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Table 1 Incidence of optimal and sub-optimal sedation in included studies

From: The incidence of sub-optimal sedation in the ICU: a systematic review

Study Study design and comparisons made Number Treatment arms (if relevant) Incidence of sub-optimal sedation Incidence of over-sedation Incidence of under-sedation Incidence of optimal sedation Sedation scale/monitoring system used Definition of optimal sedation
Weinert, et al., 2007 [44] Cohort study 274    326 (2.6%) of 12,414 assessments.
111 patients (40%) had ≥ 1 rating of over-sedation. Patients were unarousable/minimally arousable 32% of the time.
1,731 (13.9%) of 12,414 assessments.
211 (76.2%) had ≥ 1 rating of under-sedation.
10,357 (83%) of 12,414 Minnesota Sedation Assessment Tool -- nurse assessment Arousal level 3-5 (of 6-point scale)
Martin, et al., 2006 [30] Cohort study 305 (from 220 ICUs)    42.6% of 49 patients sedated 24-72 hours, 39.5% of 157 patients sedated >72 hours, and 43.9% of 57 patients under weaning had significantly deeper sedation than desired level 5.2% of 157 patients sedated >72 hours and 3.5% of 57 patients under weaning had significantly lower sedation than desired level In patients sedated >72 hours, the desired Ramsay score was 0-4 in 44% of cases -- this was achieved in 28%; in 55% of patients, the desired value was 4-5, which was achieved in 68%; in 1% of patients, the desired score was 6, which was achieved in 6%. Ramsay scale Individual to each patient
Payen, et al., 2007 [43] Cohort study 1,381    258 (57%) of 451 patients on sedation day 2; 169 (48%) of 355 patients on day 4; 109 (41%) of 266 patients on day 6    Multiple: most commonly Ramsay, RASS, Sedation-Agitation scale Over-sedation defined as Ramsay 5-6, RASS -5 or --4, Sedation-Agitation scale 1-2
Sandiumenge, et al., 2000 [36] RCT/observational study of sedative drugs 63 Midazolam 19 (7%) of 266 hours    247 (93%) of 266 hours Modified Ramsay scale Equivalent of Ramsay 5-6 (for deep sedation)
    2% propofol 14 (9%) of 156 hours    142 (91%) of 156 hours   
Carrasco, et al., 1993 [26] RCT (with economic study) of sedative drugs 88 Midazolam 18% of time (hours)    82% of time (hours) Ramsay scale; Glasgow coma scale (modified by Cook and Palma) Ramsay scale 2-5, Glasgow coma scale 8-13
    Propofol 7% of time (hours)    93% of time (hours)   
McCollam, et al., 1999 [23] RCT of sedative drugs 30 Lorazepam 32% of assessments 14% of assessments 18% of assessments 68% of assessments Ramsay scale Ramsay scale 2-4
    Midazolam 21% of assessments 6% of assessments 16% of assessments 79% of assessments   
    Propofol 38% of assessments 7% of assessments 31% of assessments 62% of assessments   
Chinachoti, et al., 2002 [40] RCT of sedative drugs 152 Remifentanil 28% of patients; 17.3% of time (hours) 13% of time (hours) 4% of time (hours) 78% of patients (without midazolam), 83% of time (hours) (maintenance phase) SAS SAS 4 with no or mild pain
    Morphine 27% of patients; 16% of time (hours) 13% of time (hours) 3% of time (hours) 73% of patients (without midazolam), 84% of time (hours) (maintenance phase)   
Harper, et al., 1991 [25] RCT of sedative drugs 37 Alfentanil low, moderate and high doses -- results reported together   4 patients had >10% of time at sedation level 6 3 patients had >10% of time at sedation level 1   Ramsay (assessed hourly) 2-5
Manley, et al., 1997 [46] RCT (and economic study) of sedative drugs 26 Morphine + midazolam 56.8% of time    43.2% of time North Staffordshire ICU (modification of Ramsay/Addenbrooke's scores) 3-4
    Alfentanil + propofol 57.8% of time    42.2% of time   
Millane, 1992 [21] RCT of sedative drugs 24 Isoflurane for 24 hours followed by propofol 3.4%     Ramsay plus subjective nurse assessment 2-3 (plus subjective nurse assessment)
    Propofol for 24 hours followed by isoflurane 3.6%      
Muellejans, et al., 2004 [41] RCT of sedative drugs 152 Remifentanil 11.7% of time (hours)    88.3% of time (hours) SAS 4
