single etiologic or pathologic factors, postoperative delirium appears to be a consequence of multiple factors acting synergistically to bring about widespread cerebral dysfunction. Factors most often associated with the development of postoperative delirium are listed in Table 3. One or Prim
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DELIRIUM another of these factors may play a predominant role in a particular case, but it is important to exclude or correct other contributing factors. The role anesthetic technique plays in the development of postoperative delirium is controversial. In 1980, Hole et alI8 reported that none of the 29 elderly patients who underwent total hip arthroplasty under epidural anesthesia, but seven of 31 patients who received general anesthesia, developed postoperative mental status changes. The authors concluded that confusion was related to the degree of postoperative hypoxemia in patients who received general anesthesia. In contrast, Gustafson et all3 found that more arthroplasty patients given spinal or epidural block than halothane anesthesia developed postoperative delirium (55% versus 26%; P < 0.05). The authors hypothesized that intraoperative hypotension and use of anticholinergic medications contributed to the development of delirium. Other studies have found that mental performance is impaired regardless of anesthetic type and emphasize the importance of careful patient monitoring intra- and postoperative14,19.20 ly* Cholinergic mechanisms appear to be involved in memory, attention, arousal, and rapid eye movement sleep, and it is hypothesized that deficient acetylcholine synthesis or cholinergic blockade plays a central role in the development of delirium. In anesthesia, atropine and scopolamine have been widely used as premeditations to reduce secretions, to protect against vagal over-activity, and to induce sedation and amnesia. Delirium has been reported in 20% of patients premeditated with scopolamine and in about 10% of obstetric patients undergoing “twilight sleep” anesthesia.l’ Premeditation with glycopyrrolate, an anticholinergic agent that does not cross the bloodbrain barrier, is reported to reduce Volume
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the incidence of postoperative confusion Other medications commonly used postoperatively that may cause delirium include narcotic and non-narcotic analgesics, sedativehypnotics, and antibiotics. Of the narcotic analgesics, meperidine is most likely to induce delirium. It is hypothesized that the drug’s active metabolite, normerperidine, which has anticholinergic activity, produces central nervous system excitatory effects mimicking delirium.*’ Butorphanol (Stadol) and nalbuphine (Nubain), synthetically derived opioid agonist-antagonist analgesics, are reported to induce confusion in about 1% of patients. Nonsteroidal anti-inflammatory agents, including aspirin, ibuprofen, indomethacin, naproxen, and sulindac, rarely cause delirium. Acetaminophen in therapeutic doses has virtually no side effects, but an overdose may cause acute hepatic necrosis and encephalopathy with delirium. Indomethacin appears to cause delirium to occur more commonly than other nonsteroidal anti-inflammatory agents. Sedative-hypnotic drugs are often prescribed postoperatively to treat anxiety and insomnia. Any of these may cause delirium, particularly in the high-risk patient, even at therapeutic doses. Although intoxication is the most common organic mental syndrome induced by these medications, delirium occasionally develops. In addition to causing delirium, benzodiazepine use in elderly patients may lead to the development of daytime drowsiness, decreased mental acuity, and impaired balance and memory, If benzodiazepine therapy is deemed essential, prescribe short- and intermediate-acting agents, such as oxazepam, lorazepam, temazepam, alprazolam, and triazolam, because their elimination half-lives are not affected by aging. Avoid long-acting benzodiazepines, such as flurazepam or diazepam.
Many of the antimicrobial agents commonly used in obstetrics and gynecology, including penicillin, cephalosporins, erythromycin, gentamicin, sulfonamides, and metronidazole, have been reported to cause delirium in an occasional patient.
Postpartum Delirium It is estimated that O.l-0.3% of women develop postpartum psychosis, characterized by hallucinations and/or delusions.‘l Most patients who develop postpartum psychoses have affective disorders (ie, manic or depressive episodes), but other psychiatric disorders, including delirium, may have psychotic features. Among patients who develop postpartum psychoses, the reported incidence of delirium ranges from l-33%.12 There is no evidence that an organic factor unique to the postpartum period causes delirium; however, rapid changes in serum estrogen and progesterone concentrations may play a role. In the pre-antibiotic era, puerperal sepsis was a common cause of delirium; today, obstetric variables seem to play little role in the development of postpartum delirium.‘l Bromocriptine and Methergine can produce delirium. Bromocriptine alters awareness and behavior, sometimes accompanied by hallucinations, in l-Z% of patients, even at dosages as low as 1.25 mg twice daily.22,23 Bromocriptine is no longer approved by the U.S. Food and Drug Administration for the indication of lactation suppression. Ergot alkaloids are widely used postpartum for their uterotonic effects. Iffy et alz4 reported three patients who developed postpartum psychoses after receiving Methergine (along with other medications) and attributed their mental status changes to ergotism. 83
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When Should You Suspect Delirium? Anything that suggests your patient is not appropriately processing environmental information should stimulate an evaluation for delirium. For example, does the patient you have known for years have difficulty recognizing you or remembering your name? Does she appear sleepy or agitated? Does it take her a long time to answer questions? Do you need to keep repeating your questions? Is her speech rambling or incoherent? Is the patient disoriented? Are there perceptual disturbances such as visual or auditory hallucinations or paranoid thoughts? If the nurse informs you that your patient needs to be restrained because she is pulling out an intravenous line or a nasogastric tube, she may be developing delirium. Although these devices may cause discomfort, the cognitively intact patient will not pull them out. If a patient falls or develops urinary incontinence, delirium must be suspected. If a patient is “sundowning” and this is not a previously known behavior for her, this may be the first sign of delirium.
