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2006;88:2060-2068.  doi:10.2106/JBJS.F.00049 J Bone Joint Surg Am.Benjamin D. Robertson and Timothy J. Robertson    

Postoperative Delirium After Hip Fracture

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Current Concepts Review

Postoperative Delirium After Hip FractureBY BENJAMIN D. ROBERTSON, MD, AND TIMOTHY J. ROBERTSON, MD

➤ A hip fracture is sustained by 250,000 Americans every year. The most common complication associated withhip fracture is delirium.

➤ Delirium is a serious medical condition that consists of a disturbance of consciousness with a reduced ability tofocus, sustain, or shift attention.

➤ Multiple studies have shown that patients with postoperative delirium are less likely to return to their prein-jury level of function, are more frequently placed in nursing homes, and ultimately have an increased rate ofmortality.

➤ Delirium can be completely prevented in up to one-third of at-risk patients. When delirium cannot be prevented,the prevalence of severe delirium can be reduced by up to 50%.

➤ Optimal treatment of delirium requires excellent teamwork among the orthopaedic surgeon, anesthesiologist, in-ternist or geriatrician, and others.

A hip fracture is sustained by 250,000 Americans every year1,and that number is expected to double by 20402. The most fre-quent complication associated with hip fracture in elderly pa-tients is postoperative delirium3, with a prevalence rangingbetween 5% and 61%, depending on the patient population1,3-8.Delirium is often undetected, misdiagnosed, or undertreated9-11.However, this condition has severe consequences for the pa-tient4,5,11. The focus of this article is to provide an overview ofcurrent knowledge regarding the outcomes, pathogenesis, diag-nosis, prevention, and treatment of postoperative delirium inelderly patients treated for a hip fracture.

DefinitionFor the purposes of this article, delirium and acute confu-sional states are synonymous. Delirium consists of a “distur-bance of consciousness…. with reduced ability to focus,sustain, or shift attention.” There is also “a change in cogni-tion… or the development of a perceptual disturbance that isnot better accounted for by a preexisting, established, orevolving dementia.”12 The diagnostic criteria for delirium havebeen established by the American Psychiatric Association (Ta-ble I)12. It is important to be aware of, and to use, these criteriabecause many of the signs and symptoms of delirium are alsoassociated with conditions such as dementia, depression, andpsychosis. Table II summarizes some of the distinguishingcharacteristics of these diagnoses13.

Why Should We Care?Deep vein thrombosis and the subsequent risk of death frompulmonary embolus have received a great deal of attention inthe orthopaedic literature. The morbidity and mortality asso-ciated with postoperative delirium are far greater than thoseassociated with deep vein thrombosis6, and yet postoperativedelirium has received very little attention in the orthopaedicliterature.

Gustafson et al. studied 111 consecutive patients who hadundergone surgery for a femoral neck fracture6. They evaluatedthe patients for preexisting dementia and, with use of the DSM-III6 (Diagnostic and Statistical Manual of Mental Disorders,Third Edition), examined them preoperatively and postopera-tively for the development of delirium. Sixty-eight (61%) of the111 patients became acutely confused: 33% were in an acuteconfusional state preoperatively and another 28% were in anacute confusional state postoperatively. Gustafson et al. followedall patients for six months after the operation and found a sig-nificant difference in the length of the stay in the hospital (p <0.05) as well as in postoperative complications such as urinaryincontinence (p = 0.0005), feeding problems (p = 0.05), and de-cubitus ulcers (p = 0.01). In addition, patients with deliriumhad an increased likelihood of dying or being placed in a nurs-ing home for the first time, and they were less likely to regaintheir prefracture walking level.

In a similar study, Marcantonio et al. evaluated 126 con-

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secutive patients, more than sixty-five years old, who had sus-tained a hip fracture1. They examined them preoperatively,daily after the operation, and at one and six months postoper-atively. Delirium developed in 41% (fifty-two) of the 126 pa-tients; it persisted in fifteen patients at one month and in threepatients at six months. Patients who had delirium had a signif-icantly greater decline in activities of daily living (odds ratio,2.6; 95% confidence interval, 1.1 to 6.1), a significantly greaterdecline in walking ability (odds ratio, 2.6; 95% confidence in-terval, 1.03 to 6.5), and a significantly higher rate of death ornew placement in a nursing home (odds ratio, 3.0; 95%confidence interval, 1.1 to 8.4) during the follow-up periodthan those without delirium. In addition, patients whose de-lirium persisted had worse outcomes in those categories thanpatients whose delirium resolved.

