delirium detection in intensive care patients willemijn van der kooi department of intensive care...
TRANSCRIPT
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Delirium detection in Intensive Care patients
Willemijn van der KooiDepartment of Intensive Care MedicineUniversity Medical Center Utrecht, The Netherlands
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• Orion Pharma: contributed to printing costs of my thesis
• NPK design: contributed to printing costs of my thesis
Disclosures
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Delirium prevalence:•50%-80% for ICU patients•10-15% for cardiac surgery patients
ICU delirium is associated with:•Long term cognitive impairment•Increased hospital and ICU length of stay•Increased mortality
Introduction
* Actor
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Delirium often (71%) missed by ICU physicians1
• questionnaires developed for screening
Daily practice• Sensitivity of questionnaire with best performance
(Cam-ICU):–47% in ICU patients2
–28% in post-operative patients3
• Cognitive screening may not fit well in the culture of the ICU
Introduction
1 Van Eijk et al. Crit Care Med 2009;37:1881-52 Van Eijk et al. Am J Respir Crit Care Med 2011;184:340-43 Neufeld et al. Br J Anaesth 2013;111:612-8
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New approach: delirium detection using physiological alterations
Introduction
Ultimate goal:•2 sensors coupled to a monitor•Monitor shows on a scale the chance of having delirium
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Three physiological parameters studied:•Temperature variability•Eye movements•Brain activity (EEG)
Future perspective
Content
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Temperature variability during delirium in ICU patients
Van der kooi et al. PLoS One. 2013; 8:e78923
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Delirium: manifestation of encephalopathy •In delirium tremens, Wernicke encephalopathy and schizophrenia: temperature regulation is disturbed•Does delirium affect thermoregulation?
Introduction
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To investigate whether:
•ICU delirium is related to absolute body temperature
•ICU delirium is related to temperature variability
Aim of the study
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• Subjects from 3 previous delirium studies• Daily delirium assessments by research-
nurse/physician
Temperature: measured per minute 24/7
Methods
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Inclusion: •Patients with delirious + non-delirious days during ICU admission of >24 hrs
Exclusion criteria: • Disturbed body temperature regulation
(treatment/diagnoses)• Neurological/neurosurgical disease• Days with sepsis, coma or death were excluded
from analysis
*All patients received paracetamol 1000 mg 4 times daily
Methods
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Methods
day 1 day 2 day 335
36
37
38te
mpe
ratu
re ( C
)
day 1 day 2 day 30
0.5
1
1.5
2
tem
p ac
c.(
C/m
in2 )
day 1 day 2 day 30.0
0.05
0.1
0.15
0.2
0.25
mea
n te
mp
acc.
(C
/min
2 )
A
B
C
Coma No Delirium Delirium
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Linear Mixed models: •Univariable (unadjusted) •Multivariable (adjusted for confounders RASS and SOFA)
Outcome: •body temperature [°C]•temperature variability (absolute second derivative) [°C/min2]
Methods
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Results
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Results
Patient characteristics
Age: mean (SD) 68 (14)
Gender: number of males (%) 15 (63%)
Admission type: number (%)
-internal medicine 3 (12%)
-surgery 12 (50%)
-cardiothoracic surgery 9 (38%)
Delirium type: number (%)
-Hypoactive 6 (25%)
-Hyperactive 0 (0%)
-Mixed type 18 (75%)
Number of analyzed days: median (IQR)
-Delirium 2.0 (1.0)
-Non-delirium 1.0 (1.8)
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Body Temperature:
Results
Model Variable Effect estimate 95% Confidence interval p-value
Unadjusted
Delirium [yes] -0.03 -0.17; 0.10 0.61
Adjusted
Delirium [yes] -0.03 -0.17; 0.10 0.63
Rass 0.01 -0.09; 0.10 0.90
Sofa 0.001 -0.04; 0.04 0.95
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Temperature Variability:
Results
Model Variable Effect estimate 95% Confidence interval p-value
Unadjusted
Delirium [yes] 0.005 0.003; 0.008 <0.001
Adjusted
Delirium [yes] 0.005 0.002; 0.008 <0.001
Rass -0.001 -0.003; 0.001 0.20
Sofa -0.0001 -0.001; 0.001 0.71
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Strengths:
•Delirium diagnoses prospectively
•Within subjects comparisons
•Easy method temperature variability
Limitations
•Possible effect of medication
•Natural circadian rhythm bias
Discussion
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Temperature variability: increased during delirium in ICU patients • encephalopathy that underlies delirium
Future studies: •Monitoring temperature variability in total ICU population •Combine with EEG for objective tool to detect delirium
Discussion
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Delirium detection based on monitoring of blinks and eye movements
Van der kooi et al. Am J Geriatr Psychiatry. 2014
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Delirium associated with change in motor level activity•Actigraphy not practical•Eye movements less affected by muscle weakness, restraints, pain
Introduction
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Goal
Determine whether eye blinks and eye movements differ in patients with delirium compared to patients without delirium.