Evaluating the Delirious Patient Although delirium affects behavior and thus appears to be in the domain of the psychiatrist, delirium is almost always due to a medical condition and should be considered a medical emergency. As with any acute medical problem, the first step in evaluating the delirious patient is to gather data. How long has the patient been delirious? How rapidly are the symptoms progressing? Have any new medications been administered? For patients presenting to the hospital with delirium, inquire about use of over-the84
counter medications that contain anticholinergic ingredients (eg, Tylenol-PM contains diphenhydramine). Is the patient on insulin or an oral hypoglycemic agent that could be causing hypoglycemia? To determine whether the patient is withdrawing from alcohol or sedative use at home, ask family members about heavy use of alcohol-containing cough syrups and consumption of alcoholic beverages like brandy for medicinal purposes. If the patient recently underwent a procedure requiring sedation, such as endoscopy, did she aspirate during the procedure and become delirious from either pneumonia or hypoxemia? If the patient is malnourished or abuses alcohol, did she receive intravenous fluids containing glucose, thereby precipitating Wernicke encephalopathy? Does the patient have osteolytic bone metastases and hypercalcemia caused by prolonged bedrest? Next, perform a thorough physical examination. Begin with the vital signs. Is the patient hypotensive, suggesting delirium caused by cerebral hypoperfusion? Hyperadrenergic states, characterized by tachycardia or fever, suggest alcohol withdrawal or infection. Is the patient dyspneic, suggesting pneumonia or pulmonary embolism? Look for evidence of infection, dehydration, congestive heart failure, and focal neurologic signs. There is no specific battery of laboratory tests to order in the delirious patient. Laboratory evaluation will be guided by the information obtained from the history and physical examination. Table 4 lists diagnostic tests that aid in determining the etiology of delirium. Assessment of mental state, including cognitive function, is an integral part of the evaluation of the patient suspected of having delirium. Although signs of delirium are often noted in the course of routine history and physical examination, formal mental status evaluation
Table 4. Laboratory Studies To Investigate Delirium Basic tests
Complete blood count with differential Blood chemistry (electrolytes, blood
urea nitrogen, creatinine, glucose, calcium, phosphate, liver enzymes, albumin, ammonia) Erythrocyte sedimentation rate Urinalysis and urine culture Chest x-ray Electrocardiogram Pulse oximetry Other studies as indicated Arterial blood gases Toxicology screen of urine or blood Blood levels of medications Serology for syphilis Blood cultures Special blood chemistries (vitamin B-12, thiamine
and folate levels, magnesium, serum proteins,
osmolality) Thyroid function tests Lupus erythematous preparation Antinuclear antibody levels Lumbar puncture (cells, protein, glucose, culture, serology, opening pressure) Computed tomography or magnetic resonanceimaging scan of the head Urine osmolality and porphobilinogen Electroencephalography
may uncover subtle disturbances of attention, orientation, and memory that might otherwise be missed. Serial mental status evaluation allows the clinician to monitor cognitive performance for improvement or deterioration. Several brief, easily administered rating scales have been developed for bedside use; some are specifically designed to diagnose delirium. The screening test used by most clinicians is the Mini-Mental State Exam (MMSE).25 The MMSE can be administered in less than 10 minutes and screens for orientation, recall, attention, calculation, language, and constructional abilities. The MMSE has been criticized because it is relatively insensitive to mild impairment, does not distinguish between delirium and demenPrim
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DELIRIUM tia, and is of limited value in patients with less than an eighth-grade education or aged older than 59 years. 26 Despite these shortcomings, MMSE remains a widely used standard for patient evaluation and data collection. The electroencephalogram (EEG) is rarely of value in the diagnosis of delirium, as the diagnosis rests on clinical signs. The EEG abnormalities in delirium usually are nonspecific and rarely assist in diagnosis or treatment. EEG may be helpful when a seizure disorder is suspected, if a psychiatric disorder such as a manic episode is felt to be mimicking delirium, or if a patient has been treated with benzodiazepines to prevent symptoms of alcohol withdrawal. In the last instance, it may not be clear whether delirium is due to the withdrawal state or the benzodiazepine. During alcohol withdrawal, the EEG is more likely to show low amplitude fast activity; in benzodiazepine intoxication, the EEG usually reveals diffuse slow wave activity.27 Brain-imaging studies (magnetic resonance imaging or computed tomography) rarely are necessary to diagnose or manage acute delirium. They may even obfuscate the search for causes of delirium by uncovering preexisting, but undiagnosed abnormalities, such as old strokes or cerebral atrophy that are unlikely to be the cause of the delirium.
ularly sensitive to any additional insults to cognitive function. Treat any underlying precipitants such as infection, hypoxia, and fluid or electrolyte abnormalities. If Wernicke encephalopathy is suspected, administer thiamine at 50 mg intravenously and 50 mg intramuscularly. These measures usually result in clearing of delirium within 24-48 hours. If a patient remains delirious after removal of the precipitating cause, continue to reevaluate for new causes of delirium. For example, the elderly postoperative patient who initially became delirious from opioid analgesics may now be delirious from a urinary tract infection or be hyponatremic. In the patient who became delirious after being premeditated with midazolam for a procedure or diphenhydramine prior to blood transfusion, delirium may have been precipitated by medication use, but be perpetuated by aspiration pneumonia that developed during the initial delirious state. Reassurance and reorientation may calm the delirious patient.’ Many hospitals have “bedsitters” who can ensure patient safety and provide nighttime reorientation if awakening occurs. Place a clock and calendar in the patient’s room and administer medications at intervals that do not interrupt sleep. Avoid the use of physical restraints until all treatment options have been exhausted.