Edelstein et al. followed 921 patients for the develop-ment of delirium after hip fracture5. Although they reported amuch lower prevalence (5.1%) than the authors mentionedabove, they examined the patients for delirium at only onepoint in time after the operation and they selected healthierpatients with their inclusion and exclusion criteria. They did

show that patients with delirium had a significant increase inthe length of the overall hospital stay (p < 0.001) and in-creased mortality (p = 0.02) at one year. In addition, their pa-tients were less likely to regain their prefracture level ofwalking (p = 0.03) and activities of daily living (p < 0.001).

Medically ill elderly individuals in whom delirium devel-ops during hospitalization have an increased chance of dyingduring that hospitalization (an 11% rate of death in the firstmonth after discharge and a 25% rate within six months12).

The above reports document the substantial impact ofdelirium on patient outcomes, with increased rates of mortalityor new nursing home placement postoperatively and longer,more expensive14 hospital stays. Prolonged delirium is also a riskfactor for the development or worsening of dementia. Finally,delirium is upsetting for the patient and their loved ones. For allof these reasons, delirium requires our attention.

PathogenesisThe pathogenesis of delirium is not fully understood. Part ofthe difficulty in studying delirium stems from the fact that itis transient and may often have multiple underlying causes15-19.

TABLE I Diagnostic Criteria for Delirium*

Disturbance in consciousness (impaired ability to focus, sustain, or shift attention)

Change in cognition (memory impairment, disorientation, or language disturbance) or perceptual disturbance (misinterpretations, illusions, or hallucinations)

The disturbance develops over a short period of time and fluctuates during the course of the day

There is laboratory or clinical evidence that the delirium state is caused by the direct physiological consequences of a general medical condition

*Adapted from: Delirium, dementia, and amnestic and other cognitive disorders. In: Diagnostic and statistical manual of mental disorders:DSM-IV. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000. p 135-80.

TABLE II Distinguishing Characteristics of Delirium, Dementia, Psychotic Disorders, and Depression*

Disorder Distinguishing Feature Associated Symptoms Course

Delirium Fluctuating levels of con-sciousness with decreased attention

Disorientation, visual halluci-nations, agitation, apathy, withdrawal, impairment in memory and attention

Acute onset; most cases remit with correction of un-derlying medical condition

Dementia Memory impairment Disorientation, agitation Chronic, slow onset, progressive

Psychotic disorders Deficits in reality testing Social withdrawal, apathy Usually slow onset with prodromal syndrome; chronic with exacerbations

Depression Sadness, loss of interest and pleasure in usual activities

Disturbances of sleep, appetite, concentration, and energy; feelings of hopeless-ness and worthlessness; thoughts of suicide

Single episode or recurrent episodes; may be chronic

*Reprinted, with permission, from: Gleason OC. Delirium. Am Fam Physician. 2003;67:1027-34.

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Delirium has been considered to be a generalized, nonspecificdysfunction of the higher cortical processes because electro-encephalograms of delirious patients have shown diffuseslowing16,18. However, studies of animals15 as well as studies oflesions in patients who have sustained a stroke or traumaticbrain injury and functional brain imaging in humans18 offerinsight regarding which areas of the brain and which neu-rotransmitters are primarily affected.

Similar to specific tracts in the spinal cord, there aretracts within the brain that are involved in our higher corticalfunctioning. These tracts are best thought of as parallel yet in-tegrated circuits19,20. Wakefulness, attention, mood, and sleepappear to require sustained coherent activity in these variouscorticothalamic networks. These neural networks seem to beuniquely sensitive to the metabolic and other changes that arethought to generate delirium. Areas in the parietal and tempo-ral cortices related to attention as well as in the reticular acti-vating system in the brainstem are also affected18-23.

Within the brain, there are a number of neurotransmit-ters that are responsible for overall brain function15-18,24. Thereare two major neurotransmitters: gamma-aminobutyric acid,which is inhibitory, and glutamate, which is excitatory. Thereare also four modulatory neurotransmitters that are very im-portant in brain function and dysfunction: acetylcholine,dopamine, serotonin, and norepinephrine. Psychiatrists target

these modulatory neurotransmitters with various psychotropicmedications in order to treat psychiatric illnesses25-27. Alterationsin each of these neurotransmitters have been found in patientswith delirium15-19. In addition, these neurotransmitter systemsare not mutually exclusive but interact extensively24.

