Sedation in the ICU:Liberation strategies

for improved outcomes

Leanne Boehm, MSN, RN, ACNS-BCDelirium and Cognitive Impairment Study Group

Vanderbilt University Medical Center

Nashville, TN USA

Disclosures

• Hospira

Need for Sedation & Analgesia

• Prevention of pain and anxiety

• Decrease oxygen consumption

• Decrease the stress response

• Patient-ventilator synchrony

• Avoid adverse neurocognitive sequelae

• Depression, PTSD

Rotondi AJ, et al. Crit Care Med. 2002;30:746-52A.Weinert C, et al. Curr Opin in Crit Care. 2005;11(4):376-380.Kress JP, et al. J Respir Crit Care Med. 1996;153:1012-1018.

Pitfalls of sedatives and analgesics

• Oversedation:• Failure to initiate spontaneous breathing trials (SBT)

leads to increased duration of mechanical ventilation

• Longer duration of ICU stay

• Impede assessment of neurologic function

• Increase risk for delirium

• Numerous agent-specific adverse events

Kollef M, et al. Chest. 1998;114:541-548.Pandharipande, et al. Anesthesiology. 2006;124:21-26.

Identifying and Treating Pain

Behavioral Pain Scale (BPS) 3-12

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

Item Description Score

Facial expression

Relaxed 1

Partially tightened (eg, brow lowering) 2

Fully tightened (eg, eyelid closing) 3

Grimacing 4

Upper limbs

No movement 1

Partially bent 2

Fully bent with finger flexion 3

Permanently retracted 4

Compliance with ventilation

Tolerating movement 1

Coughing but tolerating ventilation for most of the time

2

Fighting ventilator 3

Unable to control ventilation 4

A note on pain control

• Pain can cause agitation and lead to excessive use of sedatives

• Adequate pain management often reduces the need for sedation1

• Reports suggest narcotic-based sedation may result in improved patient outcomes2-3

1 Kress JP et al, AJRCCM 2002; 168(8): 1024-8

2 Breen D et al, Crit Car 2005; 9(3): R200-10

3 Pandharipande P & Ely EW, Crit Car 2005; 9(3): 247-8

Analgosedation• “Analgesia-first sedation” & sedative if needed

• Increasingly used in many countries

• Acknowledges discomfort as a cause of agitation

• Usually continuous infusion

• 30-74% required benzodiazepine/propofol rescue

• Study of remifentanil vs midazolam sedation

– Reduction in vent time (2 d) and ICU LOS (1d)

• Not appropriate for drug or alcohol withdrawal

Dahaba AA, et al. Anesthesiology. 2004;101:640-646.Park G, et al. Br J Anaesth. 2007;98:76-82. Rozendall FW, et al. Intensive Care Med. 2009;35:291-298.Strøm T, et al. Lancet. 2010;375(9713):475-480

Sedation assessment and maintaining a

sedation goal

Sedation Scales

Pun & Dunn, AJN 2007; 107(7):40-48

Richmond Agitation Sedation Scale (RASS)

Ely EW, et al. JAMA. 2003;289(22):2983-2991.Sessler CN, et al. Am J Respir Crit Care Med. 2002;166(10):1338-1344.

Verbal Stimulus

Physical Stimulus

ICU Sedation: The Balancing Act

Oversedation

Patient Comfort and Ventilatory Optimization

GOAL

Undersedation• Patient recall• Device removal• Ineffectual mechanical ventilation• Initiation of neuromuscular blockade• Myocardial or cerebral ischemia• Decreased family satisfaction w/ care• Severe discomfort• Hypertension• Tachycardia• Increased ICP• Increase metabolic demand• Delirium

• Prolonged mechanical ventilation• Increase length of stay• Increased risk of complications (I.e. VAP)• Increased diagnostic testing• Inability to evaluate for delirium• Cardio/respiratory depression• Decreased GI motility• Immunosuppression• Delirium

Jacobi J, et al. CCM. 2002;30:119-141Carrasco G. Crit Care. 2000;4:217-225

McGaffigan PA. CCN. 2002;Feb(suppl):29-36Blanchard AR. Postgrad Med. 2002;111:59-74

ASHP Therapeutic Guidelines. Best Practices for Health-System Pharmacy. 2003-2004;486-512

Setting Targets

1Bekker AY, et al. Neurosurgery 2005;57(1 Suppl 1):1-10

Aim for Cooperative:• Calm & Easily Arousable State while minimizing pain,

anxiety, or agitation unless contraindicated

• Easy transition from sleep to wakefulness1

• Can participate in weaning and physical therapy1

• Perform therapeutic maneuvers

• Able to perform a cognitive evaluation

Adjust depending on patient need• Over the course of Illness/Treatment

• Initial Intubation vs Stabilization

• Weaning Phase

The importance of preventing and

identifying delirium

What is delirium?

