SymptomManagement and Supportive Care

The Frequency, Characteristics, and Outcomes Among Cancer Patients

With Delirium Admitted to an Acute Palliative Care UnitMAXINE DE LA CRUZ,a VIRAJ RANSING,a SRIRAM YENNU,a JIMIN WU,b DIANE LIU,b AKHILA REDDY,a MARVIN DELGADO-GUAY,a

EDUARDO BRUERAa

Departments of aPalliative Care and RehabilitationMedicine and bBiostatistics, University of TexasMDAnderson Cancer Center, Houston,Texas, USADisclosures of potential conflicts of interest may be found at the end of this article.

Key Words. Delirium x Terminal delirium x Palliative care x End-of-life symptoms

ABSTRACT

Background. Delirium is a common neuropsychiatric condi-tion seen in patients with severe illness, such as advancedcancer. Few published studies are available of the frequency,course, and outcomes of standardized management ofdelirium in advanced cancer patients admitted to acutepalliative care unit (APCU). In this study, we examined thefrequency, characteristics, and outcomes ofdelirium in patientswith advanced cancer admitted to an APCU.Methods.Medical records of 609 consecutive patientsadmitted to the APCU from January 2011 through December2011 were reviewed. Data on patients’ demographics; Me-morial Delirium Assessment Scale (MDAS) score; palliativecare specialist (PCS) diagnosis of delirium; delirium etiology,subtype, and reversibility; late development of delirium; anddischarge outcome were collected. Delirium was diagnosedwith MDAS score $7 and by a PCS using Diagnostic andStatistical Manual, 4th edition, Text Revision criteria. All

patients admitted to the APCU received standardized assess-ments and management of delirium per best practice guide-lines in delirium management.Results. Of556patients in theAPCU,323 (58%)hadadiagnosisof delirium. Of these, 229 (71%) had a delirium diagnosis onadmission and 94 (29%) developed deliriumafter admission tothe APCU. Delirium reversed in 85 of 323 episodes (26%). Halfof patients with delirium (n 5 162) died. Patients with thediagnosis of delirium had a lower median overall survival thanthosewithoutdelirium.Patientswhodevelopeddeliriumafteradmission to the APCU had poorer survival (p # .0001) anda lower rateofdeliriumreversal (p5 .03) comparedwith thoseadmitted with delirium.Conclusion.More than half of the patients admitted to theAPCU had delirium. Reversibility occurred in almost one-thirdof cases. Diagnosis of delirium was associated with poorersurvival. The Oncologist 2015;20:1425–1431

Implications for Practice: Delirium is themost commonneuropsychiatric condition in patientswith severemedical illness and thoseat the end of life. It can be a source of distress for patients, their families, and the medical team.When missed, or if symptoms aremisinterpreted, delirium may also lead to unnecessary interventions. This underlines the importance of diagnosis and detection ofdelirium in populations that are at increased risk.This study has important implications in practice, as it can assist clinicians inmakingdecisions regarding other medical interventions, advance care planning, and communicating with families relating to end-of-life issues.

INTRODUCTION

Delirium is a common neuropsychiatric condition seen inpatients with severe illness such as advanced cancer and ischaracterized by an acute disorder of cognition and attention,diminished level of consciousness, and inability to maintainfocus and attention.This often occurs in the setting of an acutemedical illness in vulnerable individuals [1, 2]. It is a source ofsignificant suffering topatients and their families, aswell as forthe medical team delivering care for the patient [3, 4]. It issometimes a source of conflict associated with misinterpreta-tion of symptoms that can occur with cognitive dysfunction

[5, 6]. The development of delirium is also associated withincreased mortality and morbidity [7–9].

The incidenceofdeliriumvaries from15% to50%ofelderlypatients admitted to a general medical floor, to as high as 80%of patients who are near the end of life [10, 11]. Previousstudies have shown that the prevalence ofdeliriumat the timeofadmission toanacutepalliativecareunit rangedfrom28%to42% [12, 13]. The wide variation in the prevalence of deliriummaybeattributed to failureof recognitionby themedical teamand underuse of validated tools to screen for at-risk patients

Correspondence: Maxine de la Cruz, M.D., University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030,USA.Telephone: 713-794-1723; E-Mail:mdelacruz@mdanderson.org ReceivedMarch19, 2015; accepted forpublication July 3, 2015; publishedOnline First on September 28, 2015. ©AlphaMed Press 1083-7159/2015/$20.00/0 http://dx.doi.org/10.1634/theoncologist.2015-0115

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[14, 15]. Despite the implications of the presence of deliriumon prognosis, few published studies are available on the fre-quency, course, andoutcomesof standardizedmanagementofdelirium in advanced cancer patients [2, 13, 16]. In this study,we examined the frequency, characteristics, and outcomes ofdelirium in patients with advanced cancer who were admittedto an APCU.This knowledgewould assist clinicians in improvingcare for patients with advanced cancer.