Management The consensus among experts is that all drugs not deemed absolutely necessary be discontinued in the delirious patient.7 This includes medications that the patient may have been taking without any problem before delirium developed (eg, ophthalmologic agents such as timolol or atropine, histamine H,receptor antagonists, and antidepressants). It is hypothesized that, during delirium, the brain is particVolume
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Pharmacologic Therapy Pharmacologic therapy is indicated if the patient is excessively agitated or anxious, psychotic, or potentially dangerous to herself or others. Although the alternative pharmacologic regimens have not been compared in randomized studies, the expert consensus is that haloperidol is the drug of choice.5,7 The advantages of haloperidol over other an-
tipsychotics are as follows: it can be given by any route, it does not cause significant hypotension, it is nonsedating, it does not affect other disease states such as hypertension and heart failure, it has a rapid onset of action, and physicians often have clinical experience with it.27 The starting dose can be as low as 0.25 mg in elderly patients, increasing by 0.25 mg every 30 minutes as needed. If symptoms have not resolved after a total of 5 mg has been given, psychiatric consultation should be sought to exclude the possibility that schizophrenia, mania, or another organic mental syndrome has been misdiagnosed as delirium. Another consideration in this event is neuroleptic-induced akathisia. This movement disorder may make the patient appear agitated and cause the physician to erroneously conclude that the delirium is persisting or progressing. The role of benzodiazepines as pharmacologic therapy of delirium remains controversial. Some physicians recommend administering benzodiazepines in low doses to treat mild delirium or in conjunction with antipsychotics to treat more severe delirium. Others believe that benzodiazepines further impair cognitive function and invariably make delirium more severe. These physicians recommend benzodiazepine use only when delirium is caused by alcohol or sedative withdrawal. Benzodiazepines occasionally are used to induce sleep in terminally ill cancer patients who become delirious from large doses of narcotics. Here, patient comfort is the objective. Civil commitment procedures often are necessary to involuntarily treat patients with psychiatric illnesses. Delirium, on the other hand, constitutes a medical emergency, and court authorization to administer antipsychotic medication is unnecessary. In this setting, the doctrine of “implied consent” applies. 85
Summary Delirium is a common and potentially lethal condition. Obstetrician/gynecologists can help to prevent delirium by identifying high-risk patients, monitoring them for prodromal signs, and avoiding nonessential medications whenever possible. Once delirium develops, careful history and physical examination will guide evaluation and therapy by revealing precipitating factors. In severe cases, pharmacologic treatment with low doses of haloperidol may be necessary.
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9.
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References 1.
2. 3.
4.
5. 6.
7.
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Pompei P, Foreman M, Rudberg MA, Inouye SK, Braund V, Cassel CK. Delirium in hospitalized older persons: predictors and outcomes, J Am Geriatr Sot 1994;42:809-15. Francis J, Kapoor WN. Delirium in hospitalized elderly. J Gen Intern Med 1990;5:65-79. Wise MG, Gray KF. Delirium, dementia, and amnestic disorders. In: Hales RE, Yudofsky SC, Talbott JA, editors. The American Psychiatric Press textbook of psychiatry. 2nd ed. Washington (DC): American Psychiatric Press, 1994:311-53. American Psychiatric Association diagnostic and statistical manual for mental disorders. 4th ed. Washington (DC): APA, 1994. Beresin EV. Delirium in the elderly. J Geriatr Psychiatry Neurol 1988;l: 127-43. Chedru F, Geschwind N. Writing disturbances in acute confusional states. Neuropsychologia 1972;lO: 343-53. Levkoff SE, Liptzin B, Evans DA, et al. Progression and resolution of
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delirium in elderly patients hospitalized for acute care. Am J Geriatr Psychiatry 1994;2:230-8. Lipowski ZJ. Delirium (acute confusional states). JAMA 1987;258: 1789-92. Erkinjuntti T, Wikstrom J, Palo J, Autio L. Dementia among medical inpatients. Arch Intern Med 1986; 146:1923-6. Inouye SK, Viscoli CM, Horwitz RI, Hurst LD, Tinetti ME. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993;119:474-81. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1999; 263:1097-101. Lipowski ZJ. Delirium: acute confusional states. New York (NY): Oxford University Press, 1999. Gustafson Y, Berggren D, BrannStrom B, et al. Acute confusional states in elderly patients treated for femoral neck fracture. J Am Geriatr Sot 1988;36:525-30. Berggren D, Gustafson Y, Eriksson B, et al. Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth Analg 1987;66:497-504. Marcantonio ER, Goldman L, Mangione CM, et al. A clinical prediction rule for delirium after elective noncardiac surgery. JAMA 1994; 2711134-9. Rogers MP, Liang MH, Daltroy LH, et al. Delirium after elective orthopedic surgery: Risk factors and natural history. Int J Psychiatry Med 1989;19:109-21. Millar HR. Psychiatric morbidity in elderly surgical patients. Br J Psychiatry 1981;183:17-20. Hole A, Terjesen T, Breivik H. Epidural versus _general _ anaesthesia __ _ for total hip arthroplasty in elderly pa-
tients. Acta Anaesthesiol Stand 1980;24:279-87. 19. Riis J, Lomholt B, Haxholdt 0, et al. Immediate and long-term mental recovery from general versus epidural anesthesia in elderly patients. Acta Anaesthesiol Stand 1983;27: 44-9. 20 Ghoneim MM, Hinrichs JV, O’Hara MW, et al. Comparison of psychologic and cognitive functions after general or regional anesthesia. Anesthesiology 1988;69:507-15. 21. Brockington IF, Winokur G, Dean C. Puerperal psychosis. In: Brockington IF, Kumar R editors. Motherhood and mental illness. San Diego (CA): Academic, 1982:37-69. 22. Parkes D. Bromocriptine. N Engl J Med 1979;301:873-8. 23. Einarson TR, Turchet EN. Psychotic reaction to low-dose bromocriptine. Clin Pharm 1983;2:273-4. 24. Iffy L, Lindenthal JJ, McArdle JJ, McNamara RE, Szodi Z, Ganesh V. Ergotism: a possible etiology for puerperal psychosis. Obstet Gynecol 1989;73:475-7. 25. Folstein MF, Fostein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98. 26. Tune L, Ross C. Delirium. The American Psychiatric Press textbook of neuropsychiatry. Washington (DC): APP 1994:352-65. 27. Steinhart MJ. The use of haloperido1 in geriatric patients with organic mental disorder. Curr Ther Res 1983;33:132-43. Address correspondence and reprint requests to Michael W. Weinberger, MD, Department of Obstetrics and Gynecology, H4/662 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792.
