Assessing and Managing Sedation

Assessing and Managing Sedation

William R. Beam, MD, FCCPMedical Director of Critical Care ServicesMedical Director, Sleep Disorders Center

Program Director, Sleep Medicine FellowshipSt. Mary's Hospital

St. Mary's Medical Center Clinical Assistant Professor in MedicineMarshall University School of Medicine

Huntington, West Virginia

Faculty Disclosure

It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity.

William R. Beam, MD, FCCP, has nothing to disclose.

Assessing and Managing Sedation

Learning Objectives

• Describe current guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit

• Use validated scales to measure sedation, pain, agitation, and delirium in critically ill patients

• Compare the benefits and limitations of available sedatives and analgesics in the acute care, procedural, and surgical settings

Goals for Sedation and Analgesia

• Prevent pain and anxiety

• Decrease oxygen consumption

• Decrease the stress response

• Patient-ventilator synchrony

• Avoid adverse neurocognitive sequelae

– Depression

– PTSD

– Dementia

– Anxiety

Rotondi AJ, et al. Crit Care Med. 2002;30:746-752.Weinert C. Curr Opin in Crit Care. 2005;11:376-380.Kress JP, et al. Am J Respir Crit Care Med. 1996;153:1012-1018.

Assessing Pain: FACES Scale 0–10

Wong DL, et al. Wong’s Essentials of Pediatric Nursing. 6th ed. St. Louis, MO: Mosby, Inc; 2001. p.1301.

Other Scales

•Behavioral Pain Scale (BPS) 3-12

– Payen JF, et al. Crit Care Med. 2001;29(12):2258-2263.

•Critical Care Pain Observation Tool 0-8

– Gélinas C, et al. Am J Crit Care. 2006;15:420-427.

Assessing and Managing Sedation

Managing Pain in the ICU: Opioids

• Hormonal changes

• Withdrawal symptoms

• Tolerance

• Constipation

• Bradycardia

• Hypotension• Sedation

• Respiratory depression• Analgesia

Adverse EffectsClinical Effects

Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S105-120.

Fentanyl

Morphine

Remifentanil

What Is the ABCDE Bundle?We Need Coordinated Care

• Many tasks and demands on critical care staff

• Great need to align and support the people, processes, and technology already in ICUs

• ABCDE bundle is multicomponent, interdependent, and designed to:

– Improve clinical team collaboration

– Standardize care processes

– Break the cycle of oversedation and prolonged ventilation

Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.

What Is the ABCDE Bundle?

Awakening and Breathing Trial coordination

Coordination/Choice of Sedation

Delirium Monitoring and Management

Early Mobility

Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.

Assessing and Managing Sedation

Awakening BreathingCoordination/Choice of SedationDelirium Monitoring and ManagementEarly Mobilization

ABCDE

ICU Sedation: The Balancing Act

Oversedation

• Prolonged mechanical ventilation• Increase length of stay• Increased risk of complications- Ventilator-associated pneumonia

• Increased diagnostic testing• Inability to evaluate for delirium

Undersedation

• Patient recall• Device removal• Ineffectual mechanical ventilation• Initiation of neuromuscular blockade• Myocardial or cerebral ischemia• Decreased family satisfaction w/ care

Patient Comfort and Ventilatory Optimization

G

O

A

L

Jacobi J, et al. Crit Care Med. 2002;30:119-141.

Improper Sedation

• Continuous sedation carries the risks associated with oversedation and may increase the duration of mechanical ventilation (MV)1

• MV patients accrue significantly more cost during their ICU stay than non-MV patients2

– $31,574 versus $12,931, P < 0.001

• Sedation should be titrated to achieve a cooperative patient and daily wake-up, a JC requirement1,2

1. Kress JP, et al. N Engl J Med. 2000;342:1471-1477.2. Dasta JF, et al. Crit Care Med. 2005;33:1266-1271.3. Kaplan LJ, Bailey H. Crit Care. 2000;4(suppl 1):P190.

Undersedated3

Oversedated

On Target

15.4%

54.0%

30.6%

Assessing and Managing Sedation

Assessing Agitation and Sedation

• Sedation-Agitation Scale (SAS)

– Riker RR, et al. Crit Care Med. 1999;27:1325-1329.

– Brandl K, et al. Pharmacotherapy. 2001;21:431-436.

• Richmond Agitation-Sedation Scale (RASS)

– Sessler CN, et al. Am J Respir Crit Care Med. 2002;166(10):1338-1344.

