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November 11, 2013
Delirium in Critically Ill Mechanically Ventilated Patients Enrolled in the
SLEAP Multicenter Randomized Trial
Geeta Mehta MD, FRCPC
And The SLEAP Investigators
For the Canadian Critical Care Trials Group
Disclosures
I have no disclosures
Funding: Canadian Institutes of Health
Research
Background
Delirium is common in critically ill patients
Delirium is associated with worse outcomes
– Prolonged durations of MV, and lengths of stay
Patient and ICU risk factors
Sedation minimization may reduce delirium
All patients managed
with an RN driven
analgesia/sedation protocol
Daily interruption Sedation/analgesia
No daily interruption
randomized
SLEAP - Sedation Lightening and Evaluation of A Protocol
JAMA 2012
Eligibility
Inclusion criteria – 18 years – MV and anticipated need for MV ≥ 48 hours – ICU team has decided to initiate continuous opioid
and/or benzodiazepine infusion(s)
Exclusion criteria – Admission after cardiac arrest – Traumatic Brain Injury – Receiving Neuromuscular blockers – Withdrawal or limitation of life support – Previous enrolment in SLEAP – Enrolment in confounding trial – Lack of informed consent
Primary Outcome
Duration of MV: from intubation to extubation or tracheostomy mask, for 48 hours
Secondary outcomes
Delirium – Intensive Care Delirium Screening Checklist
Both groups…
Nurse-implemented algorithm for management of analgesia and sedation Analgesia: morphine, fentanyl or hydromorphone
Sedation: midazolam or lorazepam
Sedation Scale: SAS or RASS
Ventilator Weaning protocol
Intensive Care Delirium Screening Checklist
Sedation-agitation scale
7 Dangerous Pulling ET, trying to remove catheters, climbing bed agitation rail, striking staff, thrashing
6 Very agitated Not calm, despite verbal reminding; requires physical restraints, biting ET tube
5 Agitated Mildly agitated, attempting to sit up, calms with verbal instructions
4 Calm and cooperative Calm, awakens easily, follows commands
3 Sedated Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands
2 Very sedated Arouses to physical stimuli but does not communicate nor follow commands, may move spontaneously
1 Unarousable Minimal or no response to noxious stimuli, does not communicate nor follow commands
Riker RR et al. Crit Care Med 1999;27:1325
Richmond Agitation Sedation Scale
+4 Combative Overtly combative, violent, immediate danger to staff
+3 Very agitated Pulls or removes tube(s) or catheter(s); aggressive
+2 Agitated Frequent non-purposeful movement, fights ventilator
+1 Restless Anxious but movements not aggressive, vigorous
0 Alert and Calm Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands
-1 Drowsy Not fully alert, but has sustained awakening (eye- opening/eye contact) to voice (≥ 10 seconds)
-2 Light Sedation Briefly awakens with eye contact to voice (< 10 seconds)
-3 Moderate Sedation Movement or eye opening to voice (but no eye contact)
-4 Deep Sedation No response to voice, but movement or eye opening to physical stimulation
-5 Unarousable No response to voice or physical stimulation
Sessler CN et al. AJRCCM 2002;166:1338
Daily interruption group
Bedside nurses interrupted opioid and benzodiazepine infusions daily
Assessed hourly for wakefulness: SAS 4-7 (RASS -1 to +4) and able to perform at least 3 of:
1) eye opening 2) tracking 3) hand squeezing 4) toe moving
If infusions no longer required (patient free of discomfort and agitation, SAS 2-5, or RASS -4 to +1), oral or bolus IV therapy used
If infusions required, resumed at half prior dose(s), titrated to achieve target level of light sedation
Intensive Care Delirium Screening Checklist
Bergeron et al. ICM 2001;27:859
Altered level of consciousness (A-E) If A or B do not complete patient evaluation for the period Inattention Disorientation Hallucination - delusion – psychosis Psychomotor agitation or retardation Inappropriate speech or mood Sleep/wake cycle disturbance Symptom fluctuation TOTAL SCORE (0-8)
1. Altered level of consciousness:
A) No response
B) Need for vigorous stimulation to obtain any response signifies severe alteration in LOC
precluding evaluation
If coma (A) or stupor (B) there is no further evaluation during that period.
C) Drowsiness or requirement of a mild to moderate stimulation for a response implies an
altered level of consciousness and scores 1 point.
D) Wakefulness/sleeping state that is easily aroused - considered normal, scores no point.
E) Hypervigilance is rated as an abnormal level of consciousness and scores 1 point.
2. Inattention: Difficulty in following a conversation or instructions. Easily distracted by
external stimuli. Difficulty in shifting focuses.
3. Disorientation: Any obvious mistake in time, place or person
4. Hallucination, delusion or psychosis: The unequivocal manifestation of hallucination or of
behaviour probably due to hallucination or delusion. Gross impairment in reality testing.
