delirium in critically ill patients bogota043009
TRANSCRIPT
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Acute Brain Dysfunction in the Critically Ill Patient:
Data from recent delirium studies
Pratik Pandharipande, MD, MSCIAnesthesiology/ Critical Care
Vanderbilt University, Nashville, TN
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…The biggest problem is that “doctors are focused only on the organs that got patients into the hospital, ignoring newly acquired brain problems…”
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Delirium• Disturbance of consciousness• Rapid onset• Fluctuating course• Inattention• Impaired ability to receive, process, store and
recall information• Perceptual disturbances- illusions,
hallucinations
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Prevalence of ICU Delirium • 60-80% MICU/SICU/TICU ventilated patients develop
delirium • 20-50% of lower severity ICU patients develop
delirium• Hypoactive or mixed forms most common • Majority goes undiagnosed if routine monitoring is not
implemented
Ely EW, ICM 2001;27:1892-900Ely EW, JAMA 2001;286,2703-2710Pandharipande J Trauma 2008;65(1):34-41 Ely EW, CCM 2001;29,1370-79Pandharipande, ICM 2007;33(10):1726-31
Roberts B, Aust Crit Care. 2005;18(1):6, 8-9 Thomason J, Crit Care. 2005;9(4):375-81 Ely EW CCM 2004;32:106-112Peterson JAGS 2006;54(3):479-84Ouimet S, ICM 2007;33(1):66-73
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Key Points: ICU Delirium• $15k to $25k higher hospital costs
• Longer hospital stays
• 3 times higher risk of death by 6 months
• Prolonged neuropsychological dysfunction
Milbrandt E et al, Crit Care Med 2004;32:955-962 Ely EW et al, JAMA 2004;291-1753-1762Ouimet S, ICM 2007;33(1):66-73Lin et al, Crit Care Med 2004;32:2254-59
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Long-term cognitive impairment (LTCI) after ICU survival
• 10 cohorts (~500 pts) and the largest with neuropsychological testing was 74 patients
• Summary: ~2 out of 3 ICU survivors leave the ICU with long-term cognitive impairment that equates to mild/moderate dementia (sometimes severe)
• Deficits tend to be diffuse and occur in domains including memory, attention/concentration, language, executive functioning
Rothenhausler, Gen Hosp Psych 2001;23:90-96Hopkins, AJRCCM 1999;160:50-56Jackson, Crit Care Med 2003;31;1226-34Hopkins, JINS 2004; 10:1005-1017Hopkins, AJRCCM 2005; 171:340-347
Marquis, AJRCCM 2000;161:A383 (Curtis)Al Saidi, AJRCCM 2003:167:A737 (Herridge) Sukantarat, Anaesthesia 2005;60:847-853Suchyta, AJRCCM 2004; 169:A18Christie, AJRCCM 2004; 169:A781
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0
10
20
30
40
50
60
0 5 10 15 20
Days of ICU Delirium
Cog
nitiv
e F
unct
ion
at 1
2 m
onth
s(p
redi
cte
d m
ean
T-s
core
)
Girard TD, et al. 2008, unpublished dataGirard TD, et al. 2008, unpublished data
p=.005
Delirium and Long-Term Cognitive OutcomesDelirium and Long-Term Cognitive Outcomes
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Delirium risk factors
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Risk Factors, Prevention, and Treatment
• Aging• Baseline dementia• Psychiatric disorders• Underlying illness
– Inflammation
– Coagulation
• Metabolic Disturbances• Hypoxemia• Genetic Predisposition (?)