MATERIALS AND METHODS

We reviewed the electronic medical records of 609 consecu-tive patients admitted to the acute palliative care unit (APCU)atamajor academic cancer centerduring theperiodof January1, 2011, to December 31, 2011. This study was approved bythe institutional review board of The University of Texas MDAnderson Cancer Center.

The electronic medical records were reviewed to obtainpatient demographics, Eastern Cooperative Oncology Group(ECOG) status, Memorial Delirium Assessment Scale (MDAS)score [17], Edmonton Symptom Assessment Scale (ESAS) score[18], and discharge disposition. For those patients with delir-ium, information also was gathered on the use of psychoactivemedications, possible underlying delirium etiology, deliriumsubtype, and delirium reversibility.

Patients are admitted to the APCU when there is severesymptom distress that precludes optimal management on theregular medical floors and those who are transitioning to end-of-life care. In most cases, patients have discontinued activetherapy at themoment of admission to the APCU. None of thepatients had any recent surgery. Patients admitted from theemergency department, intensive care unit, other medicalfloors, and the outpatient center often present with acutemedical complications related to their malignancy.

OutcomeMeasures

Memorial Delirium Assessment ScaleTheMemorialDeliriumAssessment Scale (MDAS) is a clinician-rated, 10-item scale for assessing delirium and its severity, andit covers all delirium phenomenological areas. Each item isscored from 0 to 3 depending on its intensity and frequency(possible range: 0–30).The cutoff score of 7has beenvalidatedin the advanced cancer population [17].

Diagnosis of DeliriumPatientswere grouped into thosewith adiagnosis ofdeliriumonadmissionand thosewithnodeliriumonadmission.Diagnosisofdeliriumwas made by a board-certified palliative care specialist(PCS) using the MDAS and Diagnostic and Statistical Manual(DSM), 4th edition, Text Revision criteria. Patients were diag-nosed as having delirium if they scored 7out of 30on theMDAS.The MDAS is used routinely to screen for delirium and monitorseverity.Deliriumisnotedtobereversed if theMDASscore is lessthan 7 outof 30, or if the PCS reports thedelirium tobe resolvedintheprogressnotesforat least2consecutivedays.Patientswhowere not initially determined to havedeliriumbut subsequentlydevelop delirium during their stay in the APCUwere consideredtobeadifferentgroup. In all, therewere threegroupsofpatientsthat were analyzed: those with delirium from admission, thosewith no delirium on admission and who developed it during the

course of the admission, and those who never developeddelirium at any time during the hospitalization.

Precipitating Variables Associated With DeliriumInformation on the potential precipitating factors for deliriumwere determined from PCS progress notes along with informa-tion on its management, which included those factors thattargeted symptoms as well as those that treated the underly-ing medical condition thought to precipitate delirium. In theabsence of a potential precipitating factor for the delirium, theinvestigator reviewed laboratory and other pertinent medicalinformation to determine possible underlying medical issuescausing the delirium.We adapted criteria that were similar tothoseusedbyLawloretal. todetermineprecipitating factors fordelirium [19]. Each precipitating factor we considered wasassessed using the following criteria: (a) evidence of a medicalconditions present using specific clinical, laboratory, or radio-logical findings; (b) temporal association of the course of de-lirium and the potential precipitating factor; and (c) changes indelirium severity in association with changes of the potentialprecipitating factor.

