Assessing and Managing Sedation
in the Intensive Care and the
Perioperative Settings
Assessing and Managing Sedation
SEDATION Curriculum
Learning Objectives
• Manage adult patients who need sedation and
analgesia while receiving ventilator support according
to current standards and guidelines
• Use validated scales for sedation, pain, agitation and
delirium in the management of these critically ill
patients
• Assess recent clinical findings in sedation and
analgesia management and incorporate them into the
management of patients in the acute care,
procedural, and surgical sedation settings
Predisposing and Causative Conditions
Acute Medical
or Surgical Illness
Mechanical
Ventilation
Invasive,
Medical, &
Nursing
Interventions
Medications
Underlying
Medical
Conditions
Hospital
Acquired
Illness
ICU
Environmental
Influences
Anxiety Pain Delirium
Management
of predisposing
& causative
conditions
Interventions
Calm Alert
Dangerous Agitation, vent Pain,
agitation dyssynchrony anxiety Free of pain and anxiety
Agitation
Sedative,
analgesic,
antipsychotic,
medications
Lightly
sedated
Deeply
Unresponsive
sedated
Spectrum of Distress/Comfort/Sedation
Sessler CN, Varney K. Chest. 2008;133(2):552-565.
Need for Sedation and Analgesia
• Prevent 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;30:746-752.
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.
Potential Drawbacks of Sedative
and Analgesic Therapy
• Oversedation:
– Failure to initiate spontaneous breathing trials (SBT) leads to
increased duration of mechanical ventilation (MV)
– Longer duration of ICU stay
• Impede assessment of neurologic function
• Increase risk for delirium
• Numerous agent-specific adverse events
Kollef MH, et al. Chest. 1998;114:541-548.
Pandharipande PP, et al. Anesthesiology. 2006;104:21-26.
American College of Critical Care Medicine
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
• Update expected in 2012
Jacobi J, et al. Crit Care Med. 2002;30:119-141.
Identifying and Treating Pain
FACES Pain Scale 0–10
Wong DL, et al. Wong’s Essentials of Pediatric Nursing. 6th ed.
St. Louis, MO: Mosby, Inc; 2001. p.1301.
Behavioral Pain Scale (BPS) 3-12
Item
Facial
expression
Upper limbs
Compliance with
ventilation
Description
Score
Relaxed
1
Partially tightened (eg, brow lowering)
2
Fully tightened (eg, eyelid closing)
3
Grimacing
4
No movement
1
Partially bent
2
Fully bent with finger flexion
3
Permanently retracted
4
Tolerating movement
1
Coughing but tolerating ventilation for
most of the time
2
Fighting ventilator
3
Unable to control ventilation
4
Payen JF, et al. Crit Care Med. 2001;29(12):2258-2263.
BPS Validation
Sedated Mechanically Ventilated Patients
Is BPS Sensitive to Pain?
Is BPS Reproducible?
Weighted  = 0.74, P < 0.01
□ Not painful n = 104
BPS
▲ Retested painful n = 31
Re-Exposed to Pain
● Painful n = 134
Exposed to Pain
* P < 0.05 vs rest period
†P < 0.05 vs not painful
Payen JF, et al. Crit Care Med. 2001;29:2258–2263.
Critical Care Pain Observation Tool 0-8
Gélinas C, et al. Am J Crit Care. 2006;15:420-427.
Critical Care Pain Observation Tool
Sensitivity/Specificity DURING Painful Procedure
Gélinas C, et al. Am J Crit Care. 2006;15:420-427.
Correlating Pain Assessment with
Analgesic Administration in the ICU
• Pain scoring used in 21%
of surveyed ICUs in 20062
Assessed
100
Patients (%)
• Fewer patients assessed for
pain, more treated with
analgesics in ICUs without
analgesia protocols
compared with ICUs with
protocols1
Treated
*
92
87
80
60
60
40
*
25
20
0
Protocol
No Protocol
* P < 0.01 vs ICUs using a protocol
1. Payen JF, et al. Anesthesiol. 2007;106:687-695.
2. Martin J, et al. Crit Care. 2007;11:R124.
Assessing Pain Reduces
Sedative/Hypnotic Use
What proportion of MV ICU patients received
sedative or hypnotic medication?
