Prevention, Diagnosis, and Management of Postoperative Delirium in Older Adults

Prevention, Diagnosis, and Management of Postoperative Delirium in Older Adults

COLLECTIVE REVIEW Prevention, Diagnosis, and Management of Postoperative Delirium in Older Adults Denise R Flinn, MD, Kathleen M Diehl, MD, FACS, Lis...

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Prevention, Diagnosis, and Management of Postoperative Delirium in Older Adults Denise R Flinn, MD, Kathleen M Diehl, MD, FACS, Lisa S Seyfried, MD, Preeti N Malani, MD Approximately half of all operations performed in the United States are in patients greater than 65 years of age.1 The aging of the US population is expected to result in an increased need for surgical services among all subspecialties.1 Older adults represent a unique challenge to the surgeon, often presenting with multiple medical comorbidities and higher risk for postoperative complications. Despite the increasing need for surgical procedures among the elderly population, scant literature exists to address the specific perioperative needs of older adults. Among the many postoperative complications that result in increased morbidity, mortality, and health care costs, delirium represents a vital concern for surgeons. But research targeting prevention and management of postoperative delirium is limited. In this review, we highlight the available evidence for prevention and management of delirium. We also provide guidelines for optimal supportive care of the delirious surgery patient.

200 patients undergoing hip surgery and found that 3 years after hospital discharge, rates of cognitive impairment were more than 50% in the patients who had postoperative delirium versus 4.4% in the nondelirious patients. Kat and associates7 and Kalisvaart and coworkers8 followed more than 100 patients admitted for hip surgery, who participated in a clinical trial of haloperidol prophylaxis. Rates of mild cognitive impairment, dementia, and institutionalization were all higher for patients with postoperative delirium.7 These studies suggest that postoperative delirium predicts future cognitive decline and an increased risk of dementia. Delirium is defined as a disturbance of consciousness and cognition that presents over a short period of time and has a fluctuating course.9 Characterized by perceptual disturbances and a reduced ability to focus, sustain, or shift attention, delirium can be difficult to recognize, and may be confused with other conditions common among the elderly such as dementia or depression (Tables 1 and 2).10,11 Several clinical tools have been developed and validated to assist clinicians in identifying patients with delirium, such as the Confusion Assessment Method and a variation of this tool, the Confusion Assessment Method -ICU, which is more specifically tailored to improving diagnosis of delirium among patients in ICUs12,13 (Table 3).

Defining the problem

Delirium is a common cause of postoperative morbidity and mortality. In one study of more than 1,300 patients aged 50 and older presenting for major, elective noncardiac surgery, 9% of patients developed postoperative delirium.2 Other studies report even higher rates of 15% to 53%, and up to 70% to 87% among older patients in the intensive care setting.3-5 The development of delirium is associated with increased mortality, increased length of stay, and an increased rate of discharge to longterm care facilities.2 Delirium is also associated with increased risk of major medical complications including myocardial infarction, pulmonary edema, pneumonia, and respiratory failure.2 In addition to immediate complications, postoperative delirium is associated with increased risk of cognitive decline in succeeding years.6,7 Bickel and colleagues6 followed

Pathogenesis of delirium

Delirium is a complex phenomenon, often multifactorial in origin and likely affecting multiple spheres of the central nervous system. The most recent emerging hypothesis involves the cholinergic pathways, suggesting a deficiency in these pathways may be one of the underlying factors causing delirium.14 Factors that predispose or exacerbate delirium in the nonsurgical patient can affect elderly patients in the postoperative period as well. Hypoxia, hypoglycemia, electrolyte imbalances, volume depletion, infection, and drug interactions are all common contributors to the development of delirium in the postoperative patient. Specific attention should be paid to the patient’s overall volume status throughout the postoperative period, with efforts to maintain euvolemia and overall electrolyte balance because even modest changes in sodium and water balance have been associated with delirium.15 Pain is a common postoperative complaint, and delirious patients may not be able to effectively communicate with providers about pain. Both undertreatment of pain

Disclosure Information: Nothing to disclose. Received January 21, 2009; Revised March 5, 2009; Accepted March 11, 2009. From the Department of Internal Medicine, Divisions of Geriatric Medicine (Flinn, Malani) and Infectious Diseases (Malani); the Departments of Surgery (Diehl) and Psychiatry (Seyfried); the University of Michigan Health System; and the Veterans Affairs Ann Arbor Healthcare System (Malani) and the Geriatric Research Education and Clinical Center (GRECC) (Malani), Ann Arbor, MI. Correspondence address: Preeti N Malani, MD, VA Healthcare System, 2215 Fuller Rd, Ann Arbor, MI 48105.