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DIAGNOSIS AND MANAGEMENT OF DELIRIUM Michael
W. Weinbefger, MD,*t
Delirium is a transient, usually reversible, disorder characterized by impaired cognitive function and reduced level of consciousness. The incidence of delirum in patients hospitalized on medical wards ranges from l&50%, and up to 15% of patients over age 60 develop delirium following surgery. Delirium occasionally occurs during the puerperium. Patients who develop delirium have more complications, longer hospital stays, less improvement in functional status, and higher mortality rates than controls. Although many risk factors have been identified for delirium, medications are a predominant cause. Drugs commonly used in obstetrics and gynecology that may induce delirium in the susceptible individual include narcotic analgesics, antibiotics, uterotonic and anticholinergic agents, and dopamine receptor agonists. This article reviews the risk factors, assessment, outcomes, and clinical management of the delirious patient. (Prim Care Update OblGyns 1997;4:80-86. 0 1997 Elsevier Science Inc. All rights reserved.)
The physician caring for older women must be able to’ diagnose and treat delirium because it is a common condition; the reported incidence in patients hospitalized on acute medical and surgical wards ranges from 10-50%.~ Patients who develop delirium have longer hosFrom the Departments of *Obstetrics and Gynecology and tInterna1 Medicine, University of Wisconsin, and the *Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
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pitalizations and are at increased risk of nursing home placement and death. Despite the important consequences of delirium, nonpsychiatric physicians recognize cognitive impairment less than 50% of the time compared with standard mental status screening tests.’ This article reviews the risk factors, assessment, outcomes, and clinical management of delirium in hospitalized patients.
Terminology Delirium was one of the first mental disorders described in medicine and more than 30 diagnostic terms have been used to describe this clinical syndrome.3 Delirium is defined as a transient, usually reversible, dysfunction in cerebral metabolism of acute or subacute onset that manifests itself by disturbance of consciousness and change in cognition. Delirium is diagnosed clinically, and criteria for making this diagnosis have been established by the American Psychiatric Association in the Diagnostic and Statistical Manual for Mental Disorders, Fourth edition (DSM-IV)4 (Table 1).
Clinical Features One of the cardinal features of delirium is a reduction in the ability to focus, maintain, and shift attention. Delirious patients are easily distracted by activities in the environment. If one were interviewing a delirious patient and someone walked by, the patient might attend to the distraction, then turn to the examiner and say, “Did you ask me Inc.,
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a question?” The delirious patient may perseverate when answering questions, have difficulty completing a thought, or even fall asleep during the interview. The attention disturbance typically fluctuates and may recede altogether for minutes or hours (so called lucid intervals). Delirium impairs the brain’s major functions: perception, memory, and thought. Perceptual abnormalities may involve illusions or hallucinations. Misinterpretation of actual sensory stimuli (illusions) may cause the delirious patient to believe, for example, that an intravenous tubing is a snake. False perceptions that the patient believes to be real (hallucinations) may be visual or both auditory and visual. Visual hallucinations are most common and range in complexity from simple shapes, lights, or colors to complex inanimate objects, animals, or ghost-like forms. Auditory hallucinations have been reported to occur in up to 40% of delirious patients and are represented by simple sounds, music, or voices. Olfactory and tactile hallucinations are rare. Delirious patients interpret their illusions and hallucinations as real; some may reach out to them, cry out, converse with them, or attempt to flee. Although these behaviors may disturb others, they may prove life threatening to the patient herself. Agitated, confused, and fearful, she may try to “escape;” sustaining a fracture or other injury. She may tear open her sutures and pull out intravenous lines or Foley catheters. Delirium impairs the key aspects of memory: registration, retention, and recall. Whether due to attention
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DELIRIUM Table 1. DSM-IV Diagnostic for Delirium
Criteria
A.
Disturbance of consciousness (ie, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention. B. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. C. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. D. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by one of the following: 1. A general medical condition 2. Substance intoxication or withdrawal (including medications) 3. Multiple etiologies 4. Delirium not otherwise specified DSM-IV, Diagnostic and Statistical Mental Disorders, Fourth edition.
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deficits or perceptual disturbances, the delirious patient is unable to transfer events into memory. As a result, tests of immediate recall and recent memory are abnormal. Following recovery from the delirium, some patients are amnestic for the entire episode; others are able to recall isolated events. Abnormalities in the flow, form,
and content of thought are prominent in delirium. Attention deficits impair the acquisition, organization, and utilization of information. As a result, thinking becomes illogical, undirected, and incoherent. The delirious patient is unable to make appropriate decisions, perform simple tasks, or maintain self-care. As bizarre thoughts, iminto ages, and fantasies intrude consciousness, the delirious patient may develop delusions. Unlike schizophrenic delusions, those in delirium are vague, transient, Volume
