Sedation in the
ICU
from A to E
The ABCDE Bundle
Salvatore Vitale M.D.
Director
Cardio-vascular Anesthesia
Westchester Medical Center
Assistant Professor
Dept. of Anesthesiology
New York Medical College
Immediate Past President
New York State Society of
Anesthesiologists
Westchester Medical Center
TAVR Team
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.
American College of Critical Care
Medicine (ACCM)
Clinical practice guidelines for the sustained use of
sedatives and analgesics in the critically ill adult
• Guideline focus
– Prolonged sedation and analgesia
– Patients older than 12 years
– Patients during mechanical ventilation
• Assessment and treatment recommendations
–
–
–
–
Analgesia
Sedation
Delirium
Sleep
Jacobi J, et al. Crit Care Med. 2002;30:119-141
What Is the ABCDE Bundle?
• ABCDE bundle is designed to:
– Standardize care processes
– Break the cycle of oversedation and prolonged
ventilation
Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233
What Is in the ABCDE
Bundle?
1. Awakening and Breathing Trial coordination
2. Coordination/Choice of Sedation
3. Delirium Monitoring and Management
4. Early Mobility
Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.
ABCDE
• Awakening
Breathing
Coordination/Choice of Sedation
Delirium Monitoring and Management
Early Mobilization
Daily Sedation Interruption
(DSI)
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
• 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
Kress JP, et al. N Engl J Med. 2000;342:1471-1477.
The ABC Trial:
Objectives
• 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
Girard TD, et al. Lancet. 2008;371:126-134.
ABC Trial: Main
Outcomes
Outcome*
SBT
SAT+SBT
P-value
12
15
0.02
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
Coma
3.0
2.0
0.002
Delirium
2.0
2.0
0.50
Ventilator-free days
Time-to-Event, days
Days of brain dysfunction
*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.
Daily Sedation Interruption
(DSI)
•
•
•
•
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.
Barriers to Daily Sedation Interruption
(Survey of 904 SCCM members)
•
•
•
•
•
•
•
•
Increased device removal
Poor nursing acceptance
Compromises patient
comfort
Leads to respiratory
compromise
Difficult to coordinate
with nurse
No benefit
Leads to cardiac
ischemia
Leads to PTSD
#1 Barrier
#2 Barrier
#3 Barrier
0
10
20
30
40
50
60
70
Number of respondents (%)
Clinicians preferring propofol were more likely use daily interruption
than those preferring benzodiazepines (55% vs 40%, P < 0.0001)
Tanios MA, et al. J Crit Care. 2009;24:66-73.
Awakening and Breathing (AB)
Safety Screens
Awakening Trial
•
No active seizures
•
No active alcohol withdrawal
•
No active agitation
•
No active paralytic use
•
No myocardial ischemia (24h)
•
Normal intracranial pressure
Girard TD, et al. Lancet. 2008;371(9607):126-134.
Breathing Trial
•
No active agitation
•
Oxygen saturation ≥ 88%
•
FiO2 ≤ 50%
•
PEEP ≤ 8 cm H2O
•
No myocardial ischemia (24h)
•
Normal intracranial pressure
•
No significant vasopressor or
inotrope use
ABCDE
Awakening
Breathing
Coordination/Choice
of Sedation
Delirium Monitoring
and Management
Early Mobilization
ICU Sedation: The Balancing Act
Patient Comfort
and Ventilatory Optimization
Oversedation
Undersedation
• Patient recall
• Device removal
• Ineffectual mechanical ventilation
• Initiation of neuromuscular blockade
• Myocardial or cerebral ischemia
• Decreased family satisfaction w/care
Jacobi J, et al. Crit Care Med. 2002;30:119-141.
G
O
A
L
• Prolonged mechanical ventilation
• Increased length of stay
• Increased risk of complications
- Ventilator-associated pneumonia
• Increased diagnostic testing
• Inability to evaluate for delirium
Targeted
Sedation
30.6%
•
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
15.4%
–
•
$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
54.0%
Undersedated3
Oversedated
On Target
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.