A decrease in acetylcholine and an increase in dopamineappear to have important roles in the development of deliri-um15,17,19. Decreased acetylcholine is also found in dementia28.Acetylcholine is important in arousal, attention, memory, andrapid eye movement (REM) sleep, all of which can be affectedduring delirium15,17,19. Delirium can be induced experimentallyby administering anticholinergic drugs, and it can be reversedby administering physostigmine (a cholinergic agent) or anti-psychotic medications such as haloperidol19. Furthermore, serumlevels of anticholinergic activity, which are usually measuredonly in research settings, are increased during delirium, andhigher levels correlate with greater cognitive impairment.Dopamine, on the other hand, is thought to change reciprocallywith acetylcholine15,19; intoxication with dopamine can inducedelirium19. The use of postoperative opiates can contribute todelirium by increasing dopamine activity while decreasing ace-tylcholine levels19. Hypoglycemia or hypoxia also can result indecreased levels of acetylcholine and, in susceptible individu-als, delirium19,29,30. Finally, anything that causes an inflammatoryresponse, such as infection, trauma, or operative intervention,

A schematic diagram showing how various risk factors can affect acetylcholine and dopamine levels, leading

to delirium. ACH = acetylcholine, DA = dopamine, and HOTN = hypotension.

Fig. 1

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causes the release of cytokines15,17. Cytokines, which include in-terleukins, tumor necrosis factor (TNF), and interferon-alpha,also increase dopamine levels and decrease acetylcholinelevels15,17,31.

The impact of aging on the brain also needs to be con-sidered17. With aging, there are morphologic changes in thebrain, including a decrease in overall volume, a decrease in thenumber and volume of neurons, and a loss of dendrites andsynapses. In addition to these morphologic changes, there arehormonal changes, such as an increased basal level of cortisol.Also, there is an overall decrease in the level of acetylcholine asa result of a decrease in choline acetyl transferase activity,which is important in acetylcholine synthesis, combined withno change in acetylcholinesterase, the enzyme responsible foracetylcholine breakdown. This decrease in acetylcholine con-tributes to the memory impairment that occurs with agingand, in a more pronounced way, with Alzheimer’s dementia.Lastly, there is an increase in the basal release of dopamine.The result of these age-related changes is a decreased brain re-serve for handling metabolic and other stresses. The impact ofvarious risk factors on the levels of acetylcholine and dopa-mine is summarized in Figure 15,17,32,33.

DiagnosisDiagnosing delirium requires a high index of suspicion, withan understanding that delirium will develop in nearly 50% ofpatients who have sustained a hip fracture. Use of the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disor-ders, Fourth Edition, Text Revision) criteria (Table I) or an in-strument such as the CAM (Confusion Assessment Method)algorithm (Table III)11,16 at the bedside increases the likelihoodof making the correct diagnosis7,11,15,34. The CAM, which isbased on DSM-III-R criteria, has been validated in a number

of settings11,15,34. It has high sensitivity and specificity and canbe administered in approximately two to five minutes11,15. Aspart of the assessment for symptoms of delirium, it is impor-tant to understand the patient’s baseline level of cognitive andother functioning. If the patient is not displaying symptoms ofdelirium on admission, baseline cognitive functioning can beassessed at that time with use of the Mini-Mental State Exami-nation35. This simple examination is easy to administer andshould be part of the preoperative evaluation36. Baseline func-tioning can also be determined by interviewing family mem-bers and reviewing medical records.

Symptoms such as agitation, delusions, or hallucinationsare easy to observe but are present in only a minority of cases4.The more common, or core, symptoms are reduced clarity ofawareness of the environment with a reduced ability to focus,shift, or sustain attention and cognitive changes such as mem-ory loss, disorientation, or changes in language, including ram-bling, incoherent, or difficult-to-follow speech7. These findingscan be more subtle and in part account for missed diagnoses.Also, recognizing delirium as it is developing may be helpful37.Disorientation and urgent calls for attention by the patient arethe most predictive prodromal changes38.

When a diagnosis of delirium is being considered dur-ing the perioperative period for a patient with a hip fracture, itis important to keep in mind the differential diagnosis of alco-hol withdrawal, delirium tremens, or fat emboli syndrome39,40.These conditions will be discussed only briefly because theyare not the focus of this article.

