Severity of delirium in the ICU is associated with short term cognitive impairment. A prospective cohort study

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Intensive and Critical Care Nursing (2015) xxx, xxx—xxx

Available online at www.sciencedirect.com

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Severity of delirium in the ICU is associated with short term cognitive impairment. A prospective cohort study Hideaki Sakuramoto a,∗, Jesmin Subrina b, Takeshi Unoki a, Taro Mizutani b, Hiroko Komatsu c a

Intensive Care Unit, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan1 Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan c Faculty of Nursing and Medical Care, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, Japan1 b

Accepted 16 January 2015

KEYWORDS Intensive Care Delirium Screening Checklists; Delirium; Cognitive impairment; Critical illness

Summary Objectives: To examine the hypothesis that severity of delirium in the intensive care unit (ICU) is positively associated with cognitive impairment at the time of hospital discharge. Design: A prospective cohort study. Setting: Adult medical and surgical ICU of a tertiary-care teaching hospital in Japan in ICU patients who were enrolled and admitted for more than 48 hours. Methods: Severity of delirium was represented as a score of the Intensive Care Delirium Screening Checklist (ICDSC) during the patients’ stay in the ICU under the assumption that higher ICDSC score indicated severe delirium. After discharge from the ICU, the patients were followed up for cognitive impairment using the Mini-Mental State Examination (MMSE). Results: Of the 79 patients enrolled, 50 (63.3%) developed delirium during their stay in the ICU. Patients who developed delirium had higher rates of cognitive impairment (28.0% vs. 3.4%, p = 0.03). After adjusting for covariates, the averaged ICDSC score during the ICU stay indicated a positive association between severity of delirium and cognitive impairment at the time of hospital discharge (adjusted odds ratio (OR) 1.6; 95% confidential interval (CI), 1.02—2.54; p = 0.041). Conclusions: Our findings indicate that severity of delirium during ICU stay may be associated with cognitive impairment at the time of discharge from the hospital in ICU survivors. © 2015 Elsevier Ltd. All rights reserved.

∗

Corresponding author at: Intensive Care Unit, Tsukuba University of Hospital, Tsukuba, Ibaraki 305-8575, Japan. Tel.: +81 29 853 3210/3081; fax: +81 29 853 3092. E-mail address: [email protected] (H. Sakuramoto). 1 Formerly, Department of Adult Nursing, St Luke’s College of Nursing, Chuo-ku, Tokyo, Japan. http://dx.doi.org/10.1016/j.iccn.2015.01.001 0964-3397/© 2015 Elsevier Ltd. All rights reserved.

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Implications for Clinical Practice • A rise in ICDSC score (an indicator of severity of delirium) increased the odds of developing cognitive impairment by 1.6 times, at the time of hospital discharge. Based on insights gained from these observations, important steps can be taken that could improve the care of critically ill patients. Such measures may subsequently lead to a decrease in ICDSC score by preventing the risks related to delirium in the ICU, such as untreated pain; heart failure and prolonged immobilisation. • In 19% patients, after critical illness, cognitive impairment was observed at the time of hospital discharge and 34.2% patients were found to have improved cognitive status during the first week after they were discharged from the ICU. This implies that one week post-discharge, critically ill patients may need special care in order to prevent falls and for cognitive rehabilitation. • The severity of cognitive impairment, as observed in the present study, was between mild to moderate. Despite the high incidence of cognitive impairment, as reported here (mild to moderate), it is surprising that many health care providers fail to recognise cognitive impairment in post ICU settings. Thus cognitive impairment needs to be evaluated in critically ill patients during hospitalisation.