Commonly identified causes of delirium includemedicationssuch as opioids or benzodiazepines, infection, organic brainlesions, electrolyte abnormalities, dehydration, and terminal de-lirium (whenpatients are actively dying). For the purposes of thisstudy, the etiologies of delirium were classified into infection,medication, metabolic, multifactorial, and terminal, as thesewere the commonly cited etiologies on review of the medicalrecords.Forthosepatientsforwhomtheetiologyfordeliriumwasnotclearly identified,the investigatorsusedthe followingcriteria.Infection was considered a cause if the patient was receivingantibiotics, antivirals, or antifungals; had positive cultures; uri-nalysis results suggestive of a urinary tract infection; or imagingstudies suggestive of infection (e.g., chest radiograph suggestiveofpneumonia).Medicationswereconsideredacause ifdrugs likeopioids, benzodiazepines, anticholinergic drugs, corticosteroids,hypoglycemic agents, dopamine agonists, muscle relaxants, andother psychotropic medications were present and were sub-sequently discontinued, decreased, or, in the case of opioids,changed to a different one. Metabolic etiologies included medi-cal conditions such as hypercalcemia, dehydration, electrolyteabnormalities, liver and renal failure, glucose abnormalities,hypoxia, and anemia. A multifactorial etiology was reported ifthere were more than three possible etiologies of delirium,including underlying advanced cancer. Terminal delirium wasreported if the patient was imminently or actively dying and allother possible reversible etiologies of delirium had beenaddressed, and improvement in the conditionwas not observed.

Also included in the etiologic criteria were treatmentstrategies and discharge outcome. Treatment for underlyingmedical cause included antibiotics, hydration, electrolytereplacements, and medication changes (e.g., opioid rotation,discontinuation of drugs). Medications targeting symptomsof delirium include antipsychotics (e.g., haloperidol, chlor-promazine, and olanzapine) and benzodiazepines (lorazepam)as a single agent or in combination. Nonpharmacologic inter-ventions are routinely provided to patients and families whendelirium is diagnosed and include family education on de-lirium,asitteratthebedsidewhenappropriate,minimalnursingintervention and stimulation, and orientation techniques. A

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patient’s discharge disposition was designated as either dis-charged to home, hospice, or hospital death.

Process of Standardized DeliriumManagementin APCUThe APCU is an acute care, 12-bed unit dedicated to patientswith severe symptom burden and those who are near the endof life. The APCU staff is composed of a trained palliative carephysician, anursepractitioner, apalliative care fellow, achaplain,a social worker, counselors, a case manager, occupational andphysical therapists, and specially trained palliative care bedsidenurses. ECOG, MDAS, and ESAS are assessment tools that areroutinely used by the PCS on initial consult and follow-up visits.MDAS and other formal assessments are done at the time ofadmissionandonadaily basis by thePCS. It is routinely assessedat least once during the day, andmore frequently if the situationrequires it. For those patients who were unresponsive, a di-agnosis of deliriumwas made by a PCS. Cognitive assessment isuniversally done using the MDAS. For those patients withborderline MDAS scores and older patients with increased riskfactors for cognitive impairment, further assessment using theDSM-V criteria for dementia is conducted.

Statistical AnalysisData were first summarized using standard descriptivestatistics and contingency tables. Association between cate-gorical variables was examined by chi-square test or Fisherexact test. The Wilcoxon-Mann-Whitney test was used toexamine the difference on continuous variables between oramong groups. Univariate and multivariate logistic regressionmodelswereapplied toassess theeffectof variablesof intereston presence of delirium at admission and resolution ofdelirium.Overall survival (OS)was estimatedusing the Kaplan-Meiermethod and the comparison between or among patientcharacteristics groups was evaluated by log-rank test.Univariate and multivariate Cox regression models wereapplied to assess the effect of variables of interest on OS.

RESULTS

A total of 609 patients were admitted to the APCU during thetime period of interest. However, for 44 patients who hadmultiple admissions, a randomsamplingwas done to select foronly 1 admission to be analyzed in the study. A total of 556patients were included in the analysis. Figure 1 shows thedistribution of the different patient groups. Of the remaining556patients, 323 (58%) had deliriumduring their admission totheAPCU,with229of the556 (41%)having thediagnosis at thetime of APCU admission.Themedian age was 58 years (range:19–91 years; mean age: 56.51 years [SD: 6 13.85 years]).Table 1 summarizes the patient characteristics of the threegroups of patients: those with delirium on admission, thosewho developed delirium after admission to the APCU, andthose without delirium throughout the admission. Patientswith poor ECOG status were more likely to have a diagnosis ofdelirium.WhenwecomparedECOGstatusbycancerdiagnosis,we found that of the73patientswith hematologicmalignancy,4 (5%) had ECOGstatus 1or 2, 14 (19%) had ECOGstatus 3, and55 (75%) had ECOG status 4; of those with solid tumors (n5481), 38 (8%) had ECOG 1 or 2, 204 (42%) had ECOG status 3,and 235 (49%) had ECOG status 4 (p, .0001).