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poorly systematized, and highly influenced by the environment. Language functions are always abnormal in delirium. Speech may be slurred, rambling, tangential, irrelevant, or incoherent. Fluency may be reduced and word-finding difficulties or paraphasias often develop. Writing ability is commonly disturbed in delirium. Chedru and Geschwind” found that dysgraphia, characterized by poorly drawn letters, spatially misaligned letters and lines, and syntactical and spelling errors, is a highly sensitive indicator of delirium. Although dysgraphia is not specific to delirium, occurring in dementia and acute psychiatric disorders, delirious patients tend to be more severely impaired. The delirious patient is usually disoriented to time, often disoriented to place, but very rarely to person. She typically mistakes unfamiliar surroundings and people for familiar ones. The extent of the patient’s disorientation will fluctuate with the severity of the delirium. Delirium is characterized by a rapid onset (hours to days) and may be heralded by nocturnal episodes of cognitive disorganization. Levkoff and colleagues7 found that almost 70% of patients who developed delirium had a prodromal period of at least 1 day before fullblown delirium occurred. During this prodrome, patients may wake from vivid dreams or nightmares grossly disoriented and agitated. Sleep disruption, anxiety, or restlessness may cause reversal of the sleep-wake cycle. Ultimately, patients become unable to judge the passage of time and have difficulty distinguishing dreams from valid perceptions. Patients have described their delirium as a “dreamlike” state that hovers between full wakefulness and sleep. Symptoms tend to fluctuate during the course of the day, and are often most severe at night. Psychomotor activity may be ei-
Table 2. Risk Factors for Development of Delirium While Hospitalized Age over 80 years Preexisting dementia Admission from a nursing home Severe illness, particularly end-stage cancer Symptomatic infection Postoperative state, particularly following cardiotomy and repair of femoral neck fracture Use of psychoactive drugs or narcotic analgesics Visual impairment Azotemia Dehydration Fever or hypothermia
ther reduced, with decreased wakefulness and alertness (hypoactive variant) or increased, with heightened vigilance and an increased response to stimuli [hyperactive variant). Hyperactive
delirium,
ex-
emplified by drug-withdrawal or delirium tremens, is characterized by marked autonomic arousal including diaphoresis, tachycardia, dilated pupils, flushing, hyperpyrexia, and tremor. Hyperactive patients, with their disruptive behavior, typically come to the attention of medical staff, hypoactive patients are more likely to be labeled as depressed, uncooperative, or as having a character disorder. Four categories of delirium are recognized based on whether the etiology is a general medical condition, substance intoxication or withdrawal, multiple etiologies, or not otherwise specified (Table 1). Because the clinical manifestations of delirium are similar regardless of the underlying cause, the diagnostic criteria are the same for each catePY*
Causes of Delirium Many risk factors have been identified for the occurrence of delirium (Table 2). In most studies, medications are the predominant cause of 81
WEINBERGERANDCARNES delirium. Lipowski’ states that virtually any drug is capable of inducing delirium in the susceptible individual. Narcotic analgesics, neuroleptics, benzodiazepines, medications with anticholinergic properties, cycloplegics and mydriatics, glucocorticoids, lidocaine, and digoxin are commonly used medications that may cause delirium. Advancing age increases the risk of delirium, with an age of 80 years or older usually cited as being associated with greatest risk. Among elderly patients, the incidence of delirium ranges from 15% to more than 50% depending on the population studied and the methods used to detect the syndrome.’ Patients with baseline cognitive impairment are at greatest risk of delirium. Erkinjuntti et al9 found that, whereas delirium was present in 12% of patients older than age 55 admitted to medical wards, it was present in 41% of those with underlying dementia. Other impediments to completely normal brain function, such as depression, visual impairment, and previous stroke, have been found to be associated with the development of deliriurn.l,‘O Cerebral hypoperfusion states resulting from dehydration, hypotension, low cardiac output, or stroke may cause delirium. In one retrospective study, 3% of patients with acute strokes presented with delirThe post-ictal state may ium.” mimic delirium and should be considered in any patient with a preexisting seizure disorder, or in older patients a history of stroke, which can cause the new onset of seizures. Alcohol use is associated with delirium during both acute intoxication and withdrawal. Typically, symptoms of withdrawal such as tremulousness, tachycardia, and hypertension precede the development of delirium, but these symptoms may be less prominent in older patients. It should be remembered
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that the patient who chronically abuses alcohol or is malnourished may develop Wernicke encephalopathy (characterized by confusion, nystagmus, and ataxia) due to acute thiamine deficiency caused by glucose administration. Intoxication with other substances of abuse, including amphetamines, cocaine, hallucinogens, and phencyclidine, can cause delirium also. Altered fluid and electrolyte status and symptomatic infection can cause delirium.lO~ll Metabolic abnormalities that adversely affect neurotransmission and thus cause delirium include hypo- or hypernatremia, hypo- or hyperglycemia, hypercalcemia, uremia, liver failure, and hypoxia. Infections of any kind may cause delirium, particularly in patients with underlying dementia; a high index of suspicion for a urinary tract or pulmonary infection should be maintained. No specific cause of delirium can be identified in up to 50% of cases, and multiple factors may contribute in older patients. In general, the older, sicker patient with underlying cognitive impairment and a high burden of illness is at greatest risk of developing delirium. The more risk factors a patient has, the greater the likelihood that delirium will develop*
1,ll
Postoperative
Delirium
The true incidence of postoperative delirium is unknown, but it is estimated that s-10% of patients undergoing general surgery and lo15% of those older than age 60 become delirious.2~12 Postoperative delirium is an important cause of morbidity and mortality. When compared with control subjects, patients who develop postoperative delirium have hospital stays that are 150-200% longer, a 20-fold higher mortality rate, and a threefold to fivefold increased likelihood of discharge to a nursing home.13-15 Pa-
Table 3. Risk Factors for Postoperative Delirium Age 60 years or older Addiction to alcohol and/or sedative hypnotics Personal history of delirium or functional psychosis Poor preoperative cognitive status (assessed by Mini-Mental Status Examination) Poor preoperative functional status (classified by ASA physical status) Abnormal preoperative serum chemistry results (particularly sodium, potassium, and glucose) Emergency surgery Duration of operation of more than 4 hours Iatrogenic drug intoxication (particularly agents for premeditation, anesthesia, and analgesia) Sensory deprivation or overload (?] Sleep deprivation (?) Immobilization (?) Psychologic stress (?) Psychiatric illness, including depression, paranoid personality disorder (?) ASA,
American
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of Anesthesiologists.