Introduction Numerous studies have documented that persistent cognitive impairment affects 4—78% of intensive care unit (ICU) survivors from six months to six years post-hospital discharge (Hopkins et al., 1999, 2004, 2005; Jackson et al., 2003; Rothenhausler et al., 2001; Sukantarat et al., 2005; Wolters et al., 2013). Cognitive impairment after critical illness can reduce quality of life (Hopkins et al., 1999, 2005), increase health care costs (Jonsson et al., 1999) and lead to institutionalisation (Chodosh et al., 2004). To date, very little information that addresses the severity of delirium and its relationship with cognitive impairment in ICU patients is available. Although a number of previous studies have demonstrated a positive association between duration of delirium and cognitive impairment (Girard et al., 2010; Jackson et al., 2004; Pandharipande et al., 2013), to date, no single study has examined the association between severity of delirium and cognitive impairment. Longer durations of delirium are particularly closely associated with smaller brain volumes, which, in turn, are associated with long term cognitive impairment (Gunther et al., 2012). Sub-syndromal delirium, a clinically important syndrome diagnosed by Intensive Care Delirium Screening Checklists (ICDSC), identifies patients that fall on a continuum between those with no neuropsychiatric symptoms and those with DSM IV-defined delirium (Ouimet et al., 2007). Notably, patients with sub-syndromal delirium have a mortality and length of stay that lies between normal patients and those with delirium, and represents a cohort of patients especially responsive to treatment measures for delirium. Thus, based on these observations, we speculate that higher ICDSC score may indicate severe acute brain dysfunction (Ouimet et al., 2007) and that severity of delirium is represented as a score of ICDSC during the ICU stay. Indeed, the outcome of patients with delirium has been linked to the particular delirium symptoms identified with ICDSC evaluation (Marquis et al., 2007). In view of the above, we hypothesise that severity of delirium during ICU stay is positively associated with cognitive impairment after critical illness. The present study aims to examine the relationship between severity of delirium as assessed by ICDSC in ICU and cognitive impairment at hospital discharge.

Methods Design and sample In the present study, a prospective cohort design was used and the study was pre-approved by the St Luke’s College of Nursing Institutional Ethical Review Board. Prior to the study, the patients or their surrogates reviewed a comprehensive brochure that explained the purpose of the registry and the intended use of the data, including interviewing the patient’s nurse and abstraction of their charts for a full clinical data set, as well as follow-up interviews on cognitive impairment. Informed consents were then obtained. If patients were unable to provide their informed consents, due to unarousal or comatic conditions, informed consents were obtained from their surrogates, and patients were later informed of this development when they re-gained consciousness. Enrollment criteria included all patients admitted ≥48 hours to the medical and surgical ICUs of the St Luke’s International Hospital between the dates of July and December 2009. All patients were carefully screened and assessed prior to enrollment by a research nurse. Exclusion criteria were: (a) pre-existing cognitive impairment; (b) intellectual disability; (c) brain lesions; (d) neurologic disorders affecting cognitive function and (e) major psychiatric illness. Screening for pre-existing cognitive impairment was performed at the time of enrollment through surrogate interviews that included the Modified Blessed Dementia Rating Scale (mBDRS) (scale range, 0—17) (Blessed et al., 1968). Patients were defined as having suspected pre-existing cognitive impairment if their mBDRS score was 3.5 or if they had a history of dementia, based on the information obtained from review of their medical records and other available information. A cutoff point of 3.5 was used for the mBDRS, rather than the recommended cutoff point of 4, to provide a more sensitive criterion to detect suspected pre-existing cognitive impairment. It was determined a priori that patients who met this criterion would be excluded from further analysis.

Delirium assessment in the ICU patients The ICDSC tool used in the present study was developed in 2001 by Bergeron et al. (2001). The validity of ICDSC

Please cite this article in press as: Sakuramoto H, et al. Severity of delirium in the ICU is associated with short term cognitive impairment. A prospective cohort study. Intensive Crit Care Nurs (2015), http://dx.doi.org/10.1016/j.iccn.2015.01.001