– Ely EW, et al. JAMA. 2003;289:2983-2991.

Daily Sedation Interruption Decreases

Duration of Mechanical Ventilation• Hold sedation infusion until

patient awake and then restart at 50% of the prior dose

• “Awake” defined as any 3 of the following:

– Open eyes in response to voice

– Use eyes to follow investigator on request

– Squeeze hand on request

– Stick out tongue on request

Kress JP, et al. N Engl J Med. 2000;342:1471-1477.

• Fewer diagnostic tests to assess changes in mental status• No increase in rate of agitated-related complications or

episodes of patient-initiated device removal• No increase in PTSD or cardiac ischemia

• To determine the efficacy and safety of a protocol linking:

spontaneous awakening trials (SATs) &

spontaneous breathing trials (SBTs)

– Ventilator-free days

– Duration of mechanical ventilation

– ICU and hospital length of stay

– Duration of coma and delirium

– Long-term neuropsychological outcomes

ABC Trial: Objectives

Girard TD, et al. Lancet. 2008;371:126-134.

Assessing and Managing Sedation

ABC Trial: Main Outcomes

Outcome* SBT SAT+SBT P-value

Ventilator-free days 12 15 0.02

Time-to-Event, days

Successful extubation, days 7.0 5 0.05

ICU discharge, days 13 9 0.02

Hospital discharge, days 19 15 0.04

Death at 1 year, n (%) 97 (58%) 74 (44%) 0.01

Days of brain dysfunction

Coma 3.0 2.0 0.002

Delirium 2.0 2.0 0.50

*Median, except as noted

Girard TD, et al. Lancet. 2008;371:126-134.

ABC Trial: 1 Year Mortality

Girard TD, et al. Lancet. 2008;371:126-134.

Despite Proven Benefits of Spontaneous Awakening/Daily Interruption Trials, They Are Not

Standard of Practice at Most Institutions

• Canada – 40% get SATs (273 physicians in 2005)1

• US – 40% get SATs (2004-05)2

• Germany – 34% get SATs (214 ICUs in 2006)3

• France – 40–50% deeply sedated with 90% on continuous infusion of sedative/opiate4

1. Mehta S, et al. Crit Care Med. 2006;34:374-380.2. Devlin J. Crit Care Med. 2006;34:556-557.3. Martin J, et al. Crit Care. 2007;11:R124.4. Payen JF, et al. Anesthesiology. 2007;106:687-695.

Assessing and Managing Sedation

Awakening BreathingCoordination/Choice of SedationDelirium Monitoring and ManagementEarly Mobilization

ABCDE

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

Ostermann ME, et al. JAMA. 2000;283:1451-1459.Jacobi J, et al. Crit Care Med. 2002;30:119-141.Dasta JF, et al. Pharmacother. 2006;26:798-805.Nelson LE, et al. Anesthesiol. 2003;98:428-436.

Consider Patient Comorbidities When

Choosing a Sedation Regimen

• Chronic pain

• Organ dysfunction

• CV instability

• Substance withdrawal

• Respiratory insufficiency

• Obesity

• Obstructive sleep apnea

Assessing and Managing Sedation

GABA AgonistBenzodiazepine 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 EffectsClinical 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.

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 Effects

• Pain on injection

• Respiratory depression

• Hypotension

• Decreased myocardial contractility

• Increased serum triglycerides

• Tolerance

• Propofol infusion syndrome

• Prolonged effect with high adiposity

• Seizures (rare)

αααα2222Agonist 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 activity

Adverse EffectsClinical Effects

Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349.Bhana N, et al. Drugs. 2000;59(2):263-268.

Assessing and Managing Sedation

Comparison of Clinical Effects

1. Blanchard AR. Postgrad Med. 2002;111:59-74.2. Kamibayashi T, et al. Anesthesiol. 2000;95:1345-1349.3. Maze M, et al. Anesthetic Pharmacology: Physiologic Principles and Clinical Practice. Churchill Livingstone; 2004.4. Maze M, et al. Crit Care Clin. 2001;17:881-897.

XXAlleviate anxiety1,2

XXControl delirium1-4

XFacilitate ventilation during weaning2-4

XPromote arousability during sedation2-4

XXAnalgesic properties1-4

XXXXXSedation

Haloperidolαααα2 AgonistsOpioidsPropofolBenzodiazepines

X

Comparison of Adverse Effects

1. Harvey MA. Am J Crit Care. 1996;5:7-18.2. Aantaa R, et al. Drugs of the Future. 1993;18:49-56.3. Maze M, et al. Crit Care Clin. 2001;17:881-897.