Alcohol withdrawal occurs primarily in heavy drinkers(more than five drinks per day). It is essential to obtain a his-tory regarding alcohol (or other substance) abuse from the pa-tient and family members in order to be alert to the possibilityof alcohol or other withdrawal syndromes. Withdrawal symp-

TABLE III Confusion Assessment Method (CAM) Diagnostic Algorithm*†

Feature 1: acute onset and fluctuating course This feature is usually obtained from a family member or nurse and is shown by positive responses to the following questions: 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 This feature is shown by a positive response to the following question: 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 This feature is shown by a positive response to the following question: Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevant con-versation, unclear or illogical flow of ideas, or unpredictable switching from sub-ject to subject?

Feature 4: altered level of consciousness This feature is shown by any answer other than “alert” to the following question: Overall, how would you rate the patient’s level of consciousness? (alert [nor-mal]), vigilant [hyperalert], lethargic [drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable])

*Reprinted with permission from: Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion as-sessment method. A new method for detection of delirium. Ann Intern Med. 1990:113:941-8. †The diagnosis of delirium by CAM requiresthe presence of features 1 and 2 and either 3 or 4.

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toms generally begin five to ten hours after the last drink, peakwithin forty-eight to seventy-two hours, and subside withinfive to seven days, although they can last longer. Postoperativepain medication can mask withdrawal symptoms as can con-current illness or an operation39.

Alcohol withdrawal is characterized by symptoms of au-tonomic hyperactivity such as diaphoresis; tachycardia; sys-tolic hypertension; hand and body tremors; transient tactile,auditory, or visual hallucinations; anxiety; nausea and vomit-ing; psychomotor agitation; and occasionally seizures. A pa-tient undergoing alcohol withdrawal is alert, oriented, awareof his or her environment, and able to attend. In patients withdelirium tremens, alcohol withdrawal is complicated by frankdelirium39.

Fat emboli syndrome occurs within twenty-four toforty-eight hours following femoral neck fracture in 0.5% to3% of individuals. It is characterized by pulmonary distress,changes in mental status, and a petechial rash in nondepen-dent areas such as the axillae, the anterior surface of the neck,the chest, the area around the navel, and the conjunctiva andoropharynx. There can also be fever, tachycardia, jaundice, re-nal changes, and retinal changes40.

Prevention and TreatmentOften, delirium is preventable or its severity can be lessened,but unfortunately there is no single intervention that has beenshown to prevent delirium1,7,37. Instead, reducing the inci-dence and severity of delirium relies on optimizing the medi-cal and surgical care of the patient1,7,37 in order to maximizeneuronal functioning. If delirium does develop, treatmentthen centers on supportive care and identifying and address-ing the underlying cause or causes1,41.

Most surgeons direct the postoperative pain control fortheir patients. Opiates can contribute to delirium by increasingdopamine levels and decreasing acetylcholine levels16,19. How-ever, Morrison et al. demonstrated that delirium can also be as-sociated with too little pain control3. They used multiple logisticregression analysis to identify risk factors in a study of 541 pa-tients with a hip fracture. Severe pain significantly increased therisk of delirium (risk ratio, 9; 95% confidence interval, 1.8 to45.2). In addition, delirium was more likely to develop in pa-tients who received <10 mg of parenteral morphine sulfateequivalents per day than it was in patients who received moreanalgesia (risk ratio, 5.4; 95% confidence interval, 2.4 to 12.3).Finally, patients who received meperidine (Demerol) were at in-creased risk for the development of delirium compared withthose who received other opioid analgesics (risk ratio, 2.4). Thiswas probably due to the anticholinergic effects of meperidine.

The type of anesthesia administered does not appear toaffect the development of delirium. In the same study by Mor-rison et al.3, there was no significant difference between thedelirium rates associated with regional and general anesthesia.Gustafson et al.6 showed a trend toward increased deliriumwith spinal anesthesia; however, it was not significant. Theyfound that a drop in blood pressure below 80 mm Hg wasmore important, and this more commonly occurred with spi-

nal anesthesia. Approximately 90% of their patients who hadthis decrease in blood pressure went on to have delirium6,33.Edelstein et al.5 reported a higher prevalence of delirium withgeneral anesthesia and postulated that that higher prevalancemay be due to cerebral hypoxia during general anesthesia.However, it appears that the ability to maintain oxygen deliv-ery to the brain during surgery is more important than thetype of anesthesia administered.