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Delirium is associated with cognitive impairment in meta-analysis of ICU patients was evaluated and found to have a pooled sensitivity of 74% (95% confidence interval [CI]: 77.1—82.6%), a pooled specificity of 81.9% (95% CI 76.7—86.4%), a diagnostic odds ratio (OR) of 21.5 (95% CI: 8.51—54.4) and a pooled area under the curve (AUC) of 0.89 (Gusmao-Flores et al., 2012). Thus, ICDSC when used to perform meta-analysis data has a moderate sensitivity and good specificity compared with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). However, ICDSC can be used as a screening tool for the diagnosis of delirium in critically ill patients (Gusmao-Flores et al., 2012). Despite the limitations described above, the inter-rater reliability of the ICDSC appears to be good (Bergeron et al., 2001; Gusmao-Flores et al., 2012). In the current protocol, severity of delirium was assessed using the ICDSC (Bergeron et al., 2001) by two trained research nurses every eight hours during the ICU stay. The principal investigator provided research nurses with a detailed hands-on and face-to-face training on how to use the ICDSC. Patients with an ICDSC score of 4 or higher were considered delirious and those with a score of 3 or less were not (Bergeron et al., 2001). If the patient could not be interviewed after three attempts, due to either unarousal or comatic conditions, the information regarding the reasons of unarousal and any evidence of confusion or delirium in the previous 24 hours were obtained by reviewing the medical record of that particular patient and in such a case, the patient’s nurse was then interviewed by the research nurse. Unarousal (stupor or coma) was based on the Richmond Agitation-Sedation Scale (RASS) -4 or -5 point (Sessler et al., 2002). The results of the checklist ICDSC and RASS scoring were recorded as follows: (a) average score, i.e., the average of every eight hours score during the ICU stay; (b) maximum score, i.e., the highest score during the ICU stay and (c) ICU discharge score, i.e., the ICU discharge score on the day of discharge at the ICU.

Demographics and risk factor of cognitive impairment during the ICU stay Patients’ characteristics that could affect neurological outcomes were documented. Research nurses enrolled patients each day and recorded the patients’ demographic information and treatment conditions during their stay in the ICU. Demographic information collected included age, gender, vision and hearing deficits, pre-existing comorbid conditions, prior diagnoses (evidence for dementia or depression), type of diagnosis at admission, category of admission (surgical vs. medical, urgent vs. non-urgent) and severity of illness using the most abnormal values obtained during the first 24 hours of ICU stay in order to accurately calculate Acute Physiology and Chronic Health Evaluation II (APACHE II) (scale range, 0—71) (Knaus et al., 1985) and Sequential Organ Failure Assessment (SOFA) (scale range, 0—24) scores (Ferreira et al., 2001). The Charlson Comorbidity Index, which represents the sum of a weighted index that takes into account the number and seriousness of preexisting comorbid conditions, was calculated as described by Deyo et al. (1992). Other risk factors of cognitive impairment during the ICU stay were documented, including minimum PaO2 , minimum

3 systolic blood pressure (SBP), minimum serum haemoglobin level, maximum C-reactive protein (CRP), administrations of sedative and opiate drugs, sedation score and the Glasgow Coma Scale (GCS) at ICU discharge and duration of mechanical ventilation. Each patient’s level of sedation was evaluated every shift using the RASS (Ely et al., 2003; Sessler et al., 2002), ranging from comatose (score of −5) to combative (score of +4). Follow-up to hospital discharge was completed in all patients. ICU, as well as hospital length of stay and mortality, was also recorded.

Cognitive assessment in the post-ICU patient interviews After discharge from the ICU, the patients were followed up for cognitive impairment with Mini-Mental State Examination (MMSE) (Folstein et al., 1975) during the second day, and thereafter, every 7th day, until patients were finally discharged from the hospital. The time points of MMSE assessment were adopted from previous studies, with some minor modifications (McNicoll et al., 2003). Patients were defined as cognitively impaired if their MMSE score was <24. The MMSE score determined how patients were categorised, i.e., either as: (a) ‘‘Normal Cognitive’’, with scores of 24 or higher; (b) ‘‘Mild Cognitive impairment’’, with scores between 19 and 23 and (c) ‘‘Severe Cognitive Impairment’’, with scores between 0 and 18 (Karlawish et al., 2005; Pruchno et al., 1995).

