Prospective Observational Study of Delirium RecoveryTrajectories and Associated Short-Term Outcomes in OlderAdults Admitted to a Specialized Delirium Unit

Ching-yu Lam, MRCP,*† Laura Tay, MRCP,* Mark Chan, MRCP,* Yew Yoong Ding, MRCP,*and Mei Sian Chong, MRCP*

OBJECTIVES: To describe the recovery trajectories ofdelirium and to determine factors predicting the course ofrecovery and adverse outcome.

DESIGN: A prospective observational study.

SETTING: Geriatric monitoring unit (GMU), a five-bedunit specializing in managing older adults with delirium.

PARTICIPANTS: Individuals admitted to the GMUbetween December 2010 and August 2012 (N = 234;mean age 84.1 � 7.4).

MEASUREMENTS: Information was collected on demo-graphic characteristics; comorbidities; severity of illness;functional status; and daily cognitive, Delirium RatingScale, Revised-98 (DRS-R98) severity, and functionalscoring. Resolution of delirium, and thus GMU discharge,was determined according to clinical assessment. The pri-mary outcome was residual subsyndromal delirium (SSD)(DRS-R98 severity ≥13) upon GMU discharge. Univariateand multivariate methods were used to determine the pre-dictors of residual SSD and adverse outcomes (inpatientmortality and incident nursing home admission upondischarge).

RESULTS: Participants with residual SSD had a slowerrecovery in terms of delirium severity, cognition, and func-tional status than those with no residual SSD. ResidualSSD predictors included underlying dementia, admissionDRS-R98 severity, DRS-R98 severity on Day 1 minus Day3 of GMU stay, and admission modified Barthel Index.Only presence of residual SSD at discharge predictedadverse outcomes (odds ratio = 5.27, 95% confidenceinterval = 1.43–19.47).

CONCLUSION: Individuals with residual SSD had pro-longed recovery trajectory of delirium. These new insights

into the recovery trajectories of delirium may help formulateearly discharge planning and provide the basis for futureresearch on delirium treatment. J Am Geriatr Soc 62:1649–1657, 2014.

Key words: subsyndromal delirium; outcomes; mortality

Delirium is a common clinical syndrome affecting olderhospitalized persons, with a reported incidence of

14% to 24% at admission and 6% to 56% during hospi-talization.1 It is independently associated with poor clinicaloutcomes, in terms of inpatient mortality, risk of subse-quent mortality for up to 12 months, long hospital stay,and likelihood of institutionalization at hospital dis-charge.1–3

To make a diagnosis of delirium, Diagnostic and Sta-tistical Manual of Mental Disorders, Fourth Edition(DSM-IV), Text Revision, and International Classificationof Diseases, Tenth Revision, diagnostic criteria requirecoexistence of symptoms from multiple domains,4,5 butmany hospitalized older adults may display only one orsome of these symptoms.6,7 There is substantial interest inthis intermediate state, termed subsyndromal delirium(SSD). Although specific diagnostic criteria are lacking,SSD phenotypes (symptomatology and individual charac-teristics, including coexisting risk factors for delirium,length of hospital stay, and likelihood of institutionaliza-tion after discharge) are intermediate between those withno symptoms of delirium and those with full syndromaldelirium.8–14

Evidence indicates that it is common for full syndro-mal delirium12,15,16 or certain individual symptoms ofdelirium (residual SSD)1,6,8,12,17–19 to persist for a longtime. Although SSD in some people may never progress tofull syndromal delirium, in others, it precedes the develop-ment of delirium.8,12,17 In addition, upon recovery from

From the *Department of Geriatric Medicine, Tan Tock Seng Hospital,Singapore; and †Department of Medicine, Queen Elizabeth Hospital,Hong Kong, China.

Address correspondence to Dr. Chong Mei Sian, Institute of Geriatricsand Active Ageing, 7 Jalan Tan Tock Seng, S308440, Singapore.E-mail: mei_sian_chong@ttsh.com.sg

DOI: 10.1111/jgs.12995

JAGS 62:1649–1657, 2014

© 2014, Copyright the Authors

Journal compilation © 2014, The American Geriatrics Society 0002-8614/14/$15.00

an episode of delirium, some individuals may experiencecomplete resolution of all symptoms, whereas others mayexperience residual SSD or even long-term cognitiveimpairment.8,12,17–20

Most studies examining SSD have focused on theconceptual framework of incident or prevalentSSD,8,9,13,19,21 with few published data describing postde-lirious residual SSD.12 There have been only two smallseries exploring factors predicting early recovery fromdelirium.6,22 Better understanding of the disease trajecto-ries of delirium and residual SSD could aid in predictionof clinical sequelae, development of targeted interven-tions, communication with individuals and theircaregivers regarding the prognosis, and formulation ofappropriate discharge plans. Moreover, knowledge ofdelirium trajectories and residual SSD might provide thebasis for future research on therapeutic interventions fordelirium.