A summary of the delirium characteristics of patientsadmitted with delirium versus those who developed deliriumafter admission to the APCU are summarized in Table 2.Mixeddelirium was the most frequent type of delirium (112 of 246patients; 45%), followed by hypoactive (73 of 246; 30%) andhyperactive (61 of 246; 25%) types. Haloperidol was the mostcommonly used single-agent medication to treat symptoms ofdelirium (211 of 322 patients; 66%) followed by chlorpromazine(10 of 323; 3%). The use of olanzapine, lorazepam, and otherantipsychotics wasminimal. Other single interventions includedopioid rotation (66 of 176 patients; 38%), hydration (18 of 176;10%), and antibiotics (14 of 176; 8%). Most interventions werea combinationof various treatment strategies. Counselingof thecaregivers and patient, when indicated, was performed in allcases. Delirium after admission to the APCU occurred in ap-proximately 17% of total APCU admissions (94 of 556 patients).Themedian length of stay for patients with deliriumwas 6 days,and 5 days for those without delirium (p5 .0015). The mediantime to develop delirium for patients with late delirium in theAPCUwas2daysafteradmission.Nodifferenceinthetwogroupswasfoundwithregardtoage,sex, race,primarycancerdiagnosis,ECOGstatus,deliriumsubtype,medicationuse,etiology,anduseof other medical management. However, the data showed thatpatients admitted to theAPCUwithdeliriumhadahigher rateofresolution of delirium symptoms compared with those who

Figure 1. Distribution of patients admitted to the APCU withreference to the diagnosis of delirium.

Abbreviation: APCU, acute palliative care unit.

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developed delirium after admission to the APCU. Increaseddeath rate was associated with developing delirium after APCUadmission.

Table 3 summarizes the univariate regression model ofcomparing patients admitted with delirium and those whodeveloped delirium after admission to the APCU. The multivar-iatemodel showedthatmalepatients (OR:1.55;95%confidenceinterval [CI]: 1.03–2.35); p 5 .0365) and ECOG status (ECOGstatus1and2vs. 4,OR:0.17 [95%CI: 0.08–0.39;p, .0001]; 3 vs.4,OR:0.35[95%CI:0.24–0.52,p, .0001])weretheindependentcovariates significantly associatedwith the presence of deliriumat admission. For those patients who developed delirium in theAPCU, the median time to develop delirium was 2 days afteradmissiontotheAPCU.Themediantimetoresolutionofdeliriumwas 6 days. Patients with ECOG status 2 had a 5 times higherchance of delirium resolution (95% CI: 1.52–16.42; p 5 .0082)compared with patients with ECOG status 4.

A total of 180 of the 556 patients (32%) died in the APCUand the median time of overall survival was 12 days (95% CI:

9–15). The result of the multivariate Cox regression model foroverall survival is presented in Table 4 and shows that cancerdiagnosis (hematologic vs. solid tumor, hazard ratio [HR]: 1.7;95% CI: 1.17–2.48; p5 .0057), ECOG status (3 vs. 4, HR: 0.56;95%CI: 0.38–0.83;p5 .0041), anddevelopmentofdeliriumonadmission and during the stay in APCU (HR: 5.42; 95% CI:3.30–8.90; p , .0001) are independent covariates that aresignificantly associatedwith overall survival.Therewereonly 4patients who had a reported ECOG status of 1 and 42who hadECOGstatus2.With sucha low frequency, it becamedifficult tocompare with those with ECOG status 3 (n5 218) and 4 (n5290) and, therefore, the comparison was not included in theunivariate andmultivariatemodels.TheKaplan-Meier curveofoverall survival in patients who had delirium or developed itlater versus those with no delirium is also shown in Figure 2.