Analysis Patients’ characteristics were presented by using standard descriptive measures (means, standard deviations, IQR; interquartile range and proportions). Patients’ baseline demographic and clinical variables were assessed using ttest and Mann—Whitney U test for continuous variables; 2 test or Fisher’s exact test were used for comparing proportions. The presence or absence of cognitive impairment during hospital discharge was assessed and compared between groups with and without delirium using Fisher’s exact test. A logistic regression model was used to assess the association between cognitive impairment and delirium after adjusting for nine covariates (including ICDSC score, age, APACHEII score, Charlson Comorbidity Index, mBDRS score, Glasgow coma scale at ICU discharge, averaged RASS score and serum haemoglobin level). All data analyses were performed using SPSS 19.0 (SPSS Inc., Chicago, IL, USA); a significance level of ≤0.05 was used for statistical inferences.

Results Demographics and risk factors of cognitive impairment during ICU stay During the time of the present study, 100 ICU patients were admitted in the hospital for more than 48 hours, of which 79 (79%) were enrolled and 21 were excluded (Fig. 1). The enrolled cohort was divided into two groups, based on whether they exhibited cognitive impairment after intensive

Please cite this article in press as: Sakuramoto H, et al. Severity of delirium in the ICU is associated with short term cognitive impairment. A prospective cohort study. Intensive Crit Care Nurs (2015), http://dx.doi.org/10.1016/j.iccn.2015.01.001

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H. Sakuramoto et al. Table 1

The baseline characteristics of the patients.

Age, mean ± SD; year Male, no./total (%) Charlson Comorbidity Index, median (IQR) Vision deficits, no./total (%) Hearing deficits, no./total (%) mBDRS score, mean ± SD APACHE score, mean ± SD SOFA score, mean ± SD Mechanical ventilation, No./total (%) Ventilator days, median (IQR) ICU stay, median (IQR); days Hospital stay, median (IQR); days Reason for ICU admission Respiratory failure Cardiovascular surgery Myocardial infarction/congestive heart failure Gastrointestinal Trauma Sepsis Other

Total n = 79

Non-cognitive impaired n = 64

Cognitive impaired n = 15

p Value

67.4 ± 14.5 55 (69.6) 3.0 (1.0, 5.0) 9 (11.4) 6 (7.6) 0.36 ± 0.75 19.6 ± 8.59 8.05 ± 4.74 28 (35.4) 1.0 (0.0, 3.0) 4.0 (3.0, 5.0) 14.0 (9.0, 19.0)

65.0 ± 15.0 46 (71.9) 2.0 (1.0, 4.0) 6 (9.4) 4 (6.3) 0.21 ± 0.82 18.1 ± 8.11 7.71 ± 4.64 23 (35.9) 1.0 (0.0, 2.75) 3.5 (3.0, 5.0) 14.0 (9.0, 17.75)

76.0 ± 9.0 9 (60.0) 4.0 (2.0, 8.0) 3 (20.0) 2 (13.3) 1.00 ± 1.18 25.7 ± 8.12 9.46 ± 5.06 5 (33.3) 3.0 (0.0, 5.0) 5.0 (3.0, 6.0) 16.0 (9.0, 52.0)

0.001 0.369 0.021 0.360 0.319 0.000 0.002 0.201 0.849 0.094 0.167 0.416

9 (11.4) 19 (24.1) 30 (38.0) 9 (11.4) 5 (6.3) 5 (6.3) 2 (2.5)

7 (10.9) 17 (26.6) 25 (39.1) 7 (11.0) 4 (4.7) 4 (6.3) 0

2 (13.3) 2 (13.3) 5 (33.3) 2 (13.3) 1 (6.7) 1 (6.7) 2 (13.3)

0.677 0.502 0.774 0.677 0.662 0.662 0.034

Abbreviations: ICU, intensive care unit; mBDRS, modified Blessed Dementia Rating Scale; APACHE II, Acute Physiology and Chronic Health Evaluation II; SOFA, Sequential Organ Failure Assessment; IQR, interquartile range. Proportions: 2 tests, Fisher exact tests, continuous variables; t-tests, Mann—Whitney U tests for non-cognitive vs. cognitive impairment.