Assessing Agitation
and Sedation
• 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
• 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) *
Score
Term
Description
+4
Combative
Overtly combative, violent, immediate danger to staff
+3
Very agitated
Pulls or removes tube(s) or catheter(s); aggressive
+2
Agitated
Frequent non-purposeful movement, fights ventilator
+1
Restless
Anxious but movements not aggressive vigorous
0
Alert and calm
-1
Drowsy
-2
Light sedation
-3
Moderate sedation
-4
Deep sedation
Not fully alert, but has sustained awakening (eyeopening/eye contact) to voice (>10 seconds)
Briefly awakens with eye contact to voice (<10
seconds)
Movement or eye opening to voice (but no eye
contact)
No response to voice, but movement or eye opening to
physical stimulation
-5
Unarousable
No response to voice or physical stimulation
Procedure for RASS
Assessment
•
1. Observe patient
– Patient is alert, restless, or agitated. (score 0 to +4)
• 2. If not alert, state patient’s name and say to open eyes and look at speaker.
– Patient awakens with sustained eye opening and eye contact. (score –1)
– Patient awakens with eye opening and eye contact, but not sustained. (score
–2)
– Patient has any movement in response to voice but no eye contact. (score –3)
 3. When no response to verbal stimulation, physically stimulate patient by
shaking shoulder and/or rubbing sternum.
– Patient has any movement to physical stimulation. (score –4)
– Patient has no response to any stimulation. (score –5)
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.
Patient
Comorbidities to
Consider
•
•
•
•
•
•
•
Chronic pain
Organ dysfunction
CV instability
Substance withdrawal
Respiratory insufficiency
Obesity
Obstructive sleep apnea
Overview of Presently available
Intravenous Agents
The Good
•
•
•
•
•
a2 Agonist
Propofol
Acetaminophen
NSAIDs
Haldol
The Bad
• Opiates
• Benzodiazepines
The Ugly
• Flumazenil
• Naloxone
The Good
Dexmedetomidine
a2 Agonist
Clinical Effects
•
•
•
•
•
•
•
Antihypertensive
Sedation
Analgesia
Decreased shivering
Anxiolysis
Patient arousability
Potentiate effects of opioids,
sedatives, and anesthetics
• Decrease sympathetic activity
Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349.
Bhana N, et al. Drugs. 2000;59(2):263-268.
Adverse Effects
•
•
•
•
•
•
Hypotension
Hypertension
Nausea
Bradycardia
Dry mouth
Peripheral vasoconstriction at
high doses
Propofol
Clinical Effects
Adverse Effects
• Sedation
• Pain on injection
• Hypnosis
• Respiratory depression
• Anxiolysis
• Hypotension
• Muscle relaxation
• Decreased myocardial contractility
• Mild bronchodilation
• Increased serum triglycerides
• Decreased ICP
• Tolerance
• Decreased cerebral metabolic rate
• Propofol infusion syndrome
• Antiemetic
• Prolonged effect with high adiposity
• Seizures (rare)
Ellett ML. Gastroenterol Nurs. 2010;33(4):284-925.
Lundström S, et al. J Pain Symptom Manage. 2010;40(3):466-470.
Acetaminophen
Clinical Effects
 Available in po and IV forms
 Demonstrated effective relief of pain,
either alone (mild to moderate pain)
or as part of a multimodal regimen
(moderate to severe pain)
 No delerium
 Peak effect: within an hour of
administration
 Duration of effect: 4 to 6 hours
 No significant effect on platelet
aggregation5
Adverse Effects
•
•
Potential Hepatotoxicity
Antipyretic effects may mask
fever in patients treated for
post-surgical pain
NSAIDS
Ketorolac and Ibuprofen
• Lacks respiratory
depression
• Good pain control
• Anti platelet
activity
• Black box warning
for cardiac
patients
Haloperidol
Dopamine Antagonist
Clinical Effects
• Hypnotic agent with
antipsychotic properties1
• For treatment of delirium in
critically ill adults1
• Does not cause respiratory
depression1
1. Harvey MA. Am J Crit Care. 1996;5:7-16.
2. Crippen DW. Crit Care Clin. 1990;6:369-392.
Adverse Effects
• Dysphoria2
• Adverse CV effects include
QT interval prolongation
• Extrapyramidal symptoms,
neuroleptic malignant
syndrome (rare)1
• Metabolism altered by drugdrug interactions2
The Bad
Opioids
Clinical Effects
• Analgesia
• Sedation
Adverse Effects
• Hypotension
• Bradycardia
• Respiratory depression
• Tolerance
• Constipation
• Withdrawal symptoms
• Hormonal changes
Fentanyl
Morphine
Remifentanyl
Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S105-120.