A subgroup of patients who did not have a diagnosis ofterminal delirium was analyzed. After removing patients withthe diagnosis of terminal delirium, resolution of delirium wasobserved in 83 of 273 patients (30%; p5 .0786) and was not

Table 1. Admission characteristics of patients admitted to the acute palliative care unit

Covariate Total, n (%)Delirium onadmission, n (%) Late delirium, n (%) No delirium, n (%) p value

All patients 556 (100) 229 (100) 94 (100) 233 (100)

Age, years

,58 262 (47.1) 103 (45) 39 (41.5) 120 (51.5) .1815

$58 294 (52.9) 126 (55) 55 (58.5) 113 (48.5)

Sex

Unknown 1

Female 286 (51.5) 106 (46.5) 54 (57.4) 126 (54.1) .1200

Race

Unknown 12

Asian 32 (5.9) 9 (4) 6 (6.6) 17 (7.4) .7046

Black 87 (16) 37 (16.6) 15 (16.5) 35 (15.2)

Hispanic 73 (13.4) 26 (11.7) 11 (12.1) 36 (15.7)

Other 3 (0.6) 2 (0.9) 0 (0) 1 (0.4)

White 349 (64.2) 149 (66.8) 59 (64.8) 141 (61.3)

Primary cancer diagnosis

Hematological 74 (13.3) 43 (18.8) 14 (14.9) 17 (7.3) .0012

Solid tumor 482 (86.7) 186 (81.2) 80 (85.1) 216 (92.7)

ECOG status

Unknown 2

1 4 (0.7) 0 (0) 0 (0) 4 (1.7) ,.0001

2 42 (7.6) 8 (3.5) 4 (4.3) 30 (12.9)

3 218 (39.4) 62 (27.3) 28 (29.8) 128 (54.9)

4 290 (52.3) 157 (69.2) 62 (66) 71 (30.5)

Source of admission

Clinic 39 (7) 21 (9) 1 (1) 17 (7) .2533

Emergency room 18 (3) 7 (3) 4 (4) 7 (3)

Inpatient consult 499 (90) 201 (88) 89 (95) 209 (90)

Discharge disposition

Death 182 (32.7) 104 (45.4) 58 (61.7) 20 (8.6) ,.0001

Home 123 (22.1) 30 (13.1) 3 (3.2) 90 (38.6)

Hospice 251 (45.1) 95 (41.5) 33 (35.1) 123 (52.8)

Abbreviation: ECOG, Eastern Cooperative Oncology Group.

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Table 2. Summary of patient and clinical characteristics of patients admitted with delirium vs. patients who developed delirium

after admission to the acute palliative care unit

Covariate Total (%) Delirium on admission (%) Late delirium (%) p value (%)

Delirium subtype

Unknown 77

Hyperactive 61 (24.8) 47 (26.3) 14 (20.9) .5356

Hypoactive 73 (29.7) 50 (27.9) 23 (34.3)

Mixed 112 (45.5) 82 (45.8) 30 (44.8)

Medications used to control symptoms of delirium

Unknown 2

Lorazepam 3 (0.9) 2 (0.9) 1 (1.1) .5295

Lorazepam, chlorpromazine 3 (0.9) 2 (0.9) 1 (1.1)

Lorazepam, haloperidol 21 (6.5) 13 (5.7) 8 (8.6)

Lorazepam, haloperidol, chlorpromazine 7 (2.2) 5 (2.2) 2 (2.1)

Lorazepam, olanzapine 1 (0.3) 1 (0.4) 0 (0)

Haloperidol 211 (65.7) 156 (68.4) 55 (59.1)

Haloperidol, chlorpromazine 51 (16) 35 (15) 16 (17)

Haloperidol, olanzapine 8 (2.5) 4 (1.8) 4 (4.3)

Haloperidol, chlorpromazine, olanzapine 1 (0.3) 0 (0) 1 (1.1)

Olanzapine 5 (1.6) 4 (1.8) 1 (1.1)

Thorazine 10 (3.1) 6 (2.6) 4 (4.3)

Etiology of delirium

Unknown 74

Infection 15 (6) 12 (6.6) 3 (4.5) .0863

Infection, medications 10 (4) 9 (4.9) 1 (1.5)

Infection, metabolic 9 (3.6) 7 (3.8) 2 (3)

Medication 32 (12.9) 25 (13.7) 7 (10.4)

Metabolic 22 (8.8) 15 (8.2) 7 (10.4)

Metabolic, medications 9 (3.6) 6 (3.3) 3 (4.5)

Multifactorial 103 (41.4) 81 (44.5) 22 (32.8)

Terminal 49 (19.7) 27 (14.8) 22 (32.8)