≥48 h stay in ICU (n = 100) Excluded (n = 21) 1. Dementia (n = 8) 2. Death (n = 5) 3. Other (n = 8)

Included in outcome (n = 79)

Figure 1

Flow of patients in study cohort.

care using a criteria defined a priori (see ‘‘Methods’’ Section). The baseline demographics of the patients are shown in Table 1. Significant differences were found between groups based on age, comorbidity index, mBDRS or severity of illness, as measured by APACHE II. The risk factors for cognitive impairment are shown in Table 2. Significant differences in minimum serum haemoglobin concentrations were found between groups or averaged RASS levels. However, no significant differences in minimum PaO2 , maximum CRP, minimum SBP or GCS score were observed between groups at the time of discharge from the ICU.

Prevalence of delirium The rates of delirium and their corresponding ICDSC scores are shown in Table 2. Overall, the averaged ICDSC score was 6.0 (interquartile range 2.0—8.0) and delirium was observed in 50 out of the 79 (63.3%) patients during ICU stay. However, by the time patients were discharged from ICU, delirium

had dropped to its lowest prevalence, i.e., only 22 out of the 79 (27.8%) patients at the time of ICU discharge exhibited it. Further, of the 22 delirious patients diagnosed during discharge, a total of 16 (72.7%) patients had earlier been diagnosed as such during their stay in the ICU. Overall, during the ICU stay, the median of delirium prevalence was 1.0 day (interquartile range 0.0—3.0 days).

Prevalence and trajectory of change of cognitive status after ICU discharge Fig. 2 demonstrates the trajectory of cognitive status change during the post ICU period. During this period, patients were assigned to the cognitive impairment group, if they exhibited signs of cognitive impairment on any day. The diagram (Fig. 2) reflects the post ICU period and changes from baseline cognitive status at the initial assessment (normal cognitive, mild cognitive impairment, severe cognitive impairment) through the rest of the post ICU stay. In 19% patients (15/79), cognitive impairment was observed during ICU discharge and eight of the 21 (38%) affected patients displayed initial improvement in cognition. However, two of the 58 patients (3%) who initially exhibited normal cognition later developed cognitive impairment during the post-ICU stay. Of the 79 patients, 27 (34.2%) patients improved their MMSE score, and with admission MMSE score improved by 2 or more points at the time of ICU discharge (interquartile range 1—6 points). Overall, MMSE scores were 27.2 (23.0—30.0) at baseline vs. 29.0 (25.0—30.0) at ICU discharge (p = 0.003).

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Delirium is associated with cognitive impairment Table 2

5

Risk factors for cognitive impairment after critical illness.

Minimum PaO2 , median (IQR) Maximum CRP, median (IQR) Minimum SBP, median (IQR) Minimum HGB, median (IQR) GCS score at ICU discharge, median (IQR) Averaged RASS score, median (IQR) Sedation, n (%) Analgesia, n (%) Averaged ICDSC score, median (IQR) Maximum ICDSC, median (IQR) ICDSC score at ICU discharge, median (IQR) Duration of delirium, day, median (IQR)

Total n = 79

Non-cognitive impaired n = 64

Cognitive impaired n = 15

p Value

65.8 (57.5, 74.2) 10.3 (1.6, 19.4) 57 (48.0, 64.6) 9.3 (8.1, 11.7) 14 (14.0, 14.0) −0.7 (−1.2, 0.0) 38 (48.1) 31 (39.2) 6.0 (2.0, 8.0) 6.0 (2.0, 8.0) 1.0 (0.0, 4.0) 1.0 (0.0, 3.0)