Benzodiazepines
Clinical Effects
• Sedation, anxiolysis, and
amnesia
• Commonly used for longterm sedation
Adverse Effects
• Metabolic acidosis (propylene glycol
vehicle toxicity)
• Retrograde and anterograde amnesia
• Delirium
Midazolam
Lorazapam
Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360.
Wilson KC, et al. Chest. 2005;128(3):1674-1681.
Comparison of Clinical Effects
Benzodiazepines Propofol
Sedation
X
Alleviate anxiety1,2
X
X
Opioids
a2 Agonists
Haloperidol
X
X
X
X
Analgesic properties1-4
X
X
Promote arousability
during sedation2-4
Facilitate ventilation
during weaning2-4
X
X
Control delirium1-4
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.
X
X
X
Comparison of Adverse Effects
Benzodiazepines
Propofol
Opioids
Prolonged weaning 1
X
X
X*
Respiratory depression 1
X
X
X
Hypotension 1-3
X
X
X
Constipation 1
Deliriogenic
a2 Agonists
Haloperidol
X
X
X
X
X
X
X
X
X
X
Tachycardia 1
Bradycardia 1
*Excluding remifentanil
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.
The Ugly
Flumazenil
Flumazenil reverses the effects of sedatives
from the benzodiazepine group of drugs.
Naloxone
• An opioid antagonist drug developed in the
1960s.
• Naloxone is a drug used to counter the effects of
opiate overdose, for example heroin or morphine
overdose.
• Use with caution in the opioid addicted patient
• It is not to be confused with naltrexone, an
opioid receptor antagonist with qualitatively
different effects, used for dependence treatment
rather than emergency overdose treatment.
ABCDE
Awakening
Breathing
Coordination/Choice of Sedation
Delirium Monitoring and Management
Early Mobilization
Cardinal Symptoms of Delirium and
Coma
Morandi A, et al. Intensive Care Med. 2008;34:1907-1915.
ICU Delirium
• 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%
cases
Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.
of
Patient Factors
Predisposing Disease
Increased age
Alcohol use
Male gender
Living alone
Smoking
Renal disease
Cardiac disease
Cognitive impairment
(eg, dementia)
Pulmonary disease
Less
Modifiable
Acute Illness
Environment
Admission via ED or through transfer
Isolation
No clock
No daylight
No visitors
Noise
Physical restraints
DELIRIUM
More
Modifiabl
e
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.
Length of stay
Fever
Medicine service
Lack of nutrition
Hypotension
Sepsis
Metabolic disorders
Tubes/catheters
Medications:
- Anticholinergics
- Corticosteroids
- Benzodiazepines
Mechanisms for Delirium
in the Critically Ill: Numerous and
Not Clearly Understood
• 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)
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)
Sequelae of Delirium
During the
ICU/Hospital Stay
After Hospital
Discharge
• 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
Kaplan-Meier
Survival Curve
P < 0.001
Each day of delirium in the ICU increases the hazard of mortality by 10%
Pisani MA. Am J Respir Crit Care Med. 2009;180:1092-1097.
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
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 Assessment
Tools
• Confusion Assessment Method for
the ICU (CAM-ICU)
– Ely EW, et al. Crit Care Med. 2001;29:13701379.
– Ely EW, et al. JAMA. 2001;286:2703-2710.
• Intensive Care Delirium Screening
Checklist (ICDSC)
–
–
Bergeron N, et al. Intensive Care Med.
2001;27:859-864.
Ouimet S, et al. Intensive Care Med.
2007;33:1007-1013.
Confusion Assessment Method
(CAM-ICU)
1. Acute onset of mental status
changes or a fluctuating course
and
2. Inattention
and
3. Altered level of
consciousness
or
= Delirium
Ely EW, et al. Crit Care Med. 2001;29:1370-1379.
Ely EW, et al. JAMA. 2001;286:2703-2710.
