Delirium in the ICU Donald Crabtree DO - PowerPoint Presentation

Slide1

Delirium in the ICU

Donald Crabtree DOAssistant Professor for Anesthesiology/Critical CareUAMSSlide2

Disclosure/Declaration of Commercial Support

Today’s presenter did NOT receive financial support from nor have any commercial relationship with any drug or equipment product manufacturers or vendors that may be mentioned or displayed in the course of this presentation.Slide3

Ground Rules for Conferences

Attendees will not talk or behave in a way that is disruptive to other attendees or the speakers/presenters/moderators.Please place pagers

and cell

phones in silent mode.

Attendees will not ask a question or otherwise address other attendees during case conference without first being acknowledged or called upon by the case presenters or

moderator.Slide4

Ground Rules, continued

Attendees will respect the confidential nature of case presentations and not discuss (verbally or in writing, including e-mail) events or opinions regarding specific cases outside of the conference room, unless in another private, protected, and authorized forum or

meeting

Constructive criticism or comments arising from professional disagreement are acceptable as long as the comments are not mean-spirited or intended to hurt another person

Attendees will not laugh at, attempt to intimidate, belittle, or inappropriately criticize case presenters or moderators during or following a presentation

(Good-natured humor and associated laughing are acceptable!)Slide5

Learning Objectives

At the conclusion of todays discussion the learner should be able to:

Identify at risk populations and common risk factors for the development of delirium

Recognize the need for a standardized approach for recognition and treatment of pain, agitation and

Design a pharmacologic protocol to prevent/manage pain, agitation and deliriumSlide6

What is Delirium

Defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as “a disturbance of consciousness that is accompanied by a change in cognition that develops over a short period of time, usually hours to days, and tends to fluctuate during the course of the day.”

American Psychiatric Association.

Diagnostic and Statistical Manual of Mental Disorders

. 4

th

ed

, text revision. Washington, DC: American Psychiatric Association; 2000.Slide7
Slide8

What’s Different about this Version of the

PAD Guidelines? Methods

GRADE measures quality and strength

Quality of Evidence

:

Evaluation of the available data

High

or

low

quality

?

A (high), B (

moderate

), C (

low)Strength of Recommendation:Confidence that following the recommendation will cause more good than harm (1 or 2)Strong “We Recommend” Weak “We Suggest”

Grading of Recommendations Assessment, Development and Evaluation method

http

://

www.gradeworkinggroup.org. Accessed March 2013.Slide9

Subtypes of Delirium

Hyperactive described as agitated violent or emotionally labileHypoactive most common flat affect, lethargicMixedStudies are split on outcomes of subtypes

Peterson JF, Pun BT,

Dittus

RS, et al.

Delerium

and its motoric subtypes: a study of 614 critically ill patients.

J Am

Geriatr

Soc.

2006;54(3):479-484Slide10

ICU Delirium

Vasilevskis EE, et al.

Chest

. 2010;138(5):1224-1233.

Develops in ~2/3 of critically ill patients

Hypoactive or mixed forms most common

Increased risk

Benzodiazepines

Extended ventilation

Immobility

Associated with weakness

Undiagnosed in up to 72% of casesSlide11

After Hospital Discharge

During the ICU/Hospital Stay

Sequelae of Delirium

Increased mortality

Longer intubation time

Average 10 additional days in hospital

Higher costs of care

Increased mortality

Development of dementia

Long-term cognitive impairment

Requirement for care in chronic care facility

Decreased functional status at 6 months

Bruno JJ, Warren ML.

Crit Care Nurs Clin North Am

. 2010;22(2):161-178.Shehabi Y, et al. Crit Care Med. 2010;38(12):2311-2318.Rockwood K, et al. Age Ageing. 1999;28(6):551-556.Jackson JC, et al. Neuropsychol Rev. 2004;14:87-98.Nelson JE, et al. Arch Intern Med.

2006;166:1993-1999

.Slide12

Delirium Duration and Mortality

Pisani MA.