• Common clinical syndrome that is characterized by:

– Inattention

– Acute cognitive dysfunction

• Thought to be due to disruption of neurotransmission related to:

– Drug toxicity

– Inflammation

– Acute stress responses

Delirium

Morandi, A et al., ICM 2009;34:1907-15

Prevalence of Delirium in the ICU

• 60–80% MICU/SICU/TICU ventilated patients develop delirium

• 20–50% of lower severity ICU patients develop delirium

• Majority goes undiagnosed if routine monitoring is not implemented

• Hypoactive or mixed forms most common

Ouimet S, et al. Intensive Care Med. 2007;33:66-73 Ely EW, et al. JAMA. 2001;286,2703-2710Pandharipande PP, et al. J Trauma. 2008;65:34-41Ely EW, et al. Intensive Care Med. 2001;27:1892-1900.Dubois MJ, et al. Intensive Care Med 2001;27:1297-1304

Patient FactorsIncreased ageAlcohol useMale genderLiving aloneSmokingRenal diseaseDepressionVision/Hearing impaired

EnvironmentAdmission via ED or through transferIsolationNo clockNo daylightNo visitorsNoiseUse of physical restraintsSleep deprivation

Predisposing DiseaseCardiac diseaseCognitive impairment (eg, dementia)Pulmonary diseaseHIV

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

Less Modifiable

More Modifiable

DELIRIUM

Inouye SK, et al. JAMA .1996;275:852. Van Rompaey B, et al. Crit Care 2009;13:R77.Skrobik Y. Crit Care Clin. 2009;25(3):585-591. Devlin J, et al. ICM, 2007; 33:929-940.

After Hospital Discharge

During the ICU/Hospital Stay

Sequelae of Delirium

- Increased mortality - 3x greater re-intubation rate - Average 10 additional days in hospital - Higher costs of care

- Increased mortality - Long-term cognitive impairment- D/c requirement for chronic care facility- Decreased functional status at 6 months

Milbrandt EB, et al. Crit Care Med. 2004;32:955-962. Nelson JE, et al. Arch Intern Med. 2006;166:1993-1999.Ely EW, et al. JAMA. 2004;291:1753-1762. Jackson JC, et al. Neuropsychol Rev. 2004;14(2):87-98.

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

Confusion Assessment Method(CAM-ICU)

or3. Altered level of

consciousness4. Disorganized

thinking

= Delirium

Ely EW, et al. Crit Care Med. 2001;29:1370-1379.Ely EW, et al. JAMA. 2001;286:2703-2710.

1. Acute onset of mental status changes or a fluctuating course

2. Inattention

and

and

Feature 1: Alteration/Fluctuation in Mental Status

Is the pt different than his/her baseline mental status? OR

Has the patient had any fluctuation in mental status in the past 24 hours (eg fluctuating

RASS, GCS, previous delirium assessments, etc)?

Positive/Present: If either question is YES.

Feature 2: Inattention

Attention Screening Exam

• Auditory: Letter “A”– Say 10 letters & tell patient to squeeze on “A”– Letters: S A V E A H A A R T– Scoring: Count error if patient fails to squeeze on “A” and

when they squeeze on any letter other than “A”

• Visual: Pictures– Similar to letters but with pictures

Positive/Present: If score is <8

Feature 4: Alt Level of Consciousness

Any LOC other than Alert.

Positive/Present: If the Actual RASS score is anything other than “0”

Feature 3: Disorganized Thinking

A: Yes/No Questions1. Will a stone float on water? 2. Are there fish in the sea? 3. Does one pound weigh more than two pounds?4. Can you use a hammer to pound a nail?