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Methods
Population: post-cardiac surgery patientsReference: psychiatrist, geriatrist, neurologist using DSM
4 criteria
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Methods
Standard 21 electrode EEG recording (30 minutes) with periods of eyes open and closed
First artifact free minute selected with eyes closed and open
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Methods: Eye movements
Eye movements compared between delirium and non-delirium
Number (per min) and duration (sec) of:•Blinks
•Vertical eye movements
•Horizontal eye movements
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Results: study population
Delirious patients (n=28)
Non-delirious patients (n=28)
p-value
Age, mean (SD) 76 (5.6) 74 (8.6) 0.16
Gender: male, n (%) 16 (57%) 16 (57%) 1
Apache IV score, median (IQR) 58 (45-65) 43 (35-51) <0.01
Charlson comorbidity index,
median (IQR)
2 (1-3) 1 (0-1) 0.02
Haloperidol use past 24 hours
n (%)
17 (61%) 2 (7%) <0.01
Postsurgical day of EEG,
median (IQR)
3 (2-5) 3 (2-4) 0.78
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Results: eye movements
Variable DeliriumMedian (IQR)
Non-deliriumMedian (IQR)
p-value
Number of Vertical eye movements
(min-1)
1 (0-13) 15 (2-54) 0.01
Number of Blinks (min-1) 12 (5-18) 18 (8-25) 0.02
Duration of Blinks (s) 0.50 (0.36-
0.96)
0.34 (0.23-
0.53)
<0.01
Eyes Open
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Results: eye movements
Variable DeliriumMedian (IQR)
Non-deliriumMedian (IQR)
p-value
Duration of Horizontal eye
movements (s)
0.41 (0.15-
0.75)
0.08 (0.06-
0.22)
<0.01
Eyes Closed
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Results: Eye movements haloperidol
Eyes Variable Delirium with haloperidolMedian (IQR)
Delirium without haloperidol Median (IQR)
p-value
Open Number of vertical eye
movements
2 (0-17) 0 (0-17) 0.69
Open Number of blinks
12 (4-19) 12 (6-17) 0.87
Open Duration of blinks (s) 0.49 (0.39-1.01) 0.52 (0.34-0.93) 0.81
Close
d
Duration of horizontal of
eye movements (s)
0.59 (0.23-1.40) 0.27 (0.13-0.69) 0.19
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Conclusion
Especially blinks are affected in delirious patients
Strengths: •non-invasive •Only 1 minute of data necessary
Limitations:•22 electrodes needed for eye movement measurement, except for blinks• Difference in Apache and Charlson Comorbidity score
Future studies: •Detection of eye movements in general population of ICU patients•Determining whether eye movements can detect delirium at early stage
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Delirium detection using EEG: what and how to measure?
Van der kooi et al. Chest. 2014
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Delirium characterized by EEG abnormalities•EEG not practical
Introduction
Without Delirium With Delirium
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Goal
Determine the electrode derivation and EEG characteristic that have the best capability of discriminating delirium from non-delirium
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Methods
Standard 21 electrode EEG recording (30 minutes) with periods of eyes open and closed
First artifact free minute selected with eyes closed
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Methods: EEG
Eyes closed= 210 different derivations
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Methods: EEG
For every derivation 6 parameters: 1
Relative delta power (0.5-4 Hz), Relative theta power (4-8 Hz),Relative
alpha power (8-13 Hz), Relative beta power (13-20 Hz), Peak frequency, Slow-
fast ratio
1van der Kooi, et al. J Neuropsychiatry Clin Neurosci 2012; 24: 472-477.