© 2009 by the American College of Surgeons Published by Elsevier Inc.


ISSN 1072-7515/09/$36.00 doi:10.1016/j.jamcollsurg.2009.03.008


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Table 1. Diagnostic Criteria for Delirium Based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition9 1. Disturbance of consciousness (that is, reduced clarity of awareness of the environment, with reduced ability to focus, sustain, or shift attention). 2. A change in cognition (such as memory deficit, disorientation, language disturbance) or development of a perceptual disturbance that is not better accounted for by a preexisting established or evolving dementia. 3. The disturbance developed over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. 4. The delirium is due to a general medical condition—there is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiologic consequences of a general medical condition (further criteria for specific forms of delirium caused by substance intoxication or withdrawal).

and overuse of narcotics can exacerbate delirium, making postoperative pain management a challenge. Among postoperative orthopaedic patients, Morrison and colleagues16 found that avoidance of opioids or limited use of opioids increased the risk of delirium, presumably because of inadequate control of pain in those patients. Postoperative patients are frequently immobilized, with catheters and lines in place that can contribute to discomfort. Finally, patients with underlying dementia are at increased risk of delirium with any hospitalization and this risk is increased even more in the postoperative period. Risk factors for delirium

Several investigators have attempted to determine risk factors associated with the development of postoperative delirium. Marcantonio and colleagues2 identified seven predictors that could be used preoperatively to stratify an individual patient’s risk of delirium. These factors include age greater than 70 years, self-reported alcohol abuse, poor cognitive status, poor functional status, abnormalities of serum sodium, potassium, or glucose, noncardiac thoracic

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surgery, or abdominal aneurysm surgery. Litaker and associates17 found the incidence of delirium among 500 patients presenting for elective surgery was 11.4%; risk factors included age greater than 70 years, preexisting cognitive impairment, greater preoperative functional limitations, and self-reported alcohol use. Patients who reported narcotic use before operation were also at increased risk for postoperative delirium. Litaker’s findings largely confirmed those of Marcantonio, suggesting these risk factors may be useful in identifying high risk patients who might benefit from targeted delirium prevention measures during the perioperative period. Robinson and coauthors18 recently published results of their study among veterans 50 years and older presenting for elective surgery requiring an ICU stay. Their study confirmed once again that preexisting cognitive dysfunction was the strongest predictor of postoperative delirium. Additional studies among patients undergoing spinal surgery, cardiac surgery, or gynecologic surgery have identified other risk factors in those populations, although across the surgical literature, the risk factors most commonly reported include baseline cognitive impairment, advanced age, and multiple medical comorbidities19-22 (Table 4). Interventions to prevent delirium

A 2001 landmark trial conducted by Marcantonio and coworkers23 demonstrated the effectiveness of proactive geriatrics consultation among patients undergoing hip fracture repair. In this study, implementation of the recommendations from a geriatrics consultation service reduced the incidence of delirium from 50% in the control group to 32% in the intervention group, and also reduced the incidence of severe delirium from 29% in the control group to 12% in the intervention group. Many institutions have focused recent efforts on identifying high risk patients and developing interventions to prevent delirium among those patients, such as prophylactic administration of atypical antipsychotic medications or assigning patients to mul-

Table 2. Distinguishing Characteristics of Delirium, Dementia, and Depression10,11 Characteristic

Distinguishing characteristic Onset Course Consciousness and orientation Attention and memory Psychosis present?