B: CommandSay to patient: “Hold up this many fingers” (Examiner holds two fingers in front of patient) “Now do the same thing with the other hand” (Not repeating the number of fingers).

Positive/Present: If combined score (questions + command) is less than 4

If sedation is required,what is the optimal

sedative choice?

Characteristics of an Ideal Sedative

• Rapid onset of action allows rapid recovery after d/c1

• Effective at providing adequate sedation with predictable dose response1,2

• Easy to administer1,3

• Lack of drug accumulation1

• Few adverse effects1-3

• Minimal adverse interactions with other drugs1-3

• Cost-effective3

• Promotes natural sleep4

1. Ostermann ME, et al. JAMA. 2000;283:1451-1459.2. Jacobi J, et al. Crit Care Med. 2002;30(1):119-141.

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

Choice of Sedatives Benzodiazepines

– GABAA receptor modulation in CNS• Facilitates binding of GABA

– Hyperpolarize cells, making them more resistant to excitation Propofol

– Not well understood – GABA receptor modulation is likely

Dexmedetomidine– α2-adrenergic agonist (inhibits NE release in CNS & PNS)

• CNS: sedation/hypnosis, anxiolysis, and analgesia• PNS: decreases BP and HR; activates endogenous sleep-promoting

pathway– No respiratory suppression– Enables cognitive evaluation & patient communication

Consider Comorbidities When Choosing a Sedation

Regimen• Chronic pain

• Organ dysfunction

• CV instability

• Substance withdrawal

• Respiratory insufficiency

• Obesity

• Obstructive sleep apnea

Risk of delirium with benzodiazepines

Pandharipande P, et al. J Trauma. 2008; 65:34-41. Pandharipande P, et al. Anesthesiol. 2006:104:21-26.

Propofol vs benzodiazepines

Outcomes improved by propofol: sedation quality, ventilator synchrony, time to awakening, variability of awakening, time to extubation from discontinuation of sedation, overall time to extubation, ventilator days, ICU LOS among survivors, costs of sedation

MENDS

MICU/SICU PatientsVentilated & Sedated

N=103

ControlLorazepam (GABA)

± Fentanyl

InterventionDexmedetomidine (α2)

± Fentanyl

Pandharipande PP, et al. JAMA 2007;298:2644-53

• Double-blind RCT of dexmedetomidine vs lorazepam infusion• Intervention:

– Dexmedetomidine 0.15–1.5 mcg/kg/hr– Lorazepam infusion 1–10mg/hr

• No daily interruption, patient targeted sedation

MENDS: dexmedetomidine vs

lorazepam

Pandharipande P et al – JAMA, 2007; 298:2644-2653

Dexmedetomidine resulted in:

• More days alive without delirium or coma (p=.01)

• Lower prevalence of coma (p=.001)

• More time spent within sedation goals (p=.04)

Differences in 28-day mortality and delirium-free days were not significant

SEDCOM

MICU PatientsVentilated & Sedated

n=366

ControlMidazolam (GABA)

± Fentanyl

InterventionDexmedetomidine (α2)

± Fentanyl

Riker, R., et al. JAMA 2009; 301(5): 489-499

• Double-blind, RCT comparing long-term dexmedetomidine vs midazolam

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

• Daily arousal assessments and drug titration Q4h

SEDCOM:dexmedetomidine vs

midazolam Dexmedetomidine resulted in:

• less time on the ventilator (p=.01)

• less delirium (p<.001)

• less tachycardia (p<.001)

• less hypertension (p=.02)

Most notable adverse effect of dexmedetomidine was bradycardia (p<.001)

Strategies to Reduce the Duration of Mechanical Ventilation in Patients Receiving Continuous

Sedation

Daily sedation interruption decreases days of MV

• Hold infusion until patient awake, then restart at 50% of prior dose

• “Awake” defined as 3 of the following 4:– 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

The ABC Trial(both groups get patient targeted sedation)