Am J Respir Crit Care Med

. 2009;180:1092-1097.

Kaplan-Meier

Survival

C

urve

Each day of delirium in the ICU increases the hazard of mortality by 10%

P

< 0.001Slide13

Pathogenesis of Delirium

ComplexMultiple mechanisms proposedSlide14
Slide15

Risk factors

Multiple some modifiable others notSlide16

Patient Factors

Increased age

Alcohol use

Male gender

Living alone

Smoking

Renal disease

Environment

Admission via ED or

through transfer

Isolation

No clock

No daylight

No visitors

Noise

Use of physical restraints

Predisposing DiseaseCardiac diseaseCognitive impairment (eg, dementia)Pulmonary diseaseAcute IllnessLength of stayFeverMedicine service Lack of nutritionHypotensionSepsisMetabolic disorders Tubes/cathetersMedications: Anticholinergics Corticosteroids- BenzodiazepinesLess ModifiableMore Modifiable

DELIRIUM

Van Rompaey B, et al.

Crit Care.

2009;13:R77.

Inouye SK, et al.

JAMA

.1996;275:852-857.

Skrobik Y.

Crit Care Clin

. 2009;25:585-591

.Slide17

Recognition of Delirium

Important to recognize and treat early Studies suggest 46-76% may go unrecognizedIn order to recognize delirium in the ICU numerous protocols have been studied

Armstrong SC,

Cozza

KL, Watanabe KS. The misdiagnosis of delirium. Psychosomatics. 1997;38:433-439Slide18

Pain, Agitation, and Delirium

Are Interrelated

Barr J, et al.

Crit

Care

Med.

2013;41:263-306.

Agitation

Pain

DeliriumSlide19

PAD

Pain AssessmentRecommendations

We recommend that pain be routinely monitored

in all

adult ICU patients (+1B

)

The BPS and the CPOT

are the most valid

and reliable

behavioral pain scales for monitoring pain

in adult

ICU patients who are unable to self-report and

in whom

motor function is intact and behaviors are

observable (

B

)We do not suggest that vital signs be used alone for pain assessment in adult ICU patients (–2C)We suggest that vital signs may be used as a cue to begin further assessment of pain (+2C)Barr J, et al. Crit Care Med. 2013;41:263-306. Slide20

Critical Care Pain Observation Tool

Gélinas

C, et al.

Am J Crit

Care.

2006;15:420-427.Slide21

Correlating Pain Assessment with

Analgesic Administration in the ICU

Fewer patients assessed for pain, more treated with analgesics in ICUs without analgesia protocols compared with ICUs with protocols

1

Pain scoring used in 21%

of surveyed ICUs in 2006

2

1. Payen JF, et al.

Anesthesiol.

2007;106:687-695.

2. Martin J, et al.

Crit Care.

2007;11:R124.

Patients (%)

Protocol

No ProtocolAssessedTreated* P < 0.01 vs ICUs using a protocol**Slide22

Assessing Pain Reduces

Sedative/Hypnotic Use

Payen JF, et al.

Anesthesiology.

2009;111:1308-1316.

What proportion of MV ICU patients received sedative or hypnotic medication?

Day 2 Pain Assessment?

P

value

No

(n = 631)

Yes

(n = 513)

Any

s

edative

86 %

75 %

< 0.01

Midazolam

65 %

57 %

< 0.01

Propofol

21 %

17 %

0.06

Other

6 %

4 %

0.03Slide23

Prevention is Key

Constant reassessment Aware of potential medication contributions (benzodiazepines)Daily interruption of sedation and SBTAvoid disrupting the sleep cycleSlide24

Depth and quality of sedation should be routinely assessed in all ICU patients (1B)

The RASS and SASS are the most valid and reliable scales for assessing quality and depth of sedation in ICU patients (B)

Suggest using objective measures of brain function to adjunctively monitor sedation in patients receiving neuromuscular blocking agents (2B)

Use EEG monitoring either to monitor non-convulsive seizure activity in ICU patients at risk for seizures, or to titrate electrosuppressive medication to achieve burst suppression in ICU patients with elevated intracranial pressure (1A)

PAD

Agitation/Sedation

Assessment

Recommendations

Barr J, et

al.

