Electronic Supplementary Material:
Effect of Sedation Level on the Prevalence of Delirium when Assessed with CAM-ICU and ICDSC
Matthias Haenggi, Sina Blum*, Ruth Brechbuehl*, Anna Brunello, Stephan M. Jakob, Jukka Takala
Sedation concept:
In our ICU the nurse-implemented sedation protocol mandates sedative boli, and allows continuous sedation
only if more than 6 boli per 4 hours are needed. The use of propofol is encouraged; midazolam is reserved for
hemodynamically unstable patients. Pain medication consists of scheduled intravenous acetaminophen and
additional fentanyl boli as needed. Continuous fentanyl is rarely used.
Delirium and sedation level assessment:
Delirium assessment with CAM-ICU and ICDSC was established in this ICU prior to this study [1], but preceding
study start, all nursing staff, fellows, residents and attending physicians received a 50-minute session on
delirium assessment – a refresher of CAM-ICU, and introduction of ICDSC, including material downloaded from
the Vanderbilt University Medical Center’s webpage www.icudelirium.org. We did not formally test the success
of the introduction of ICDSC and the impact of the refresher training of CAM-ICU.
Presence or absence of delirium was evaluated using CAM-ICU as initially developed and presented by Ely et al.
[2], in a German or French translation, provided at www.icudelirium.org. CAM-ICU considers patients delirious
when an acute onset of altered mental status or its fluctuation is accompanied by inattention and either an
altered level of consciousness or disorganized thinking. CAM-ICU was assessed together with RASS.
Delirium was also assessed by a second scale, the ICDSC, developed by Bergeron et al. [3] in a German
translation [4]. The domains like inattention, disorganized thinking and level of consciousness were evaluated
during sedation stop. The evaluation of other domains required observations during a whole shift (e.g.
psychomotor activity, speech, mood and sleep disturbance or fluctuation of symptoms), therefore additional
information was obtained from the bedside nurse in charge of the patient. The ICDSC considers patients are
delirious when at least four of the above 8 items are deviant.
The level of consciousness was determined with the Richmond Agitation-Sedation Scale (RASS), a scale ranging
from –5 (unarousable) to +4 (combative)[5].
When the sedation stop was initiated, the assessors (clinical team) followed the patient up until he/she had
reached a stable level of RASS (at least -3 allowing delirium assessment) without further changes, for a
maximum of 120 minutes after stopping the drugs. In some instances, sedation stop had to be discontinued
prematurely due to clinical reasons, typically hemodynamic or gas exchange instability, or poor tolerance of
mechanical ventilation or endotracheal tube, and sedation was resumed. If the patient remained comatose
(RASS level -4 to -5), the observation was stopped after 2 hours and the patient was not assessed for delirium
due to coma.
Statistical Details:
Because in clinical practice either CAM-ICU or ICDSC is performed, the analysis were stratified and done once
for CAM-ICU and once for ICDSC. Post-hoc, as a second step, we included in the models the medication each
patient received, and their interaction with the assessment method, to confirm that the differences between
assessment methods are not strongly influenced by these. The interactions were removed from the model if
insignificant (p > 0.05), and probabilities were calculated under the different assessment methods, while
controlling for medication used. The effects of the different medications are reported in the electronic
supplemented material. In addition, the analyses were repeated excluding patients with neurological
admissions.
Differences in incidence was analysed with the z-test (chi-square-test within one category), and applying the
Yates Correction Factor.
Reference List electronic supplementary material
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5.
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J, Dexmedetomidine for Continuous Sedation I, (2009) Dexmedetomidine versus propofol/midazolam
for long-term sedation during mechanical ventilation. Intensive Care Med 35: 282-290 DOI
10.1007/s00134-008-1296-0
Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R,
Hart RP, Dittus R, (2001) Delirium in mechanically ventilated patients: validity and reliability of the
confusion assessment method for the intensive care unit (CAM-ICU). JAMA 286: 2703-2710 DOI
11730446
Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y, (2001) Intensive Care Delirium Screening
Checklist: evaluation of a new screening tool. Intensive Care Med 27: 859-864 DOI 11430542
Radtke FM, Franck M, Oppermann S, Lutz A, Seeling M, Heymann A, Kleinwachter R, Kork F, Skrobik Y,
Spies CD, (2009) [The Intensive Care Delirium Screening Checklist (ICDSC)--translation and validation of
intensive care delirium checklist in accordance with guidelines]. Anasthesiologie, Intensivmedizin,
Notfallmedizin, Schmerztherapie : AINS 44: 80-86 DOI 10.1055/s-0029-1202647
Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK, (2002) The
Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J
Respir Crit Care Med 166: 1338-1344 DOI 10.1164/rccm.2107138
Table 1. Type of sedation prior to scheduled sedation stop. Individual patients could receive more than one
type of sedation during the study – hence the sum of patients receiving each type of sedation exceeds the total
number of patients in the study. The last column shows the proportion of the use of propofol and midazolam
before assessment.