67.4 (57.5, 76.0) 9.72 (2.1, 17.3) 83.0 (70.0, 98.8) 9.6 (8.2, 11.9) 14.0 (14.0, 15.0) −0.7 (−1.0, 0.0) 29 (45.3) 26 (40.6) 2.5 (1.0, 4.7) 5.0 (2.0, 7.0) 1.0 (0.0, 2.8) 1.0 (0.0, 2.0)

60.0 (48.9, 66.4) 16.9 (1.0, 27.2) 86.0 (66.0, 101.0) 8.2 (7.4, 10.2) 14.0 (13.0, 14.0) −1.0 (−1.5, 0.6) 9 (60) 5 (33.3) 5.5 (3.8, 7.0) 7.0 (6.0, 8.0) 4.0 (2.0, 7.0) 3.0 (2.0, 4.0)

0.283 0.176 0.846 0.034 0.087 0.032 0.305 0.603 0.000 0.006 0.001 0.002

SBP: systolic blood pressure; HGB: Serum haemoglobin level; GCS: Glasgow coma scale; RASS: Richmond Agitation Sedation Scale; ICDSC: Intensive Care Delirium Screening Checklists; IQR: interquartile range. Proportions: 2 test, Fisher’s exact test, continuous variables; t-test, Mann—Whitney U test for non-cognitive vs. cognitive impairment.

Days after ICU discharge

2 days

7 days

14 days

21 days

28 days

35 days

(n = 79)

(n = 58)

(n = 23)

(n = 13)

(n = 9)

(n = 6)

15

Normal Cognitive Function MMSE ≥ 24 58 ( 73.4% )

41

30

48 (82.8)

18 (78.3)

18

4

9

9 (69.2)

9

5

At hospital

discharge (n = 79)

3

5 (55.6)

2

2 (33.3)

2

64 (81)

1

1

Mild Cognitive Impairment MMSE 19-23 15 ( 19% ) 1

6 4 1

6 (10.3)

2

2 (8.7)

1

4

4

1 (7.7)

1

1 (11.1)

1

1 (16.7)

1

12 (15.2)

1

1

Severe Cognitive Impairment MMSE ≤ 18 6 ( 7.6% )

1 3

4 (6.9)

3

3 (13)

3

3 (23.1)

3

3 (33.3)

3

3 (50)

1 2

3 (3.8)

1

No Change Improve

Discharge before Next followed up deleterious change

Figure 2 Trajectory of change in cognitive status during hospitalisation. The flow chart demonstrates the trajectory of change in cognitive status of patients during the post-ICU period stratified by MMSE Score of normal cognitive (upper box), mild cognitive impairment (middle box) or severe cognitive impairment (lower box). If patients were with severe cognitive impairment at two days after ICU discharge, they were assigned to ‘‘severe cognitive impairment’’ group. Only 58 patients are represented in the ‘‘7 days after ICU discharge’’ group because 21 patients did not have interviews by the time of discharge, before the next follow up meeting. In that case, patients had interviews at the time of hospital discharge. The number of Figure indicates the number of patients whose status are changed at the initial interviews to another (status) at the following interviews.

Relationship between severity of delirium and cognitive impairment During the ICU discharge period, patients with delirium exhibited higher cognitive impairment rates (28.0% vs. 3.4%, p = 0.03). Fig. 3 shows the relationship between MMSE and corresponding ICDSC scores. We observed that the value of the MMSE score slightly diminished in correspondence to increasing ICDSC score (Fig. 3). Also, patients with cognitive impairment had higher ICSDC scores in terms of averaged and maximum values (Table 2). Table 3 shows the rates of cognitive impairment stratified by each ICDSC score. The OR (odds ratios) and 95% CI

reflect the risk of cognitive impairment incidence at the time of hospital discharge, given the severity of delirium. After adjusting for covariates, the averaged ICDSC score during the patients’ stay in the ICU and ICDSC score at the point of ICU discharge were associated with cognitive impairment at the time of hospital discharge. Maximum ICDSC score during ICU stay was not associated with cognitive impairment at the time of hospital discharge.