This study therefore aimed to examine the disease tra-jectories of delirium during an acute-care hospital admis-sion and to determine factors associated with subsequentdevelopment of residual SSD (Delirium Rating Scale (DRS)severity score ≥13) and adverse outcomes.

METHODS

Participants and Setting

Individuals admitted to the Geriatric Monitoring Unit(GMU), Department of Geriatric Medicine, Tan Tock SengHospital, Singapore, between December 2010 and August2012 with delirium were recruited.

Inclusion and Exclusion Criteria

Individuals aged 65 and older admitted to the geriatricmedicine department whose primary geriatrician deter-mined that they had definite delirium (established in accor-dance with the Confusion Assessment Method (CAM))23

on admission or incident delirium during their hospitalstay were considered for admission to the GMU. TheGMU study coordinator further screened all referred indi-viduals daily for eligibility of GMU stay (based on inclu-sion and exclusion criteria). Individuals were excludedfrom GMU admission if they had medical illnesses necessi-tating special monitoring (e.g., telemetry for arrhythmiasor acute myocardial infarction), respiratory precautions,or contact precautions. Individuals were also excludedfrom the GMU if they were deemed to be dangerously illor in a coma or to have a terminal illness, were uncom-municative or severely aphasic, behaved combatively withhigh risk of harm, had conditions contraindicating the useof bright light therapy (e.g., mania, severe eye disorders,or use of photosensitizing medications), or if they, theirfamily members, or their physician in charge refused aGMU stay. Finally, for the purpose of this study, individu-als who were prematurely transferred out of the GMU(for reasons such as instability of medical conditionsrequiring intensive monitoring or when new contact pre-cautions had to be instituted) and those admitted from along-term care facility were excluded from subsequentanalysis.

Geriatric Monitoring Unit

Modeled after a delirium room,24 the GMU is a five-bedunit with specific elder-friendly room design and low staff-patient ratios. Core interventions have been adopted fromthe Hospital Elder Life Program25 involving the use ofstandardized protocols for managing cognitive impairment,sleep deprivation, immobility, visual impairment, hearingimpairment, and dehydration. In addition, light therapy(2,000–3,000 Lux) was used to assist in consolidatingsleep rhythms using lights installed in the ceiling andturned on from 6:00 p.m. to 10:00 p.m. daily. Well-trained geriatric nurses administered all these using a semi-structured protocol. Full adherence to all core interven-tions in the protocol was obtained.

The GMU has a dynamic system for transfers (akinto an intensive care unit) whereby people are transferredin and out of the unit quickly once they have beenassessed to have met entry or discharge criteria. Individu-als in the GMU were discharged directly home or toAcute Care for the Elderly (ACE) units to continue theirmedical management. Beyond the acute hospital stay,individuals who required further rehabilitation or institu-tionalization were transferred to an appropriate subacutecare facility. Description of the GMU has previously beenpublished.26

Ethics approval for the study was obtained from theNational Healthcare Group domain specific review board,and consent was obtained from the primary caregiver or alegally acceptable representative.

Data Collection

Data collected included participant demographic character-istics (age, sex, race, duration of delirium (days)), medicalcomorbidities using a modified Charlson ComorbidityIndex,27 and severity of illness data using a modified Sever-ity of Illness Index.28 Cognitive status was assessed usingthe locally validated Chinese Mini-Mental State Examina-tion (CMMSE),29 and functional status was scored on themodified Barthel Index (MBI)30 serially throughout eachparticipant’s GMU admission. Trained assessors (a GMUcoordinator and nurses) administered the above scales aspart of daily clinical care in the morning (7–9 a.m.). Therate and frequency of chemical restraint use were alsoexamined. Because this was a restraint-free unit, the physi-cal restraint rate was 0%. To adjust for the different anti-psychotics prescribed, chlorpromazine equivalence31 wasused to assess total antipsychotic usage during the admis-sion, and the frequency of benzodiazepine use wascharted.