Continuous sedation
Intermittent sedation
No sedation,
intubated
No sedation, not
intubated
Patients n
(% of total 80)
54 (67.5%)
52 (65%)
39 (48.8%)
assessments n
(% of total 467)
180 (38.5%)
153 (32.8%)
101 (21.6%)
number of assessments
per patient during study
2.3 ± 3.1
1.9 ± 2.8
1.3 ± 2.0
18 (22.5%)
33 (7.1%)
0.4 ± 1.1
propofol vs
midazolam (%)
80 vs 20
68 vs 32
Table 2 Prevalence of CAM-ICU/ICDSC positive assessments after exclusion of 32 patients with neurological
admission diagnosis
original
CAM-ICU pos
without
RASS -3 and -2
CAM-ICU pos
without
RASS -3 and -2
“not vigilant”
prevalence
107/257
41.6%
48/257
18.7 %
85/257
33.1 %
Probability of being
classified positive
46.9%
22.4%*
32.9%*
ICDSC pos
original
ICDSC pos
without
RASS -3 and -2
ICDSC pos
without
RASS -3 and -2
“not vigilant”
prevalence
113/253
44.7 %
53/253
20.9 %
89/253
35.2 %
Probability of being
classified positive
43.1%
20.7%*
28.2%*
CAM-ICU pos
*= p-value < 0.001;
Table 3: Admission diagnosis, demographics and type of sedation before sedation stop of the 11 patients who
were CAM-ICU positive only at RASS-2/-3. All patients received intermittent fentanyl as analgesic.
Patient ID
Age (years)
Admission diagnosis
Epilepsia
SAPS II
score
72
Number of
assessments
1
9
43
11
62
pneumonia
52
2
18
52
64
1
29
49
Respiratory failure due to
Guillain-Barré-Syndrome
traumatic brain injury
64
5
36
51
63
63
Sepsis due to endocarditis
pneumonia
50
57
1
2
55
72
71
53
complicated cardiac surgery
traumatic brain injury
77
41
1
9
73
59
48
1
76
83
83
49
respiratory failure following
traumatic brain injury
traumatic brain injury
pneumonia
50
61
1
2
average of
all patients
61 ± 17
40% admission for
neuro/neurotrauma
55 ± 18
5.9 ± 5.1
Type of sedation
1x propofol
continuous
1x midazolam cont.
1x propofol
intermittent
1x propofol cont.
2x propofol cont.
3x propofol interm.
1x propofol cont.
2x midazolam
intermittent
1x propofol interm.
4x propofol cont.
1x propofol interm.
2x fentanyl only
2x none
1x propofol cont.
1x fentanyl only
2x midazolam
intermittent
Table 4: numbers of patients with the different types of delirium, diagnosed according either CAM-ICU or ICDSC
Coma only
CAM-ICU
ICDSC
9
9
Delirium only
at RASS-2/-3
(hypoactive)
11
9
Hypoactive
delirium
Hyperactive
delirium
Mixed
No delirium
20
18
8
8
19
19
13
17
Table 5 ANOVA on ranks (p-values) of length of stay (LOS) in the ICU or in the hospital and probability of
death/logistic regression (p-values) 28-day or 90-day mortality
ICU LOS
Hospital LOS
28-day
mortality
90-day
mortality
Pat ever CAM-ICU positive
vs. never positive
0.15
0.57
0.39
0.45
Pat ever CAM-ICU pos (excluding RASS
-2/-3) vs never positive
0.10
0.38
0.70
0.96
Pat ever CAM-ICU pos (excluding
insufficient vigilance at RASS -2/-3)
vs. never positive
0.05
0.58
0.41
0.54
Pat ever ICDSC pos
vs. never positive
0.01
0.61
0.78
0.92
Pat ever ICDSC pos (excluding RASS 2/-3) vs. never positive
0.01
0.78
1
0.69
Pat ever ICDSC pos (excluding
insufficient vigilance at RASS -2/-3)
vs. never positive
0.00
0.90
0.69
0.88
Admitted for
neuro/neuro
-trauma
yes
no
no
yes
age
SAPS II
60
54
79
62
47
58
27
61
no
no
yes
yes
yes
no
no
yes
yes
no
84
31
74
62
73
62
63
75
25
82
50
69
26
72
32
52
39
58
44
59
no
yes
yes
yes
71
70
67
45
36
64
32
86
yes
no
no
yes
34
78
60
57
65
34
63
86
Table 6: admission data, with details of diagnosis and preexisting illness
Admission diagnosis
Intracerebral hemorrhage
ARDS after post laparotomy
Anaphylaxis
Multiple trauma including traumatic brain injury
(tbi)
Post cardiac surgery
Post cardiac surgery
Tbi
Status epilepticus
Spinal trauma
Pneumonia
Post cardiac surgery
Subarachnoidal hemorrhage
Multiple trauma including tbi
ARDS post lung surgery
Typ B aortic dissection