Discussion The major findings of the present study are that: (a) delirium frequently occurs in ICU patients, as much as in 63%

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Figure 3 Relationship between median MMSE score at the time of discharge from the ICU and each ICDSC score of three separate stratified scores: averaged score, the average of every 8 hours score during the ICU stay; maximum score, the highest score during the ICU stay and ICU discharge score and the ICU discharge score on the day of discharge at the ICU. Table 3 Multivariate analysis of variables associated with cognitive impairment.

Averaged ICDSC score Maximum ICDSC score ICDSC Score at ICU discharge

Adjusted Oddsa

95% CI

p Value

1.6 1.2 1.6

1.02—2.55 0.82—1.82 1.08—2.40

0.004 0.318 0.002

Abbreviations: CI, confidence interval; ICDSC, intensive care delirium screening checklist; ICU, intensive care unit. a Multivariate analysis incorporating covariates including patient age at enrollment, Acute Physiology and Chronic Health Evaluation II score, Charlson Comorbidity Index, modified Blessed Dementia Rating Scale score, Glasgow coma scale at ICU discharge, mean Richmond Agitation Sedation Scale score and serum haemoglobin level.

patients, (b) 19% of the patients (15/79) were noted to have cognitive impairment at the time of hospital discharge, (c) the changes in the trajectories of mental status in ICU patients reflects a complex and dynamic process throughout the course of hospitalisation and (d) severity and duration of delirium (higher ICDSC score) in ICU patients during their stay in the ICU may correspond with the extent of their cognitive impairment at the time of their discharge from the hospital. The present study is the first report to demonstrate a positive association between severity of delirium, as determined by ICDSC, and cognitive impairment, at the time of hospital discharge in ICU patients. One key point highlighted by the ICDSC score in these ICU patients is the 1.6-fold increase in the risk of cognitive impairment in ICU patients, even after controlling for pre-existing comorbidities,

severity of illness, GCS at ICU discharge, sedative condition and serum haemoglobin levels. These data suggest that higher ICDSC score may be indicative of the severity of acute brain dysfunction and delirium. Additionally, the present study demonstrates that the duration of delirium, as assessed by ICDSC, is associated with cognitive impairment at the time of hospital discharge, i.e., the longer the duration of delirium, the stronger the association with cognitive impairment. These data are consistent with earlier reports that also demonstrated that delirium is associated with cognitive impairment in ICU survivors (Girard et al., 2010; Gunther et al., 2012; Jackson et al., 2004; Pandharipande et al., 2013; van den Boogaard et al., 2012). Based on ICDSC scores, 63% of patients in the present study were considered to have clinical delirium. Only 12.6% of our cohort lacked any of the ICDSC scores, implying that these patients could likely be considered cognitively normal, meaning that 87% of our patients, at some time during their stay in the ICU, demonstrate at least one feature of delirium. Such patients could have a pivotal effect in dichotomous characterisations of delirium, because their inclusion among patients considered not having delirium (i.e., normal patients) (Ouimet et al., 2007). Conversely, if such patients were included among those considered to have delirium, the resulting group’s prognosis would be improved. The concept of a continuous, instead of a categorical (or dichotomous) characterisation of delirium (i.e. ICDSC), may allow us to better understand the association of psychiatric symptoms with clinical outcomes. Indeed, our present findings show that one of the most important factors in improving the care of critically ill patients in the ICU may subsequently be decreased ICDSC score through the prevention or reduction of risk and symptoms for delirium in the ICU. For example, numerous preventable risk factors for delirium have been identified, including use of psychoactive drugs; mechanical ventilation and a variety of medical conditions, such as untreated pain, heart failure, prolonged immobilisation, abnormal blood pressure, anaemia and sleep deprivation (Jones and Pisani, 2012). Here, we also found that cognitive impairment is common among general medical and surgical ICU patients at the time of hospital discharge and that cognitive status changes during the post ICU period. Further, we also show here that 19% of patients considered to have cognitive impairment and 34.2% of patients were found to have improved MMSE score during hospital discharge. These findings are consistent with an earlier report by Inouye et al. (2006), which showed that 179 of 460 (39%) older patients improved their MMSE scores to their baseline level, ranging from 3 to 13 points (median = 5.0 points) by the time of their discharge from the hospital and that further improvement was observed a year later, based on their MMSE scores. Similar trends, as observed by Inouye et al., were also found in the present study, i.e., improvement in MMSE score during hospital discharge. Notably, MMSE score in patients of the current study were found to be the most improved one week after ICU. This finding implies that during this period (one week after ICU), patients may need special care, such as preventing falls and cognitive rehabilitation. Finally, the severity of cognitive impairment in patients of the current study was almost mild to moderate and is consistent to those observed in some earlier studies (de Rooij

