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 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 sedation
1
Reports suggest narcotic-based sedation
may result in improved patient outcomes
2-3

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.
Strm 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;4:217-225
McGaffigan PA. CCN. 2002;Feb(suppl):29-36
Blanchard AR. Postgrad Med. 2002;111:59-74
ASHP Therapeutic Guidelines. Best Practices for Health-System Pharmacy. 2003-2004;486-512
Setting Targets
1
Bekker 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 wakefulness
1

Can participate in weaning and physical therapy
1

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
6080% MICU/SICU/TICU ventilated patients
develop delirium
2050% 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;286,2703-2710
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 Factors
Increased age
Alcohol use
Male gender
Living alone
Smoking
Renal disease
Depression
Vision/Hearing impaired
Environment
Admission via ED or
through transfer
Isolation
No clock
No daylight
No visitors
Noise
Use of physical restraints
Sleep deprivation
Predisposing Disease
Cardiac disease
Cognitive impairment
(eg, dementia)
Pulmonary disease
HIV

Acute Illness
Length of stay
Fever
Medicine service
Lack of nutrition
Hypotension
Sepsis
Metabolic disorders
Tubes/catheters
Medications:
- 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)
or
3. Altered level of
consciousness
4. 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 Questions
1. 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 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/c
1

Effective at providing adequate sedation with predictable dose
response
1,2

Easy to administer
1,3

Lack of drug accumulation
1

Few adverse effects
1-3

Minimal adverse interactions with other drugs
1-3

Cost-effective
3
Promotes natural sleep
4
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 to
excitation
Propofol
Not well understood
GABA receptor modulation is likely
Dexmedetomidine
2-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 (2)
Fentanyl
Pandharipande PP, et al. JAMA 2007;298:2644-53
Double-blind RCT of dexmedetomidine vs lorazepam infusion
Intervention:
Dexmedetomidine 0.151.5 mcg/kg/hr
Lorazepam infusion 110mg/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 Patients
Ventilated & Sedated
n=366
Control
Midazolam (GABA)
Fentanyl
Intervention
Dexmedetomidine (2)
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 g/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)
OUTCOMES
delirium, LOS, 12-mo NPS testing, QOL
Spontaneous Breathing Trial (SBT)
ventilator off
safely monitored
OUTCOMES
delirium, 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 Consent
Control
Intervention
Girard TD, et al. Lancet. 2008;371:126-134.
The ABC Trial
SBT+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) .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 case
Male 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.org
delirium@vanderbilt.edu
leanne.m.boehm@vanderbilt.edu