XXXRespiratory depression 1

XXfentanylBradycardia 1

morphineTachycardia 1

XXXDeliriogenic

XConstipation 1

XXXXXHypotension 1-3

X *XXProlonged weaning 1

HaloperidolOpioidsPropofolBenzodiazepines

*Excluding remifentanil

X

αααα2 Agonists

OutcomeMidazolam

(n = 122)

Dexmedetomidine

(n = 244)

P-

Value

Time in target sedation range, % (primary EP) 75.1 77.3 0.18

Duration of sedation, days 4.1 3.5 0.01

Time to extubation, days 5.6 3.7 0.01

Delirium prevalence 93 (76.6%) 132 (54%) 0.001

Delirium-free days 1.7 2.5 0.002

Patients receiving open-label midazolam 60 (49%) 153 (63%) 0.02

• Double-blind, randomized, multicenter trial comparing long-term (> 24 hr) dexmedetomidine (dex, n = 244) with midazolam (mz, n = 122)

• Sedatives (dex 0.2-1.4 µg/kg/hr or mz 0.02-0.1 mg/kg/hr) titrated for light sedation (RASS -2 to +1), administered up to 30 days

• All patients underwent daily arousal assessments and drug titration Q 4 hours

Riker RR, et al. JAMA. 2009;301:489-499.

SEDCOM: Dexmedetomidine vs Midazolam

Assessing and Managing Sedation

Midazolam

Dexmedetomidine

Dexmedetomidine versus Midazolam, P < 0.001

Reduced Delirium Prevalence with

Dexmedetomidine vs MidazolamSEDCOM

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

Pati

en

ts W

ith

Deliri

um

, %

Riker RR, et al. JAMA. 2009;301:489-499.

SEDCOM Trial:Safety Outcomes

OutcomeMidazolam

(n = 122)

Dexmedetomidine

(n = 244)

P-

Value

Bradycardia 18.9% 42.2% 0.001

Tachycardia 44.3% 25.4% 0.001

Hypertension requiring intervention 29.5% 18.9% 0.02

Hyperglycemia 42.6% 56.6% 0.02

Infections 19.7% 10.2% 0.02

Riker RR, et al. JAMA. 2009;301:489-499.

Bradycardia needing treatment 0.8% 4.9% 0.07

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.

Assessing and Managing Sedation

Analgosedation

• 140 critically ill adult patients undergoing mechanical ventilation in single center

• Randomized, open-label trial

– Both groups received bolus morphine (2.5 or 5 mg)

– Group 1: No sedation (n = 70 patients) - morphine prn

– Group 2: Sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n = 70, control group)

• Endpoints

– Primary

� Number of days without mechanical ventilation in a 28-day period

– Other

� Length of stay in ICU (admission to 28 days)

� Length of stay in hospital (admission to 90 days)

Strøm T, et al. Lancet. 2010;375:475-480.

AnalgosedationResults

• Patients receiving no sedation had

– More days without ventilation (13.8 vs 9.6 days, P = 0.02)

– Shorter stay in ICU (HR 1.86, P = 0.03)

– Shorter stay in hospital (HR 3.57, P = 0.004)

– More agitated delirium (N = 11, 20% vs N = 4, 7%, P = 0.04)

• No differences found in

– Accidental extubations

– Need for CT or MRI

– Ventilator-associated pneumonia

Strøm T, et al. Lancet. 2010;375:475-480.

AwakeningBreathingCoordination/Choice of SedationDelirium Monitoring and ManagementEarly Mobilization

ABCDE

Assessing and Managing Sedation

Morandi A, et al. Intensive Care Med. 2008;34:1907-1915.

Cardinal Symptoms of Delirium and Coma

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 cases

Patient FactorsIncreased ageAlcohol useMale genderLiving aloneSmokingRenal disease

EnvironmentAdmission via ED or

through transferIsolationNo clockNo daylightNo visitorsNoisePhysical restraints

Predisposing DiseaseCardiac diseaseCognitive impairment

(eg, dementia)Pulmonary disease

Acute IllnessLength of stayFeverMedicine service Lack of nutritionHypotensionSepsisMetabolic disorders Tubes/cathetersMedications:- Anticholinergics- Corticosteroids- Benzodiazepines

Less Modifiable

More 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.

