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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.