Day 2 Pain Assessment?
P-value
No (n = 631)
Yes (n = 513)
Any sedative
86%
75%
< 0.01
Midazolam
65%
57%
< 0.01
Propofol
21%
17%
0.06
Other
6%
4%
0.03
Payen JF, et al. Anesthesiology. 2009;111;1308-1316.
Assessing Pain Improves
Some Outcomes
Outcome
Day 2 Pain
Assessment?
Unadj.
OR
P-value
Adjusted
OR
P-value
No
Yes
ICU Mortality
22%
19%
0.91
0.69
1.06
0.71
ICU LOS
18 d
13 d
1.70
< 0.01
1.43
0.04
MV duration
11 d
8d
1.87
< 0.01
1.40
0.05
Vent-acquired
pneumonia
24%
16%
0.61
< 0.01
0.75
0.21
Thromboembolic events, gastroduodenal hemorrhage, and CVC
colonization were less than 10%, and not changed by pain assessment.
Payen JF, et al. Anesthesiology. 2009;111:1308-1316.
Maintaining Patients at the Desired
Sedation Goal
Sedation-Agitation Scale (SAS)
Score
State
Behaviors
7
Dangerous
Agitation
Pulling at ET tube, climbing over bedrail, striking at staff,
thrashing side-to-side
6
Very Agitated
5
Agitated
4
Calm and
Cooperative
3
Sedated
2
Very Sedated
Arouses to physical stimuli but does not communicate or
follow commands
1
Unarousable
Minimal or no response to noxious stimuli, does not
communicate or follow commands
Does not calm despite frequent verbal reminding,
requires physical restraints
Anxious or mildly agitated, attempting to sit up, calms
down to verbal instructions
Calm, awakens easily, follows commands
Difficult to arouse, awakens to verbal stimuli or gentle
shaking but drifts off
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
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
-4
Deep sedation
-5
Unarousable
Verbal Stimulus
no eye contact
physical stimulation
Physical Stimulus
no response even with physical
Ely EW, et al. JAMA. 2003;289:2983-2991.
Sessler CN, et al. Am J Respir Crit Care Med. 2002;166(10):1338-1344.
Sedation Scale Reliability
r2
0.83
Kappa
0.92
0.93
SAS
Riker, 1999
Brandl, 2001
RASS
Sessler, 2002
Ely, 2003
0.80
0.91
Ramsay
Riker, 1999
Ely, 2003
Olson, 2007
0.88
0.94
0.28
MAAS
Devlin, 1999
Hogg, 2001
0.83
0.81
MSAT
Weinert, 2004
0.72-0.85
Correlating Sedation Assessment with
Sedative Administration in the ICU
• 1381 ICU patients included
in an observational study of
sedation and analgesia
practices1
• Use of sedation protocols
and scores increased
between 2002 and 20062
Patients (%)
• Fewer patients assessed,
more treated with sedatives
in ICUs without sedation
protocols compared with
ICUs with protocols1
Assessed
80
70
60
50
40
30
20
10
0
Treated
*
76
68
56
*
31
Protocol
No Protocol
* P < 0.01 vs ICUs using a protocol
1. Payen JF, et al. Anesthesiol. 2007;106:687-695.
2. Martin J, et al. Crit Care. 2007;11:R124.
The Importance of Preventing and
Identifying Delirium
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%
of cases
Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.
Patient Factors
Increased age
Alcohol use
Male gender
Living alone
Smoking
Renal disease
Predisposing Disease
Less Modifiable
Cardiac disease
Cognitive impairment
(eg, dementia)
Pulmonary disease
Acute Illness
DELIRIUM
Environment
Admission via ED or
through transfer
Isolation
No clock
No daylight
No visitors
Noise
Use of physical restraints
More Modifiable
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
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.