Determination of Underlying Dementia

The consultant geriatrician (LT, MC, or CMS; subspeci-alty interest in cognition and memory disorders) evaluatedall participants for cognition upon admission to the GMU.A family member or other designated caregiver was rou-tinely interviewed to establish the participant’s cognitivefunctioning before the current admission. The medicalrecords of all participants were reviewed to ascertainwhether a diagnosis of dementia had been previously

1650 LAM ET AL. SEPTEMBER 2014–VOL. 62, NO. 9 JAGS

established. In participants who had not been diagnosedwith dementia, a diagnosis was made during the currentadmission if the corroborative history suggested presenceof cognitive symptoms consistent with DSM-IV criteria fordementia4 of at least 6 months’ duration, in accordancewith the standardized process for cognitive evaluation.32

Delirium Assessment

The GMU coordinator and nurses assessed delirium sever-ity daily using the DRS-R98 severity.11 DRS-R98, a16-item scale with 13 severity items and three diagnosticitems, is a well-validated tool for rating severity of delir-ium.33 It has a maximum total score of 46 points and amaximum severity score of 39 points, with higher scoresindicating more-severe delirium. The 13-item severityscale is more easily repeated at shorter intervals for treat-ment studies or to elucidate which symptom changes con-stitute the characteristic waxing and waning of deliriumduring a 24-hour period. The tool was designed fortrained physicians, psychiatrists, and nurses to use. Recei-ver operating characteristic analysis showed that a cutoffscore of 15.25 for the DRS-R98 severity scale diagnoseddelirium with 92% sensitivity and 93% specificity. A par-ticipant was deemed to have recovered from delirium andwas discharged from the GMU once the CAM criteria fordefinite delirium were no longer met, with a diagnosis ofrecovery being indicated by improvement in cognitive anddelirium severity scores. Delirium subtype classification(hyperactive, hypoactive, mixed) was documented duringthe initial admission to the GMU. SSD data were ana-lyzed as part of this study and were not predefined duringdata collection.

Defining Residual SSD

Residual SSD, during the recovery phase from full syndro-mal delirium, is currently not well characterized, anddefinitive diagnostic criteria remain to be established.11

For the purpose of this study, participants discharged fromthe GMU were categorized as having residual SSD or not,defining residual SSD as a DRS-R98 severity score of 13or greater at resolution from full syndromal deliriumbecause this score corresponds to the 75th percentile ofindividuals with baseline SSD in a previous study.21 Inaddition, the analyses showed that a DRS-R98 severityscore greater than 13 represented an intermediate statebetween the two extreme cutoff values of 8 and 15 forSSD as arbitrarily defined in previous studies.21

Outcomes

Data were collected on pressure ulcer rate, nosocomialinfection, length of hospital stay, inpatient mortality, anddischarge destination (home or incident institutionaliza-tion). Adverse outcomes were defined as inpatient mortal-ity or incident institutionalization.

Statistical Analysis

Univariate analysis of clinical variables was performedusing independent-sample t-tests for parametric variables

(confirmed by normality testing) and Mann–Whitney Utests for ordinal variables or nonparametric continuousvariables. Chi-square and Fisher exact tests were per-formed for categorical variables.

Delirium disease trajectory was examined in rate ofimprovement in DRS-R98 severity and CMMSE scores(change per day, computed as difference between scores atadmission and discharge from GMU divided by durationof delirium (days)) and graph plots of DRS-R98 severityscores and CMMSE scores for the groups with and with-out residual SSD. Cognitive and functional recovery inthese two groups were also compared.

Lastly, multiple logistic regression analyses includinga priori–defined covariates (age, sex, comorbidity, severityof illness, dementia diagnosis, delirium subtype, DRS-R98severity on admission, DRS-R98 severity score Day 1minus Day 3 of GMU stay, and admission CMMSE andMBI) were performed for the outcome variable of residualSSD. The association between residual SSD and short-termadverse outcomes (inpatient mortality or incident institu-tionalization) was further examined, adjusting for age, sex,comorbidity, severity of illness, and dementia diagnosis.Residents of long-term care institutions before the currentadmission who were discharged back to institutionalizedcare were excluded from the regression model for adverseoutcomes.

Statistical analyses were performed using SPSS soft-ware version 19.0 (SPSS, Inc., Chicago, IL) and STATAversion 12 (Stata Corp., College Station, TX). Statisticalsignificance was set at two-tailed P < .05.