Other investigators have concentrated more on optimiz-ing the perioperative medical care of patients with a hip frac-ture in an attempt to decrease the prevalence of delirium. Theintervention reported by Gustafson et al.33 consisted of pre-operative and postoperative geriatric assessments as well asaggressive management of perioperative conditions and post-operative complications. The prevalence of delirium de-creased from 61.3% in their observational cohort to 47.6% intheir intervention group (p < 0.05). The prevalence of severedelirium was also significantly lower in their interventiongroup (30% compared with 7%) (p < 0.0001). The hospitalstay decreased from seventeen to eleven days (p < 0.001), andrates of postoperative complications such as urinary retention,decubitus ulcers, and severe falls all decreased.

Milisen et al.42 evaluated the impact of increased involve-ment by nurses on delirium in a prospective, randomized studyof two groups of sixty patients with a hip fracture. Their inter-vention consisted of educating nursing staff to recognize delir-ium, systematic cognitive screening of patients, a scheduledpain protocol, and the availability of a consulting geriatric nurseor physician. Although they did not find a significant decreasein the prevalence of delirium, they did observe a significantdecrease in the duration (p = 0.03) and severity (p = 0.015) ofdelirium.

Marcantonio et al.8 performed a prospective, random-ized, blinded study to investigate the effect of a structured ge-riatrics consultation on the development of delirium after hipfracture surgery. The intervention group received a proactivegeriatrics consult either preoperatively or within twenty-fourhours after surgery. The geriatrician made daily visits for theduration of the hospital stay and gave targeted recommenda-tions based on a structured protocol. The prevalence of delir-ium was 32% in the intervention group compared with 50%in the usual-care group (p = 0.04), and the prevalence of se-vere delirium was decreased as well (12% compared with29%). This study emphasized that delirium can be preventedor lessened in many patients but that there is no single inter-vention that consistently prevents delirium. Efforts to preventdelirium need to focus on minimizing the number of meta-bolic or other potential central nervous system insults that thepatient experiences once admitted to the hospital. A patient’sage, cognitive status, fracture, or need for surgery cannot beprevented. In some patients, these four factors alone will besufficient to induce delirium. However, some patients haveenough brain reserve to withstand these insults, and it is otherinsults, such as a decrease in blood pressure, hypoxia, urinarytract infection, or uncontrolled pain, that eventually triggerdelirium. Reducing or eliminating these insults can prevent

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delirium in many patients or can decrease its severity.If delirium does develop, treatment then focuses on

supportive care, identification of likely precipitants, and treat-ment of any underlying causes that can be corrected (TableIV)8,33,41. This generally involves a dedicated team including theorthopaedic surgeon, nursing staff, and consulting special-ist(s) with experience and expertise in diagnosing and treatingdelirium. Medical management must be reviewed and opti-mized, and the team must systematically rule out potentialcauses of new-onset delirium. Table V provides an organizedapproach for prevention and treatment of delirium in patientswith a hip fracture.

Physical examination should include measurement ofvital signs with pulse oximetry, assessment of signs suggestiveof alcohol withdrawal, and an investigation for evidence of fatemboli syndrome. It is also important to look for any localiz-ing signs of wound or other infections and to assess hydration.Thyroid, heart, lung, abdominal (including the lower abdo-men because a distended bladder can be evidence of anticho-linergic excess), and neurological examinations are importantas well. A rectal examination is recommended if there is con-cern about severe constipation or impaction15,16,36,41. Importantlaboratory and radiographic studies are listed in Table IV.

Any pertinent abnormalities identified through a reviewof the history, a review of systems, or physical and laboratoryexaminations should be corrected, with a focus on adequate ox-ygenation, restoring fluid and electrolyte balance, treating pain,eliminating or weaning the patient off of unnecessary medica-tions, regulating bowel and bladder function, providing ade-quate nutritional intake, mobilizing the patient if possible,addressing any vision or hearing impairments, normalizing thesleep-wake cycle, and providing appropriate environmentalstimuli, reassurance, orientation, and support8,15,16,37,41. Regardingpain control, the natural response when a patient has delirium

is to withdraw narcotic medication. However, as Morrison et al.3

demonstrated, inadequate pain control may also contribute todelirium.