Ruwe EEG
δ 0-4 Hz
θ 4-8 Hz
α 8-13 Hz
β 13-20 Hz
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Methods: EEG
210 derivations x 6 parameters = 1260 combinations
All 1260 combinations • Compared between delirium and non-delirium (Mann-whitney U)
• P-values ranked
• smallest p-value is optimal combination (Bonferoni correction )
1van der Kooi, et al. J Neuropsychiatry Clin Neurosci 2012; 24: 472-477.
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Results: EEG
Eyes closedRank
p-value* Deriviation
Parameter
1 1.8e-12 F8-Pz Relative δ2 3.7e-12 F8-P3 Relative δ3 1.1e-11 F8-O2 Relative δ4 1.5e-11 Fp2-O1 Relative δ5 1.7e-11 F8-F4 Relative δ6 2.2e-11 F8-O1 Relative δ7 2.4e-11 F8-Cz Relative δ8 2.4e-11 F8-C3 Relative δ9 2.9e-11 Fp2-Pz Relative δ10 3.0e-11 Cz-O1 Relative δ
*p< 4.0*10-5 is significant
Delirium Non-delirium
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Rel. d
elta
pow
er
F8-Pz
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Results: EEG
Most optimal
electrode
locations, based
on first 4
rankings.
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Conclusion
EEG easily detects delirium from non-delirium using •2 electrodes in frontal-parietal derivation and relative delta power
Strengths: new approach, non-invasive, only 2 electrodes and 1 minute data necessary
Future studies: •Validation study in unselected population of postoperative- and critically ill patients•Determine whether it recognizes delirium at an early stage
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Future Directions
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Overall Conclusion
EEG most promising method for delirium detection.
Project started: Development of delirium monitor
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Product development
Product and algorithm
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Validation study
Goal: To determine sensitivity, specificity and predictive values of the delirium monitor when compared to reference standard (specialized geriatric nurse) in elderly postoperative patients (n=154).
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Usability study
• Practical?• Easy to Use?• Opinion of nurses of different medical departments
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Extra slides
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Results: EEG eyes open
Ogen OpenRang
p-waarde*
Afleiding
Parameter
1 2.0e-07 P7-P4 Relative alpha2 4.2e-07 P3-P4 Relative alpha3 1.6e-06 P7-O1 Relative delta4 3.2e-06 P7-O1 Relative alpha5 3.5e-06 P3-P4 Slow Fast ratio6 4.0e-06 P4-O1 Relative alpha7 6.1e-06 P7-P8 Relative alpha8 7.9e-06 P7-P4 Slow Fast ratio9 9.4e-06 P3-P8 Relative alpha10 1.1e-05 P7-O2 Relative alpha
*p< 5.6*10-4 is significant
Delirium met/zonder haloperidol geen
verschil (p=0.37)
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0.55
D NDre
l. al
pha
powe
r
0.1
0.2
0.3
0.4
0.5
0.6
D ND
rel.
alph
a po
wer
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
D ND
rel.
delta
pow
er
1: P7-P4 2: P3-P4 3: P7-O1
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Results: Eye movements eyes openEyes
Variable DeliriumMedian (IQR)
Non-deliriumMedian (IQR)
p-value
AUC (95% CI)
Ope
n
Number of eye
movements
Horizontal
6 (0-51)
n=23
26 (0-55)
n=28
0.54 0.55 (0.39-
0.71)
Vertical
1 (0-13)
n=23
15 (2-54)
n=28
0.01 0.70 (0.55-
0.85)
Blinks
12 (5-18)
n=23
18 (8-25)
n=27
0.02 0.65 (0.50-
0.80)
Ope
n
Duration of eye
movements (s)
Horizontal 0.24 (0.10-
0.56)
n=14
0.14 (0.04-
0.27)
n=17
0.14 0.66 (0.47-
0.85)
Vertical 0.14 (0.06-
0.49)
n=10
0.07 (0.04-
0.60)
n=18
0.46 0.59 (0.37-
0.81)
Blinks 0.50 (0.36-
0.96)
n=20
0.34 (0.23-
0.53)
n=27
<0.01 0.74 (0.59-
0.88)
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Results: Eye movements eyes closedEyes Variable Delirium