RESULTS

Study Sample

Two hundred seventy-seven individuals were admitted tothe GMU during the study period; 43 were excluded (41who were prematurely transferred out of the GMUbecause of changes in their medical condition as statedearlier in the methods section, one whose familyrequested transfer out of the GMU, and one who wastransferred out early because of extremely combativebehavior). A flowchart of included participants is shownin Figure 1. There were no age, sex, or ethnic differencesbetween the study group and those excluded from theanalyses.

The mean age of the 234 subjects included in analyseswas 84.1 � 7.4; 43.6% were male, 87.6% were of Chi-nese ethnicity, and 74.4% had a diagnosis of dementia(Table 1). The median duration of delirium was 5.0 days(interquartile range (IQR) 4.0–8.0 days). Mean DRS-R98severity upon discharge from the GMU was 15.1 � 6.0(Table 2).

One hundred fifty-five participants (66.2%) had resid-ual SSD upon resolution of full syndromal delirium. Partic-ipants with residual SSD differed significantly from thosewithout the condition in terms of age, sex, diagnosis ofdementia, prevalence of behavioral and psychologicalsymptoms of dementia, antipsychotic use, benzodiazepineuse, and antidepressant use. The rest of the variables areshown in Table 1.

JAGS SEPTEMBER 2014–VOL. 62, NO. 9 DELIRIUM RECOVERY TRAJECTORIES AND SHORT-TERM OUTCOMES 1651

Trajectories of Recovery from Delirium

Participants with residual SSD had a slower rate ofimprovement in delirium severity (1.09 � 1.20 vs2.90 � 2.23 decrease in DRS-R98 severity per day,P < .001) and cognition (0.39 � 0.89 vs 1.59 � 1.89increase in CMMSE per day, P < .001) than those withoutresidual SSD (Table 2). Delirium duration was significantly

longer in participants with residual SSD than in thosewithout residual SSD (median number of days in delirium6.0 (IQR 4.0–9.0) vs 4.0 (IQR 3.0–6.0), P = .03).

Figure 2 further illustrates two different recovery tra-jectories of delirium, classified according to the presence orabsence of residual SSD upon recovery from full syndro-mal delirium. Mean daily DRS-R98 severity and CMMSEscores were plotted for the first 5 days (corresponding to

Patients admitted to GMU

n = 277

Excluded from SSD analysis (n = 43)

- 41 prematurely transferred out due to changes in medical condition - 1 family requested for transfer out ofGMU - 1 premature transferred out due to extremely combative behavior

Included for SSD analysis n = 234

Excluded from adverse outcome analysis due to nursing home residence prior to admission (n = 19) - all 19 patients discharged back to nursing home

Inpatient mortality

n = 4

Discharged to nursing home

n = 21

Rehabilitation in community

hospital n = 28

Discharged back to own

home n = 190

Discharged home n = 28

Included for adverse outcome analysis

n = 215

Patients screened for GMU admission

n = 402

Not meeting admission criteria (n=125) - Due to medical condition (need for special monitoring, respiratory/ contact precautions, critically ill, severely aphasic/ uncommunicative, contraindication to bright light) - Patient or family refusal

Figure 1. Flowchart of participants with delirium admitted to the geriatric monitoring unit (GMU). SSD = subsyndromaldelirium.

1652 LAM ET AL. SEPTEMBER 2014–VOL. 62, NO. 9 JAGS

median delirium duration of study cohort) of GMU stay.Figure 2A shows that participants who recovered withoutresidual SSD had significantly lower DRS-R98 severity onadmission to the GMU and subsequently exhibited faster

decline in DRS-R98 severity during their GMU stay thantheir counterparts who recovered with residual SSD (bothP < .001). In terms of cognitive status, Figure 2B shows thatparticipants who recovered without residual SSD had higher

Table 1. Demographic and Clinical Characteristics of All Participants and Subgroups with and without ResidualSubsyndromal Delirium (SSD)

Characteristic

Overall GMU

Cohort, N = 234

Residual SSD

P-ValueNo, n = 79 Yes, n = 155

DemographicAge, mean � SD 84.1 � 7.4 82.3 � 6.6 85.1 � 7.6 .005Male, n (%) 102 (43.6) 44 (55.7) 58 (37.4) .008Chinese, n (%) 205 (87.6) 72 (91.1) 133 (85.8) .40

Weighted Charlson Comorbidity Index, n (%)Low 20 (8.5) 10 (12.7) 10 (6.5) .24Medium 131 (56.0) 39 (49.4) 92 (59.4)High 65 (27.8) 22 (27.8) 43 (27.7)Very high 18 (7.7) 8 (10.1) 10 (6.5)