4. Disorganized
thinking
Confusion Assessment Method for the ICU (CAM-ICU) Flowsheet
1. Acute Change or Fluctuating Course of Mental Status:
Is there an acute change from mental status baseline?
OR
NO
Hashe
t patient’s mental status fluctuated
u
dr h
i ng a
t e p st 24 hours?
CAM-ICU negative
NO DELIRIUM
YES
2. Inattention:
“Squeeze my hand when I say the letter ‘A’.”
Read the following sequence of letters: S A V E A H A A R T
ERRORS: No squeeze with ‘A’ & Squeeze
t on letter o
hher tan ‘A’
If unable to complete Letters
0-2
Errors
CAM-ICU negative
NO DELIRIUM
Pictures
> 2 Errors
3. Altered Level of Consciousness
Current RASS level
RASS other
than zero
RASS = zero
4. Disorganized Thinking:
1. Will a stone float on water?
2. Are there fish in the sea?
3. Does one pound weigh more than two?
4. Can you use a hammer to pound a nail?
Command:
“Hold
ih up ti s many fH
nge rs” ( p
oldi u 2 fnge e
rs)
“Now
o d th same ti nh
h
g witht t e oa
h er h nd” (Do
o n
e t dm onstrate)
n
OR “Add o e moren
Ii fnge r” (f pv
a tient ua bleo t m
o e bt h arms)
> 1 Error
0-1
Error
Copyright © 2002, E. Wesley Ely, MD, MPH and Vanderbilt University, all rights reserved
CAM-ICU negative
NO DELIRIUM
Page 8
Page 8
Delirium Assessment
Tools
• Confusion Assessment Method for the ICU
(CAM-ICU)
– Ely EW, et al. Crit Care Med. 2001;29:1370-1379.
– Ely EW, et al. JAMA. 2001;286:2703-2710.
• Intensive Care Delirium Screening Checklist
(ICDSC)
–
Bergeron N, et al. Intensive Care Med.
2001;27:859-864.
–
Ouimet S, et al. Intensive Care Med.
2007;33:1007-1013.
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
• Stop
• THINK
• 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
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
There is little evidence that
sedatives in the ICU restore
normal sleep
Friese R. Crit Care Med. 2008;36:697-705.
Weinhouse GL, Watson PL. Crit Care Clin. 2009;25:539-549.
Boosting Sleep
Quality in ICU
•
Optimize environmental strategies
– Day/night variation, reduce night interruptions,
noise reduction
•
Avoid benzodiazepines (↓ Slow wave sleep (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.
Effect of Common Sedatives
and Analgesics on Sleep
There is little evidence that administration of
sedatives in
the 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
Analgesics
Abnormal sleep architecture
Dexmedetomidine
↑ SWS
Weinhouse GL, et al. Sleep. 2006;29:707-716.
Nelson LE, et al. Anesthesiology. 2003;98:428-436.
Elder Life Program
Targeted Risk Factor
Standardized Intervention
Cognitive impairment
Orientation & therapeutic activity protocol
(discuss current events, word games, reorient, etc)
Sleep deprivation
Sleep enhancement & nonpharm sleep protocol
(noise reduction, back massages, schedule adjustment)
Immobility
Visual impairment
Hearing impairment
Dehydration
Early mobilization protocol
(active ROM, reduce restraint use, ambulation, remove
catheters)
Vision protocol
(glasses, adaptive equipment, reinforce use)
Hearing protocol
(amplification devices, hearing aids, earwax disimpaction)
Dehydration protocol
(early recognition of dehydration & volume repletion)
Inouye SK, et al. N Engl J Med. 1999;340:669-676.
Results
Outcome
Incidence of delirium, N
(%)
•
•
•
•
Interventi
Control
on
Pvalue
42 (9.9)
64 (15)
0.02
Total days of delirium
105
161
0.02
Episodes of delirium
62
90
0.03
↓ delirium incidence in patients with intermediate baseline risk
Improved orientation score with targeted intervention (P = 0.04)
Reduced rate of sedative use for sleep (P = 0.001)
87% overall adherence to protocol
Inouye SK, et al. N Engl J Med. 1999;340:669-676.