Fluctuating level of consciousness with decreased attention Acute Fluctuating Clouded, disoriented

Memory impairment

Poor short-term memory, marked inattention Common (hallucinations are often simple, fleeting)

Poor short-term memory without inattention Less common

Gradual Chronic, progressive Clear until advanced stages


Sadness, decreased interest in activities Varies Diurnal variation Unimpaired Poor attention but memory intact Less common (hallucinations are often complex)

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Table 3. The Confusion Assessment Method Diagnostic Algorithm12 Feature 1. Acute onset and fluctuating course Is there evidence of an acute change in mental status from the patient’s baseline? Did the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity? Feature 2. Inattention Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficulty keeping track of what was being said? Feature 3. Disorganized thinking Was the patient’s thinking disorganized or incoherent (eg, rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject)? Feature 4. Altered level of consciousness Overall, how would you rate this patient’s level of consciousness (alert [normal], vigilant, lethargic, stupor or coma)? Diagnosis of delirium is confirmed by the presence of Features 1 and 2 and either Feature 3 or 4.

tidisciplinary teams of providers with experience caring for elderly patients. Clinical trials have addressed the potential benefits of atypical antipsychotics in terms of reducing the incidence of delirium. Kalisvaart and associates8 studied 430 patients undergoing elective hip replacement, randomizing to either preoperative haloperidol continued for up to 3 days postoperatively or placebo. Although it did not reduce the overall incidence of delirium, haloperidol did reduce the severity and duration of delirium and reduced overall length of stay. Another randomized controlled trial among patients undergoing cardiac surgery showed that a single dose of risperidone postoperatively reduced the incidence of delirium.24 More recent trials have evaluated the effectiveness of donepezil in prevention of postoperative delirium. Sampson and colleagues25 randomized 33 patients undergoing elective hip arthroplasty to donepezil or placebo beginning in the immediate postoperative period and continuing for an additional 3 days. Although donepezil did not significantly reduce the incidence of delirium or length of stay, there was a consistent trend toward possible benefit in this small trial. Liptzin and associates26 also studied the use of donepezil for 2 weeks preoperatively to prevent delirium in patients undergoing elective orthopaedic surgery. The overall incidence of delirium was 18.8%, with no difference between the two groups. But the patients in this small study were relatively young and cognitively intact. A pilot study by Leung and coworkers27 demonstrated promising results with the use of gabapentin for postoperative pain control. A larger confirmatory trial is underway.

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Table 4. Risk Factors for Postoperative Delirium Most commonly reported Preexisting cognitive impairment Multiple medical comorbidities Age ⬎65 or 70 y Elective noncardiac surgery2 Age ⱖ70 y Self-reported history of alcohol abuse Telephone Interview for Cognitive Status (TICS)-score ⬍30 (suggestion of baseline cognitive impairment) Specific Activity Scale (SAS) Class IV (severe physical impairment) Markedly abnormal preoperative sodium, potassium, or glucose levels Aortic aneurysm surgery Noncardiac thoracic surgery Spinal surgery21 Transfusion of ⬎800 mL Hemoglobin ⬎10 g/dL Cardiac surgery22,48 History of cerebrovascular accident High medical comorbidity Increased creatinine Increased preoperative pain rating Left ventricular dysfunction Diabetes mellitus Atrial fibrillation Gynecologic surgery20 Age Number of medications Amount of narcotic medications General risk factors for deliriumy49 Vision impairment Severe illness Cognitive impairment Increased blood urea nitrogen/creatinine ratio

Management of delirium

Despite the best preventive efforts, a certain percentage of patients will become delirious in the postoperative period. Optimal management of delirium requires eliminating precipitating factors and providing supportive care. In addition to the general recommendations for managing delirium in all hospitalized patients, there are several issues specific to the postoperative patient (Table 5). As noted previously, pain control is a vital issue, particularly in the elderly postoperative patient. Two studies found that increased postoperative pain is associated with higher rates of delirium.28,29 Methods of postoperative pain control include neuraxial analgesia, patient-controlled analgesia, or orally administered opioids. Vaurio and associates28 examined whether method of pain management was


