TABLE 2.
Summary of clinical studies
| Author | N | Study Setting | Type of Surgery | Delirium Criteria | Intervention | Control Group | Intervention Group | Outcomes | ||
|---|---|---|---|---|---|---|---|---|---|---|
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| Total | Delirium | Total | Delirium | |||||||
| Antipsychotics (10) | ||||||||||
| Teslyar et al.(9) United States | 1,491 | Meta-analysis (5 RCTs) | 753 | 204 (27.1%) | 738 | 106 (14.4%) | RR 0.51 (NNT 4 to 12.6) | |||
| Gilmore et al.(10) United States | 1,491 | Meta-analysis (5 RCTs) | 753 | 204 (27.1%) | 738 | 106 (14.4%) | RR 0.42 (NNT 4 to 70) | |||
| Hirota and Kishi(11) United States | 1,689 | Meta-analysis (6 RCTs) | 803 | 221 (27.5%) | 791 | 113 (14.2%) | RR 0.50 (NNT 4 to 7) | |||
| Fukata et al.(12) Japan | 119 | ≥75 years old, randomized open-label prospective trial | Elective digestive NEE-CHAM or orthopedic surgery | Confusion Scale | Haloperidol 2.5 mg IV drip infusion for 3 days (POD 1 to 3) | 60 | 20 (33.3%) | 59 | 25 (42.4%) | No reduction of delirium incidence, duration, or severity even in high risk patients |
| Wang et al.(13) China | 457 | ≥ 65 years old in ICU, RCT double-blind Excluded if use ChEIa or profound dementia | Non-cardiac surgery | CAM-ICU | Haloperidol 0.5 mg IV bolus then infusion 0.1 mg/h for 12 hours + non- pharmacological for all | 228 | 53 (23.2%) | 229 | 35 (15.3%) | Incidence of delirium was significantly reduced (OR 0.574, NNT 12), length of ICU stay, time to onset of delirium, and delirium free days |
| Kalisvaart et al.(14) The Netherlands | 430 | ≥ 70 years old, RCT double-blind Excluded if use ChEI or profound dementia | Acute or elective hip surgery | DSM-IV CAM-ICU | Haloperidol 0.5 mg po tid for 1 to 6 days (admission until POD 3) + non pharmacological for all | 218 | 36 (16.5%) | 212 | 32 (15.1%) | No statistically significant reduction of delirium incidence; but reduction in duration, intensity, and length of stay among delirious patients |
| Kaneko et al.(7) Japan | 78 | RCT non-blinded | Gastro- intestinal surgery | DSM-III-R | Haloperidol 5 mg IV die for 5 days (POD 1 to 5) | 40 | 13 (32.5%) | 38 | 4 (10.5%) | Incidence of delirium was significantly reduced (NNT 4.55) |
| Hakim et al.(15) Egypt | 90 | ≥ 65 years old RCT double-blinded Excluded if MMSE < 25 | On-pump cardiac surgery | ICDSCb | Risperidone 0.5 mg po q12h after extubation in SSDc (until resolution or delirium) | 45 | 17 (34%) | 45 | 7 (13.7%) | Incidence of progression to delirium in SSD patients was significantly reduced (NNT 4.9); no reduction of ICU or hospital length of stays and duration of delirium |
| Prakanrattana and Prapaitrakooi(16) Thailand | 126 | > 40 years old RCT double-blind | Elective cardiac surgery with CPBd | CAM-ICU | Risperidone 1 mg SL once post-operatively in ICU | 63 | 20 (31.7%) | 63 | 7 (11.1%) | Incidence of delirium was significantly reduced (NNT 4.85) |
| Larsen et al.(17) United States | 403 | ≥ 65 years old or <65 with prior history POD RCT double-blind Excluded if dementia |
Elective TKR or THR | DSM-III-R | Olanzapine 5 mg po immediately before and after surgery | 207 | 82 (39.6%) | 196 | 28 (14.3%) | Incidence of delirium was significantly reduced (NNT 4); however duration and severity of delirium were significantly increased |
| Cholinesterase Inhibitors (5) | ||||||||||
| Marcantonio et al.(20) United States | 16 | ≥70 years old RCT double-blind Excluded if use ChEI or profound dementia |
Surgical repair hip fracture | CAM | Donepezil 5 mg po die for 30 days (1st dose 24h pre-op) | 9 | 9/14e (64%) | 7 | 7/11 (64%) | No statistically significant reduction of delirium incidence over 6-week period |
| Sampson et al.(19) United Kingdom | 33 | RCT double-blind Excluded if MMSE ≤ 26 |
Elective THR | DSIf | Donepezil 5 mg po die after surgery for 4 days (POD 0 to 3) | 14 | 5 (35.7%) | 19 | 2 (9.5%) | No statistically significant reduction of delirium incidence |