Guillan Barré Syndrom
Stroke
Liver failure
Tbi
Mediastinitis after epiglotitis
Sepsis post CABG
Infected aortic graft, mycotic aneurysm/stroke
Pre-exixsting
neurologic disorders
no
no
no
no
no
no
no
no
no
no
no
no
no
Focal epilepsia
(treated)
narcolepsia
no
no
Cerebral lymphoma,
HIV
no
no
no
no
Tbi
Typ A aortic dissection
Tbi
Multiple trauma incl. tbi
Urosepsis
Heart failure
Post cardiac surgery
Typ A aortic dissection
Sepsis, susp. meningitis
Endocarditis with cerebral embolies
Intracerebral hemorrhage
Tbi
COPD
Post lapartomie
Tbi
Tbi
Tbi
Sepsis
Post cardiac surgery
Sepsis
Post cardiac surgery
Pneumonia
Post cardiac surgery
acute liver an renal failure
Pneumonia
Post cardiac surgery
Meningitis
Sepsis, suspicion meningitis
Stroke
Intracerebral hemorrhage
Sepsis
Post thoracic surgery
Post cardiac surgery
Sepsis
Post cardiac surgery
Cardiogenic shock
Respiratory failure post cardiac surgery
Subarachnoidal hemorrhage
Post cardiac surgery
Tbi
ARDS/pulmonary hypertension
Hepatorenal Syndrome
Decompensated cor pulmonale post laparotomy
Tbi
Heart failure
Hodgkin Lymphoma, acute coronary syndrome
Heart failure
Drug overdose (mixed) with epilepsia
Multiple trauma incl tbi
Stroke
Pneumonia
no
no
Post intracrebral
hemorrhage
no
no
no
Post transitory
ischemic attack
no
no
no
no
Multiple sclerosis
no
no
no
no
no
no
no
no
no
no
no
no
no
Parkinson’s disease
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Post tbi
no
no
no
no
no
no
Substance abuse with
epilepsia
no
no
no
yes
no
yes
61
65
75
41
70
64
yes
no
no
no
61
67
69
53
27
79
63
54
no
yes
yes
yes
yes
no
no
yes
yes
yes
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
no
no
no
no
no
no
no
yes
no
yes
no
no
no
yes
no
no
no
yes
59
46
70
83
80
75
52
31
20
61
49
59
57
22
78
80
69
45
60
54
79
62
84
31
74
62
73
62
63
75
25
82
71
70
67
45
34
78
60
57
61
57
84
50
49
26
39
57
43
65
23
67
89
44
89
57
54
75
76
77
42
35
27
61
80
75
40
59
36
45
56
50
41
48
101
33
50
52
62
60
53
yes
yes
no
65
75
61
54
57
61
no
no
no
no
Probable dementia
(mini-mental score
28/30)
no
no
Sepsis
Heart failure
Multiple trauma
ARDS
Post cardiac surgery
Acute coronary syndrome
Pneumonia
no
no
no
no
no
67
69
53
59
46
62
79
32
75
17
no
no
70
83
42
71
Table 7: Results of the secondary analysis 1: probabilities of being classified as delirious, mixed effects logistic
regression while controlling for medication given (all p<0.001).
47.0%
CAM-ICU,
after excluding 32
patients with
neurologic
admission diagnosis
46.1%
42.0%
ICDSC,
after excluding 32
patients with
neurologic
admission diagnosis
42.0%
20.1%
20.5%
19.5%
19.2%
29.9%
31.1%
27.2%
25.9%
CAM-ICU
original
without
RASS -3 and -2
without
RASS -3 and -2
“not vigilant”
ICDSC
Table 8: Results of the secondary analysis 2: mixed effects logistic regression including medication as a cofactor. The reported results are the marginal probabilities under baseline conditions, which are the original
assessment method (CAM-ICU and ICDSC, not the “without RASS-2 to -3” and the “without RASS -3 and -2 not
vigilant”) and no medication. Under other conditions the probability would be slightly different. However, the
differences between the probabilities will remain the same since the interaction assess-method/medication is
not significant. The results should be interpreted cautiously because of collinearity problems.
47.0%
43.8%
CAM-ICU,
after excluding 32
patients with
neurologic
admission diagnosis
46.1%
42.8%
42.0%
56.9%
ICDSC,
after excluding 32
patients with
neurologic
admission diagnosis
42.0%
48.9%
37.0%
41.4%
25.4%
25.2%
50.4%
52.7%
44.4%
47.5%
16.7%
16.8%
13.3%
10.7%
99.8%
100.0%
99.5%
100.0%
CAM-ICU
no medication
propofol
intermittent
midazolam
intermittent
propofol
continuous
midazolam
intermittent
other
ICDSC