This document provides an overview of delirium and agitation in the intensive care unit (ICU). It defines delirium as an acute disturbance of consciousness and cognition that fluctuates in severity, whereas agitation refers to emotional disturbance or excitement. The document discusses the importance of delirium in the ICU, risk factors that can lead to delirium, methods for diagnosing delirium including the CAM-ICU tool, potential strategies for preventing delirium, treatments for hyperactive delirium including haloperidol, and recent studies investigating the impact of treating delirium.

1. CRISMA
Critical Care Medicine
C·R·I·S·M·A
the University of Pittsburgh
Patients Gone Wild:
Agitation and Delirium in the ICU
Eric B. Milbrandt, MD, MPH
The CRISMA Laboratory
Department of Critical Care Medicine
School of Medicine
University of Pittsburgh
the Clinical Research, Investigation, and Systems Modeling of Acute illness

2. CRISMA
Critical Care Medicine
Overview C·R·I·S·M·A
the University of Pittsburgh
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?
the Clinical Research, Investigation, and Systems Modeling of Acute illness

3. CRISMA
Critical Care Medicine
Delirium vs. Agitation C·R·I·S·M·A
the University of Pittsburgh
Latin deliria “out of your furrow”
Delirium = acute brain dysfunction
Delirium ≠ agitation
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

4. CRISMA
Critical Care Medicine
Types of Delirium C·R·I·S·M·A
the University of Pittsburgh
Hyperactive
Agitation, combative behavior, pulling lines and tubes
Hypoactive
Calm, inattentive, ↓ mobility, “spaced out”
Far more common, likely due to sedating meds
the Clinical Research, Investigation, and Systems Modeling of Acute illness

5. CRISMA
Critical Care Medicine
Why is Delirium Important? C·R·I·S·M·A
the University of Pittsburgh
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
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

6. CRISMA
Critical Care Medicine
But How Could This Be? C·R·I·S·M·A
the University of Pittsburgh
Consider hyperactive delirium
Pulling lines and tubes
Danger to self and others
Excess sedation
↑ LOS, time on vent
Risk of nosocomial pneumonia, CR-BSI, etc
Mortality
the Clinical Research, Investigation, and Systems Modeling of Acute illness

7. CRISMA
Critical Care Medicine
But How Could This Be? C·R·I·S·M·A
the University of Pittsburgh
Alternatively…
Marker of illness severity
Rather than causal
Another failing organ…
the Clinical Research, Investigation, and Systems Modeling of Acute illness

8. CRISMA
Critical Care Medicine
Why Does It Happen? C·R·I·S·M·A
the University of Pittsburgh
Baseline
Deficits Underlying
Age
Illness
Vision/Hearing
Catheters/Restraints
Deficits
Metabolic
Hypoxia Derangements
Toxins Pain/Anxiety
Medications Sleep
Inflammation Deprivation
& Thrombosis
the Clinical Research, Investigation, and Systems Modeling of Acute illness

9. CRISMA
Critical Care Medicine
Medications C·R·I·S·M·A
the University of Pittsburgh
Anticholinergics (tricyclics)
Opiates
Benzos
Antihistimines (Benedryl “sleeper”)
H2 blockers
Antibiotics
Corticosteroids
Metoclopramide
Muscle relaxants
Lidocaine
the Clinical Research, Investigation, and Systems Modeling of Acute illness

10. CRISMA
Critical Care Medicine
Mnemonics C·R·I·S·M·A
the University of Pittsburgh
IWATCHDEATH
Infection
Withdrawal
Acute metabolic
Trauma/pain
CNS pathology
Hypoxia
Deficiencies (B12, thiamine)
Endocrinopathies
Acute vascular (HTN, shock)
Toxins/drugs
Heavy Metals
the Clinical Research, Investigation, and Systems Modeling of Acute illness

11. CRISMA
Critical Care Medicine
Mnemonics C·R·I·S·M·A
the University of Pittsburgh
DELIRIUM
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

12. CRISMA
Critical Care Medicine
Monitoring And Support C·R·I·S·M·A
the University of Pittsburgh
Cardiovascular
Pulmonary
Renal
the Clinical Research, Investigation, and Systems Modeling of Acute illness

13. CRISMA
Critical Care Medicine
Monitoring And Support C·R·I·S·M·A
the University of Pittsburgh
Brain?
the Clinical Research, Investigation, and Systems Modeling of Acute illness

14. CRISMA
Critical Care Medicine
How Do We Diagnose It? 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

15. CRISMA
Critical Care Medicine
How Do We Diagnose It? C·R·I·S·M·A
the University of Pittsburgh
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%
Wards: slightly less sensitive than CAM, but easier
Interrater reliability κ=0.96
2002 SCCM Sedation & Analgesia Guidelines
Vanderbilt ICU Delirium Study Group
Int Care Med, JAMA, CCM 2001
the Clinical Research, Investigation, and Systems Modeling of Acute illness

16. Confusion Assessment Method
CRISMA
Critical Care Medicine
C·R·I·S·M·A
for the ICU the University of Pittsburgh
2 step process
Step 1:
Sedation assessment (RASS)
the Clinical Research, Investigation, and Systems Modeling of Acute illness