tients who develop delirium have significantly more postoperative complications and less improvement in functional status than control subjects.13,14*1” The poor outcomes associated with delirium reflect, in part, the severity of underlying illness for which delirium is a marker. In up to 50% of cases, the development of mental status changes is the initial manifestation of an undiagnosed postoperative complication.17 The appearance of delirium must, therefore, be viewed as a medical emergency that requires immediate diagnosis and treatment. Although recent research has tended to focus on single etiologic or pathologic factors, postoperative delirium appears to be a consequence of multiple factors acting synergistically to bring about widespread cerebral dysfunction. Factors most often associated with the development of postoperative delirium are listed in Table 3. One or Prim
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DELIRIUM another of these factors may play a predominant role in a particular case, but it is important to exclude or correct other contributing factors. The role anesthetic technique plays in the development of postoperative delirium is controversial. In 1980, Hole et alI8 reported that none of the 29 elderly patients who underwent total hip arthroplasty under epidural anesthesia, but seven of 31 patients who received general anesthesia, developed postoperative mental status changes. The authors concluded that confusion was related to the degree of postoperative hypoxemia in patients who received general anesthesia. In contrast, Gustafson et all3 found that more arthroplasty patients given spinal or epidural block than halothane anesthesia developed postoperative delirium (55% versus 26%; P < 0.05). The authors hypothesized that intraoperative hypotension and use of anticholinergic medications contributed to the development of delirium. Other studies have found that mental performance is impaired regardless of anesthetic type and emphasize the importance of careful patient monitoring intra- and postoperative14,19.20 ly* Cholinergic mechanisms appear to be involved in memory, attention, arousal, and rapid eye movement sleep, and it is hypothesized that deficient acetylcholine synthesis or cholinergic blockade plays a central role in the development of delirium. In anesthesia, atropine and scopolamine have been widely used as premeditations to reduce secretions, to protect against vagal over-activity, and to induce sedation and amnesia. Delirium has been reported in 20% of patients premeditated with scopolamine and in about 10% of obstetric patients undergoing “twilight sleep” anesthesia.l’ Premeditation with glycopyrrolate, an anticholinergic agent that does not cross the bloodbrain barrier, is reported to reduce Volume
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the incidence of postoperative confusion Other medications commonly used postoperatively that may cause delirium include narcotic and non-narcotic analgesics, sedativehypnotics, and antibiotics. Of the narcotic analgesics, meperidine is most likely to induce delirium. It is hypothesized that the drug’s active metabolite, normerperidine, which has anticholinergic activity, produces central nervous system excitatory effects mimicking delirium.*’ Butorphanol (Stadol) and nalbuphine (Nubain), synthetically derived opioid agonist-antagonist analgesics, are reported to induce confusion in about 1% of patients. Nonsteroidal anti-inflammatory agents, including aspirin, ibuprofen, indomethacin, naproxen, and sulindac, rarely cause delirium. Acetaminophen in therapeutic doses has virtually no side effects, but an overdose may cause acute hepatic necrosis and encephalopathy with delirium. Indomethacin appears to cause delirium to occur more commonly than other nonsteroidal anti-inflammatory agents. Sedative-hypnotic drugs are often prescribed postoperatively to treat anxiety and insomnia. Any of these may cause delirium, particularly in the high-risk patient, even at therapeutic doses. Although intoxication is the most common organic mental syndrome induced by these medications, delirium occasionally develops. In addition to causing delirium, benzodiazepine use in elderly patients may lead to the development of daytime drowsiness, decreased mental acuity, and impaired balance and memory, If benzodiazepine therapy is deemed essential, prescribe short- and intermediate-acting agents, such as oxazepam, lorazepam, temazepam, alprazolam, and triazolam, because their elimination half-lives are not affected by aging. Avoid long-acting benzodiazepines, such as flurazepam or diazepam.
Many of the antimicrobial agents commonly used in obstetrics and gynecology, including penicillin, cephalosporins, erythromycin, gentamicin, sulfonamides, and metronidazole, have been reported to cause delirium in an occasional patient.
Postpartum Delirium It is estimated that O.l-0.3% of women develop postpartum psychosis, characterized by hallucinations and/or delusions.‘l Most patients who develop postpartum psychoses have affective disorders (ie, manic or depressive episodes), but other psychiatric disorders, including delirium, may have psychotic features. Among patients who develop postpartum psychoses, the reported incidence of delirium ranges from l-33%.12 There is no evidence that an organic factor unique to the postpartum period causes delirium; however, rapid changes in serum estrogen and progesterone concentrations may play a role. In the pre-antibiotic era, puerperal sepsis was a common cause of delirium; today, obstetric variables seem to play little role in the development of postpartum delirium.‘l Bromocriptine and Methergine can produce delirium. Bromocriptine alters awareness and behavior, sometimes accompanied by hallucinations, in l-Z% of patients, even at dosages as low as 1.25 mg twice daily.22,23 Bromocriptine is no longer approved by the U.S. Food and Drug Administration for the indication of lactation suppression. Ergot alkaloids are widely used postpartum for their uterotonic effects. Iffy et alz4 reported three patients who developed postpartum psychoses after receiving Methergine (along with other medications) and attributed their mental status changes to ergotism. 83
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When Should You Suspect Delirium? Anything that suggests your patient is not appropriately processing environmental information should stimulate an evaluation for delirium. For example, does the patient you have known for years have difficulty recognizing you or remembering your name? Does she appear sleepy or agitated? Does it take her a long time to answer questions? Do you need to keep repeating your questions? Is her speech rambling or incoherent? Is the patient disoriented? Are there perceptual disturbances such as visual or auditory hallucinations or paranoid thoughts? If the nurse informs you that your patient needs to be restrained because she is pulling out an intravenous line or a nasogastric tube, she may be developing delirium. Although these devices may cause discomfort, the cognitively intact patient will not pull them out. If a patient falls or develops urinary incontinence, delirium must be suspected. If a patient is “sundowning” and this is not a previously known behavior for her, this may be the first sign of delirium.