Crit

Care Med

.

2013;41:263-306.Slide25

Sedation Scales

Ramsay Sedation Scale RSRiker Sedation-Agitation Scale SASRichmond Agitation-Sedation Scale RASSSlide26

Sedation-Agitation Scale (SAS)

Riker

RR, et al.

Crit Care

Med

. 1999;27:1325-1329.

Brandl

K, et al.

Pharmacotherapy.

2001;21:431-436.

Score

State

Behaviors

7

Dangerous Agitation

Pulling at ET tube, climbing over bedrail, striking at staff, thrashing side-to-side

6

Very Agitated

Does not calm despite frequent verbal reminding, requires physical restraints

5

Agitated

Anxious or mildly agitated, attempting to sit up, calms down to verbal instructions

4

Calm and Cooperative

Calm, awakens easily, follows commands

3

Sedated

Difficult to arouse,

awakens

to verbal stimuli or gentle shaking but drifts off

2

Very Sedated

Arouses to physical stimuli but

does not

communicate or follow commands

1

Unarousable

Minimal or no response to noxious stimuli, does not communicate or follow commandsSlide27

Sessler

CN, et al.

Am J Respir Crit Care Med

.

2002;166(10

):

1338-1344.

Richmond Agitation

Sedation Scale (RASS) Slide28

PAD

Delirium Assessment RecommendationsWe recommend routine monitoring of delirium in adult ICU patients (+1B

)

The CAM-ICU

and the

ICDSC

are the most valid and reliable delirium monitoring tools in adult ICU patients (A

)

Barr J, et al.

Crit

Care

Med.

2013;41:263-306. Slide29

Assessment tools

Intensive Care Delirium Screening Checklist ICDSCConfusion Assessment Method for the ICU CAM-ICU98% accuracy takes about two minutes

Need for stepwise approach

Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: Validity and reliability of the confusion

assesment

method for the intensive care unit (CAM-ICU) JAMA. 2001;286:2703-2710Slide30

Confusion Assessment Method (CAM-ICU)

Ely EW, et al.

Crit Care Med

. 2001;29:1370-1379.

Ely EW, et al.

JAMA

. 2001;286:2703-2710

.

http://www.mc.vanderbilt.edu/icudelirium/assessment.html.

Accessed January 2013.Slide31

What to

THINK When Delirium Is Present

T

oxic Situations

CHF, shock, dehydration

Deliriogenic meds (

T

ight Titration

)

New organ failure, eg, liver, kidney

H

ypoxemia; also, consider giving

H

aloperidol or other antipsychotics?

I

nfection/sepsis (nosocomial),

ImmobilizationNonpharmacologic interventionsHearing aids, glasses, reorient, sleep protocols, music, noise control, ambulationK+ or Electrolyte problemsSee Skrobik Y. Crit Care Clin. 2009;25:585-591.Slide32

PAD

Choice of SedativeRecommendations

We suggest that analgesia-first sedation be used in mechanically ventilated adult ICU patients (+2B

)

Barr J, et al.

Crit

Care

Med.

2013;41:263-306. Slide33

opioids

Pain control essentialMultimodal approach necessary

Pandharipande

P, Cotton B,

Shintani

A, et al.

Prevalance

and risk factors for development of

delerium

in surgical and trauma intensive care unit patients. J Trauma. 200865:34-41.Slide34

Opioid Mechanisms

Brown EN, et al.

N

Engl

J Med

. 2010;363(27):2638-2650.

Neurotransmitters

ACh

Acetylcholine

Glu

Glutamate

NE NorepinephrineSlide35

Analgosedation

Analgesic first (A-1), supplement with sedative

Acknowledges that discomfort may cause agitation

Remifentanil-based regimen

Reduces propofol use

Reduces median MV time

Improves sedation-agitation scores

Not appropriate for drug or alcohol withdrawal

Park G, et al.

