. Author manuscript; available in PMC: 2017 Feb 1.

Published in final edited form as: J Intensive Care Med. 2014 Oct 27;31(2):127–141. doi: 10.1177/0885066614553925

Table 3. Summary of Studies of Multifaceted Care Approaches with the Reduction of Delirium in ICU Patients as a Primary or Secondary Outcome.

Authors (year)	Study Type	N	Intervention	Delirium	Coma/Ventilator ICU/Hospital Days	Sedative/Analgesia Use	Mortality
Balas et al. (2013)¹⁶	CCT	196	Standard of Care -No policies in the ICU regarding awakening and breathing trials or delirium monitoring/management -Patients not routinely assisted out of bed Intervention ABCDE bundle applied to every ICU patient on a daily basis ABCDE elements include: -Awakening trial (SAT) -Breathing trial (SBT) -Coordination of SAT/SBT -Delirium monitoring with CAM-ICU -Early exercise/mobility	Incidence of delirium I: 73 (49%) C: 91 (2%); p=0.02 Duration of delirium I: 2 days (IQR: 1-4) C: 3 days (IQR: 1-6); p=0.52	Coma days I: 2 (IQR: 1-5) C: 2 (IQR: 1-4); p=0.35 Ventilator-free days I: 24 (IQR:7-26) C: 21 (IQR: 0-25); p=0.04 ICU LOS (days) I: 4 (IQR: 3-5) C: 5 (IQR: 3-8); p=0.21 Hospital LOS (days) I: 11 (IQR:9-13) C: 13 (IQR: 9-15); p=0.99	Patients receiving benzodiazepine I: 77 (51%) C: 91 (62%); p=0.06 Patients receiving propofol I: 31 (21%) C: 25 (17%); p=0.44 Patients receiving opiates I: 134 (89%) C: 124 (85%); p=0.26	Hospital mortality I: 17 (11%) C: 29 (20%); p=0.09 ICU mortality I: 9.3% C: 16.4%; p=0.07
Colombo et al. (2012)¹⁸	CCT	314	Standard of Care -Daily sedation interruption-Daily spontaneous breathing trial (SBT) -Delirium assessment with CAM-ICU (2× daily) Intervention Standard of care plus: -Re-orientation strategy -Environmental, acoustic, and visual stimulation	Incidence of delirium I: 22.0% C: 35.5%; p=0.020 Predictors of delirium Reorientation strategy (HR: 0.504; 95% CI:0.313-0.890; p=0.034) Age (HR 1.034; 95% CI: 1.013-1.056; p=0.001) Sedation with midazolam plus opiate (HR: 2.145; 95% CI 2.247-4.032; p=0.018)	Not Reported	Not compared between intervention and control groups	In-hospital mortality in patients with delirium I: 4.5% C: 6.9%; p=0.907
Girard et al. (2008)²³	RCT	336	Standard of Care -Daily spontaneous breathing trial (SBT) Intervention Standard of care plus -Daily spontaneous awakening trial (SAT)	Incidence of delirium I: 124 (74%) C: 119 (71%); p=0.66 Duration of delirium I: 2 days (IQR: 0-5) C: 2 days (IQR: 0-6); p=0.50	Coma days I: 2 (IQR: 0-4) C: 3 (IQR: 1-7); p=0.002 Ventilator free days I: 14.7 (0.9) C: 11.6 (0.9); p=0.02 ICU LOS (days) I: 9.1 (IQR: 5.1-17.8) C: 12.9 (IQR: 6.0-24.2); p=.01 Hospital LOS (days) I: 14.9 (IQR: 8.9-26.8) C: 19.2 (IQR: 10.3->28); p=0.04	Patients receiving benzodiazepine I: 120 (72%) C: 111 (66%); p=0.25 Patients receiving propofol I: 117 (70%) C: 115 (69%); p=0.88 Patients receiving opiates I: 130 (78%) C: 128 (76%); p=0.87	28-day mortality I: 47 (28%) C: 58 (35%); p=0.21 1-year mortality I: 74 (44%) C: 97 (58%) (HR: 0.68: 95% CI:0.50-0.92; p=0.01)
Hager et al. (2013)¹⁹	CCT	202	Standard of Care -Sedation protocol utilizing goal-directed sedation Intervention: -Sedation protocol utilizing RASS -Delirium assessment with CAM-ICU (2× daily)	Median proportion of days per patient with delirium I: 38% (IQR: 0-60) C: 20% (IQR: 0-40); p=0.010 Days awake and not delirious (median % ICU days per patient) I: 19% (IQR: 0-50) C: 0% (IQR: 0-18); p<0.001	Coma days (median % ICU days per patient) I: 23% (IQR: 0-50) C 65% (IQR: 27-100); p<0.001	ICU days per patient with benzodiazepine use I: 22% (IQR: 0-50) C: 70% (IQR: 46-94); p<0.001 ICU days per patient with narcotic use I: 33% (IQR: 10-65) C: 74% (IQR: 50-100); p<0.001	Not Reported
