Patients Gone Wild: Agitation and Delirium in the ICU

CRISMA CC·RR·II·SS·MM·AACritical Care Medicine

the University of Pittsburgh

Eric B. Milbrandt, MD, MPH

Patients Gone Wild:

Agitation and Delirium in the ICU

�� the the CClinical linical RResearch, esearch, IInvestigation, and nvestigation, and SSystems ystems MModeling of odeling of AAcute illness cute illness ��

The CRISMA Laboratory

Department of Critical Care Medicine

School of Medicine

University of Pittsburgh


the University of PittsburghOverview

What is delirium?

Why is it important?

Why does it happen?

How do we diagnose it?


How do we diagnose it?

Can we prevent it?

When should we treat it?


the University of PittsburghDelirium vs. Agitation

Latin deliria “out of your furrow”

Delirium = acute brain dysfunction

Delirium ≠ agitationAgitation: violent motion or stirring; emotional

disturbance or excitement


disturbance or excitement

Delirium: acute disturbance of consciousnessand cognition that fluctuates in severity

“Can’t think straight or focus attention”


the University of PittsburghTypes of Delirium

HyperactiveAgitation, combative behavior, pulling lines and tubes

HypoactiveCalm, inattentive, ↓ mobility, “spaced out”

Far more common, likely due to sedating meds



the University of PittsburghWhy is Delirium Important?

Very common in the ICU20% 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


Namen et al., AJRCCM 2001;163:658-64

↑LOS, 6-month mortality, costEly 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 deficitsMoller et al, Lancet 1998;351:857

Williams-Russo et al, JAMA 1995;274:44

Scragg et al., Anaesthesia 2001;56:9-14


the University of PittsburghBut How Could This Be?

Consider hyperactive deliriumPulling lines and tubes

Danger to self and others

Excess sedation

↑ LOS, time on vent

Risk of nosocomial pneumonia, CR-BSI, etc


Risk of nosocomial pneumonia, CR-BSI, etc

Mortality


the University of PittsburghBut How Could This Be?

Alternatively…Marker of illness severity

Rather than causal

Another failing organ…



the University of PittsburghWhy Does It Happen?

Age

Baseline Deficits Underlying

Illness

Metabolic DerangementsHypoxia

Catheters/RestraintsVision/Hearing

Deficits


Derangements

Toxins

Inflammation & Thrombosis

Medications

Hypoxia

Sleep Deprivation

Pain/Anxiety


the University of PittsburghMedications

Anticholinergics (tricyclics)

Opiates

Benzos

Antihistimines (Benedryl “sleeper”)

H2 blockers

Antibiotics


Antibiotics

Corticosteroids

Metoclopramide

Muscle relaxants

Lidocaine


the University of PittsburghMnemonics

IWATCHDEATHInfectionWithdrawalAcute metabolicTrauma/painCNS pathology


CNS pathologyHypoxiaDeficiencies (B12, thiamine)EndocrinopathiesAcute vascular (HTN, shock)Toxins/drugsHeavy Metals


the University of PittsburghMnemonics

DELIRIUMDrugs

Electrolyte and physiologic abnormalities

Lack of drugs

Infection

Reduced sensory input


Reduced sensory input

Intracranial problems

Urinary retention and fecal impaction

Myocardial problems (MI, CHF, arrhythmia)


the University of PittsburghMonitoring And Support


CardiovascularCardiovascular

PulmonaryPulmonary

RenalRenal


the University of PittsburghMonitoring And Support


Brain?Brain?


the University of PittsburghHow Do We Diagnose It?