    Fentanyl 10.7% of time (hours)    89.3% of time (hours)   
Muellejans, et al., 2006 [47] RCT of sedative drugs 80 Remifentanil -- propofol 41% of time 28% of time 13% of time 59% of time 3 level sedation score specific to study Level 2
    Midazolam -- fentanyl 30% of time 19% of time 11% of time 70% of time   
Chamorro, et al., 1996 [45] RCT of sedative drugs 98 Propofol 332 assessments -- 3% (after first hour)    332 assessments -- 76.5% effective, 20.5% acceptable Study-specific (modified Glasgow coma scale). Patients monitored at 1 and 6 hours and then every 12 hours. 4 = effective, 3 = acceptable
less than 3 = ineffective
    Midazolam 355 assessments -- 7.6%    355 assessments -- 66.2% effective, 26.2% acceptable   
Barr, et al., 2001 [34] RCT of sedative drugs 24 Lorazepam 51% of time 47% of time   49% of time Modified Ramsay 3-4 (5-6 = over-sedation)
    Midazolam 31% of time 22% of time   69% of time   
Finfer, et al., 1999 [33] RCT of sedative drugs 40 Diazepam (intermittent) 9 (64.3%) of 14 patients; 15.0% of time (hours) 2.8% of time (hours) 21.1% of time (hours) 5 (35.7%) of 14 patients;
85.0% of time (hours)
Modified Ramsay 1-4
    Midazolam (continuous) 6 (35.3%) of 17 patients; 40.8% of time (hours) 14.8% of time (hours) 0% of time (hours) 11 (64.7%) of 17 patients;
59.2% of time (hours)
  
Richman, et al., 2006 [37] RCT of sedative drugs 30 Midazolam Mean 9.1 hours/day (SD 4.9)     Modified Ramsay Individual to each patient
    Midazolam and fentanyl Mean 4.2 hours/day (SD 2.4)      
Karabinis, et al., 2004 [39] RCT of sedative drugs 161 Remifentanil 4.4% of time    95.6% of time (median) SAS 1-3
    Fentanyl 1.9% of time    98.1% of time (median)   
    Morphine 1.0% of time    99.0% of time (median)   
Pandharipande, et al., 2007 [48], Pandharipande, et al., 2006 [59] RCT of sedative drugs 106 Dexmedetomidine 20% of patients according to nurse goals; 33% according to physician goals 15% of patients   80% of patients within 1 point of nurse goal; 67% within 1 point of physician goal RASS, confusion-assessment method for the ICU (CAM-ICU) Individual to each patient
    Lorazepam 33% of patients according to nurse goals; 45% according to physician goals 33% of patients   67% within 1 point of nurse goal; 55% within 1 point of physician goal   
Swart, et al., 1999 [50] RCT of sedative drugs 64 Lorazepam 13% of time    87.0% of time (SD 10.5) Addenbrooke's Hospital's ICU sedation scale Individual to each patient
    Midazolam 34% of time    66.2% of time (SD 23.1)   
Carson, et al., 2006 [22] RCT of sedative drugs 132 Intermittent lorazepam 42.8% (ventilator hours) 37.9% (ventilator hours) 15.1% (ventilator hours)   Ramsay 2-3
    Continuous propofol 49.9% (ventilator hours) 38.6% (ventilator hours) 11.5% (ventilator hours)    
Anis, et al., 2002 [31], Hall, et al., 2001 [60] RCT of sedative drugs 156 Propofol 39.8% of time 12.0% of time 11.2% of time 60.2% of time Ramsay Individual to each patient
    Midazolam 56.0% of time 18.4% of time 8.1% of time 44.0% of time   
Park, et al., 2007 [49] RCT of sedative drugs 134 (111 analysed) Analgesia-based sedation 50% of time    50% of time on SIMV (median) Assessor judgement Adequate judged as awake or easily rousable
    Hypnotic-based sedation 81% of time    19% of time on SIMV (median)   
Cigada, et al., 2005 [32] Observational study of sedative drugs 42 Propofol or midazolam with enteral hydroxyzine with or without supplemental lorazepam. IV drugs were tapered after 48 hours. 36.9% of assessments as judged by Ramsay score; 17% by nurse assessment 421 (24.6%) of 1,711 assessments (Ramsay score)
42 (7.3%) of 577 assessments (nurse judgement)
211 (12.3%) of 1,711 assessments (Ramsay score)
56 (9.8%) of 577 assessments (nurse judgement)
1,079 (63.1%) of 1,711 assessments (Ramsay score)
479 (83%) of 577 assessments (nurse judgement)