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Delirium is associated with cognitive impairment et al., 2008; Jackson et al., 2003; Rothenhausler et al., 2001). It is important to note that even mild cognitive impairments may pose significant problems to patients, in normal and routine low-cognitive day-to-day activities, such as driving, money management and others (Albert et al., 1999; Griffith et al., 2003; Nygard, 2003). Despite the high incidence of mild to moderate cognitive impairment, in non-ICU clinical settings, many health care providers fail to recognise cognitive impairment in 35—90% of patients (Callahan et al., 1995). Thus, cognitive impairments should be evaluated in critically ill patients during hospitalisation.

Limitations and future directions It is important to note some of the limitations of the present study. First, the present study did not investigate the longterm outcome but only short-term cognitive status. Also, the current observational study was not designed to prove a cause and effect relationship between severity of delirium and cognitive impairment. However, a previous study found that cognitive function at the time of hospital discharge was a significant predictor of long-term cognitive function (Newman et al., 2001). Therefore, cognitive impairment at the time of hospital discharge is a critical issue that predicts cognitive function during the post discharge period. Future longitudinal research should examine the relationships between ICDSC score and cognitive impairment after critical illness. Secondly, the study was based on a small sample size and was only undertaken at one academic tertiary medical centre in Japan. Thirdly, recent studies suggest that the CAM-ICU is a better predictor of outcomes than the ICDSC (Tomasi et al., 2012) for delirium in ICU patients as there might be high rates of false positives with the ICDSC (Gusmao-Flores et al., 2012). Thus, this drawback (of ICDSC) may affect the outcome of the present results. However, a recent study by Tomasi et al. (2012), which is a singlecentre study, showed relatively low delirium rates assessed by ICDSC, implying that these current results must be confirmed by multicenter studies, including larger populations. Fourthly, only cognitive screening test (MMSE) was used in the present study. Neuropsychological batteries administered to patients were not assessed. Lastly, while our cohort did incorporate the most typical range of a cardiothoracic ICU patient population, other types of critically ill patients should have been investigated, including patients in burn, renal/metabolic and hepatic disease, as well as those with baseline neurologic comorbidities.

Conclusion In conclusion, our current findings indicate that severity and duration of delirium during ICU stay may be associated with cognitive impairment at the time of hospital discharge in ICU survivors and that an important step in improving the care of critically ill patients may subsequently decrease ICDSC score through the prevention of risk and symptoms for delirium in the ICU.

Funding The authors have no sources of funding to declare.

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Conflict of interest The authors have no conflict of interest to declare.

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Please cite this article in press as: Sakuramoto H, et al. Severity of delirium in the ICU is associated with short term cognitive impairment. A prospective cohort study. Intensive Crit Care Nurs (2015), http://dx.doi.org/10.1016/j.iccn.2015.01.001