Haloperidol
Dopamine Antagonist
Clinical Effects
• Hypnotic agent with antipsychotic
properties1
– For treatment of delirium in
critically ill adults1
• Does not cause respiratory
depression1
1. Harvey MA. Am J Crit Care. 1996;5:7-16.
2. Crippen DW. Crit Care Clin. 1990;6:369-392.
Adverse Effects
• Dysphoria2
• Adverse CV effects include QT
interval prolongation
• Extrapyramidal symptoms,
• Neuroleptic malignant syndrome
(rare)1
• Metabolism altered by drug-drug
interactions2
Association Between Intravenous
Haloperidol & Prolonged QT Interval
•
•
•
•
However, ventricular tachyarrhythmia was not detected among
307 patients within a 1 year period, although the ECG was
continuously monitored for at least 8 hours after intravenous
HAL.
The modest nature of QTc prolongation and the apparent absence
of ventricular tachyarrhythmia under continuous ECG monitoring
indicate that QTc prolongation associated with intravenous HAL
is not necessarily dangerous.
However, in an emergency situation, clinicians cannot exclude
patients predisposed to torsade de pointes, such as those with
inherited ion channel disorders.
Therefore, clinicians should be aware of the association between
intravenous HAL and QT prolongation
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.
List of Atypical
Antipsychotics
•
•
•
•
•
•
•
•
•
•
•
•
Amisulpride (Solian)
Aripiprazole (Abilify)
Asenapine (Saphris)
Blonanserin (Lonasen)
Carpipramine (Prazinil)
Clocapramine
(Clofekton)
Clotiapine (Entumine)
Clozapine (Clozaril)
Iloperidone (Fanapt)
Lurasidone (Latuda)
Mosapramine (Cremin)
Olanzapine (Zyprexa)
•
•
•
•
•
•
•
•
•
Paliperidone (Invega)
Perospirone (Lullan)
Quetiapine (Seroquel)
Remoxipride (Roxiam)
Risperidone (Risperdal)
Sertindole (Serdolect)
Sulpiride (Sulpirid,
Eglonyl)
Ziprasidone (Geodon,
Zeldox)
Zotepine (Nipolept)
Use of Atypical Antipsychotic Therapy
Is Increasing
90
Respondents, %
80
70
60
2001
50
2007
40
30
20
10
0
Ely EW, et al. Crit Care Med. 2004;32:106-112.
Patel RP, et al. Crit Care Med. 2009;37:825-832.
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.
Haloperidol
(n = 229)
Placebo
(n = 229)
P-value
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
Prophylactic
Haloperidol
7 day delirium incidence (%)
Wang W, et al. Crit Care Med. 2012;40(3):731-739.
Quetiapine vs.
Placebo
Delirium + Haloperidol PRN
Quetiapine (n = 18)
Placebo (n = 18)
•
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)
Devlin JW, et al. Crit Care Med. 2010;38(2):419-427.
Patients with First Resolution of Delirium
Proportion of Patients with Delirium
Log-Rank
P = 0.001
Placebo
Quetiapine
Day During Study Drug Administration
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.
Impact of Quetiapine on the Resolution
of Individual Delirium Symptoms
Median ICDSC and individual delirium symptoms similar at study baseline
Quetiapine
Placebo
Median time to symptom resolution
P value
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
47 (19-67)%
89 (33-100)%
0.04
Symptom
fluctuation
Devlin JW, et al. Crit Care. 2011;15(5):R215.
Survival (%)
Rivastigmine for Delirium?
• FDA approved for dementia of Alzheimer’s or
Parkinson’s
• Cholinesterase inhibitor
• Result
Time (days after inclusion)
− Mortality (vs placebo): 22% vs 8%, P = 0.07
− Delirium (vs placebo): 5 vs 3 days, P = 0.06
• Conclusion:
− Need RCTs for delirium as endpoint
− Don’t use rivastigmine for ICU delirium
http://www.accessdata.fda.gov. Accessed March 2012.
Van Eijk MM, et al. Lancet . 2010;376(9755):1829-1837.
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.
Antipsychotic Therapy
Rule 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
Antipsychotics. http://www.canhr.org/ToxicGuide/Media/Articles/FDA%20Alert%20on%20Antipsychotics.pdf.