17. CRISMA
Critical Care Medicine
Richmond Agitation Sedation Scale C·R·I·S·M·A
the University of Pittsburgh
+4 Combative
+3 Very agitated
+2 Agitated
+1 Restless
0 Alert /calm
-1 Drowsy eye contact >10 sec
Verbal
-2 Light sedation eye contact <10 sec
-3 Moderate no eye contact
-4 Deep physical stimulation required Physical
-5 Unarousable no response even with physical
Sessler et al., AJRCCM 2002; 166:1338-1344
the Clinical Research, Investigation, and Systems Modeling of Acute illness

18. Confusion Assessment Method
CRISMA
Critical Care Medicine
C·R·I·S·M·A
for the ICU the University of Pittsburgh
2 step process
Step 1:
Sedation assessment (RASS)
Step 2:
Assess for 4 CAM-ICU features
the Clinical Research, Investigation, and Systems Modeling of Acute illness

19. Confusion Assessment Method
CRISMA
Critical Care Medicine
C·R·I·S·M·A
for the ICU the University of Pittsburgh
Feature 1: Acute onset of mental status
change or a fluctuating course
And
Feature 2: Inattention
Feature 3: Feature 4: Altered Level
Or
Disorganized Thinking of Consciousness
= DELIRIUM
the Clinical Research, Investigation, and Systems Modeling of Acute illness

20. CRISMA
Critical Care Medicine
CAM-ICU 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?
OR
Did behavior fluctuate in past 24 hours as
evidenced by RASS or GCS?
the Clinical Research, Investigation, and Systems Modeling of Acute illness

21. CRISMA
Critical Care Medicine
CAM-ICU C·R·I·S·M·A
the University of Pittsburgh
Feature 2: inattention
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

22. CRISMA
Critical Care Medicine
CAM-ICU C·R·I·S·M·A
the University of Pittsburgh
Feature 3: disorganized thinking
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

23. CRISMA
Critical Care Medicine
CAM-ICU C·R·I·S·M·A
the University of Pittsburgh
Feature 4: altered level of consciousness
Is the patients LOC anything other than
alert?
Hyperactive/agitated
Lethargic, stuporous, comatose
the Clinical Research, Investigation, and Systems Modeling of Acute illness

24. Confusion Assessment Method
CRISMA
Critical Care Medicine
C·R·I·S·M·A
for the ICU the University of Pittsburgh
Feature 1: Acute onset of mental status
change or a fluctuating course
And
Feature 2: Inattention
Feature 3: Feature 4: Altered Level
Or
Disorganized Thinking of Consciousness
= DELIRIUM
the Clinical Research, Investigation, and Systems Modeling of Acute illness

25. CRISMA
Critical Care Medicine
Can We Prevent It? C·R·I·S·M·A
the University of Pittsburgh
Baseline
Deficits Underlying
Age
Illness
Vision/Hearing
Catheters/Restraints
Deficits
Metabolic
Hypoxia Derangements
Toxins Pain/Anxiety
Medications Sleep
Inflammation Deprivation
& Thrombosis
the Clinical Research, Investigation, and Systems Modeling of Acute illness

26. CRISMA
Critical Care Medicine
Haloperidol Prophylaxis? C·R·I·S·M·A
the University of Pittsburgh
430 elderly hip-surgery patients w/ delirium risk
factors
Vision worse than 20/70 w/ glasses
APACHE>15, MMSE<25, BUN/Cr>17
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

27. CRISMA
Critical Care Medicine
Other Prevention Approaches C·R·I·S·M·A
the University of Pittsburgh
Alternative sedative agents
Non-GABA drugs
Dexmedetomidine, remifentanyl
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

28. CRISMA
Critical Care Medicine
When Should We Treat It? C·R·I·S·M·A
the University of Pittsburgh
Hyperactive “agitated” delirium
Haldol is the drug of choice
ICU
5-10 mg IV q20-30 minutes to control delirium then total dose
divided q6
Fixed dose of 5-10 mg IV q12h
Wards
0.5-2.0 mg IV/IM/PO 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

29. CRISMA
Critical Care Medicine
When Should We Treat It? C·R·I·S·M·A
the University of Pittsburgh
Hypoactive delirium???
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

30. CRISMA
Critical Care Medicine
Question C·R·I·S·M·A
the University of Pittsburgh
Does treating delirium matter?
Improve outcomes or just make patients (and
caregivers) feel better?
the Clinical Research, Investigation, and Systems Modeling of Acute illness

31. CRISMA
Critical Care Medicine
Haloperidol and Mortality C·R·I·S·M·A
the University of Pittsburgh
40% 36.1% 35.5%
P=0.001*
Mortality (%)
30%
20% 15.4%
10% 7.7%
0%
No Haloperidol Low Dose Medium Dose High Dose
(0.5-5.0) (5.1-12.5) (>12.5)
Mean Daily Dose (mg/day)
Milbrandt et al. CCM 2005
the Clinical Research, Investigation, and Systems Modeling of Acute illness

32. CRISMA
Critical Care Medicine
Quetiapine C·R·I·S·M·A
the University of Pittsburgh
Prospective multi-center RCT
36 adult ICU pts with delirium (ICDSC≥4)
~80% mechanically ventilated
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

33. CRISMA
Critical Care Medicine
Quetiapine C·R·I·S·M·A
the University of Pittsburgh
Results
Shorter time to delirium resolution
1 day vs. 4.5 days, p=0.001
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

34. CRISMA
Critical Care Medicine
Conclusions C·R·I·S·M·A
the University of Pittsburgh
Delirium is common in the ICU
Acute brain dysfunction
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