Br J Anaesth.

2007;98:76-82.

Rozendaal FW, et al.

Intensive Care Med.

2009;35:291-298.Slide36

Characteristics of an Ideal Sedative

Rapid onset of action allows rapid recovery after discontinuation

Effective at providing adequate sedation with predictable dose response

Easy to administer

Lack of drug accumulation

Few adverse effects

Minimal adverse interactions with other drugs

Cost-effective

Promotes natural sleep

1. Ostermann ME, et al.

JAMA.

2000;283:1451-1459.

2. Jacobi J, et al.

Crit Care Med

. 2002;30:119-141.

3.

Dasta JF, et al. Pharmacother. 2006;26:798-805.4. Nelson LE, et al. Anesthesiol. 2003;98:428-436.Slide37

Benzodiazepines

Work well treating delirium from withdrawalHighly discouraged from treatment of delirium from other causesIncreased length of stay and mortality

Pandharipande

PP, Pun BT, Herr DL, et al. Effect of sedation with

dexmetatomidine

vs

lorazepam

on acute brain dysfunction in mechanically ventilated patients: The MENDS randomized controlled trial. JAMA. 2007;298:2644-2653Slide38

GABA Agonist

Benzodiazepine Midazolam

May accumulate

with hepatic and/or

renal

failure

Anterograde amnesia

Long recovery time

Synergy with opioids

Respiratory depression

Delirium

Sedation, anxiolysis, and

amnesia

Rapid onset of action (IV)

Adverse Effects

Clinical Effects

Olkkola KT, Ahonen J.

Handb Exp Pharmacol.

2008;(182):335-360.

Riker RR, et al; SEDCOM Study Group.

JAMA

. 2009;301(5):489-499. Slide39

Clinical Effects

Sedation, anxiolysis, and amnesia

Commonly used for long-term sedation

Adverse Effects

Metabolic

a

cidosis

(propylene glycol

vehicle toxicity)

Retrograde and anterograde

amnesia

Delirium

GABA Agonist

Benzodiazepine Lorazepam

Olkkola KT, Ahonen J.

Handb Exp Pharmacol.

2008;(182):335-360.Wilson KC, et al. Chest. 2005;128(3):1674-1681.Slide40

GABA Agonist Propofol

Sedation

Hypnosis

Anxiolysis

Muscle

relaxation

Mild bronchodilation

Decreased

ICP

Decreased cerebral metabolic

rate

Antiemetic

Ellett ML.

Gastroenterol Nurs

. 2010;33(4):284-925.

Lundström S, et al.

J Pain Symptom Manage. 2010;40(3):466-470. Clinical Effects Adverse EffectsPain on injectionRespiratory depressionHypotensionDecreased myocardial contractilityIncreased serum triglyceridesTolerancePropofol infusion syndromeProlonged effect with high adipositySeizures (rare) Slide41

Central Mechanisms of Propofol

Brown EN, et al. N

Engl

J Med

. 2010;363(27):2638-2650.

Monoaminergic

pathways

Cholinergic pathways

Lateral hypothalamus neurons

Neurotransmitters

ACh

Acetylcholine

DA Dopamine

GABA

γ

-

Aminobutyric acidGAL GalaninGlu GlutamateHis HistamineNE Norepinephrine5HT SerotoninSlide42

Dexmedetomidine

Selective alpha 2 agonistAlternative to the GABA pathwayLess ventilator days and more days alive when compared to lorazepam

for sedation.Slide43

a

2 Agonist Dexmedetomidine

Hypotension

Hypertension

Nausea

Bradycardia

Dry mouth

Peripheral vasoconstriction at high doses

Antihypertensive

Sedation

Analgesia

Decreased shivering

Anxiolysis

Patient arousability

Potentiate effects of opioids,

sedatives, and anesthetics

Decrease sympathetic activityAdverse EffectsClinical EffectsKamibayashi T, et al. Anesthesiol. 2000;93:1345-1349.Bhana N, et al. Drugs. 2000;59(2):263-268.Slide44

