From the original eligible population (N=321), 121 refused to participate and 99 could not be assessed at baseline for logistical reasons leaving a total of 101 included patients (Figure 1). In addition, 8 patients could not be assessed for postoperative delirium secondary to ICU admission with intubation (N=4), early transfer to another hospital (N=1), death (N=2), and logistical problem (N=1), leaving a final sample of 93 patients. Compared to the 93 remaining patients, those 8 patients had similar median age (82.0 [IQR 4.0] vs 82.1 [10.3] years, p=.725), baseline median MMSE (28.0 [3.0] vs 28.0 [3.0], p=.829) and IADLs (8.0 [0.5] vs 8.0 [2.0], p=.151) scores. They were more frequently men (75% vs 55%, p=.460), had higher STS risk score (4.4 [4.5] vs 3.4 [2.7], p=.174), and were less often treated with TAVR (38% vs 71%, p=.105), but none of these differences achieved statistical significance.
Baseline characteristics of included patients are presented in Table 1. Participants’ median age was 82.1 years, 45% were women, essentially living at home (99%), and only a quarter (24%) received formal in-home help. Overall, 66 (71%) of the patients underwent a TAVR and 27 (29%) underwent SAVR.
Table 1: Characteristics of the overall population at baseline and comparisons in subjects with and without post-operative delirium.
Characteristics
|
Total population
N=93 (100%)
|
Post-operative delirium
|
p-value‡‡
|
Yes
N = 21 (22.6%)
|
No
N=72 (77.4%)
|
SOCIO-DEMOGRAPHIC
|
|
|
|
|
Age (years)
Median / IQR
|
82.1 / 10.3
|
83.1 / 7.6
|
81.8 / 10.1
|
.038
|
Male gender (%)
|
51 (54.8)
|
13 (61.9)
|
38 (52.8)
|
.460
|
Living at home n(%)
|
91 (98.9)
|
21 (100.0)
|
70 (98.6)
|
1.000
|
Receiving formal inhome help n(%)
|
22 (23.9)
|
8 (38.1)
|
14 (19.7)
|
.083
|
GERIATRIC ASSESSMENT
|
|
|
|
|
MMSE score *
Median / IQR
|
28.0 / 3.0
|
27.0 / 3.0
|
28.0 / 3.0
|
.029
|
Clock Drawing Test †
Median / IQR
|
10.0 / 2.0
|
9.0 / 2.0
|
10.0 / 2.0
|
.445
|
Depressive symptoms ‡ n(%)
|
23 (24.7)
|
4 (19.1)
|
19 (26.4)
|
.577
|
Basic ADLs §
Median / IQR
|
6.0 / 0.0
|
6.0 / 0.0
|
6.0 / 0.0
|
.544
|
Instrumental ADLs ‖
Median / IQR
|
8.0 / 2.0
|
7.0 / 3.0
|
8.0 / 1.5
|
.038
|
Performance Oriented Mobility Assessment ¶
Median / IQR
|
28.0 / 5.0
|
27.0 / 5.0
|
28.0 / 4.0
|
.279
|
Gait speed #
Median / IQR (m/s)
|
0.68 / 0.56
|
0.65 / 0.56
|
0.70 / 0.56
|
.443
|
SURGICAL RISK SCORES
|
|
|
|
|
STS risk score **
Median/IQR
- High risk (score>9), n(%)
- Intermediate risk (score>3 and ≤8),n(%)
- Low risk (score ≤3), n(%)
|
3.4/2.7
9 (9.7)
40 (43.0)
44 (47.3)
|
4.7/2.7
4 (19.1)
12 (57.1)
5 (23.8)
|
2.9/2.3
5 (6.9)
28 (38.9)
39 (54.2)
|
.020
.023
|
Euroscore 2 ††
Median/ IQR
High risk (score ≥15), n(%)
|
4.2 / 3.9
3 (3.2)
|
4.2 / 5.7
2 (9.5)
|
4.2 / 3.8
1 (1.4)
|
.308
.127
|
(*) MMSE : Mini Mental Status Examination (38); scores range from 0 to 30, with higher score indicating better cognitive performance.
(†) CDT : Clock Drawing Test (/10) (39); scores range from 0 to 10 with higer score indicating higher cognitive performance.
(‡) mini Geriatric Depression Scale (40); scores range from 0 to 4 with significant depressive symptoms if score ≥1/4.
(§) Basic ADLs : Basic Activities of Daily Living (36): bathing, dressing, using the toilet, transferring between bed and chair, maintaining continence, and feeding; scores range from 0 to 6, with higher scores indicating higher function
(‖) Instrumental ADLs : Instrumental Activities of Daily Living (37): using the phone, grocery shopping, cooking, housekeeping, doing the laundry, using transportation, taking medications, and handling finances; scores range from 0 to 8, with higher scores indicating higher function
(¶) Performance Oriented Mobility Assessment (41): scores range from 0 to 28 with higher scores indicating better balance
(#) Gait speed : measured at usual pace over 6 meters
(**) STS risk score = Society of Thoracic Surgeons risk score in cardiac surgery (43) :
"Low risk" if score ≤3; "Intermediate risk" if score >3 and ≤8; "High risk" if score >8
(††) Euroscore II = risk score in cardiac surgery (44) : indicates postoperative mortality rate
(‡‡) P-values from Wilcoxon rank-sum and Fischer exact test for continuous and categorical variables, respectively.
Incidence of postoperative delirium
Postoperative delirium occurred in 21 (23%) of the 93 patients. Most (18/21, 86%) developed delirium already on the first postoperative day, and all but one (20/21, 95%) within the first 3-day period after the procedure. Among these patients, only 2 remained delirious at day-7 assessment. Finally, only one additional patient developed delirium at day-7 assessment.