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Table 5. Strategies for Managing Delirium23 Ensure adequate oxygen delivery to tissues. Avoid hypoxia, hypotension, and severe anemia. Maintain fluid and electrolyte balance. Monitor fluid status to avoid volume depletion and fluid overload. Ensure adequate pain management. Scheduled acetaminophen 1 g every 8 hours Low dose scheduled oxycodone or morphine sulfate and/or as needed Review medication. Discontinue unnecessary medications. Discontinue or minimize use of anticholinergics, antihistamines, and benzodiazepines. Continue cholinesterase inhibitors. Continue carbidopa or levo-dopa for patients with Parkinsonism. Maintain bowel and bladder function. Scheduled senna tablets or sorbitol, polyethylene glycol. Avoid magnesium hydroxide, which can cause hypermagnesemia. Discontinue urinary catheter by postoperative day 2 if possible. Mobilize patients early. Get out of bed to chair with meals, or at least daily. Ambulate to toilet with assistance. Initiate physical and occupational therapy as soon as patient is able to participate. Monitor and treat major cardiac and pulmonary postoperative complications. Optimize environmental stimuli. Provide patients with glasses and hearing aids. Reorient with clocks and calendars. Try to maintain sleep/wake cycle. Family members at bedside when possible, other familiar objects in patient’s room. Transfer out of intensive care to regular floor as soon as medically appropriate. Treat agitated delirium. Low dose atypical antipsychotic such as quetiapine 12.5–25 mg nightly or as needed. If the patient is unable to take oral medications, consider low dose haloperidol 0.25 mg IV/intramuscularly as needed. For patients in whom antipsychotic use is contraindicated, use of lorazepam 0.25–0.5 mg IV can be considered. Avoid restraints.

associated with development of postoperative delirium. Surprisingly, even though doses of opioid analgesics are much lower when administered neuraxially, there was no difference in the rates of postoperative delirium among those two groups of patients; rates of postoperative delirium were lower

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among patients who received oral analgesia.28 Although overuse of narcotics can certainly predispose a patient to delirium and worsen cognition, inadequate treatment of pain also increases the possibility of delirium. Elderly postoperative patients may not be able to properly operate patient-controlled analgesia, so low-dose scheduled narcotics may provide better control of pain. Scheduled acetaminophen is also a commonly used non-narcotic pain management strategy in the geriatric population; this a relatively safe and well-tolerated regimen. We recommend up to 1 g of acetaminophen every 8 hours in all patients who do not have a contraindication. If pain is not adequately controlled, low dose scheduled IV morphine sulfate or oxycodone 5 to 10 mg every 4 to 6 hours (either scheduled or as needed) is commonly recommended by our consultation service. We prefer to avoid combination agents (narcotic and acetaminophen) in the immediate postoperative period because of a potential for acetaminophen overdose. Meperidine use should be avoided in the elderly because it is not often effective oral analgesia and may cause confusion.30 Postoperative nausea is another common symptom that may require aggressive treatment to avoid prolonged periods without adequate nutrition. Although not specifically studied among elderly postoperative patients, a recent study by Jokela and coworkers31 confirmed that ondansetron effectively relieved nausea and vomiting among a large sample of patients. Because of its different mechanism of action, this drug tends to be better tolerated among elderly patients than promethazine or prochlorperazine, both of which can have significant anticholinergic or extrapyramdial side effects.30 Review and adjustment of medications is another important management strategy for patients with delirium. Since publication of the Beers criteria, the practice of avoiding anticholinergics, antihistamines, and benzodiazepines has become more commonplace.30 Often order sets for pain management include “prn” medications such as diphenhydramine for itching or promethazine for nausea, both of which should be avoided in elderly patients because of their anticholinergic effects, which can both precipitate and exacerbate delirium. Conversely, in patients with underlying dementia on cholinesterase inhibitors, abrupt cessation of these medications can increase confusion and precipitate delirium. Patients with Parkinson’s disease should also continue on dopamine agonist therapy, receiving their medication on the morning of surgery and resuming as soon as possible postoperatively.32 Centrally acting dopamine antagonists such as promethazine or metoclopramide for nausea should be avoided in particular among patients