Median (IQR)
Non-deliriumMedian (IQR)
p-value
AUC (95% CI)
Closed Number of eye
movements
Horizontal
0 (0-42)
n=27
0 (0-51)
n=27
0.37 0.57 (0.41-
0.72)
Vertical
5 (0-47)
n=27
10 (0-52)
n=27
0.40 0.56 (0.41-
0.72)
Closed Duration of eye
movements (s)
Horizontal 0.41 (0.15-
0.75)
n=12
0.08 (0.06-
0.22)
n=13
<0.01 0.81 (0.64-
0.99)
Vertical 0.15 (0.07-
0.29)
n=15
0.07 (0.03-
0.27)
n=17
0.19 0.64 (0.44-
0.84)
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Results: Eye movements haloperidolEyes Variable Delirium with
haloperidolMedian (IQR)
Delirium without haloperidol Median (IQR)
p-value
Number of eye
movements
Open Vertical 2 (0-17)
n=14
0 (0-17)
n=9
0.69
Open Blinks
12 (4-19)
n=14
12 (6-17)
n=9
0.87
Duration of eye
movements (s)
Open Blinks 0.49 (0.39-1.01)
n=14
0.52 (0.34-0.93)
n=9
0.81
Close
d
Horizontal 0.59 (0.23-1.40)
n=6
0.27 (0.13-0.69)
n=6
0.19
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Stap1 Van onderzoek naar klinische prakti
• Ontwikkeling van delirium monitor– Product– Algoritme
• Validatie studie• Gebruiksvriendelijkheids-
studie
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Validatie studie
Doel:
Het bepalen van de sensitiviteit, specificiteit en voorspellende waarden van de delirium monitor in vergelijking met de referentie standaard in oudere postoperatieve patiënten (n=154).
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Validatie studie
Inclusie:•≥ 70 jaar•Opname voor grote operatie (min. 2 opname dagen ZH na operatie)•Preoperatieve verhoogde kwetsbaarheid en/of verhoogd risico op delirium
Exclusie:•Geen communicatie mogelijk•Neurologische chirurgische ingreep•Eerdere deelname studie•Patient in isolatie vanwege resistente bacterie
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Validatie studie - Studie verloop
OperatieT0 T1 T2 T3
= Delirium monitor
= Referentie standaard
= POS Geriatrische screening
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Validatie studie
Delirium monitor•4 elektrodes•5 minuten EEG meting OD•Relatieve δ power
Referentie standaard onderzoeker/vpk•DRS-R-98 Ernst van delirium•VAS (0-10) Kans dat patiënt delirant is•Classificatie Deliriant/Mogelijk delirant/Niet delirant
(Op basis van DSM-V criteria)
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Validatie studie - Analyses
• 1e artefact vrije minute relatieve δ power• ROC curve relatieve δ power vs. classificatie
van referentie standaard
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Validatie studie - Secundaire doelen
1) Schaal voor ernst van delirium (relatieve δ vs. DRS-R-98)
2) Vroegtijdig herkennen van delirium?
0 1 2 4 5 6 7 8 9 103
OperatieT0 T1 T2 T3
= Delirium monitor
= Referentie standaard
= Geriatrische screening
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Stap2 Van onderzoek naar klinische praktijk
• Gebruiksvriendelijkheidsonderzoek– Handig product?– Ervaring verpleegkundige
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Stap3 Van onderzoek naar klinische praktijk
• Delirium monitor bredere doelgroep– Dementie– Neurotrauma– IC: Effect sedatie op EEG
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Samenvatting
1) EEG in delirium studie = het idee– Relatieve δ power– Frontaal- Pariëtaal
2) Ontwikkeling prototype3) Validatiestudie 4) Gebruiksvriendelijkheidsstudie5) Hoe krijgen we het naar de IC
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Delirium monitor project
UMCU - IC•Arjen Slooter•Willemijn van der Kooi•Tianne Numan•Annemieke Hoekman
Pontes Medical•Rutger van Merkerk
NPK design•Tessa Souhoka•Marlies van Dullemen•Jos Oberdorf
Medische Techniek•Leonard van Schelven•Rene van de Vosse•Bert Westra•Maurice Konings
Geriatrie•Marielle Emmelot-Vonk•Jolanda Peijster- de Waal•Marcel Weterman
KNF•Geert-Jan Huiskamp•Frans Leijten