Table 3 Characteristics of included studies evaluating pharmacological, psychological or multicomponent interventions

Liptzin, 2005 [30]

DSM-IV, CAM, DSI

POD 7, POD 14

Orthopedic

Donepezil (5 mg, po) (pre-1-14+ POD 1-14) vs. placebo

I1: 25/14

I2: 21/20

I1: 67 ± 9

I2: 68 ± 9

6

I1: 8/39 (20.5%)

I2: 7/41 (17.1%)

0.694

Duration ( P = 0.12):

I1: 1 ± 0 days

I2: 1.3 ± 1.2 days

I1: 4.4 ± 0.8

I2: 4.2 ± 0.5

Sampson, 2007 [37]

DSI

POD 1-4

Orthopedic

Donepezil (5 mg, po) (pre- + POD 1-3) vs. placebo

I1: 8/11

I2: 6/8

I1: 70 ± 8

I2: 65 ± 11

10

I1: 2/19 (10.5%)

I2: 5/14 (35.7%)

0.106

I1: 9.9 ± 3.2

I2: 12.1 ± 4.1

Cholinesterase inhibitors

Marcantonio, 2011 [48]

CAM, DSI, MDAS

POD 1-discharge; 2, 4, and 6 weeks

Orthopedic

Donepezil (5 mg, po) (POD 1-30) vs. placebo

I1: 5/2

I2: 4/5

I1: 88 ± 5

I2: 87 ± 4

9

I1: 3/7 (42.9%)

I2: 4/9 (44.4%)

1

Severity based on MDAS changes ( P = 0.91):

I1: 1.3 ± 2.5

I2: 1.6 ± 5.2

N/A

Gamberini, 2009 [39]

CAM

POD 1-6

Orthopedic

Rivastigmine (1.5 mg, tid, po) (pre-1 + POD 1-6) vs. placebo

I1: 19/37

I2: 17/40

I1: 74 ± 5

I2: 74 ± 6

10

I1: 18/56 (32.1%)

I2: 17/57 (29.8%)

0.790

I1: 13 ± 6.2

I1: 13 ± 6.2

Kaneko, 1999 [22]

DSM-III-R

POD 5

Abdominal

Haloperidol (5 mg, iv) (POD 1-5) vs. saline

I1: 14/24

I2: 14/26

I1: 72 ± 8

I2: 73 ± 9

5

I1: 4/38 (10.5%)

I2: 13/40 (32.5%)

0.027

N/A

Antipsychotics (typical)

Kalisvaart, 2005 [29]

DSM-IV, CAM, DRS

POD 1-3

Orthopedic

Haloperidol (0.5 mg, tid, po) (pre-POD 3) vs. placebo

I1: 172/40

I2: 171/47

I1: 79 ± 6

I2: 80 ± 6

11

I1: 32/212 (15.1%)

I2: 36/218 (13.8%)

0.687

Severity in patients with delirium based on DRS ( P < 0.001):

I1: 14.40 ± 3.5

I2: 18.41 ± 4.4

Duration in patients with delirium ( P < 0.001):

I1: 5.41 ± 4.91 days

I2: 11.85 ± 7.56 days

Patients with delirium:

I1: 17.1 ± 11.1

I2: 22.6 ± 16.7

Wang, 2012 [54]

CAM-ICU

POD 1-7

Non-cardiovascular

Haloperidol (1.7 mg, iv) (POD) vs. saline

I1: 84/145

I2: 85/143

I1: 74 ± 6

I2: 74 ± 7

12

I1: 35/229 (15.3%)

I2: 53/228 (23.2%)

0.031

I1: 11.0 ± 0.9

I1: 11.0 ± 0.8

Larsen, 2010 [45]

DSM-III-R, CAM, DRS

POD 1-8 or discharge

Orthopedic

Olanzapine (5 mg, po) (pre- + POD) vs. placebo

I1: 94/102

I2: 123/81

I1: 73 ± 6

I2: 74 ± 6

9

I1: 28/196 (14.3%)

I2: 82/204 (40.2%)

< 0.001

Severity based on DRS ( P = 0.02):

I1: 16.44 ± 3.7

I2: 14.5 ± 2.7

Duration ( P = 0.02):

I1: 2.2 ± 1.3 days

I2: 1.6 ± 0.7 days

N/A

Antipsychotics (atypical)

Prakanrattana, 2007 [36]

CAM-ICU

POD 1-discharge

Cardiovascular

Risperidone (1 mg, sl) (POD) vs. placebo

I1: 27/36

I2: 25/38

I1: 61 ± 10

I2: 61 ± 10

12

I1: 7/63 (11.1%)

I2: 20/63 (31.7%)

0.009

I1: 10.5 ± 6.1

I2: 10.3 ± 4.4

Hakim, 2012 [52]

DSM-IV

ICU -discharge

Cardiovascular

Risperidone (0.5 mg, bid, po) (POD until 24 hours after subsidence of subsyndromal delirium or a score of more than 3 on the ICDSC was obtained) vs. placebo

