Slide 1: CRISMA
Eric B. Milbrandt, MD, MPH
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Patients Gone Wild: Agitation and Delirium in the ICU
The CRISMA Laboratory Department of Critical Care Medicine School of Medicine University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 2: CRISMA
Overview
What is delirium? Why is it important? Why does it happen? How do we diagnose it? Can we prevent it? When should we treat it?
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 3: CRISMA
Delirium vs. Agitation
Latin deliria “out of your furrow” Delirium = acute brain dysfunction Delirium ≠ agitation
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Agitation: violent motion or stirring; emotional disturbance or excitement Delirium: acute disturbance of consciousness and cognition that fluctuates in severity
“Can’t think straight or focus attention”
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 4: CRISMA
Types of Delirium
Hyperactive Hypoactive
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Agitation, combative behavior, pulling lines and tubes Calm, inattentive, ↓ mobility, “spaced out” Far more common, likely due to sedating meds
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 5: CRISMA
Why is Delirium Important?
Very common in the ICU
20% to 80% of ICU pts develop delirium
Ely et al., JAMA 2001; 286:2703-10 Dubois et al., Intensive Care Med 2001; 27:1297-1304
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Associated with
Nosocomial pneumonia and failed extubation
Cook et al., Ann Intern Med 1998;129:433-40 Namen et al., AJRCCM 2001;163:658-64
↑LOS, 6-month mortality, cost
Ely et al., Intensive Care Med 2001; 27:1982-1900 Ely et al., JAMA 2004; 291:1753-62 Milbrandt et al., CCM 2004; 32:955-62
Prolonged neuropsychological deficits
Moller et al, Lancet 1998;351:857 Williams-Russo et al, JAMA 1995;274:44 Scragg et al., Anaesthesia 2001;56:9-14
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 6: CRISMA
But How Could This Be?
Consider hyperactive delirium
Pulling lines and tubes Danger to self and others Excess sedation
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
↑ LOS, time on vent Risk of nosocomial pneumonia, CR-BSI, etc Mortality
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 7: CRISMA
But How Could This Be?
Alternatively…
Marker of illness severity
Rather than causal Another failing organ…
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 8: CRISMA
Why Does It Happen?
Age Catheters/Restraints Hypoxia Baseline Deficits Underlying Illness
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Vision/Hearing Deficits Metabolic Derangements
Toxins
Pain/Anxiety
Medications
Inflammation & Thrombosis
Sleep Deprivation
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 9: CRISMA
Medications
Anticholinergics (tricyclics) Opiates Benzos Antihistimines (Benedryl “sleeper”) H2 blockers Antibiotics Corticosteroids Metoclopramide Muscle relaxants Lidocaine
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 10: CRISMA
Mnemonics
IWATCHDEATH
Infection Withdrawal Acute metabolic Trauma/pain CNS pathology Hypoxia Deficiencies (B12, thiamine) Endocrinopathies Acute vascular (HTN, shock) Toxins/drugs Heavy Metals
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 11: CRISMA
Mnemonics
DELIRIUM
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Drugs Electrolyte and physiologic abnormalities Lack of drugs Infection Reduced sensory input Intracranial problems Urinary retention and fecal impaction Myocardial problems (MI, CHF, arrhythmia)
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 12: CRISMA
Monitoring And Support
Cardiovascular Pulmonary
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Renal
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 13: CRISMA
Monitoring And Support
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Brain?
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 14: CRISMA
How Do We Diagnose It?
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
The Spectrum of “Septic Encephalopathy”
Normal
Delirium
Stupor
Coma
The diagnosis of delirium represents a particular challenge, since traditionally this requires “talking” to a patient
Eidelman, JAMA 1996;275:470-473 Papadopoulos, Crit Care Med 2000;28:3019-24
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 15: CRISMA
How Do We Diagnose It?
CAM-ICU (Confusion Assessment Method for the ICU) DSM-IV criteria modified for nonverbal pts Administered by anyone 1-2 minutes Objective, valid, reliable Sensitivity 93-100% & specificity 98-100% Interrater reliability κ=0.96 2002 SCCM Sedation & Analgesia Guidelines
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Wards: slightly less sensitive than CAM, but easier
Vanderbilt ICU Delirium Study Group Int Care Med, JAMA, CCM 2001
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 16: CRISMA
2 step process Step 1:
Sedation assessment (RASS)
Confusion Assessment Method for the ICU
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 17: CRISMA
Richmond Agitation Sedation Scale
+4 +3 +2 +1 Combative Very agitated Agitated Restless
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
0 Alert /calm
-1 -2 -3 -4 -5 Drowsy Light sedation Moderate Deep Unarousable eye contact >10 sec eye contact <10 sec no eye contact physical stimulation required no response even with physical
Sessler et al., AJRCCM 2002; 166:1338-1344
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Verbal
Physical
Slide 18: CRISMA
2 step process Step 1:
Sedation assessment (RASS)
Confusion Assessment Method for the ICU
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Step 2:
Assess for 4 CAM-ICU features
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 19: CRISMA
Feature 1: Acute onset of mental status change or a fluctuating course And Feature 2: Inattention
Confusion Assessment Method for the ICU
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Feature 3: Disorganized Thinking
Or
Feature 4: Altered Level of Consciousness
= DELIRIUM
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 20: CRISMA
CAM-ICU
OR
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Feature 1: acute onset or fluctuating course
Evidence of acute change in mental status from baseline? Did behavior fluctuate in past 24 hours as evidenced by RASS or GCS?