Ramsay score plus nurse assessment Adequate sedation defined as the achievement of the planned Ramsay score or nurse judgement as adequate
Barrientos-Vega, et al., 2001 [29] Observational study of sedative drugs 51 2% propofol (compared with historical cohort on 1% propofol -- not reported here) 8 (15.6%) of 51 patients judged therapeutic failure on 2% propofol (inadequate level of sedation)     Ramsay score 4-5
MacLaren, et al., 2007 [42] Observational study of sedative drugs 40 Dexmedetomidine as adjunct to lorazepam/midazolam/propofol 35% of patients with dexmedetomidine; 52% without 12 (30%) patients with dexmedetomidine; 9 (23%) without 4 (10%) patients with dexmedetomidine; 12 (30%) without 65% of patients with dexmedetomidine; 48% without SAS 3-4
Shehabi, et al., 2004 [24] Observational study of sedative drugs 20 Dexmedetomidine with supplemental midazolam if required 455 (33%) of 1,381 assessments 97 (7%) of 1,381 assessments were Ramsay level 6 137 (10%) of 1,381 assessments were Ramsay level 1 926 (67%) of 1,381 Ramsay 2-4
Sackey, et al., 2004 [51] RCT of sedation devices 40 Isoflurane using AnaConDa 46% of time; nursing staff estimate 11% of time 44% of time 2% of time 54% of time;
nursing staff estimate 89% of time
Bloomsbury scale - 1 to +1
    IV midazolam 41%; nursing staff estimate 13% of time 37% of time 4% of time 59% of time; nursing staff estimate 87% of time   
Walsh, et al., 2008 [52] Observational study of sedation devices 30 All sedated patients   137 (32.9%) of 416 assessments (Ramsay score 5-6) 5 (1.2%) of 416 assessments (Ramsay score 1)   Entropy Module/Modified Ramsay scale None stated. Refers to guidelines suggesting 2-3 is adequate and heavy/over-sedated is 5-6.
Hernández-Gancedo, et al., 2006 [28] Observational study of sedation scales 50    44% (66 cases) -- Ramsay level 6   25% (38 cases) Ramsay, Observer's Assessment of Alertness and Sedation Ramsay 3-4
Roustan, et al., 2005 [27] Observational study of sedation scales 40 All sedated patients -- treated with midazolam and morphine   93 (61.6%) of 151 records 19 (12.6%) of 151 records   Ramsay, Comfort score, EEG Ramsay 3-4
McMurray, et al., 2004 [38] Observational study of sedation scales 122 Propofol-containing regimens 15.6% of time Mean 5.0% of time (SD 12.7) Mean 10.6% of time (SD 14.5) Mean 84.4% of time (SD 18.0) Modified Ramsay Individual to each patient
Detriche, et al., 1999 [53] Before-after study of introduction of sedation protocol 55 Before    20 (30%) of 67 assessment days   Brussels sedation scale 3-4
    After protocol introduction    9 (12%) of 77 assessment days    
Costa, et al., 1994 [54] RCT of controlled and empirical sedation 40 Controlled 17% of time    83% of time Ramsay, and Glasgow coma scale modified by Cook and Palma  
    Empirical 65% of time    35% of time   
MacLaren, et al., 2000 [35] Before-after comparison of sedation protocol 158 Before    22.4% (experience of anxiety or pain)   Modified Ramsay 4
    After    11.0% (P < 0.001)    
Tallgren, et al., 2006 [3] Before-after comparison of sedation protocol 53 Before reinforcement    Median Ramsay level was 4 during the day and 5 at night, in contrast to the study's stated aim of Ramsay level 2-3 during the day and 3-4 at night    Ramsay
    After reinforcement    Median Ramsay level was 4 during the day and 5 at night, in contrast to the study's stated aim of Ramsay level 2-3 during the day and 3-4 at night    
Samuelson, et al., 2007 [61], Samuelson, et al., 2006 [62] Observational study 250    50% of patients had MAAS 0-2 (although 2 was target for study, 0-1 could be viewed as over-sedated) 0% 39% of patients achieved MAAS 3 in ventilated period MAAS Stated 2-3 but results reported for patients achieving 3
  1. EEG, electroencephalogram; ICU, intensive care unit; IV, intravenous; MAAS, Motor Activity Assessment Scale; RASS, Richmond Agitation-Sedation Scale; RCT, randomised controlled trial; SAS, Riker Sedation-Agitation Scale; SD, standard deviation; SIMV, synchronised intermittent mandatory ventilation.