If the underlying cause or causes of delirium are cor-rected, the course of the delirium is often self-limited and thepatient recovers completely. If the cause or causes persist, de-lirium can persist and progress to dementia. Although demen-tia is a risk factor for delirium, delirium is also a risk factor fordementia9,43. Thus, the prognosis for an episode of deliriumappears to improve when the duration is shorter8.

If a patient with delirium is agitated, delusional, or hallu-cinating or is too inattentive or confused to cooperate withtreatment, adjunctive medication may be needed15,36,41. Treatingthese symptoms can diminish the patient’s distress, decrease therisk of patient injury, and reduce excessive energy expenditure.The most frequently used and studied medication in this situa-tion is Haldol (haloperidol), a first-generation antipsychoticmedication, although there are few studies to guide treat-ment15,35,36,41. Haldol; the second-generation antipsychotic medi-cations Zyprexa (olanzapine), Risperdal (risperidone), Seroquel(quetiapine fumarate), and Geodon (ziprasidone); or the third-generation antipsychotic agent Abilify (aripiprazole) can helpto reduce confusion, agitation, or hallucinations by decreas-ing dopamine levels, thereby improving the acetylcholine-to-dopamine ratio. Because there is a small risk of potentially fataltorsade de pointes (ventricular tachycardia characterized bypolymorphic QRS complexes) with intravenous Haldol, base-line and follow-up electrocardiograms (to look for prolonga-tion of the QTc interval) and serum potassium and magnesiummonitoring are needed41. Safety is further increased by utilizingcontinuous cardiac telemetry monitoring19.

The newer antipsychotic agents can be more difficult toregulate than Haldol, which has minimal anticholinergic sideeffects and no active metabolites44. The newer antipsychotic

TABLE IV Important Laboratory Studies To Consider in Work-up for Patients with Delirium

Laboratory Tests To Evaluate

Complete blood-cell count with differential Anemia, infection

Complete metabolic profile Electrolyte disturbance, dehydration, glucose level, kidney or liver abnormalities

Albumin Nutritional deficiency

Urinalysis/culture Urinary tract infection

Chest radiograph Pneumonia, congestive heart failure

Serum ammonia* Hepatic encephalopathy

Thyroid-stimulating hormone and free T4* Thyroid dysfunction

Urine toxicology* Benzodiazepines, tricyclic antidepressants, opioids

Computed tomography scan or magnetic resonance imaging of head* Stroke, hemorrhage, hematoma, space-occupying lesion

Spinal tap* Central nervous system infection

*If indicated by history.

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agents also have pharmacologic effects beyond reducingdopamine levels44 that can make it difficult to determinewhether they are diminishing or exacerbating delirium. Theyare sometimes utilized on a scheduled basis with use of Haldolas an as-needed agent for breakthrough symptoms45.

In addition to extrapyramidal side effects (muscle tight-ening or Parkinson symptoms), antipsychotic medication cancause akathisia (a subjective sense of restlessness and an in-ability to sit still) or, rarely, neuroleptic malignant syndrome(which consists of a high fever, muscle rigidity, and autonomicinstability). Tardive dyskinesia (abnormal movements of thetongue, mouth, arms, legs, and trunk) primarily occurs withlong-term use but can occur with short-term use. Elderlywomen constitute a group at high risk for tardive dyskinesia44.Also, the United States Food and Drug Administration (FDA)recently determined that second and third-generation anti-psychotic medications are associated with a 1.6 to 1.7-foldincrease in death (from cardiac-related events such as heartfailure or sudden death, or infections, especially pneumonia)of elderly patients with dementia when used to treat behav-

ioral disorders46. The FDA is considering adding a similarwarning to Haldol and other first-generation antipsychotics46.Zyprexa and Risperdal are also associated with a small risk ofstroke and other adverse cerebrovascular events in elderly pa-tients with dementia47,48. Because of these possible adverse ef-fects, antipsychotic medication should be carefully titrated tothe most effective dose and used only as long as it is needed tocontrol the above-noted deleterious behaviors associated withdelirium.