Other treatments for delirium

Unknown 147

Antibiotics 14 (8) 11 (8.3) 3 (7) .3125

Hydration 18 (10.2) 14 (10.5) 4 (9.3)

Hydration, antibiotics 8 (4.5) 7 (5.3) 1 (2.3)

Opioid rotation 66 (37.5) 47 (35.3) 19 (44.2)

Opioid rotation, antibiotics 9 (5.1) 8 (6) 1 (2.3)

Opioid rotation, hydration 16 (9.1) 13 (9.8) 3 (7)

Opioid rotation, hydration, antibiotics 17 (9.7) 9 (6.8) 8 (18.6)

Others 6 (3.4) 4 (3) 2 (4.7)

Stop medication 22 (12.5) 20 (15) 2 (4.7)

Resolution of delirium

Unknown 1

No 237 (73.6) 160 (70.2) 77 (81.9) .0298

Yes 85 (26.4) 68 (29.8) 17 (18.1)

Discharge disposition

Death 162 (50.2) 104 (45.4) 58 (61.7) .0050

Home 33 (10.2) 30 (13.1) 3 (3.2)

Hospice 128 (39.6) 95 (41.5) 33 (35.1)

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significantly different among patients with delirium on ad-mission and those with late delirium. Median time of overallsurvival was 15 days (95% CI: 12–26). Patients who were aliveat discharge were censored. Patients who developed deliriumafteradmission to theAPCUalsohadahigher rateofdeathandwere less likely to be discharged to home than those admitted

with delirium (death: 39 [54%] vs. 84 [42%]; home: 3 [4%] vs. 27[13%]; hospice: 30 [42%] vs. 91 [45%]; p 5 .0471). In addition,therewas no significant difference among patientswith deliriumonadmissionandthosewith latedeliriumforanyof thevariables.

DISCUSSION

We found a higher frequency of delirium among patientsadmitted to our APCU in comparisonwith that of other studiesin advanced cancer patients [12, 16, 20]. Almost 60% ofpatients admitted to the APCU had delirium either at the timeadmission or at any time during the course of their hospitalstay. This is similar to that shown in the study by Lawlor et al.[19]. When present, delirium interferes with effective com-munication and reporting of symptoms, and can also lead toinappropriate interventions [5, 21]. In fact, a previous studyconducted by our group showed that approximately 60% ofcases of delirium in patients with advanced cancer can bemissed by the primary referring team [22]. This findinghighlights one of the important roles that APCUs have inmanaging these challenging patients and is reflected in theadmissions to the APCU from the primary oncology team.Delirium is a highly distressing condition that requires promptrecognition and control of symptoms that can be addressedbest in the APCU where the PCS is much more familiar withsymptommanagement, bedsidenurses are trained to respondto patient and family distress, and where an interdisciplinaryteamcanprovide supportandauniformmessageofcaregoals.

Our study has shown that those patients with poor ECOGstatus are more likely to develop delirium, have a lower rate ofreversibility, and a higher rate of death. Patients admitted to theAPCUmaybesickerandmore frail, and,therefore,moreat riskofdeveloping delirium. This is consistent with studies in geriatricand other vulnerable patient populations that report an as-sociation between patient vulnerability factors and risk fordelirium [23]. Hematologic malignancy was associated witha higher rate ofdelirium likely because these patients hadworseECOG status, were more frail, and possibly at increased risk ofdeveloping delirium. The high percentage of terminal deliriumthat was observed could indicate that those admitted to theAPCU were closer to the end of life in their disease trajectory.

It is importanttonotethedifferencebetweenthoseadmittedwithdeliriumandthosewhodevelopeddeliriumduringtheAPCUadmission. Those admitted with delirium had higher rates ofreversibility and lowermortality rates than those that developeddeliriumduring the APCUadmission.This finding suggests that inthose patients with some adjustments in medications andcorrection of identifiable causes, delirium can be reversed. Thepercentage,however, isstill lowerthanthatpresentedinpreviousstudies. For those with delirium on admission, reversibility wasstill only approximately 30% (68 of 229 patients).

Once patients are admitted to the APCU, efforts are madeto modify potential factors that can cause delirium, such asmedications, electrolyte abnormalities, and other metabolicissues. Despite these measures, delirium was still shown tooccur in almost one-fifth of total APCU admissions. Develop-ment of delirium in the APCU may be considered an ominoussign. In fact, of patients who developed delirium whileadmitted in the APCU, approximately one-third had terminaldelirium, a higher rate than that of patients with delirium onadmission.