I1: 18/33

I2: 14/36

> 65

12

I1: 7/51 (13.7%)

I2: 17/50 (34%)

0.031

Duration in patients with delirium ( P = 0.669):

I1: 3 ± 1.5 days

I2: 3 ± 0.8 days

I1: 6 ± 1.5

I2: 6 ± 2.3

Leung, 2006 [33]

CAM

POD 1-3

Orthopedic

Gabapentin (900 mg, po) (pre- + POD 1-3) vs. placebo

I1: 5/4

I2: 5/7

I1: 57 ± 10

I2: 61 ± 11

10

I1: 0/9 (0)

I2: 5/12 (41.7%)

0.045

N/A

Anticonvulsants

Pesonen, 2011 [50]

CAM-ICU

POD 1-5

Abdominal

Pregabalin (150 mg, po) (pre- + POD 1-5) vs. placebo

I1: 14/21

I2: 19/16

I1: 80 ± 11

I2: 80 ± 12

10

N/A

N/A

Severity based on CAM-ICU ( P = 0.04):

I1: 24 ± 8

I2: 21 ± 19

N/A

Sleep restoration (diazepam/flunitrazepam/pethidine)

Aizawa, 2002 [26]

DSM-IV

POD 1-7

Abdominal

Diazepam (0.1 mg/kg, im)/flunitrazepam (0.04 mg/kg, iv)/pethidine (1 mg/kg, iv) (POD 1-3) vs. standard

I1: 5/15

I2: 9/11

I1: 76 ± 5

I2: 76 ± 4

8

I1: 1/20 (5%)

I2: 7/20 (35%)

0.023

I1: 25.6 ± 9.4

I2: 29.9 ± 6.2

Sleep restoration (Bright light)

Taguchi, 2007 [38]

NEECHAM

POD 1-5

Thoracic

Bright light (2 hours per day; morning; 5000 lx) vs. standard

I1: 0/6

I2: 0/5

I1: 56 ± 14

I2: 59 ± 14

7

I1: 1/6 (16.7%)

I2: 2/5 (40%)

0.545

Severity based on NEECHAM ( P = 0.014):

I1: 6.7 ± 0.7

I2: 21.1 ± 7

N/A

Ono, 2011 [49]

NEECHAM, DSM-IV

POD 1-6

Thoracic

Bright light (POD2-5; 2 hours per day; morning; 2500-5000 lx) vs. standard

I1: 0/6

I2: 0/5

I1: 63 ± 10

I2: 64 ± 8

6

I1: 1/10 (10%)

I2: 5/12 (41.7%)

0.162

I1: 24.8 ± 3.9

I2: 24.8 ± 4.0

Psychological interventions

Schindler, 1989 [18]

DSM-III

discharge

Cardiovascular

Daily psychiatric intervention vs. standard

I1: 13/3

I2: 13/4

I1: 58 ± 8

I1: 61 ± 6

3

I1: 0/17 (0)

I2: 2/16 (12.5%)

0.227

I1: 15.7 ± 5

I2: 18.7 ± 6

Music

McCaffrey, 2009 [42]

NEECHAM

POD 1-3

Orthopedic

Music vs. standard

I1: 7/4

I2: 7/4

I1: 75 ± 5

I1: 76 ± 6

6

N/A

N/A

Severity based on NEECHAM ( P = 0.000):

I1: 24 ± 0.97

I2: 22.5 ± 1.22

N/A

Multi-component interventions

Marcantonio, 2001 [25]

CAM

POD 1-discharge

Orthopedic

Geriatrics consultation (a geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol including 10 modules) vs. standard

I1: 49/13

I2: 50/14

I1: 78 ± 8

I2: 80 ± 8

9

I1: 20/62 (32.3%)

I2: 32/64 (50%)

0.043

The number of patients with severe delirium ( P = 0.02):

I1: 7/62 (11.3%)

I2: 18/64 (28.1%)

Duration in patients with delirium ( P = 0.72):

I1: 2.9 ± 2 days

I2: 3.1 ± 2.3 days

I1: 5 ± 1.5

I2: 5 ± 1.5

Lundstrom, 2007 [35]

DSM-IV, OBS-scale

POD 1-discharge

Orthopedic

Comprehensive intervention (staff education, team work, individual care planning, prevention and treatment delirium and delirium-related complications) vs. standard

I1: 74/28

I2: 74/23

I1: 82 ± 7

I2: 82 ± 6

9

I1: 56/102 (54.9%)

I2: 73/97 (75.3%)

0.003

Duration ( P = 0.009):

I1: 5.0 ± 7.1 days

I2: 10.2 ± 13.3 days

I1: 28 ± 17.9

I2: 38 ± 40.6

H ₂ receptor blockers

Kim, 1996 [21]

DSM-III

POD1, discharge

Cardiovascular

Cimetidine vs. ranitidine

I1: 14/39

I2: 17/41

I1: 68 ± 10

I2: 64 ± 11

4

I1: 13/53 (24.5%)

I2: 15/58 (25.9%)

0.872

I1: 8.9 ± 3.9

I2: 8.7 ± 2.9