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Sedation in the ICU:

Liberation strategies for

improved outcomes

Leanne Boehm, MSN, RN, ACNS-BC

Delirium 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 time2

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): R200-103 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)

Score State

+ 4 Combative

+ 3 Very agitated

+ 2 Agitated

+ 1 Restless

0 Alert and calm

-1 Drowsy eye contact > 10 sec

-2 Light sedation eye contact < 10 sec

-3 Moderate sedation no eye contact

-4 Deep sedation physical stimulation

-5 Unarousable no response even with physical

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

G

O

A

L

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;30:119-141

Carrasco G. Crit Care. 2000;4:217-22

McGaffigan PA. CCN. 2002;Feb(suppl):29-3

Blanchard AR. Postgrad Med . 2002;111:59-7 ASHP Therapeutic Guidelines. Best Practices for Health-System Pharmacy. 2003-2004;486-51



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 patientsdevelop delirium

• 20 –50% of lower severity ICU patients developdelirium

• Majority goes undiagnosed if routine monitoringis 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;286,2703-2710

Pandharipande PP, et al. J Trauma. 2008;65:34-41

Ely EW, et al. Intensive Care Med . 2001;27:1892-1900.Dubois MJ, et al. Intensive Care Med 2001;27:1297-1304



Patient FactorsIncreased age

Alcohol use

Male genderLiving alone

Smoking

Renal disease

Depression

Vision/Hearing impaired

Environment Admission via ED or

through transfer

Isolation

No clock

No daylightNo visitors

Noise

Use of physical restraints

Sleep deprivation

Predisposing DiseaseCardiac disease

Cognitive impairment

(eg, dementia)Pulmonary disease

HIV

Acute IllnessLength of stay

FeverMedicine service

Lack of nutrition

Hypotension

Sepsis

Metabolic 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 consciousness2. 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 ofconsciousness

4. Disorganizedthinking

= 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 mentalstatus?

ORHas the patient had any fluctuation in mentalstatus 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

F t 4 Alt L l f



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: Command Say to patient: “Hold up this many fingers” (Examiner holds twofingers 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 administer 1,3

• 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

– GABA A receptor modulation in CNS• Facilitates binding of GABA

– Hyperpolarize cells, making them more resistant toexcitation

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.



Randomized Trial ICU Comparato

r

Superior

Ronan et al.1995 Surgical Midazolam Propofol

Chamorro et al. 1996 General Midazolam Propofol

Hsiao et al. 1996 Surgical Midazolam Equivalen

t

Kress et al. 1996 Medical Midazolam Propofol

Barrientos-Vega et al. 1997 General Midazolam Propofol

Searle et al. 1997 Cardiac Midazolam Equivalen

t

Weinbroum et al. 1997 General Midazolam Both

Sanchez-Izquierdo-Riera JA, et al.

1998

Trauma Midazolam Superior

Hall et al. 2001 Mixed Midazolam Propofol

Carson et al. 2006 Medical Lorazepam Propofol

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 Patients

Ventilated & Sedated

N=103

Control

Lorazepam (GABA)

Fentanyl

Intervention

Dexmedetomidine (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



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 Patients

Ventilated & Sedated

n=366

Control

Midazolam (GABA)

Fentanyl

Intervention

Dexmedetomidine (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 dexmedetomidinewas bradycardia (p<.001)



Strategies to Reduce theDuration of Mechanical

Ventilation in Patients

Receiving Continuous

Sedation

D il d ti i t ti



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 Ventilator

Surrogate Informed ConsentControl 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

Outcome

Intervention

(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) .02Hospital 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 case

Male patient, age 74Hx: 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

Cli i l



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 22Current 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 samepage?

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

[email protected]

[email protected]

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