Severity of Illness Index, n (%)1 6 (2.6) 1 (1.3) 5 (3.2) .302 209 (89.3) 74 (93.7) 135 (87.1)3 19 (8.1) 4 (5.1) 15 (9.7)

Delirium precipitant, n (%)Precipitating factor

UTI 76 (32.5) 25 (31.6) 51 (32.9) .25Pneumonia 34 (14.5) 7 (8.9) 27 (17.4)UTI plus pneumonia or multiple sources sepsis 24 (10.3) 7 (8.9) 17 (11.0)Stroke 6 (2.6) 3 (3.8) 3 (1.9)Laboratory abnormalities 12 (5.1) 6 (7.6) 6 (3.9)Intracranial hemorrhage 7 (3.0) 3 (3.8) 4 (2.6)Fracture 11 (4.7) 3 (3.8) 8 (5.2)Surgery 5 (2.1) 3 (3.8) 2 (1.3)Anemia 7 (3.0) 1 (1.3) 6 (3.9)Other sepsis (single) 20 (8.5) 8 (10.1) 12 (7.7)Acute urinary retention 9 (3.8) 1 (1.3) 8 (5.2)Miscellaneous (constipation, medication) 17 (7.3) 8 (10.1) 9 (5.8)Myocardial infarction or congestive heart failure 6 (2.6) 4 (5.1) 2 (1.3)

Type of precipitantSepsis 154 (65.8) 47 (59.5) 107 (69.0) .38Other medical 54 (23.1) 21 (26.6) 33 (21.3)Postoperative 5 (2.1) 3 (3.8) 2 (1.3)Other surgical 21 (9.0) 8 (10.1) 13 (8.4)

Number of precipitants1 59 (25.2) 18 (22.8) 41 (26.5) .612 79 (33.8) 30 (38.0) 49 (31.6)>2 96 (41.0) 31 (39.2) 65 (41.9)

Premorbid cognitive status, n (%)Dementia 174 (74.4) 47 (59.5) 127 (81.9) <.001Dementia with behavioral and psychologicalsymptoms of dementia

67 (28.6) 13 (16.5) 54 (34.8) .004

General ward stay before geriatric monitoringunit transfer, days, median (IQR)

3.0 (1.0–5.0) 3.0 (1.0–5.0) 3.0 (1.0–5.0) .36

Duration of delirium, days, median (IQR) 5.0 (4.0–8.0) 4.0 (3.0–6.0) 6.0 (4.0–9.0) .03Pharmacological agentChemical restraint use, n (%) 97 (41.5) 21 (26.6) 76 (49.0) .001Antipsychotic use, n (%) 64 (27.4) 15 (19.0) 49 (31.6) .04Total chlorpromazine equivalent dose, mg,median (IQR)

0.00 (0.00–0.07) 0.00 (0.00–0.00) 0.00 (0.00–0.22) .03

Benzodiazepine use, n (%) 59 (25.2) 13 (16.5) 46 (29.7) .04Antidepressant use, n (%) 147 (62.8) 40 (50.6) 107 (69.0) .007Anticonvulsant use, n (%) 51 (21.8) 12 (15.2) 39 (25.2) .09

IQR = interquartile range; UTI = urinary tract infection.

P-values were determined using the Pearson chi-square test for categorical data, the Mann–Whitney U test for nonparametric data, and the independent

sample t-test for continuous data.

JAGS SEPTEMBER 2014–VOL. 62, NO. 9 DELIRIUM RECOVERY TRAJECTORIES AND SHORT-TERM OUTCOMES 1653

CMMSE scores on admission, with a subsequent steeper risein CMMSE during their GMU stay than participants whohad residual SSD upon GMU discharge (both P < .001).After adjustment for age, sex, and underlying dementia,which are baseline variables noted to be significantly differ-ent between individuals with and without residual SSD,differences in recovery trajectories of delirium severity andcognitive status were attenuated, as expected, but remainedsignificant (P < .001).

Functionally, the group without residual SSD had asignificantly higher MBI at admission and discharge fromGMU and had a faster rate of improvement in functionalstatus than those with residual SSD (MBI increase per day3.8 � 6.0 vs 5.6 � 6.3, P = .03), although the magnitudeof functional recovery achieved at discharge from theGMU was similar between participants with and withoutresidual SSD (MBI change 18.3 � 17.5 vs 21.0 � 19.7,P = .28) (Table 2).