Other medications, such as benzodiazepines or physo-stigmine, are used less frequently41. Benzodiazepines are usefulfor managing alcohol or sedative-hypnotic withdrawal anddelirium tremens39. They can also be used to augment antipsy-chotic medication in the treatment of delirium when largerdoses appear to be needed41. Benzodiazepines are usually noteffective as monotherapy for general cases of delirium and cancause behavioral disinhibition, especially in the elderly41. Phy-sostigmine, which is a cholinergic medication, is useful onlyif the delirium is known to be caused by an anticholinergicmedication41. Physostigmine is associated with a higher risk ofside effects, including seizures, bradycardia, asystole, broncho-spasm, and pulmonary edema, than are antipsychotic medi-cations49. Aricept (donepezil) has been occasionally used as asafer alternative to physostigmine in these situations50.

OverviewDelirium is a serious medical condition that consists of adisturbance of consciousness with a reduced ability to focus,sustain, or shift attention. There are also cognitive and/or per-ceptual changes. Delirium generally develops over a period ofhours to days and tends to fluctuate over the course of the day.It is a frequent and dangerous complication of hip fracture inthe elderly that has received little attention in the orthopaedicliterature. However, multiple studies1,5,6 have shown that post-operative delirium following hip fracture is associated withprolonged hospital stays, higher costs, and poor outcomes. Pa-tients who experience delirium are less likely to return to theirprefracture level of walking or activities of daily living. Theyare also substantially more likely to be placed in a nursinghome for the first time and to die.

Although the pathophysiology of delirium is not fullyunderstood, it appears that multiple metabolic and neuro-chemical insults disrupt neuronal functioning in susceptibleareas, especially in the corticothalamic networks. These insultscommonly lead to an imbalance in the dopamine-to-acetyl-choline ratio in these important brain regions. Prevention andoptimal treatment consist of minimizing or correcting thesemetabolic and other insults. Maintaining oxygen saturation at>90%, systolic blood pressure at >90 mm Hg, and the hemat-ocrit at >30% is important, as is attention to the fluid andelectrolyte status. Pain control, careful review of the patient’smedications, regulation of bowel and bladder function, ade-quate nutritional intake, early mobilization and rehabilitation,appropriate environmental stimulation, and normalization ofthe patient’s sleep-wake cycle are also key. Early detection ofcoexisting or postoperative medical problems, infections, or

TABLE V An Organized Approach to the Prevention and Treat-ment of Delirium in Patients with Hip Fracture

Ensure adequate central nervous system oxygen delivery

Give supplemental oxygen to keep saturation >95%

Keep systolic blood pressure >90 mm Hg

Keep hematocrit >30%

Restore fluid and electrolyte balance

Treat pain

Assess and promote adequate bowel and bladder function

Evaluate medications (including herbal supplements or over-the-counter medications)

Be alert to recently added medication with anticholinergic or dopamine-increasing properties

If delirium develops, reduce or eliminate noncritical medication; watch for discontinuation or withdrawal effects

Assess nutritional intake

Provide dentures, supplements, or nasogastric tube feeding if needed

Provide early mobilization and rehabilitation

Provide appropriate environmental stimuli

Glasses, hearing aids, clock, calendar, light

Actively manage concurrent medical conditions and postopera-tive complications

Myocardial infarction or stroke

Arrhythmias

Congestive heart failure, chronic obstructive pulmonary disease

Liver or renal disease

Gastrointestinal bleeding

Urinary tract infection

Central nervous system conditions like dementia, Parkinson disease, epilepsy

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other complications is crucial. Antipsychotic medication canbe used to reduce agitation that interferes with the patient’sability to cooperate with treatment, places the patient in dan-ger of harm, or excessively increases metabolic demands.

There is no single intervention that can eliminate delir-ium. Treatment and, when possible, prevention require aware-ness of the diagnosis, reduction or elimination of modifiablerisk factors, early diagnosis and treatment, and excellent team-work among the orthopaedist, anesthesiologist, nursing staff,and other consulting medical specialists.

NOTE: The authors thank Dr. Marc Swiontkowski and Dr. Terence Gioe.

Benjamin D. Robertson, MDDepartment of Orthopaedic Surgery, University of Minnesota, 2450

Riverside Avenue South, Suite R200, Minneapolis, MN 55454. E-mail address: benbeckyr@yahoo.com

Timothy J. Robertson, MDBehavioral Health Department, Luther Midelfort/Mayo Health System, 1400 Bellinger Street, Eau Claire, WI 54702-1510

The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or non-profit organization with which the authors are affiliated or associated.

doi:10.2106/JBJS.F.00049

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