Evaluating the Delirious Patient Although delirium affects behavior and thus appears to be in the domain of the psychiatrist, delirium is almost always due to a medical condition and should be considered a medical emergency. As with any acute medical problem, the first step in evaluating the delirious patient is to gather data. How long has the patient been delirious? How rapidly are the symptoms progressing? Have any new medications been administered? For patients presenting to the hospital with delirium, inquire about use of over-the84
counter medications that contain anticholinergic ingredients (eg, Tylenol-PM contains diphenhydramine). Is the patient on insulin or an oral hypoglycemic agent that could be causing hypoglycemia? To determine whether the patient is withdrawing from alcohol or sedative use at home, ask family members about heavy use of alcohol-containing cough syrups and consumption of alcoholic beverages like brandy for medicinal purposes. If the patient recently underwent a procedure requiring sedation, such as endoscopy, did she aspirate during the procedure and become delirious from either pneumonia or hypoxemia? If the patient is malnourished or abuses alcohol, did she receive intravenous fluids containing glucose, thereby precipitating Wernicke encephalopathy? Does the patient have osteolytic bone metastases and hypercalcemia caused by prolonged bedrest? Next, perform a thorough physical examination. Begin with the vital signs. Is the patient hypotensive, suggesting delirium caused by cerebral hypoperfusion? Hyperadrenergic states, characterized by tachycardia or fever, suggest alcohol withdrawal or infection. Is the patient dyspneic, suggesting pneumonia or pulmonary embolism? Look for evidence of infection, dehydration, congestive heart failure, and focal neurologic signs. There is no specific battery of laboratory tests to order in the delirious patient. Laboratory evaluation will be guided by the information obtained from the history and physical examination. Table 4 lists diagnostic tests that aid in determining the etiology of delirium. Assessment of mental state, including cognitive function, is an integral part of the evaluation of the patient suspected of having delirium. Although signs of delirium are often noted in the course of routine history and physical examination, formal mental status evaluation
Table 4. Laboratory Studies To Investigate Delirium Basic tests
Complete blood count with differential Blood chemistry (electrolytes, blood
urea nitrogen, creatinine, glucose, calcium, phosphate, liver enzymes, albumin, ammonia) Erythrocyte sedimentation rate Urinalysis and urine culture Chest x-ray Electrocardiogram Pulse oximetry Other studies as indicated Arterial blood gases Toxicology screen of urine or blood Blood levels of medications Serology for syphilis Blood cultures Special blood chemistries (vitamin B-12, thiamine
and folate levels, magnesium, serum proteins,
osmolality) Thyroid function tests Lupus erythematous preparation Antinuclear antibody levels Lumbar puncture (cells, protein, glucose, culture, serology, opening pressure) Computed tomography or magnetic resonanceimaging scan of the head Urine osmolality and porphobilinogen Electroencephalography
may uncover subtle disturbances of attention, orientation, and memory that might otherwise be missed. Serial mental status evaluation allows the clinician to monitor cognitive performance for improvement or deterioration. Several brief, easily administered rating scales have been developed for bedside use; some are specifically designed to diagnose delirium. The screening test used by most clinicians is the Mini-Mental State Exam (MMSE).25 The MMSE can be administered in less than 10 minutes and screens for orientation, recall, attention, calculation, language, and constructional abilities. The MMSE has been criticized because it is relatively insensitive to mild impairment, does not distinguish between delirium and demenPrim
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DELIRIUM tia, and is of limited value in patients with less than an eighth-grade education or aged older than 59 years. 26 Despite these shortcomings, MMSE remains a widely used standard for patient evaluation and data collection. The electroencephalogram (EEG) is rarely of value in the diagnosis of delirium, as the diagnosis rests on clinical signs. The EEG abnormalities in delirium usually are nonspecific and rarely assist in diagnosis or treatment. EEG may be helpful when a seizure disorder is suspected, if a psychiatric disorder such as a manic episode is felt to be mimicking delirium, or if a patient has been treated with benzodiazepines to prevent symptoms of alcohol withdrawal. In the last instance, it may not be clear whether delirium is due to the withdrawal state or the benzodiazepine. During alcohol withdrawal, the EEG is more likely to show low amplitude fast activity; in benzodiazepine intoxication, the EEG usually reveals diffuse slow wave activity.27 Brain-imaging studies (magnetic resonance imaging or computed tomography) rarely are necessary to diagnose or manage acute delirium. They may even obfuscate the search for causes of delirium by uncovering preexisting, but undiagnosed abnormalities, such as old strokes or cerebral atrophy that are unlikely to be the cause of the delirium.
ularly sensitive to any additional insults to cognitive function. Treat any underlying precipitants such as infection, hypoxia, and fluid or electrolyte abnormalities. If Wernicke encephalopathy is suspected, administer thiamine at 50 mg intravenously and 50 mg intramuscularly. These measures usually result in clearing of delirium within 24-48 hours. If a patient remains delirious after removal of the precipitating cause, continue to reevaluate for new causes of delirium. For example, the elderly postoperative patient who initially became delirious from opioid analgesics may now be delirious from a urinary tract infection or be hyponatremic. In the patient who became delirious after being premeditated with midazolam for a procedure or diphenhydramine prior to blood transfusion, delirium may have been precipitated by medication use, but be perpetuated by aspiration pneumonia that developed during the initial delirious state. Reassurance and reorientation may calm the delirious patient.’ Many hospitals have “bedsitters” who can ensure patient safety and provide nighttime reorientation if awakening occurs. Place a clock and calendar in the patient’s room and administer medications at intervals that do not interrupt sleep. Avoid the use of physical restraints until all treatment options have been exhausted.