Predictors of Residual SSD

In the multiple logistic regression model includinga priori–defined covariates, underlying dementia (oddsratio (OR) = 2.35, 95% confidence interval (CI) = 1.06–5.22), DRS-R98 severity on admission (OR = 1.20, 95%CI = 1.07–1.34), and DRS-R98 severity on Day 1 minusDay 3 of GMU stay (OR = 0.81, 95% CI = 0.74–0.88)

significantly predicted presence of residual SSD at recoveryfrom full syndromal delirium (Table 3). Althoughsignificant differences in pharmacological restraint use werenoted between participants with and without SSD, such pre-scriptions were consequent to the development of deliriumto manage behavioral complications, rather than a baselinevariable at entry to the GMU. It was therefore not adjustedfor in the original regression models. Nevertheless, multipleregression analyses adjusting for pharmacological restraintuse in addition to the a priori–defined covariates were per-formed, and no difference was noted in the predictors ofSSD and short-term adverse outcomes (Table S1).

Short-Term Outcomes of Participants with ResidualSSD

Although 13 participants (5.6%) developed a new pressureulcer during their GMU stay, there was no statistically sig-nificant difference in the incidence of pressure ulcersbetween participants with and without residual SSD(Table 2). There was a trend for higher nosocomial infec-tion rate in participants with residual SSD (13.5% vs5.1%, P = .07). Participants with delirium and residualSSD had significantly longer hospital stays than those with-out residual SSD (Table 2).

Nineteen participants who were residents of long-termcare institutions before the current admission were

Table 2. Multidimensional Geriatric Assessment and Outcomes of Individuals Admitted to a Geriatric MonitoringUnit (GMU)

Assessment

Overall GMU

Cohort, N = 234

Residual Subsyndromal Delirium

P-Value

No,

n = 79

Yes,

n = 155

Delirium Rating Scale-Revised-98 severityscale score, mean � SDAdmission (0–39) 22.59 � 5.78 19.77 � 5.77 24.03 � 5.24 <.001Day 2 (0–39) 20.91 � 5.95 16.97 � 5.59 22.92 � 5.07 <.001Day 3 (0–39) 19.50 � 6.38 14.74 � 5.61 21.87 � 5.34 <.001Discharge (0–39) 15.09 � 6.04 8.49 � 2.91 18.45 � 4.16 <.001Change �7.51 � 6.27 �11.28 � 5.63 �5.59 � 5.70 <.001Change per day �1.97 � 2.01 �2.90 � 2.23 �1.09 � 1.20 <.001

Chinese Mini-Mental State Examinationscore, mean � SDAdmission (0–28) 5.72 � 5.35 9.04 � 5.89 4.03 � 4.14 <.001Discharge (0–28) 9.16 � 6.42 15.28 � 4.25 6.05 � 4.91 <.001Change 3.44 � 5.15 6.24 � 5.65 2.01 � 4.23 <.001Change per day 0.88 � 1.55 1.59 � 1.89 0.39 � 0.89 <.001

Modified Barthel Index, mean � SDAdmission (0–100) 28.79 � 24.06 37.47 � 26.16 24.37 � 21.70 <.001Discharge (0–100) 47.97 � 25.65 58.44 � 21.31 42.64 � 26.09 <.001Change 19.18 � 18.28 20.97 � 19.70 18.26 � 17.50 .28Change per day 4.40 � 6.17 5.62 � 6.33) 3.78 � 6.01 .03

OutcomeMortality or incident nursing homeadmission, n (%)

25 (10.7) 3 (3.8) 22 (14.2) .01

Pressure ulcer, n (%) 13 (5.6) 4 (5.1) 9 (5.8) >.99Nosocomial infection, n (%) 25 (10.7) 4 (5.1) 21 (13.5) .07Length of acute hospital stay, days,median (interquartile range)

12.0 (9.0–18.0) 11.0 (8.0–15.0) 13.0 (10.0–21.0) <.001

SD = standard deviation.

P-values were determined using the Pearson chi-square test for categorical data, the Mann–Whitney U test for nonparametric data, and the independent-

sample t-test for parametric data.