• Psychoactive Medications• Sleep Deprivation
Inouye, JAMA 1996;275:852-57Dubois, Intens Care Med 2001;27:1297-1304Inouye, NEJM 1999;340:669-676Jacobi, Crit Care Med 2002;30:119-141Milbrandt, Crit Care Med. 2005;33:226-9Ouimet S. Int Care Med 2007;33:66-73
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Probability of transitioning from normal to delirium after lorazepam
Lorazepam Dose (mg)
Delirium Risk
Pandharipande et al. Pandharipande et al. Anesthesiology 2006: Anesthesiology 2006: 124:21-6124:21-6
OR 1.2 (1.1-1.4), P=0.003
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Surgical Trauma
Users
Non-Users
Midazolam
Daily Midazolam Use (Exc. Coma Days)
% D
ays
De
lirio
us
02
04
06
08
01
00
p=0.014p=0.031
Surgical Trauma
Users
Non-Users
Fentanyl
Daily Fentanyl Use (Exc. Coma Days)
% D
ays
De
lirio
us
02
04
06
08
01
00
p=0.007
p=0.936
Midazolam and fentanyl as risk factors for delirium
Pandharipande et al., J Trauma.2008:65;34-41
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Sedatives/analgesics in delirium
Pandharipande et al. unpublished dataPandharipande et al. unpublished data
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Delirium in surgical ICU patients
• 134 surgical and trauma adult patients requiring mechanical ventilation
• 63% developed delirium • Delirium was associated with more MV days (9.1
vs. 4.9 days, p < 0.01), longer ICU stay (12.2 vs. 7.4 days, p < 0.01), longer hospital stay (20.6 vs. 14.7 days, p < 0.01).
• Greater cumulative lorazepam dose (p = 0.012), and higher cumulative fentanyl dose (p = 0.035) were administered in the delirium group.
Lat I. Crit Care Med. April 2009 (epub)
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0
5
10
15
20
25
Discharge One-Year Two-Years
% N
eu
roco
gn
itiv
e S
eq
uela
e
ICU RecallNo Recall
ARDS Patients
Larson MJ. JINS 2007;13:595-605
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Psychological outcomes
• Pts with delusional but not factual recall of ICU experience at 2 weeks scored highly for PTSD related symptoms and panic attacks at 8 weeks (p = 0.023 and 0.014 respectively).
Jones C et al. Crit Care Med 2001; 29: 573
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How do we prevent/ treat delirium ?
1. Prevention protocols
2. Changing sedation paradigms
-Reducing exposure
-Changing medications
3. Antipsychotics
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Prevention protocols
• Reorientation, continuity of care givers
• Improving sleep architecture
• Reducing exposure to deliriogenic medications
• Cognitive stimulation
• Role of geriatrician visits or trained personnel in neuropsychological disorders
Inouye et al. NEJM 1999; 9(340):669-676
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Reduce exposure to sedatives and analgesics
Protocol and target based sedation and analgesia
Daily awakening trials
Mascia et al. CCM 2000; 28: 2300-2306Mascia et al. CCM 2000; 28: 2300-2306Brook et al. CCM 1999; 27: 2609-2615Brook et al. CCM 1999; 27: 2609-2615Kress et al. NEJM 2000; 342: 1471-1477Kress et al. NEJM 2000; 342: 1471-1477Brattebo et al. BMJ 2002; 324: 1386-1389Brattebo et al. BMJ 2002; 324: 1386-1389
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The ABC Trial(both groups get patient targeted sedation)
O U TC O M ESd e lirium , LO S , 1 2 -m o N P S tes tin g , Q O L
S p o ntan eo u s B rea th ing T ria l (S B T)ve n tila to r o ff
sa fe ly m o n ito red
O U TC O M ESd e lirium , LO S , 1 2 -m o N P S tes tin g , Q O L
S p o ntan eo u s B rea th ing T ria l (S B T)ve n tila to r o ff
sa fe ly m o n ito red
S p on taneo us A w aken ing T ria l (SA T)tu rn se d a tio n /n a rco tics o ff
m o n ito r sa fe ly
M e d ica l IC U o n V en tila to rS u rro g a te In fo rm e d C o nse ntControl Intervention
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Study Day
Da
ily D
os
e o
f B
en
zod
iaze
pin
es
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
010
2030
4050
6070
BenzodiazepinesBenzodiazepines
Usual Care+SBTSBT+SAT
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Study Day
Da
ily D
os
e o
f O
pia
tes
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
0
2000
4000
6000
Usual Care+SBTSBT+SAT
OpiatesOpiates
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SBT- CONTROL
SAT+SBT- INTERVENTION
Treatment group
No YesSepsis
0
10
20
Day
s o
f D
elir
ium
p=.74