Accessed March 2012.
ABCDE
Awakening
Breathing
Coordination/
Choice of Sedation
Delirium Monitoring
and Management
Early Mobilization
Early Mobilization
Patient 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 Index score ≥ 70)
Exclusion criteria
−
Rapidly developing
 Neuromuscular disease
 Cardiopulmonary arrest
 Irreversible disorders with estimated 6-month mortality > 50%
 Raised intracranial pressure
 Absent limbs
 Enrollment in another trial
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
Early Mobilization
Trial Design
•
•
104 sedated patients with daily interruption
–
Early exercise and mobilization (PT & OT; intervention; n = 49)
–
PT & OT as ordered by the primary care team (control; n = 55)
Primary endpoint: number of patients returning to independent functional
status at hospital discharge
–
Ability to perform 6 activities of daily living
–
Ability to walk independently
•
Assessors blinded to treatment assignment
•
Secondary endpoints
–
Duration of delirium during first 28 days of hospital stay
–
Ventilator-free days during first 28 days of hospital stay
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
Perform Safety
Screen First
Pass
Exercise/Mobility
Therapy
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
Fail
Too Ill for
Exercise/Mobility
*Range of motion may be
started in comatose patients,
but not considered Early
Exercise/Mobility
Early Mobilization Protocol: Result
• Return to independent
functional status at
discharge
– 59% in intervention
group
– 35% in control group
(P = 0.02)
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
Early PT and OT in
Mechanically Ventilated ICU Patients
All Patients
P = 0.93
P = 0.08
P = 0.02
P = 0.02
Schweickert WD, et al. Lancet. 2009;373(9678):1874-1882.
Protocol for Early Mobility Therapy
Acute Respiratory Failure Patients
Morris PE, et al. Crit Care Med. 2008;36(8):2238-2243.
Early Mobility Therapy
Results
Primary Endpoint: more protocol patients received PT
than did usual care (80% vs. 47%, P ≤ 0.001)
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
*
Values adjusted for BMI, Acute Physiology & Chronic Health Evaluation II, and vasopressor
Morris PE, et al. Crit Care Med. 2008;36(8):2238-2243.
Post-Intensive Care Syndrome
(PICS)
• SCCM Task Force on Long-Term Outcomes
• “Post-intensive care syndrome (PICS) was
agreed upon as the recommended term to
describe new or worsening problems in
physical, cognitive, or mental health status
arising after a critical illness and persisting
beyond acute care hospitalization.
• The term could be applied to either a survivor
or family member- PICS-F.”
Needham DM, et al. Crit Care Med. 2012;40(2):502-509.
PICS Consequences
Post Intensive
Care Syndrome
(PICS)
Survivor
(PICS)
Family
(PICS-F)
Mental Health
Mental
Health
Cognitive
Impairments
Physical
Impairments
Anxiety/ASD
PTSD
Depression
Complicated Grief
Anxiety/ASD
PTSD
Depression
Executive
Function
Memory
Attention
Pulmonary
Neuromuscular
Physical Function
Needham DM, et al. Crit Care Med. 2012;40(2):502-509.
Desai SV, et al. Crit Care Med. 2011;39(2):371-379.
Davidson JE, et al. Crit Care Med. 2012;40(2):618-624.
Benefits of ABCDE Protocol
Morandi A, et al. Curr Opin Crit Care. 2011;17:43-49.
Quality Improvement Project:
Implementing ABCDE
•
Multidisciplinary team focused on reducing heavy sedation,
using SAT-SBT protocol and increasing MICU staffing to
include full-time physical and occupational therapists with
new consultation guidelines
•
Results:
–
Delirium decreased
–
Sedation use decreased
–
Physical mobility improvement
–
Decrease hospital length of stay
–
Increased MICU admissions
Needham DM, et al. Arch Phys Med Rehabil. 2010;91(4):536-542.
Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.
Results of ICU Quality
Initiative
Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.
Results of ICU Quality
Initiative (cont)
Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.
Conclusions
• Untargeted sedation in the ICU is
common, and it is associated with
negative sequelae
• Be familiar with 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
• Recognize PICS exists for patients and families
Thanks