5. Psychomotor agitation or retardation: Hyperactivity requiring additional sedatives or
restraints to control potential danger. Hypo-activity or noticeable psychomotor slowing.
6. Inappropriate speech or mood: Inappropriate, disorganised or incoherent speech.
Inappropriate display of emotion related to events or situation.
7. Sleep/wake cycle disturbance: Sleeping < 4 hrs or waking frequently at night. Sleeping
most of the day.
8. Symptom fluctuation: Fluctuation of any item or symptom over 24 hours
423 Patients
214 PS+DI, 209 PS
3 No Delirium data
420 Assessed
226 (53.8%)
ICDSC ≥ 4 163 (38.8%)
ICDSC<4
146 (34.8%)
ICDSC 1-3
31 always A or B
7.4%
17 (4%)
ICDSC 0
Delirious Non
Delirious
Baseline Characteristics
Variable Ever Delirium
N=226
Never Delirium
N=163
P
value
Age (yrs) 57 (46,68) 60 (50,71)
Female (%) 38.9% 53.4% .005
APACHE II 23 (18,27) 24 (19,29)
SOFA day 1 6 (4,9) 7 (4,9)
Type of admission (%)
Medical
Surgical
Trauma
78.8%
16.8%
4.4%
89.0%
8.6%
2.4%
.03
Baseline Characteristics
Ever Delirium
N=226
Never
Delirium
N=163
P
value
Admission Diagnosis (N)
Bacterial/viral pneumonia
Sepsis
Other respiratory disease
Aspiration pneumonia
COPD
18.6%
19.5%
10.2%
3.5%
2.2%
24.5%
18.4%
10.4%
4.3%
4.9%
Pre-ICU Conditions
Cigarette smoking
Ethanol use
Psychiatric
Neurological
31.5%
34.6%
16.8%
15.0%
16.2%
20.9%
18.4%
19.6%
.002
.02
Outcomes
Kaplan-Meier Curves - Time to Successful Extubation
Patients remaining intubated
0.2
0.4
0.6
0.8
1.0
0 5 10 15 20 25 28
Successful Extubation in First 28 days of study
Time, daysNo. of patients at risk
Delirium
Non-delirium
226
163
177
96
108
41
71
17
51
8
34
5
29
3
Delirium
Non-Delirium
P < 0.0001
0
5
10
15
20
25
Delirium
Neverdelirium
MV ICU LOS Hospital
LOS
Duration of Mechanical Ventilation and
Lengths of Stay
Days
P<.0001
Other outcomes
Ever delirium
N=226
Never delirium
N=163
P
value
Device removal
Gastric tube
ETT
Urinary catheter
C-line or A-line
31 (13.7%)
14 (6.2%)
14 (6.2%)
22 (9.7%)
15 (9.2%)
7 (4.3%)
4 (2.4%)
5 (3.1%)
.17
.41
.08
.01
Head CT or MR, N (%) 41 (18.5%) 19 (11.8%) .07
Lumbar puncture, N (%) 11 (4.9%) 2 (1.2%) .049
Physical restraint, N (%)
Study days, median (IQR)
195 (86.3%)
5 (2,9)
125 (76.7%)
2 (1,6)
.01
<.0001
Tracheostomy, N (%) 78 (34.5%) 25 (15.5%) <.0001
ICU Mortality, N (%) 40 (17.7%) 37 (22.7%) .22
Medication administration
Ever delirium
N=226
Never delirium
N=163
P
value
Midazolam equivalents (mg)
Dose/pt/day
Infusion, days
104 (356)
5 (3,9)
57 (123)
3 (2,6)
<.0001
<.0001
Fentanyl equivalents (mcg)
Dose/pt/day
Infusion, days
1497 (3565)
6 (3,10)
1150 (2234)
3 (2,7)
<.0001
<.0001
Antipsychotic, N (%)
Days
83 (36.7%)
3.1 (6.7)
21 (12.9%)
0.4 (1.2)
<.0001
<.0001
Anti-cholinergic, N (%) 41 (18.1%) 14 (8.6%) .007
SAS and workload
Ever delirium
N=226
Never delirium
N=163
P
value
SAS score, mean
3.41
3.32
.14
RN VAS score, mean
4.2
3.7
<.0001
RT VAS score, mean
3.6
3.7
.46
Coma
Ever delirium
N=226
Never delirium
N=163
P
value
Coma
Patients, N (%)
Days, mean (SD)
Occurred prior to delirium
74 (32.7%)
1.6 (4.7)
38 (51.4%)
37 (22.7%)
0.7 (2.0)
.030
.039
Coma due to sedation
Patients, N (%)
Days, mean (SD)
Occurred prior to delirium
59 (26.1%)
1.2 (4.0)
33 (55.9%)
27 (16.6%)
0.5 (1.7)
.025
.048
Coma = SAS 1 or RASS -5 for 4 or more consecutive hours
Kaplan-Meier Curves - Time to Successful Extubation
Patients remaining intubated
0.0
0.2
0.4
0.6
0.8
1.0
0 5 10 15 20 25 28