Delirium duration in septic patients in ABC studyDelirium duration in septic patients in ABC study
Girard et al. Personal communication
p=.02
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Pa
tie
nts
Aliv
e (
%)
00
20
40
60
80
100
60 120 180 240 300 360
Days
Usual Care+SBT (n=168)
SAT+SBT (n=167)
One-Year SurvivalOne-Year Survival
p=.01NNT=7
Girard TD, et al. Lancet 2008;371:126-34Girard TD, et al. Lancet 2008;371:126-34
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Hospital Discharge
3-Month Follow-Up
12-Month Follow-Up
1.86 (1.04, 3.34)
2.01 (1.09, 3.71)
2.23 (1.13, 4.41)
0.04
0.02
0.02
Time of Cognitive Assessment Odds Ratio (95% CI) P-value
0 1 2 3 4
Favors Control Favors Intervention
Long-Term Cognitive Outcomes
Jackson JC, et al. 2008, in submission
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Changing sedation paradigms
MENDS
SEDCOM
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MENDS StudyDouble blind randomized controlled trial
C o n tro lL o ra ze p a m (G A B A )
+ /- F en ta n yl
In te rve n tionD e xm e d eto m id in e (2 )
+ /- F en ta n yl
M IC U /S IC U V en tila ted o n S e da tivesIn fo rm ed C o n se n t
Vanderbilt University Medical Center and Washington Hospital CenterVanderbilt University Medical Center and Washington Hospital Center
Pandharipande P et al. JAMA Dec 2007Pandharipande P et al. JAMA Dec 2007
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Delirium/Coma-Free Days
02
46
810
12
p=.01
Delirium-Free Days
p=.09 p=.001
Coma-Free Days
DexmedetomidineLorazepam
Brain DysfunctionBrain Dysfunction
Pandharipande PP, et al. JAMA 2007;298:2644-53
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Risk of developing delirium
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Septic subgroup analysis
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MENDS: Patients Outcomes in Septic subgroupOutcome variable Lorazepam Dexmedetomidine P value
(N=20) (N=19)
Brain Dysfunction Delirium and coma free days 1.5 (1,4) 8 (4,10) 0.002
Delirium free days 7.5 (4, 8) 10 (8, 11) 0.007
Coma free days 7 (1,9) 10 (9, 12) <0.003
Prevalence of delirium 70% 79% 0.52
Prevalence of coma 95% 68% <0.03
Efficacy of sedationDays at Physician RASS goal 35% (0,60) 67% (35,85) 0.016
Pandharipande et al. Critical Care 2008, 12(Suppl 2):P275
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28-Day Survival, Sepsis Patients28-Day Survival, Sepsis Patients
0 7 14 21 28
020
4060
8010
0
Days
Pat
ient
s A
live
(%)
Dexmedetomidine
Lorazepam
Pandharipande et al. Critical Care 2008, 12(Suppl 2):P275
HR 0.3 (0.1- 0.9). P=0.04
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Data on antipsychotics and delirium in the ICU
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Olanzapine vs. haloperidol: treating delirium in a critical care setting
Mean daily delirium scores
Day
5 4 3 2 1
Mean score
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
Group
Haloperidol
Olanzapine
Skrobik et al, ICM 2004;30:444-49
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Risperidone and delirium
• Double blind randomized trial (DBRT)
• Single dose (1 mg) of risperidone administered after cardiac surgery
• Reduced the incidence of postoperative delirium – 11.1% vs.31.7%, P=0.009– RR=0.35, 95% CI=0.16-0.77)
Prakanrattana et al. Anaesth Intensive Care 2007 Oct;35(5):714-9.
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MIND Multicenter Double Blind RCT
MV Surgical, MV Surgical, Medical and Medical and Trauma ICU Trauma ICU
patientspatients
PO haloperidolPO haloperidol PO ziprasidonePO ziprasidone PlaceboPlacebo
Girard T, Pandharipande P et al. in reviewGirard T, Pandharipande P et al. in review
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Delirium rates in MIND
Girard T, Pandharipande P et al. in reviewGirard T, Pandharipande P et al. in review
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Conclusion– Delirium occurs in majority of mechanically ventilated
patients and is associated with worse outcomes – Easy to diagnose in ICU with new validated instruments– Sedatives and analgesics may be modifiable risks factors– Avoiding benzodiazepines/ using alpha2 agonists may
reduce delirium– No difference between typical and atypical antipsychotics
in delirium management in ICU patients (risperidone in 1 study)
– Prevention protocols with emphasis on restoring sleep may help