Table 3. Summary of univariate logistic regression analysis of

patients admitted with delirium vs. patients who developed

delirium after admission to the acute palliative care unit

Covariate Effect OR 95% CI p value

Age 1.01 0.997–1.02 .1203

Age $58 vs.,58 1.16 0.83–1.63 .3968

Sex Male vs. female 1.41 1.004–1.98 .0476

Race Asian vs. white 0.53 0.24–1.17 .1145

Black vs. white 0.99 0.62–1.60 .9778

Hispanic vs. white 0.74 0.44–1.25 .2654

Other vs. white 2.68 0.24–29.88 .4219

CancerDiagnosis

Hematologicvs. solid

2.21 1.34–3.63 .0018

ECOG status 1 and 2 vs. 4 0.18 0.08–0.40 ,.0001

3 vs. 4 0.34 0.23–0.49 ,.0001

Abbreviations: CI, confidence interval; ECOG, Eastern CooperativeOncology Group; OR, odds ratio.

Table 4. Multivariate Cox regression model for survival in

patients with delirium vs. those without

Covariate Effect HR 95% CI p value

Cancer diagnosis Hematologicvs solid

1.70 1.17–2.48 .0057

ECOG status 3 vs. 4 0.56 0.38–0.83 .0041

Development ofdelirium

Yes vs. no 5.42 3.30–8.90 ,.0001

Abbreviations: CI, confidence interval; ECOG, Eastern CooperativeOncology Group; HR, hazard ratio.

Figure 2. Kaplan-Meier curve of overall survival in patients withdeliriumon and after admission versus thosewho did not developdelirium.

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The resultsof this studyalsohighlight important findings inthe literature [24, 25]. Haloperidol is still the most commonlyused single agent for the treatment of delirium. There werea few patients who required rotation to a different antipsy-chotic or were given additional antipsychotics for control ofsymptoms. The mixed type of delirium was found to be themost common subtype, followed by hypoactive delirium.

About one-half the patients who developed delirium diedduringtheir stay in theAPCU.Mortalitywashighandreversibilitywas lower than previously described in the literature. Educationprovided to health-care providers and to patients’ families andcaregivers about the poor prognosis associated with thedevelopment of delirium cannot be overemphasized.

The retrospective nature of our study lends it to a numberof limitations, including missing data that are not recorded inthemedical record (e.g., ESASentries andpresence of baselinecognitive impairments). Although we had a priori definedcriteria for the diagnosis of delirium, underlying etiologies,delirium subtype, reversibility, and medical management,there were still some missing entries. Doing daily formalassessments for delirium may result in having a misseddiagnosis of delirium, given its fluctuating nature. Prospectivestudies would bemore ideal to capture such information withmore accuracy.

CONCLUSIONMore than half of the patients admitted to the APCU haddelirium. Diagnosis of delirium was associated with poorersurvival. Reversibility occurred in only one-third of patientsdespite active measures to reverse delirium by addressingunderlying etiology and controlling symptoms. Educatingmedical staff, and patients’ families and caregivers is criticalin the management of these patients. Further research iswarranted to better understand its course, vulnerabilityfeatures, factors for reversibility, and management.

AUTHOR CONTRIBUTIONSConception/Design: Maxine de la Cruz, Diane Liu, Akhila Reddy, MarvinDelgado-Guay, Eduardo Bruera

Provision of study material or patients: Maxine de la Cruz, Sriram Yennu,Eduardo Bruera

Collection and/or assembly of data:Maxine de la Cruz,Viraj Ransing, EduardoBruera

Data analysis and interpretation:Maxine de la Cruz, Sriram Yennu, Jimin Wu,Diane Liu, Akhila Reddy, Eduardo Bruera

Manuscript writing: Maxine de la Cruz, Viraj Ransing, Sriram Yennu, AkhilaReddy, Marvin Delgado-Guay, Eduardo Bruera

Final approval of manuscript:Maxine de la Cruz, Viraj Ransing, Sriram Yennu,Jimin Wu, Diane Liu, Akhila Reddy, Marvin Delgado-Guay, Eduardo Bruera

DISCLOSURES

The authors indicated no financial relationships.

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