Assessing and Managing Sedation

Mechanisms for Delirium in the Critically Ill Are Numerous and Not Clearly Understood

Maldonado JR. Crit Care Clin. 2008;24(4):789-856.Pandharipande PP. Intensive Care Med. 2009;35(11):1886-1892.Adams-Wilson JR, et al. Crit Care Med. 2012 (in press)

• Neurotransmitter imbalance

• Neuroinflammation• Blood brain barrier permeability• Impaired oxidative metabolism• Microglial activation• Abnormal levels of large neutral amino acids

(eg, tryptophan) and their metabolism (eg, kynurenine pathway)

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.

Delirium Duration and Mortality

Pisani MA. Am J Respir Crit Care Med. 2009;180:1092-1097.

Kaplan-Meier Survival Curve

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

P < 0.001

Assessing and Managing Sedation

Worse Long-term

Cognitive Performance

• Duration of delirium was an independent predictor of cognitive impairment

– An increase from 1 day of delirium to 5 days was associated with nearly a 5-point decline in cognitive battery scores

• Patient testimony

“One quite literally loses one’s grip on what is true and what is false because the true and the false are mixed together in a mess of experience.”

Girard TD, et al. Crit Care Med. 2010;38:1513-1520.Misak CJ. Am J Respir Crit Care Med. 2004;170(4):357-359.

Risk Factors Specific for ICU Delirium

• Benzodiazepine use4,10

• Coma (medical vs. pharmacologic)4,9

• Morphine use (?data

unclear)

1. Pisani MA, et al. Crit Care Med. 2009;37:177-183 2. Pisani MA, et al. Arch Intern Med. 2007;167:1629-1634. 3. Van Rompaey B, et al. Crit Care. 2009;13:R77.4. Ouimet S, et al. Intensive Care Med. 2007;33:66-73.5. Dubois MJ, et al. Intensive Care Med. 2001;27:1297-1304. 6. Pandharipande PP, et al. Anesthesiology. 2006;104:21-26. 7. Pisani MA, et al. Crit Care Med. 2009;37:177-183. 8. Pandharipande PP, et al. Intensive Care Med. 2009;35:1886-1892. 9. Ely EW, et al. Crit Care Med. 2007;35:112-117.10.Pandharipande PP, et al. J Trauma. 2008;65:34-41 .

• Dementia1,2,3

• Hypertension history4,5

• Alcoholism3,4

• Severity of illness1,4,6,7,8

• Age (?pos6,8 /neg2,3,4,9)

Delirium After Stroke

Shi Q, et al. Stroke. 2012;43(3):645-649.

• Increased 12-month mortality risk

• Stroke patients +/- delirium

• Will delirium treatment change outcome?

Assessing and Managing Sedation

Intensive Care Delirium Screening Checklist

1. Altered level of consciousness

2. Inattention

3. Disorientation

4. Hallucinations

5. Psychomotor agitation or retardation

6. Inappropriate speech

7. Sleep/wake cycle disturbances

8. Symptom fluctuation

Bergeron N, et al. Intensive Care Med. 2001;27:859-864.Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013.

Score 1 point for each component present during shift • Score of 1-3 = Subsyndromal Delirium• Score of ≥ 4 = Delirium

Helpful Approach to

Delirium Management

1. Stop

2. THINK

3. Lastly medicate

Stop and THINK

Do any meds need to be

stopped or lowered?

•Especially consider sedatives

•Is patient on minimal amount necessary?

– Daily sedation cessation– Targeted sedation plan

•Do sedatives need to be changed?

Toxic Situations• CHF, shock, dehydration• Deliriogenic meds (tight titration)• New organ failure (liver/kidney)

Hypoxemia

Infection/sepsis (nosocomial)

Immobilization

Nonpharm interventions• Hearing aids, glasses, reorient,

sleep protocols, music, noise control, ambulation

K+ or electrolyte problems

Assessing and Managing Sedation

Delirium Nonpharmacologic Interventions

• Early mobility – the only nonpharmacologic intervention shown to reduce ICU delirium1

• Other interventions:

– Environmental changes (eg, noise reduction)

– Sensory aids (eg, hearing aids, glasses)

– Reorientation and stimulation

– Sleep preservation and enhancement

Schweickert WD, et al. Lancet. 2009;373:1874-1882.

Sleep Abnormalities in the ICU

•More time in light sleep•Less time in deep sleep•More sleep fragmentation

Friese R. Crit Care Med. 2008;36:697-705.Weinhouse GL, Watson PL. Crit Care Clin. 2009;25:539-549.