Management The consensus among experts is that all drugs not deemed absolutely necessary be discontinued in the delirious patient.7 This includes medications that the patient may have been taking without any problem before delirium developed (eg, ophthalmologic agents such as timolol or atropine, histamine H,receptor antagonists, and antidepressants). It is hypothesized that, during delirium, the brain is particVolume
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Pharmacologic Therapy Pharmacologic therapy is indicated if the patient is excessively agitated or anxious, psychotic, or potentially dangerous to herself or others. Although the alternative pharmacologic regimens have not been compared in randomized studies, the expert consensus is that haloperidol is the drug of choice.5,7 The advantages of haloperidol over other an-
tipsychotics are as follows: it can be given by any route, it does not cause significant hypotension, it is nonsedating, it does not affect other disease states such as hypertension and heart failure, it has a rapid onset of action, and physicians often have clinical experience with it.27 The starting dose can be as low as 0.25 mg in elderly patients, increasing by 0.25 mg every 30 minutes as needed. If symptoms have not resolved after a total of 5 mg has been given, psychiatric consultation should be sought to exclude the possibility that schizophrenia, mania, or another organic mental syndrome has been misdiagnosed as delirium. Another consideration in this event is neuroleptic-induced akathisia. This movement disorder may make the patient appear agitated and cause the physician to erroneously conclude that the delirium is persisting or progressing. The role of benzodiazepines as pharmacologic therapy of delirium remains controversial. Some physicians recommend administering benzodiazepines in low doses to treat mild delirium or in conjunction with antipsychotics to treat more severe delirium. Others believe that benzodiazepines further impair cognitive function and invariably make delirium more severe. These physicians recommend benzodiazepine use only when delirium is caused by alcohol or sedative withdrawal. Benzodiazepines occasionally are used to induce sleep in terminally ill cancer patients who become delirious from large doses of narcotics. Here, patient comfort is the objective. Civil commitment procedures often are necessary to involuntarily treat patients with psychiatric illnesses. Delirium, on the other hand, constitutes a medical emergency, and court authorization to administer antipsychotic medication is unnecessary. In this setting, the doctrine of “implied consent” applies. 85
Summary Delirium is a common and potentially lethal condition. Obstetrician/gynecologists can help to prevent delirium by identifying high-risk patients, monitoring them for prodromal signs, and avoiding nonessential medications whenever possible. Once delirium develops, careful history and physical examination will guide evaluation and therapy by revealing precipitating factors. In severe cases, pharmacologic treatment with low doses of haloperidol may be necessary.
8.
9.
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Pompei P, Foreman M, Rudberg MA, Inouye SK, Braund V, Cassel CK. Delirium in hospitalized older persons: predictors and outcomes, J Am Geriatr Sot 1994;42:809-15. Francis J, Kapoor WN. Delirium in hospitalized elderly. J Gen Intern Med 1990;5:65-79. Wise MG, Gray KF. Delirium, dementia, and amnestic disorders. In: Hales RE, Yudofsky SC, Talbott JA, editors. The American Psychiatric Press textbook of psychiatry. 2nd ed. Washington (DC): American Psychiatric Press, 1994:311-53. American Psychiatric Association diagnostic and statistical manual for mental disorders. 4th ed. Washington (DC): APA, 1994. Beresin EV. Delirium in the elderly. J Geriatr Psychiatry Neurol 1988;l: 127-43. Chedru F, Geschwind N. Writing disturbances in acute confusional states. Neuropsychologia 1972;lO: 343-53. Levkoff SE, Liptzin B, Evans DA, et al. Progression and resolution of
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delirium in elderly patients hospitalized for acute care. Am J Geriatr Psychiatry 1994;2:230-8. Lipowski ZJ. Delirium (acute confusional states). JAMA 1987;258: 1789-92. Erkinjuntti T, Wikstrom J, Palo J, Autio L. Dementia among medical inpatients. Arch Intern Med 1986; 146:1923-6. Inouye SK, Viscoli CM, Horwitz RI, Hurst LD, Tinetti ME. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993;119:474-81. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1999; 263:1097-101. Lipowski ZJ. Delirium: acute confusional states. New York (NY): Oxford University Press, 1999. Gustafson Y, Berggren D, BrannStrom B, et al. Acute confusional states in elderly patients treated for femoral neck fracture. J Am Geriatr Sot 1988;36:525-30. Berggren D, Gustafson Y, Eriksson B, et al. Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth Analg 1987;66:497-504. Marcantonio ER, Goldman L, Mangione CM, et al. A clinical prediction rule for delirium after elective noncardiac surgery. JAMA 1994; 2711134-9. Rogers MP, Liang MH, Daltroy LH, et al. Delirium after elective orthopedic surgery: Risk factors and natural history. Int J Psychiatry Med 1989;19:109-21. Millar HR. Psychiatric morbidity in elderly surgical patients. Br J Psychiatry 1981;183:17-20. Hole A, Terjesen T, Breivik H. Epidural versus _general _ anaesthesia __ _ for total hip arthroplasty in elderly pa-
tients. Acta Anaesthesiol Stand 1980;24:279-87. 19. Riis J, Lomholt B, Haxholdt 0, et al. Immediate and long-term mental recovery from general versus epidural anesthesia in elderly patients. Acta Anaesthesiol Stand 1983;27: 44-9. 20 Ghoneim MM, Hinrichs JV, O’Hara MW, et al. Comparison of psychologic and cognitive functions after general or regional anesthesia. Anesthesiology 1988;69:507-15. 21. Brockington IF, Winokur G, Dean C. Puerperal psychosis. In: Brockington IF, Kumar R editors. Motherhood and mental illness. San Diego (CA): Academic, 1982:37-69. 22. Parkes D. Bromocriptine. N Engl J Med 1979;301:873-8. 23. Einarson TR, Turchet EN. Psychotic reaction to low-dose bromocriptine. Clin Pharm 1983;2:273-4. 24. Iffy L, Lindenthal JJ, McArdle JJ, McNamara RE, Szodi Z, Ganesh V. Ergotism: a possible etiology for puerperal psychosis. Obstet Gynecol 1989;73:475-7. 25. Folstein MF, Fostein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98. 26. Tune L, Ross C. Delirium. The American Psychiatric Press textbook of neuropsychiatry. Washington (DC): APP 1994:352-65. 27. Steinhart MJ. The use of haloperido1 in geriatric patients with organic mental disorder. Curr Ther Res 1983;33:132-43. Address correspondence and reprint requests to Michael W. Weinberger, MD, Department of Obstetrics and Gynecology, H4/662 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792.
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