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with Parkinsonism because of their potential to exacerbate tremor and rigidity and cause confusion.32 Although constipation is a common postoperative problem among patients of all ages, aggressive management is particularly important for the geriatric patient. Scheduled senna tablets or osmotic laxatives such as sorbitol or polyethylene glycol should be considered for elderly postoperative patients. Magnesium hydroxide (milk of magnesia) should be avoided in the elderly population, particularly in those with chronic renal insufficiency, because prolonged use can result in hypermagnesemia, which can itself lead to ileus.33 Discontinuation of urinary catheters as soon as possible after surgery is recommended to decrease the incidence of urinary tract infection and to facilitate mobility. Early mobilization and initiation of rehabilitation is also vital for postoperative elderly patients to prevent further decline during hospitalization. Elderly patients are at greater risk for postoperative cardiac and pulmonary complications, which may present as acute delirium and also prolong recovery. Typically, patients at high risk will be managed with perioperative electrocardiogram monitoring and cardiac enzymes for prompt detection and treatment of ischemia. Use of incentive spirometry is also the standard of care for many postoperative patients, although elderly patients may require more assistance or reminders about use of incentive spirometry. To promote optimal interaction with an unfamiliar environment, elderly patients should be provided with their eyeglasses, hearing aids, dentures, and other assistive devices. Reorientation can be facilitated with the use of clocks and calendars in the room, and placing familiar objects in the room, such as using a blanket from home on the patient’s bed or pictures of family members at the bedside. Frequent visits by family members will also help to reorient and reassure patients. Maintenance of a day-night sleep cycle should be observed if at all possible, with natural light into the room during the daylight hours and lights and television out at night. Once medically appropriate, moving patients out of the intensive care setting will eliminate the extraneous stimuli of monitors and frequent interruptions that might further disturb sleep-wake patterns. Other simple measures such as ensuring that the patient’s call light is within reach and maintaining consistency of staffing whenever possible are also helpful. Management of delirium-associated agitation

Patients who present with agitated delirium are often perceived as having a more “severe” presentation of delirium.34 But patients with hypoactive delirium (pronounced lethargy as opposed to agitation) have worse outcomes; whether this is from fundamental differences in the sub-

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types of delirium or differences in treatment has not been determined.34 Although identification and treatment of underlying causes is the definitive treatment of delirium, supportive care is often needed. Frequent reorientation and reassurance, which can often be provided best by the patient’s family members, remains the first line of management. Sitters on a short-term basis may also be an effective nonpharmacologic method for managing agitated patients. Use of restraints should be avoided whenever possible unless patient safety is threatened. When these measures fail, low dose antipsychotic medication may be used on an as needed basis for control of severe agitation, although evidence for their effectiveness is admittedly limited while evidence of their increased risks continues to emerge.35,36 The most widely studied medication is haloperidol, a first-generation antipsychotic medication. Haloperidol can be administered IV. We recommend starting with a very low dose, such as 0.25 to 0.50 mg every 4 hours as needed. Doses may initially be repeated every 30 minutes for severe agitation, and for intractable pain, continuous infusions of haloperidol have been used.37 Routine electrocardiogram monitoring to follow QTc interval is recommended by the American Psychiatric Association (APA), with consideration of discontinuing therapy or cardiology consultation if QTc reaches ⬎ 450 milliseconds or ⬎ 25% above baseline.38 Extrapyramidal side effects are less likely to occur with the IV form of haloperidol compared with oral or intramuscular forms39 and with less than 4.5 mg/day dosing, although there is a slightly higher risk of cardiac arrhythmias with IV administration.40 But higher doses of haloperidol are associated with increased incidence of extrapyramidal side effects.41 Of note, haloperidol is not approved by the FDA for IV use. Nonetheless, several consensus statements have identified IV haloperidol as the treatment of choice for delirium in the critically ill42 and postcardiac surgery population.43 Newer atypical antipsychotics such as olanzipine and risperidone are being used for treatment of delirium as well, with potential for fewer extrapyramidal side effects, but a potential for anticholinergic side effects.37 Controlled studies of these second-generation antipsychotics are lacking. A Cochrane Database review looking at the use of antipsychotics in delirium found no differences in efficacy or adverse effects between the atypical antipsychotics risperidone and olanzipine and low dose haloperidol.41 Information on the use of quetiapine is limited. Scheduled low dose atypical antipsychotics can be used with as needed dosing of haloperidol for breakthrough agitation. Antipsychotics should be used with caution in the elderly. Concerns about the safety of atypical antipsychotics in treating patients with dementia-related behavioral disorders