Central Mechanisms of Dexmedetomidine

Neurotransmitters

ACh

Acetylcholine

DA Dopamine

GABA

γ

-

Aminobutyric

acid

GAL

Galanin

Glu

Glutamate

His Histamine

NE Norepinephrine

5HT SerotoninBrown EN, et al. N Engl J Med. 2010;363(27):2638-2650.Slide45

Midazolam

Dexmedetomidine

Dexmedetomidine versus Midazolam,

P

< 0.001

Reduced Delirium Prevalence with Dexmedetomidine vs Midazolam

SEDCOM

Sample Size

118 229

109 206

92 175

77 134

57 92

42 60

44 34

Treatment Day

0

20

40

60

80

100

Baseline

1

2

3

4

5

6

Patients With Delirium, %

Riker RR, et al.

JAMA.

2009;301:489-499.Slide46

Before Considering a Pharmacologic Treatment for Delirium…

Have the underlying causes of delirium been identified and reversed/treated?

Have non-pharmacologic treatment strategies been optimized?

Does your patient have delirium?

Hyperactive

Hypoactive

Mixed hyperactive-hypoactive

Inouye SK, et al.

N Engl J Med.

1999;340:669-676.Slide47

Pharmaceutical intervention

Currently no available medication available to alter outcome of deliriumImportant to rule out all reversible causesHypoxia, hypercarbia, hypoglycemia, infections, pain or shock.Slide48

Dopamine Antagonist Haloperidol

Adverse CV effects include QT interval prolongation

Extrapyramidal symptoms, neuroleptic malignant syndrome (rare)

1

Does not cause respiratory depression

1

Dysphoria

2

Hypnotic agent with antipsychotic properties

1

Adverse Effects

Clinical Effects

1. Harvey MA.

Am J Crit Care.

1996;5:7-16.

2. Crippen DW.

Crit Care Clin. 1990;6:369-392.For treatment of delirium in critically ill adults1Metabolism altered by drug-drug interactions2Slide49

Medications

HaloperidolSociety of Critical Care Medicine recommends the use (Cat C)No change in incidence of delirium but decreased severity and duration compared to placebo

Recent Cochrane review no better than

atypicals

Side effects include prolonged

QTc

, Neuroleptic malignant syndrome,

dystoniasSlide50

Atypical Antipsychotics

RisperidoneZiprasidoneQuetiapineOlanzipine

Mixed results; may be more effective than

haldol

with less side effectsSlide51

Potential Advantages of Atypical Antipsychotics

vs Conventional Antipsychotics

Decreased extrapyramidal effects

Little effect on the QTc interval (with the exception of ziprasidone)

Less hypotension/fewer orthostatic effects

Less likely to cause neuroleptic malignant syndrome

Unlikely to cause laryngeal dystonia

Lower mortality when used in the elderly to treat agitation related to dementia

Tran PV, et al.

J Clin Psychiatry.

1997;58:205-211.

Lee PE, et al.

J Am Geriatr Soc.

2005;53:1374-1379.

Wang PS, et al.

N Engl J Med.

2005;353:2235-2341.Slide52
Slide53

Putting it all togetherSlide54
Slide55
Slide56

Summary

Delirium is a disturbance of consciousness Three subtypes hypoactive, hyperactive, and mixedHigh incidence with increased mortality and morbidity, recognition is vitalProtocols are recommended to recognize and reduce severity

Avoid benzodiazepines except for withdrawal, other medications reduce but do not prevent delirium.Slide57

Further reading

www.icudelirium.orgwww.Sedation-cme.orgSocitety of Critical Care MedicineSlide58

Question

Which of the following is not associated with delirium?SerotoninCortisol

Cholinergic inhibition

Dopamine inactivationSlide59

questions