1654 LAM ET AL. SEPTEMBER 2014–VOL. 62, NO. 9 JAGS

excluded from the analyses for the adverse outcomeof inpatient mortality and incident institutionalization.Twenty-one participants (9.8%) not previously institution-alized were transferred to a nursing home upon discharge,and four participants (1.9%) died during the acute hospitaladmission. In the multiple logistic regression model adjust-ing for age, sex, comorbidty, severity of illness, anddementia diagnosis, only the presence of residual SSD sig-nificantly predicted adverse outcome of inpatient mortalityor incident institutionalization (OR = 5.27, 95%CI = 1.43–19.47) (Table 3).

DISCUSSION

SSD may not necessarily progress to full syndromal delir-ium and may feature in the recovery phase from full syn-dromal delirium.8 The current study explored the conceptof residual SSD, including its utility in the prediction ofdelayed recovery of delirium during the early phase ofacute illness. Using a DRS-R98 severity score of 13 as thecutoff for residual SSD, the prevalence of residual SSD was

66.2%, consistent with results of a previous study inwhich more than half of the elderly study cohort wasfound to have one or more symptoms of delirium, withoutfulfilling CAM-defined delirium, on admission to postacuteskilled nursing facilities.7

The current study further contributed to the limitedliterature on delirium as a spectrum disorder with differen-tial trajectories of cognitive recovery. Daily charting ofDRS-R98 severity and CMMSE showed that the deliriumof participants with residual SSD lasted longer and thatthey had a slower trajectory of recovery than those with-out residual SSD, as reflected in the rate of moderation ofdelirium severity and improvement in cognition, as well asimprovement in functional status (Figure 2). To the best ofthe knowledge of the authors, this is the first study of anon-intensive care unit for hospitalized older adults toexamine recovery trajectories of delirium through dailyassessment of delirium severity on the DRS-R98 severityscale, cognitive status, and functional performance.

The course of delirium is notoriously heterogeneousand unpredictable. The ability to prognosticate recoverytrajectory early in the course of delirium will thus facilitatedischarge planning, including referrals for continuation ofcare in appropriate step-down facilities for individuals athigh risk of protracted illness, while offering reassuranceto relatives of individuals in whom rapid and full resolu-tion of the delirious episode is anticipated. In the multipleregression model of residual SSD, greater improvement indelirium severity achieved on Day 3 (represented by DRS-R98 severity score on Day 1 minus Day 3), independentlypredicted recovery without residual SSD, whereas deliriumseverity at admission and presence of underlying dementiawere predictive of SSD despite apparent resolution of theacute episode.

Only two other studies have examined predictors ofearly recovery from delirium in older adults receiving med-ical care. One found that, of the 28 individuals aged 50 to83 defined as having delirium according to the DSM,Third Edition, Revised, 12 whose delirium improved

0

5

10

15

20

25

30

Day 1 Day 2 Day 3 Day 4 Day 5

Mea

n D

RS-s

ever

ity

(ran

ge 0

to 3

9)

Day in GMU

Residual SSDa

No residual SSDa

Residual SSD

No residual SSD

0

2

4

6

8

10

12

14

Day 1 Day 2 Day 3 Day 4 Day 5

Mea

n CM

MSE

(ran

ge 0

to 2

8)

Day in GMU

Residual SSDa

No residual SSDa

Residual SSD

No residual SSD

A

B

Figure 2. Disease trajectories of delirium classified according topresence or absence of residual subsyndromal delirium (SSD).(A) Trend of recovery of delirium of participants in the first5 days of admission to the geriatric monitoring unit (GMU) asreflected by mean daily of Delirium Rating Scale-Revised-98(DRS-R98) severity scale score. (B) Trend of cognitive return ofparticipants in the first 5 days of admission to the GMU asreflected by mean daily Chinese Mini-Mental State Examina-tion score. aAdjusted for age, sex, and underlying dementia.Higher mean DRS-R98-severity score indicates more-severedelirium. Higher Chinese Mini-Mental State Examination(CMMSE) indicates better cognitive performance.

Table 3. Predictive Models for Residual SubsyndromalDelirium (SSD) and Adverse Outcomes

Multivariable Logistic

Regression Model

Odds Ratio

(95% Confidence

Interval)

P-

Value

Residual SSDa (n = 234)Dementia diagnosis 2.35 (1.06–5.22) .04DRS-R98-severity on admission 1.20 (1.07–1.34) .001DRS-R98-severity Day 1 minus Day 3 0.81 (0.74–0.88) <.001

Adverse outcome (mortality or incident nursinghome admission)b (n = 215)Presenceof residualSSD

5.27 (1.43–19.47) .01

aAdjusted for age, sex, Charlson Comorbidity Index, severity of illness

index, dementia diagnosis, delirium type, admission Delirium Rating

Scale-Revised-98 severity scale (DRS-R98-severity), DRS-R98-severity

score Day 1 minus Day 3, admission Chinese Mini-Mental State Examina-

tion, and admission modified Barthel Index.b Adjusted for age, sex, comorbidity, severity of illness, and dementia

diagnosis.