There is little evidence that sedatives in the ICU restore

normal sleep

Boosting Sleep Quality in ICU

• Optimize environmental strategies

– Day/night variation, reduce night interruptions, noise reduction

• Avoid benzodiazepines (↓ SWS & REM)

• Consider dexmedetomidine (↑ SWS)

• GABA receptor agonists (eg, zolpidem)

• Sedating antidepressants (eg, trazodone) or antipsychotics

• Melatonin

– Pilot: may improve sleep quality of ICU COPD patients

Weinhouse GL, Watson PL. Crit Care Clinics. 2009;25:539-549.Faulhaber J, et al. Psychopharmacology. 1997;130:285-291.Shilo L, et al. Chronobiol Int. 2000;17:71-76.

Assessing and Managing Sedation

Effect of Common Sedatives and Analgesics on Sleep

There is little evidence that administration of sedatives inthe ICU achieves the restorative function of normal sleep

• Benzodiazepines ↑ Stage 2 NREM↓ Slow wave sleep (SWS) and REM

• Propofol↑ Total sleep time without enhancing REM ↓ SWS

• AnalgesicsAbnormal sleep architecture

• Dexmedetomidine↑ SWS

Weinhouse GL, et al. Sleep. 2006;29:707-716.Nelson LE, et al. Anesthesiology. 2003;98:428-436.

Dopamine Antagonist Haloperidol

• Adverse CV effects include QT interval prolongation

• Extrapyramidal symptoms, neuroleptic malignant syndrome (rare)1

• Does not cause respiratory depression1

• Dysphoria2• Hypnotic agent with antipsychotic properties1

Adverse EffectsClinical 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 adults1

• Metabolism altered by drug-drug interactions2

But…Use of Haloperidol Is an Independent

Predictor for Prolonged Delirium

Pisani MA, et al. Crit Care Med. 2009;37:177-183.

Assessing and Managing Sedation

Atypical Antipsychotics

• Receptor adherence is variable between agents

• Use has increased substantially

• Possible safety benefits

– Decreased extrapyramidal effects

– Little effect on the QTc interval (except ziprasidone)

– Less hypotension/fewer orthostatic effects

– Less likely to cause neuroleptic malignant syndrome

• Possible limitations

– No IV formulations available

– Little published experience in ICU patients

– Troublesome reports of adverse events but most associated with prolonged use in non-delirium patients

Devlin JW, et al. Harv Rev Psychiatry. 2011;19:59-67.

Prophylactic Haloperidol

• RCT of short-term low-dose IV haloperidol

• Patients

– N = 457

– Age > 65 years

– ICU after noncardiac surgery

• Intervention

– Haloperidol

� 0.5 mg IV bolus then

� Infusion 0.1 mg/h for 12 hrs

– Placebo

• Primary endpoint

– Incidence of delirium within the first 7 days after surgery

Wang W, et al. Crit Care Med. 2012;40(3):731-739.

Prophylactic Haloperidol

Wang W, et al. Crit Care Med. 2012;40(3):731-739.

Haloperidol (n = 229)

Placebo (n = 229)

P-value

7 day delirium incidence (%) 15.3 23.2 0.031

Mean time to delirium onset (days) 6.2 5.7 0.021

Mean time delirium-free (days) 6.8 6.7 0.027

Median ICU LOS (hours) 21.3 23.0 0.024

All-cause 28-day mortality (%) 0.9 2.6 0.175

Assessing and Managing Sedation

Quetiapine vs. Placebo

• Randomized, double-blind, placebo-controlled

• Multisite (3 centers)

• 36 ICU patients

• PO delivery of study drug

• Quetiapine dose: 50-200 mg q12h

• Primary outcome: time to first resolution of delirium (ie, first 12-hour period when ICDSC ≤ 3)

Quetiapine (n = 18) Placebo (n = 18)

Delirium + Haloperidol PRN

Devlin JW, et al. Crit Care Med. 2010;38(2):419-427.

TIME TO DELIRIUM RESOLUTION

0.00

0.25

0.50

0.75

1.00

0 2 4 6 8 10

Placebo

Quetiapine

Pro

po

rtio

n o

f P

ati

en

ts w

ith

De

liri

um

Day During Study Drug Administration

Log-Rank P = 0.001

Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation.

Devlin JW, et al. Crit Care Med. 2010;38:419-427.