OUTCOMESdelirium, LOS, 12-mo NPS testing, QOL

Spontaneous Breathing Trial (SBT)ventilator off

safely monitored

OUTCOMESdelirium, LOS, 12-mo NPS testing, QOL

Spontaneous Breathing Trial (SBT)ventilator off

safely monitored

Spontaneous Awakening Trial (SAT)turn sedation/narcotics off

monitor safely

Medical ICU on VentilatorSurrogate Informed Consent

Control Intervention

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

The ABC TrialSBT+usual care vs SAT+SBT

• Patients in the intervention group:– Less time in coma (p=.002)– 2 days less on the ventilator (p=.02)– 4 days less in the ICU (p=.02)– 4 days less in the hospital (p=.04)– Less exposure to benzodiazepines– Were more likely to be alive in 1 year (p=.01)– More self extubations, but not more

reintubations

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

Early Mobilization

Schweickert et al, Lancet 2009;373:1874-82

Mobility

• A fundamental nursing activity

• Enhances gas exchange

• Reduces VAP rates

• Shortened duration of MV

• Enhances long-term functional ability

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

24% improvement (1.7-fold better) return to independent functional status at discharge

(NNT=4)

Daily Wake-Up + Early Mobility

OutcomeIntervention

(n=49)Control(n=50) P

Functionally independent at discharge 29 (59%) 19 (35%) .02

ICU delirium (days) 2.0 (0.0-6.0) 4.0 (2.0-7.0) .03

Time in ICU with delirium (%) 33% (0-58) 57% (33-69) .02

Hospital delirium (days) 2.0 (0.0-6.0) 4.0 (2.0-8.0) .02

Hospital days with delirium (%) 28% (26) 41% (27) .01

Barthel Index score at discharge 75 (7.5-95) 55 (0-85) .05

ICU-acquired paresis at discharge 15 (31%) 27 (49%) .09

Ventilator-free days 23.5 (7.4-25.6) 21.1 (0.0-23.8) .05

Length of stay in ICU (days) 5.9 (4.5-13.2) 7.9 (6.1-12.9) .08

Length of stay in hospital (days) 13.5 (8.0-23.1) 12.9 (8.9-19.8) .93

Hospital mortality 9 (18%) 14 (25%) .53

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

Implementation challenges

Many issues to address

Multiple disciplines are involved

– RN, RT, MD, PT/OT, pharmacist

Timing

Coordination, collaboration, & teamwork

Protocol development

Change in culture of workplace

Costs

Resistance to change

Putting it all together

Clinical caseMale patient, age 74

Hx: Dementia, coronary artery disease, diabetes, hypertension

CC: altered mental status, shortness of breath

Currently hypoxic and required MV

Dx: Septic shock, ARDS, acute renal failure

Clinical case

• Current vent settings: A/C 16, TV 400, PEEP 14, FiO2 80%

• Current infusions: norepinephrine 10 mcg/min, vasopressin 0.4 units/min, insulin gtt, IVF

• Assessment: Target RASS -4, actual RASS +1 to -1, displaying vent asynchrony, CAM-ICU positive, bilat rhonchi, pulses present

• Receiving intermittent boluses of fentanyl and lorazepam

Nursing interventions?

Clinical case

Current vent settings: A/C 16, TV 400, PEEP 5, FiO2 40%

Current infusions: propofol 40 mcg/kg/hr, norepinephrine 4 mcg/min, vasopressin 0.4 units/min, insulin gtt, IVF

Intermittent fentanyl for analgesia

Assessment: Target RASS -1, actual RASS -3, CAM-ICU positive, not breathing over vent set rate, bilat rhonchi, pulses present, moving extremities spontaneously

Nursing interventions:for sedation?for delirium? (pharm/nonpharm)

Clinical case

Current vent settings: PS 5, PEEP 5, FiO2 40%, RR 22

Current infusions: Norepinephrine/vasopressin off, insulin gtt, IVF, propofol off

Septic shock resolved, passed SAT/SBT

Assessment: Target RASS 0, actual RASS 0, CAM-ICU positive, lungs clear, moves all extremities

Nursing interventions:for sedation?for delirium? (pharm/nonpharm)

Clinical Case

• What if the patient had not passed the SBT and was beginning to become agitated?

• Would you consider pharmacologic treatment for delirium at this point?

• What if we extubated this patient and he later became agitated?

Summary

Goals for sedation: Are we on the same page?

Daily Sedation Cessation: Did you wake up your patient today?

Sedative Choice: What is the best option for my patient right now?

Roadmap: How do we put it all together at the bedside?

Educational Delirium Website

www.ICUdelirium.orgdelirium@vanderbilt.edu

leanne.m.boehm@vanderbilt.edu