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prompted the FDA to issue a black box warning in 2005 noting increased mortality from cardiovascular events and infections.37 In June 2008, the FDA expanded the black box warning to include the conventional antipsychotics, stating that they “share the increased risk of death in elderly patients” that has been observed for the atypical antipsychotics. In light of these warnings, the decision to start an antipsychotic must come from a consideration of the potential risks and benefits. It is important to note that there are significant risks associated with untreated agitation in delirium because the patients often pose a risk to themselves and others. Antipsychotics are not considered first line treatment for certain patients with delirium. Benzodiazepines are the agents of choice for delirium secondary to central nervous system-depressant withdrawal (eg, alcohol, benzodiazepines, barbiturates).40 Patients with Parksinon’s disease or Lewy body dementia are at high risk for extrapyramidal side effects with dopamine antagonists. Although there is some evidence to suggest that quetiapine does not worsen Parkinsonian symptoms in these patients, data about efficacy are limited.44 For these patients, judicious use of benzodiazepines may also be indicated, although there is a higher risk of oversedation and respiratory depression and increased potential for paradoxical agitation and worsened delirium.40 Lorazepam is the benzodiazepine of choice when indicated because of its rapid onset of action and short duration of action. Future directions

Several studies have been conducted to evaluate the effectiveness of identifying patients at risk for delirium and implementing coordination of care to prevent delirium throughout the hospital stay. Beaupre and colleagues45 conducted a study in Canada to evaluate the effectiveness of a perioperative evidence-based clinical pathway among hip fracture patients aged 65 or greater. The incidence of delirium in the clinical pathway group was 22% compared with 51% in the control group. A British trial evaluated the feasibility and effectiveness of a proactive evidence-based comprehensive geriatric assessment service for at-risk older elective surgical patients. Among their findings were reduced incidences of delirium (6% in the intervention group versus 19% in the control group) and pneumonia (4% versus 20%) and decreased incidence of pressure sores, improved mobilization, and decreased inappropriate catheter use. Length of stay was also reduced by 4.5 days among the intervention group.46 Lundstrom and associates47 completed a randomized controlled trial among patients admitted to the hospital with femoral fractures. Patients selected for the intervention group were admitted to a specialized geriatrics ward; control patients were admitted to the con-

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Table 6. Some Characteristics of Patients Who Might Benefit from Geriatrics Consultation Age ⬎ 80 y Baseline cognitive dysfunction or dementia Multiple medical comorbidities Chronic use of psychotropic medications Dependence on alcohol or other drugs Poor social support Hearing or vision impairment Immobility or history of functional decline Recurrent hospitalizations within the last year Urgent or emergent surgery Prolonged hospital and/or ICU stay

ventional orthopaedics ward. These interventions were associated with a lower incidence of delirium, shorter duration of delirium, fewer major complications, and decreased length of stay. Given that several studies have determined risk factors for delirium, it would seem feasible and cost-effective to implement programs for identification of high risk patients, and then pair those patients with a consultative team to follow the patient throughout the perioperative period. We have provided a list of patient characteristics that might help the surgeon identify patients most likely to benefit from a geriatrics consultation, particularly if multiple factors are present (Table 6). In summary, delirium is a common postoperative complication among elderly patients, and it contributes significantly to postoperative morbidity and mortality. Distinguishing delirium from other conditions that also affect mental status, such as dementia and depression, can be difficult, although diagnostic criteria and clinical tools have been developed to assist the clinician in identifying delirium. Proactive geriatrics consultation has been shown in a randomized controlled trial to decrease incidence of delirium among postoperative orthopaedic patients. Clinical trials of prophylactic antipsychotic administration or anticholinesterase therapy have produced conflicting results so far. Despite the best preventive efforts, a certain proportion of patients will develop postoperative delirium. Identifying and treating underlying causes remains the mainstay of treatment, along with emphasizing nonpharmacologic interventions to decrease severity and duration of delirium. Previous studies among selected surgery groups have identified risk factors for postoperative delirium, and recent studies have confirmed that multidisciplinary management of high risk patients has resulted in decreased incidence of delirium. Future directions will likely include larger clinical trials of prophylactic medication administration for prevention of delirium, multidisciplinary team management,

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and medications for the management of agitation associated with delirium.

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