Factors associated with postoperative delirium
Comparisons of baseline characteristics in patients with and without delirium are presented in Table 1. In bivariate analysis, patients with delirium had significantly lower cognitive performance (MMSE score [IQR] 27.0 [3.0] vs 28.0 [3.0], p=.029), lower performance in Instrumental ADLs (7.0 [3.0] vs 8.0 [1.5], p=.038), and higher STS risk score (4.7 [2.7] vs 2.9 [2.3], p=.020) than patients without delirium. Indeed, the proportion of patients who developed postoperative delirium steadily increased across levels of baseline STS risk score, from 11% in the lowest risk group (STS risk score ≤3), to 30% in the intermediate risk group (STS risk score>3 to ≤8), and to 44% in the highest risk group (STS risk score >8). Patients with TAVR had lower incidence of delirium (13/66=20%) than those with SAVR (8/27=30%), but this difference did not reach statistical significance (p=.298).
In multivariate analysis (APPENDIX Table A), a higher cognitive performance at baseline remained associated with significantly decreased odds of developing delirium (AdjOR 0.8, 95%CI 0.7-0.9, p=.001).
Similarly, an independent association between STS risk score and delirium remained significant as patients with intermediate (score>3 to ≤8) and high (score>8) STS risk scores had 4.3 (95%CI 1.2-15.1, p=.025) and 16.5 (95%CI 2.0-138.2, p=.010), respectively, higher odds of incident delirium compared to patients with low (score≤3) STS risk score (Figure 2). Finally, TAVR was associated with 80% (AdjOR 0.2, 95% CI 0.1-0.8, p=.020) lower odds of delirium than SAVR. In contrast, baseline performance in instrumental ADLs did not remain associated with delirium once adjusting for the other covariates. The final multivariate model correctly classified 80.7% of the patients with an area under the ROC curve of 0.80.
Length of stay
Overall length of hospital stay was 11.2 (SD 6.9) days. Although patients with delirium had longer stays than patients without delirium (14.5 days; SD 11.4, IQR 7 vs 10.3 days; SD 4.6, IQR 7), this difference did not achieve statistical significance (p=.128 from Wilcoxon rank-sum test)
Cognitive outcome at 3-month follow-up
Sixteen (17%) of the 93 patients initially enrolled did not complete the 3-month follow-up assessment because they were unable to travel to the examination site (N=10), had been institutionalized (N=2), refused (N=1), or were lost (N=3). Compared to those who did complete the 3-month follow-up, these patients were older (83.6 [12.9] vs 81.8 [9.9] years, p=.433), had lower baseline MMSE (27.5 [3.0] vs 28.0 [3.0], p=.257) and instrumental ADLs (6.5[3.0] vs 8.0 [2.0], p=.074) scores, and higher STS risk score (4.4 [4.9] vs 3.2 [2.4], p=.079). They also did more frequently experience a delirium (38% vs 20%, p=.117), but, due to the limited sample size, none of these differences achieved statistical significance.
Among patients who completed the 3-month follow-up (Table 2), those who experienced delirium had lower MMSE at follow-up (27.0 [8.0] vs 28 [2.0], p=.007). However, this association did not remain once adjusting for baseline MMSE performance (β coefficient -1.11, 95% CI [-3.03-0.80], p=.248) (APPENDIX Table B).
Table 2. Comparisons of cognitive and functional performance in basic and instrument activities of daily living ADLs) at 3-month in patients with and without post-operative delirium.
Characteristics at 3-month follow-up
|
Total population
(N=77)
|
Post-operative delirium
at baseline
|
p-value
|
|
|
Yes
(N=15)
|
No
(N=62)
|
|
MMSE *
Median / IQR
Range
(min, max)
|
28.0 / 3.0
17.0
(13.0, 30.0)
|
27.0 / 8.0
16.0
(13.0, 29.0)
|
28.0 / 2.0
9.0
(21.0, 30.0)
|
.007
|
Clock Drawing Test †
Median / IQR
Range (min, max)
|
10.0 / 1.0
10.0 (0.0, 10.0)
|
9.0 / 3.0
5.0 (5.0, 10.0)
|
10.0 / 1.0
10.0 (0.0, 10.0)
|
.136
|
Basic ADLs ‡
Median / IQR
Range (min, max)
|
6.0 / 0.0
3.0 (3.0, 6.0)
|
6.0 / 0.0
3.0 (3.0, 6.0)
|
6.0 / 0.0
2.0 (4.0, 6.0)
|
.678
|
Instrumental ADLs §
Median / IQR
Range
(min, max)
|
7.0 / 2.0
7.0 (1.0, 8.0)
|
7.0 / 2.0
7.0 (1.0, 8.0)
|
8.0 / 2.0
6.0 (2.0, 8.0)
|
.147
|
(*) MMSE: Mini Mental Status Examination (38); scores range from 0 to 30, with higher score indicating better cognitive performance.
(†) Clock Drawing Test (39); scores range from 0 to 10 with higer score indicating higher cognitive performance.
(‡) Basic ADLs: Basic Activities of Daily Living (36): bathing, dressing, using the toilet, transferring between bed and chair, maintaining continence, and feeding. Scores range from 0 to 6, with higher scores indicating higher function
(§) Instrumental ADLs: Instrumental Activities of Daily Living (37): using the phone, grocery shopping, cooking, housekeeping, doing the laundry, using transportation, taking medications, and handling finances. Scores range from 0 to 8, with higher scores indicating higher function