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 21: CRISMA
CAM-ICU
Feature 2: inattention
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Difficulty focusing attention as evidenced by score <8 on attention screening exam (ASE)? Visual: picture recognition OR Auditory: vigilance “A” random letter test
SAVEAHAART
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 22: CRISMA
CAM-ICU
Feature 3: disorganized thinking
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Incorrect answers to 3 or more of 4 questions or inability to follow commands Questions
Will a stone float on water? Are there fish in the sea? Does 1 pound weigh more than 2? Can you use a hammer to pound a nail?
Commands
Hold up this many fingers.
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 23: CRISMA
CAM-ICU
Hyperactive/agitated Lethargic, stuporous, comatose
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Feature 4: altered level of consciousness
Is the patients LOC anything other than alert?
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 24: CRISMA
Feature 1: Acute onset of mental status change or a fluctuating course And Feature 2: Inattention
Confusion Assessment Method for the ICU
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Feature 3: Disorganized Thinking
Or
Feature 4: Altered Level of Consciousness
= DELIRIUM
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 25: CRISMA
Can We Prevent It?
Age Catheters/Restraints Hypoxia Baseline Deficits Underlying Illness
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Vision/Hearing Deficits Metabolic Derangements
Toxins
Pain/Anxiety
Medications
Inflammation & Thrombosis
Sleep Deprivation
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 26: CRISMA
Haloperidol Prophylaxis?
Vision worse than 20/70 w/ glasses APACHE>15, MMSE<25, BUN/Cr>17
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
430 elderly hip-surgery patients w/ delirium risk factors
Haloperidol 1.5 mg/day vs. placebo
Preoperatively and up to 3 days post-op
Did not reduce incidence Did reduce severity, duration of delirium Hospital LOS ↓ 5.5 days! (among those w/ delirium)
Kalisvaart, JAGS 2005;53:1658-1666
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 27: CRISMA
Other Prevention Approaches
Alternative sedative agents
Non-GABA drugs Dexmedetomidine, remifentanyl
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Daily sedation interruption and early PT/OT
Pandharipande et al. JAMA 2007 Riker et al. JAMA. 2009 Schweickert et al, Lancet 2009
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 28: CRISMA
When Should We Treat It?
Hyperactive “agitated” delirium
Haldol is the drug of choice
ICU Wards
0.5-2.0 mg IV/IM/PO q12h
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
5-10 mg IV q20-30 minutes to control delirium then total dose divided q6 Fixed dose of 5-10 mg IV q12h
Goal is to reduce need for drugs which we know can prolong stay (benzos, opiates) Avoid if QTc >500 msec
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 29: CRISMA
When Should We Treat It?
Hypoactive delirium???
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
No one knows what to do Risks of treatment may outweigh benefits Focus should be on reducing modifiable risk factors
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 30: CRISMA
Question
Does treating delirium matter?
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Improve outcomes or just make patients (and caregivers) feel better?
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 31: CRISMA
Haloperidol and Mortality
40% 36.1% 35.5%
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Mortality (%)
30% 20% 10% 0% No Haloperidol Low Dose
(0.5-5.0)
P=0.001*
15.4% 7.7%
Medium Dose
(5.1-12.5)
High Dose
(>12.5)
Mean Daily Dose (mg/day) Milbrandt et al. CCM 2005
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 32: CRISMA
Quetiapine
Prospective multi-center RCT
~80% mechanically ventilated
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
36 adult ICU pts with delirium (ICDSC≥4) Quetiapine vs. placebo
50 mg q12h orally or per feeding tube Increased q24 if >1 dose haloperidol needed Max 200 mg q24h Until ICU d/c, 10+ days, or ICU team decision
Devlin et al. CCM 2009 (Epub ahead of print )
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 33: CRISMA
Quetiapine
Results
Shorter time to delirium resolution
1 day vs. 4.5 days, p=0.001
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Reduced delirium duration
36 hrs vs. 120 hrs, p=0.006
Less agitation
Less time w/ SAS≥5, 6 hrs vs. 36 hrs, p=0.02
Non-significant hospital mortality reduction
11% vs. 17%, p=1.0
Trend to ↑ discharge to home or rehab
89% vs 56%, p=0.06
Devlin et al. CCM 2009 (Epub ahead of print )
the Clinical Research, Investigation, and Systems Modeling of Acute illness
Slide 34: CRISMA
Conclusions
Delirium is common in the ICU Acute brain dysfunction
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Associated w/ poor outcomes and increased cost National guidelines recommend monitoring & treatment Always start w/ modifiable risk factors before drugs Antipsychotics, non-GABA sedatives, sedation interruption & early PT may prevent or reduce delirium Antipsychotics may improve outcomes, but further study is needed
the Clinical Research, Investigation, and Systems Modeling of Acute illness