Mehta et al. (2012)¹⁷	RCT	423	Standard of Care -Continuous opioid and/or benzodiazepine infusions -Protocolized sedation Intervention Standard of care plus: -Daily sedation interruption	Incidence of delirium I: 113 (53.3%) C: 113(54.1%); (RR 0.98, 95% CI, 0.82-1.17; p=0.83)	Days on ventilator I: 7 (IQR: 4-13) C: 7 (IQR:3-12); (HR 1.08, 95% CI 0.86-1.35, p=0.52) ICU LOS (days) I: 10 (IQR:5,17) C:10 (IQR:6,20); p=.36 Hospital LOS (days) I: 20 (IQR: 10,36) C: 20 (IQR:10,48); p=.42	Total benzodiazepine dose per patient per day I: 102 mg (326) C: 82 mg (287); p=0.04 Total opiate dose per patient per day I: 550 μg (IQR: 50-1850)	ICU mortality I: 50 (23.4%) C: 52 (24.9%); (RR: 0.94; 95% CI:0.67-1.32; p=.72) Hospital mortality I: 63 (29.6%) C: 63 (30.1%); (RR: 0.98; 95% CI:0.73-1.31; p=.89)
Needham et al. (2010)²⁰	CCT	57	Standard of Care -Repositioning patient in bed every 2 hours -Use of pain & sedation scales -Nurse-titrated sedation protocol -Daily reduction in sedation infusions Intervention -Standardized ICU orders with default activity level = “as tolerated” -Sedation practice changed from continuous infusion to “as needed” bolus doses -Guidelines for PT, OT, & physical medicine and rehabilitation consultation -PT, OT & rehabilitation assistant on staff -Consultations to neurologists for patients with severe or prolonged muscle weakness	ICU Days Alert w/o Delirium I: 243 (53%) C: 61 (21%); p=0.003 ICU Days Alert with Delirium I: 125 (28%) C: 107 (36%)	ICU LOS (days) I: 4.9 (mean) C: 7.0; p=.020 Hospital LOS I: 14.1 (mean) C: 17.2; p=.030	Patients receiving benzodiazepine I: 26 (96%) C: 22 (73%); p=0.030 ICU days with benzodiazepine use I: 150 (50%) C: 118 (26%); p=0.002 Patients receiving narcotics I: 26 (96%) C: 23 (77%); p=0.050 ICU days with narcotic use I: 188 (62%) C: 299 (66%); p=0.650	In-hospital mortality (all-ICU, not limited to patients meeting study inclusion criteria) I: 21% C: 23%; p=.550
Schweickert et al. (2009)²¹	RCT	104	Standard of Care -Daily interruption of sedation -Goal-directed sedation guided by RASS -PT and OT as ordered by physician Intervention -Daily interruption of sedation -Goal-directed sedation guided by RASS -Early exercise and mobilization	Hospital days with delirium I: 28% (26) C: 41% (27); p=0.01 Duration of hospital delirium I: 2.0 days, (IQR: 0.0-6.0) C: 4.0 days, (IQR: 2.0-8.0); p=0.02	Coma days I: 0.0 (IQR: 0.0-0.2) C: 1.0 (IQR: 0.0-3.0); p=0.12 Days on ventilator I: 3.4 (IQR 2.3-7.3) C: 6.1 (IQR 4.0-9.6); p=0.02 ICU LOS (days) I: 5.9 (IQR 4.5-13.2) C: 7.9 days (IQR 6.1-12.9); p=0.08 Hospital LOS (days) I: 13.5 (IQR 8.0-23.1) C: 12.9 (IQR 8.9-19.8); p=0.93	Patients receiving benzodiazepine I: 39 (80%) C: 48 (87%); p=0.43 Patients receiving propofol I: 48 (98%) C: 53 (96%); p=1.0 Patients receiving opiates I: 48 (98%) C: 54 (98%); p=1.0	Hospital mortality I: 9 (18%) C: 14 (25%); p=0.53
Skrobik et al. (2010)²⁴	CCT	1214	Standard of Care -Evaluation for pain, sedation, and delirium (≥ 1 × per 8-hour shift -ICU Delirium Screening Checklist Intervention Standard of Care plus: -Management protocol for analgesia, sedation, and delirium with standardized prescription sheets -Reorientation treatments (music therapy, reassurance)	Incidence of delirium I: 34.2% C: 34.7%; p=0.9 Incidence of subsyndromal delirium I: 24.6% C: 33.0%; p=0.0009	Rate of iatrogenic coma I: 8.7% C: 20.5%; p<0.0001 Days on ventilator I: 5.93 (6.59) C: 7.51 (9.78); p=0.01 ICU LOS (days) I: 5.35 (6.26) C: 6.32 (8.16); p=0.009 Hospital LOS (days) I: 27.1 (29.9) C: 55.0 (97.8); p<0.0001	No benzodiazepine I: 47.4% C: 42.1%; p=0.07 No propofol I: 77.7% C: 69.9%; p=0.003 No opioid I: 36.9% C: 28.7%; p=0.003	30-day mortality risk I: 22.9% C: 29.4%; p=0.009

I = Intervention

C = Control

LOS = Length of stay

Data are reported as mean (SD), median (IQR), or n (%).