Successful Extubation in First 28 days of study
Time, daysNo. of patients at risk
No Delirium, No Coma
Delirium, No Coma
Delirium, Coma
No Delirium, Coma
126
152
74
37
65
106
71
31
20
55
53
21
8
32
39
9
3
21
30
5
2
15
19
3
2
13
16
1
No Delirium, No Coma
Delirium, No Coma
Delirium, Coma
No Delirium, Coma
P < 0.0001
Comparison of PS+DI vs. PS groups
PS+DI
N=214
PS
N=209
Patients with ≥ 1 day delirium, N (%) 113 (53.3) 113 (54.3)
Patient-days with delirium, median (IQR) 1 (0,2) 1 (0,3)
Patients with ≥ 1 day sub-syndromal delirium, N (%) 74 (34.9) 72 (34.6)
Patient-days sub-syndromal delirium, median (IQR) 2 (1,4) 3 (1,5)*
Coma, N (%) 66 (31.0) 71 (34.0)
Patient-days with coma, median (IQR) 0 (0,1) 0 (0,1)
Patients who received ≥ 1 dose AP, N (%) 52 (24.4) 54 (25.8)
Days patients received ≥ 1 dose AP, median (IQR) 0 (0,0) 0 (0,1)
*P=.03
Delirium risk factors Multivariate analysis
• Age
• APACHE II
• Tobacco
• Alcohol (2 or more/day)
• Neurological condition
• Cardiac disease
• Randomization group
• Coma
• Renal Replacement
• Physical restraint
• Total midazolam
• Total fentanyl
• Antipsychotics
Delirium risk factors Multivariate analysis
• Age
• APACHE II
• Tobacco
• Alcohol (2 or more/day)
• Neurological condition
• Cardiac disease
• Randomization group
• Coma
• Renal Replacement
• Physical restraint HR 1.87 95%CI 1.33, 2.63 p=.0003
• Total midazolam HR 0.998 95%CI 0.997, 1.0 p=.049
• Total fentanyl
• Antipsychotics HR 1.67 95%CI 1.01, 2.77 p=.047
Conclusions
53.8% of SLEAP patients had positive delirium screening on 1 or more days
ICDSC positive patients:
Received more benzodiazepines, opioids, anti-psychotics, and anti-cholinergics
Longer durations of MV, ICU, Hospital LOS
More accidental vascular catheter removals
More tracheostomies
More restraint use
Higher nurse workload
Conclusions
No difference in delirium between PS+DI and PS group
Between delirious and non-delirious patients, there was no difference in
Discharge destination
Mortality
Delirium most strongly associated with physical restraint use
SLEAP Steering Committee
Sangeeta Mehta
Lisa Burry
Marilyn Steinberg
Deborah Cook
Maureen Meade
Paul Hebert
Karen Antoni
Dean Fergusson
Investigators
MSH Marilyn Steinberg, Lisa Burry
UHN-TGH Paulina Farias, John Granton, Margaret Herridge
UHN-TWH Paulina Farias, Niall Ferguson
Tufts Medical Center John Devlin, Russ Roberts
St Joseph’s Med Center France Clarke, Ellen McDonald, Deborah Cook
Long Beach Memorial Hyunsoon Park, Maged Tanios
Sunnybrook HSC Nicole Marinoff, Rob Fowler
St Paul’s Hospital Betty-Jean Ashley, Peter Dodek
St Michael’s Hospital Kerri Poretta, Yoon Lee, Orla Smith, Karen Burns
WC Mackenzie HSC Michael Jacka
Hamilton HSC Lori Hand, Maureen Meade
Winnipeg HSC Wendy Janz, Kendiss Olafson
Maisonneuve-Rosemont Johanne Harvey, Yoanna Skrobik
Royal Columbian Steven Reynolds, Sean Keenan
Surrey Memorial Hospital Steven Reynolds, Sean Keenan
Royal Alexandra Patricia Thompson, Jim Kutsogiannis
Data Monitoring Committee
Jesse Hall MD
Scott Epstein MD
Rollin Brant PhD
Ventilator weaning
• Awake
• Cough with suctioning
• PaO2 60, SpO2 90%, FiO2 ≤ 0.4
• PEEP ≤ 10 cm H2O
• RR ≤ 35
• VE ≤ 15 L/min
• No inotropes or vasopressors
• Mean arterial pressure > 60 mmHg
• No myocardial ischemia
Weaning mode: PEEP with PS
Daily screen for trial of unassisted breathing
UBT: T-tube, a tracheostomy tube, or CPAP 5 cmH2O
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