Patients with First Resolution of Delirium

Impact of Quetiapine on the Resolution of Individual Delirium Symptoms

Median ICDSC and individual delirium symptoms similar at study baseline

Quetiapine Placebo P value

Median time to symptom resolution Log rank

Inattention 3 hrs 8 hrs 0.10

Disorientation 2 hrs 10 hrs 0.10

Symptom fluctuation

4 hrs 14 hrs 0.004

Agitation 5 hrs 1 hrs 0.04

Time with each symptom [median (IQR)] Comparison of

Proportions

Inattention 47 (0-67)% 78 (43-100)% 0.02

Hallucinations 0 (0-17)% 28 (0-43)% 0.10

Symptom

fluctuation

47 (19-67)% 89 (33-100)% 0.04

Devlin JW, et al. Crit Care. 2011;15(5):R215.

Assessing and Managing Sedation

Before Considering a Pharmacologic Treatment for Delirium…

• Does your patient have delirium?

– Assessed with scale?

• Which type of delirium?

– Hyperactive

– Hypoactive

– Mixed hyperactive-hypoactive

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

• Have non-pharmacologic strategies been optimized?

Inouye SK, et al. N Engl J Med. 1999;340:669-676.

Antipsychotics. http://www.canhr.org/ToxicGuide/Media/Articles/FDA%20Alert%20on%20Antipsychotics.pdf. Accessed March 2012.

Antipsychotic TherapyRule Out Dementia

• Antipsychotic drugs are not approved for the treatment of dementia-related psychosis

– No drug is approved for dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death

• Physicians considering antipsychotics for elderly patients with dementia-related psychosis should discuss this increased risk of mortality with their patients, patients’ families, and caregivers

AwakeningBreathingCoordination/Choice of SedationDelirium Monitoring and ManagementEarly Mobilization

ABCDE

Assessing and Managing Sedation

Early MobilizationPatient Selection

• Inclusion criteria

− Medical ICU

− Adults (≥ 18 years of age)

− On MV < 72 h, expected to continue for at least 24 h

− Met criteria for baseline functional independence (Barthel Indexscore ≥ 70)

• Exclusion criteria

− Rapidly developing

� Neuromuscular disease

� Cardiopulmonary arrest

� Irreversible disorders with estimated 6-month mortality > 50%

� Raised intracranial pressure

� Absent limbs

� Enrolment in another trial

Schweickert WD, et al. Lancet. 2009;373:1874-1882.

Early Mobilization Protocol: Result

Schweickert WD, et al. Lancet. 2009;373:1874-1882.

• Return to independent functional status at discharge

– 59% in intervention group

– 35% in control group (P = 0.02)

Early PT and OT in

Mechanically Ventilated ICU Patients

Schweickert WD, et al. Lancet. 2009;373(9678):1874-1882.

P = 0.02

P = 0.08

P = 0.02

P = 0.93

All Patients

Assessing and Managing Sedation

Protocol for Early Mobility TherapyAcute Respiratory Failure Patients

Morris PE, et al. Crit Care Med. 2008;36(8):2238-2243.

Early Mobility Therapy Results

Morris PE, et al. Crit Care Med. 2008;36(8):2238-2243.

Usual Care*

(n = 135)

Protocol*

(n = 145)P-Value

Days to first out of bed 11.3 5.0 0.001

Ventilator days 10.2 8.8 0.163

ICU LOS days 6.9 5.5 0.025

Hospital LOS days 14.5 11.2 0.006

Primary Endpoint: more protocol patients received PT than did usual care (80% vs. 47%, P ≤ 0.001)

*Values adjusted for BMI, Acute Physiology and Chronic Health Evaluation II, and vasopressors

Morandi A, et al. Curr Opin Crit Care. 2011;17:43-49.

Benefits of ABCDE Protocol

Assessing and Managing Sedation

Conclusions

• Oversedation in the ICU is common; associated with negative sequelae

• Analgosedation has been shown to improve outcomes; consider sedation only if necessary

• Use the ABCDE protocol

• Titrate all sedative medications using a validated assessment tool to keep patients comfortable and arousable if possible

• Use of benzodiazepines should be minimized

Conclusions

• Consider nonpharmacological management of delirium and reduce exposure to risk factors

• Typical and atypical antipsychotic medications may be used to treat delirium if nonpharmacological interventions are not adequate

• Early mobility in ICU patients decreases delirium and improves functional outcomes at discharge