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within 1 week scored significantly lower on the 10-itemDRS at the time of psychiatric consultation than thosewhose delirious episodes lasted longer than 1 week.22 In aprospective observational study, 14 of 33 participants withCAM-positive delirium recovered during hospitalization.5

Predictor variables for recovery during hospitalizationwere initial MMSE and severity of delirium, as measuredusing the 10-item DRS, at the second assessment, whichwas conducted 3 days after the first postadmissionassessment.

The current study highlighted that dementia mightinfluence residual SSD outcomes. Low cognitive reserve inthe presence of dementia with acute illness in hospitalizedolder adults might explain this in part. DRS subitems thatinclude cognitive outcomes might also partly explain it.Finally, delirium itself might affect brain functions in gen-eral, especially in individuals with dementia, thus possiblyslowing recovery. Thus, further investigations of factors ofDRS and possibly in the newer area of research, “deliriumsuperimposed on dementia,” are warranted.

It was also found that poor outcomes were associatedwith presence of residual SSD at recovery from the fullsyndromal delirium episode, with higher risks of inpatientmortality and incident institutionalization. The negativeoutcomes in the study were rare, so these findings requiremore in-depth study.

Because there are no officially recognized diagnosticcriteria for SSD, the convergent validity of a DRS-R98 cut-off score of 13 (DRS13) was compared with CAM-definedresidual SSD, whereby the presence of two or more CAMcore symptoms not meeting CAM criteria for definite delir-ium (CAM2) was used to define residual SSD.34 The latterdefinition yielded 185 (79.1%) participants with residualSSD, with agreement between DRS13 and CAM2 definitionsof residual SSD observed for 176 (75.2%) individualsadmitted to the GMU. In addition, significant differences inrates of improvement in delirium severity, cognition, andfunctional status between participants with and withoutresidual SSD were observed when the CAM2 definition ofresidual SSD was used. Nevertheless, the authors favorusing the DRS-R98 over the CAM for the operational defi-nition of residual SSD because it allows for more-precisecalibration as a scale and better facilitates critique, compar-ison, and modification by others.

A limitation of this study was the lack of data on pre-morbid functional status to allow comprehensive interpre-tation of cognitive and functional measures. There couldalso be sample selection bias because the delirium recoverytrajectories of only individuals admitted to the GMU werestudied. There was also potential observer bias of asses-sors, although the definition of residual SSD was deter-mined only as part of this study and not as part of GMUassessment. Nevertheless, the main thrust of this studyfocuses on the pattern of recovery from delirium and cog-nitive and functional recovery during the acute episode.Analysis of data from 6 and 12 months of follow-up isplanned in order to examine the effects of residual SSD onlonger-term outcomes.

In summary, this study shows that delirium is a spec-trum disorder and that residual SSD is a common condi-tion in hospitalized older adults recovering from delirium.Individuals with SSD after an acute delirious episode

have a longer delirium trajectory to recovery, which maylead to short-term adverse outcomes.

ACKNOWLEDGMENTS

Conflict of Interest: None of the authors have any financialconflict of interest.

This study was funded by FY2010 Ministry of HealthQuality of Improvement Funding (MOH HQIF) “Optimis-ing Acute Delirium Care in Tan Tock Seng Hospital”(HQIF 2010/17). CMS is supported by the NationalHealthcare Group Clinician Scientist Career Scheme 2012/12002.

Author Contributions: Lam, Tay: statistical analysis,writing the manuscript. Chan, Ding: study design, participantrecruitment, writing the manuscript. Chong: study design,supervision of data collection, writing the manuscript.

Sponsor’s Role: The sponsors had no involvement inthe conduct of the study or study findings.

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SUPPORTING INFORMATION

Additional Supporting Information may be found in theonline version of this article:

Table S1. Predictive Models for Residual SSD andAdverse Outcome (additional adjustments for antipsy-chotic and benzodiazepine usage).

Please note: Wiley-Blackwell is not responsible for thecontent, accuracy, errors, or functionality of any support-ing materials supplied by the authors. Any queries (otherthan missing material) should be directed to the corre-sponding author for the article.

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