The Spectrum of “Septic Encephalopathy”


Normal Normal Delirium Stupor ComaDelirium Stupor Coma

Eidelman, JAMA 1996;275:470-473

Papadopoulos, Crit Care Med 2000;28:3019-24

The diagnosis of delirium represents a particular challenge, The diagnosis of delirium represents a particular challenge, since traditionally this requires “talking” to a patientsince traditionally this requires “talking” to a patient


the University of PittsburghHow 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%Wards: slightly less sensitive than CAM, but easier


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



Confusion Assessment Methodfor the ICU

2 step process

Step 1:Sedation assessment (RASS)



the University of PittsburghRichmond Agitation Sedation Scale

+4 +4 CombativeCombative

+3 +3 Very agitatedVery agitated

+2 +2 AgitatedAgitated

+1+1 RestlessRestless

0 Alert /calm0 Alert /calm


0 Alert /calm0 Alert /calm

--11 Drowsy Drowsy eye contact >10 seceye contact >10 sec

--22 Light sedation Light sedation eye contact <10 seceye contact <10 sec

--33 Moderate Moderate no eye contactno eye contact

--44 Deep Deep physical stimulation requiredphysical stimulation required

--55 UnarousableUnarousable no response even with physicalno response even with physical

Sessler et al., AJRCCM 2002; 166:1338-1344

Verbal

Physical




2 step process

Step 1:Sedation assessment (RASS)

Step 2:Assess for 4 CAM-ICU features


Assess for 4 CAM-ICU features




Feature 1: Acute onset of mental status

change or a fluctuating course

Feature 2: Inattention

And


Feature 3:

Disorganized Thinking

Feature 4: Altered Level

of Consciousness

= DELIRIUM

Or


the University of PittsburghCAM-ICU

Feature 1: acute onset or fluctuating course

Evidence of acute change in mental status from baseline?

ORDid behavior fluctuate in past 24 hours as


Did behavior fluctuate in past 24 hours as evidenced by RASS or GCS?



Feature 2: inattention

Difficulty focusing attention as evidenced by score <8 on attention screening exam (ASE)?

Visual: picture recognition


Visual: picture recognition

OR

Auditory: vigilance “A” random letter test

SAVEAHAART



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?


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.



Feature 4: altered level of consciousness

Is the patients LOC anything other than alert?

Hyperactive/agitated

Lethargic, stuporous, comatose


Lethargic, stuporous, comatose




Feature 1: Acute onset of mental status

change or a fluctuating course

Feature 2: Inattention

And


Feature 3:

Disorganized Thinking

Feature 4: Altered Level

of Consciousness

= DELIRIUM

Or


the University of PittsburghCan We Prevent It?

Age

Baseline Deficits Underlying

Illness

Metabolic DerangementsHypoxia

Catheters/RestraintsVision/Hearing

Deficits


Derangements

Toxins

Inflammation & Thrombosis

Medications

Hypoxia

Sleep Deprivation

Pain/Anxiety


the University of PittsburghHaloperidol Prophylaxis?

430 elderly hip-surgery patients w/ delirium risk

factorsVision worse than 20/70 w/ glasses

APACHE>15, MMSE<25, BUN/Cr>17

Haloperidol 1.5 mg/day vs. placeboPreoperatively and up to 3 days post-op


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 University of PittsburghOther Prevention Approaches

Alternative sedative agentsNon-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 University of PittsburghWhen Should We Treat It?

Hyperactive “agitated” deliriumHaldol 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


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 University of PittsburghWhen Should We Treat It?

Hypoactive delirium???No one knows what to do

Risks of treatment may outweigh benefits

Focus should be on reducing modifiable risk

factors



the University of PittsburghQuestion

Does treating delirium matter?Improve outcomes or just make patients (and

caregivers) feel better?



the University of PittsburghHaloperidol and Mortality

36.1%

15.4%

35.5%

20%

30%

40%

Mo

rtali

ty (

%) P=0.001*


7.7%

0%

10%

No Haloperidol Low Dose(0.5-5.0)

Medium Dose(5.1-12.5)

High Dose(>12.5)

Mean Daily Dose (mg/day)

Mo

rtali

ty (

%)

Milbrandt et al. CCM 2005


the University of PittsburghQuetiapine

Prospective multi-center RCT

36 adult ICU pts with delirium (ICDSC≥4)~80% mechanically ventilated

Quetiapine vs. placebo50 mg q12h orally or per feeding tube

Increased q24 if >1 dose haloperidol needed


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 University of PittsburghQuetiapine

ResultsShorter 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 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 University of PittsburghConclusions

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


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

Documents

Patients Gone Wild: Agitation and Delirium in the ICU