| Liptzin et al.(21) United States | 80g | ≥50 years old RCT double-blind Excluded if use of donepezil |
Elective THR or TKR | DSM-IV | Donepezil 5 mg po die total 28 days (14 days pre-op and post-op) | 41 | 7 (17.1%) | 39 | 8 (20.5%) | No reduction of delirium incidence |
| Zaslavsky et al.(22) United States | 28 | ≥ 65 years old RCT double-blind | Elective major surgery Patients at risk |
CAM-ICU | Rivastigmine patch 5 cm2 before surgery for 24h | 17 | 4 (23%) | 11 | 2 (18%) | No statistically significant reduction of delirium incidence Study halted prematurely |
| Gamberini et al.(23) Switzerland | 113 | ≥ 65 years old RCT double-blind surgery with CPB Excluded if use ChEI or MMSE < 15 |
Elective cardiac | CAM | Rivastigmine 1.5 mg po tid evening pre-op until POD 6 (total 33 mg) | 57 | 17 (29.8%) | 56 | 18 (32.1%) | No reduction of delirium incidence |
| Statins (3) | ||||||||||
| Mariscalco et al.(27) Italy | 3,154 | Observational cohort study | CABG with CPB | CAM-ICU | Pre-operative statins at admission and day before operation | 1577 | 36 (2.3%) | 1577 | 53 (3.4%) | No reduction of delirium incidence |
| Katznelson et al.(28) Canada | 1,059 | Prospective observational study | Cardiac surgery with CPB | CAM-ICU | Pre-operative statins use | 383 | 49 (12.8%) | 676 | 73 (10.8%) | Incidence of delirium was significantly reduced, particularly ≥ 60 years old |
| Redelmeier et al.(29) Canada | 284,158 | ≥ 65 years old Retrospective cohort study |
Elective surgery | ICD | Pre-operative statins use | 264,657 | N/A (1.1%) | 19,501 | N/A (1.4%) | Incidence of delirium was significantly increased (OR 1.28) |
| Melatonin (4) | ||||||||||
| de Jonghe et al.(41) The Netherlands | 372 | ≥ 65 years old RCT double-blind | Acute hip fracture surgery | DSM-IV | Melatonin 3 mg po hs (at admission total 5 evenings) | 192 | 49 (25.5%) | 186 | 55 (29.6%) | No reduction of delirium incidence, duration, severity or functional outcome |
| Robinson et al.(42) United States | 301 | ≥ 60 year-old RCT double-blind | Elective major surgery with ICU stay | CAM-ICU | Tryptophan 1 g po tid postop (total 9 doses or until ICU d/c) | 149 | 55 (36.9%) | 152 | 61 (40.1%) | No reduction of delirium incidence |
| Yamaguchi et al.(43) Japan | 42 | ≥ 70 years old RCT double-blind | Elective TKR | ICDSC | Ramelteon 8 mg po qhs (total 4 doses) | 21 | 0 (0%) | 21 | 2 (9.5%) | No statistically significant reduction of delirium incidence NOTE: Only abstract available |
| Sultan(40) Egypt | 203 | ≥ 65 years old RCT double-blind Excluded if dementia |
Elective hip arthroplasty | AMTh | Melatonin 5 mg po x 2 pre-op | 49 | 16 (32.7%) | 53 | 5 (9.4%) | Incidence of delirium was significantly reduced |
| Others (3) | ||||||||||
| Mardani and Bigdelian(31) Iran | 93 | ≤ 80 years old RCT | Elective CABG | MMSE DSM-IV | Dexamethasone 8 mg IV pre-op and q8h until POD 3 | 50 | 19 (38.0%) | 43 | 7 (16.3%) | Incidence of delirium was significantly reduced for POD1, ICU and hospital length of stay |
| Leung et al.(36) United States | 21 | ≥ 45 years old RCT double-blind | Spinal surgery | CAM | Gabapentin 900 mg po die pre-op until POD 3 | 12 | 5 (41.7%) | 9 | 0 (0%) | Incidence of delirium was significantly reduced |
| Aizawa et al.(37) Japan | 40 | >70 years old RCT non-double-blind Excluded if ≥ 86 years old or psychiatric disorder |
Gastric or colorectal cancer resection | DSM-IV | DFP (Diazepam IM, Flunitrazepam IV, Pethidine IV) pre-op until POD 3 | 20 | 7 (35.0%) | 20 | 1 (5.0%) | Incidence of delirium was significantly reduced |
a
Cholinesterase inhibitor.
b
Intensive Care Delirium Screening Checklist.
c
Subsyndromal delirium.
d
Cardiopulmonary bypass.
e
More than one interview per subject during hospitalization.
f
Delirium Symptom Interview.
g
58 patients actually completed the study with 28 days of Donepezil (most stopped after randomization).
h
Abbreviated Mental Status.