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
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
Score 1 point for each component present during shift
• Score of 1-3 = Subsyndromal Delirium
• Score of ≥ 4 = Delirium
Bergeron N, et al. Intensive Care Med. 2001;27:859-864.
Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013.
Subsyndromal Delirium and Clinical Outcomes
No
delirium
(ND)
Subsyndromal
(SD)
Clinical
(CD)
P value*
ICU
Mortality
2.4%
10.6%
15.9%
P < 0.001
ICU LOS
2.5 d
5.2 d
10.8 d
Hospital
LOS
Severity of
illness
(APACHE II)
31.7 d
12.9
40.9 d
16.7
P < 0.001
36.4 d
ND vs. SD, P = 0.002
ND vs. CD, P < 0.001
SD vs. CD, P = 0.137
18.6
ND vs. SD, P < 0.001
ND vs. CD, P < 0.001
SD vs. CD, P < 0.016
*Pairwise comparison
Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013.
What to THINK When Delirium Is Present
• Toxic Situations
– CHF, shock, dehydration
– Deliriogenic meds (Tight Titration)
– New organ failure, eg, liver, kidney
• Hypoxemia; also, consider giving Haloperidol
or other antipsychotics?
• Infection/sepsis (nosocomial), Immobilization
• Nonpharmacologic interventions
– Hearing aids, glasses, reorient, sleep protocols,
music, noise control, ambulation
• K+ or Electrolyte problems
See Skrobik Y. Crit Care Clin. 2009;25:585-591.
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
• Increase length of stay
• Increased risk of complications
- Ventilator-associated pneumonia
• Increased diagnostic testing
• Inability to evaluate for delirium
Consequence of Improper Sedation
•
30.6%
15.4%
•
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
•
54.0%
Sedation should be titrated to achieve a
cooperative patient and daily wake-up,
a JC requirement1,2
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.
Opioids
Clinical Effects
Adverse Effects
• Respiratory depression
• Analgesia
• Sedation
• Hypotension
• Bradycardia
• Constipation
• Tolerance
Fentanyl
• Withdrawal symptoms
• Hormonal changes
Morphine
Remifentanil
Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S105-120.
Opioid Mechanisms
Neurotransmitters
ACh
Acetylcholine
Glu
Glutamate
NE
Norepinephrine
Brown EN, et al. N Engl J Med. 2010;363(27):2638-2650.
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.
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.
Analgosedation Intervention
Morphine prn at 2.5 or 5 mg for comfort
Physician consult if patient seemed uncomfortable
Haloperidol prn for delirium
If still uncomfortable, propofol infusion for 6 hours
Transitioned back to prn morphine
Strøm T, et al. Lancet. 2010;375:475-480.
Analgosedation
Results
• 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.
Options for Sedation:
Recent Clinical Results
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
1. Ostermann ME, et al. JAMA. 2000;283:1451-1459.
2. Jacobi J, et al. Crit Care Med. 2002;30:119-141.
3. Dasta JF, et al. Pharmacother. 2006;26:798-805.
4. 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
GABA Agonist
Benzodiazepine Midazolam
Clinical Effects
• Sedation, anxiolysis, and
amnesia
• Rapid onset of action (IV)
Adverse Effects
• May accumulate with hepatic
and/or renal failure
• Anterograde amnesia
• Long recovery time
• Synergy with opioids
• Respiratory depression
• Delirium
Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360.
Riker RR, et al; SEDCOM Study Group. JAMA. 2009;301(5):489-499.
Midazolam Pharmacodynamics:
It’s About Time
• Highly lipid soluble
• α-OH midazolam metabolite
• CYP3A4 activity decreased in critical illness
• Substantial CYP3A4 variability
Time to Endpoint (h)
60
50
40
Extubation
Alertness Recovery
30
20
10
0
<1
1-7
>7
Sedation Time (days)
Carrasco G, et al. Chest. 1993;103:557-564.
Bauer TM, et al. Lancet. 1995;346:145-147.
GABA Agonist
Benzodiazepine Lorazepam
Clinical Effects
 Sedation, anxiolysis, and
amnesia
 Commonly used for longterm sedation
Adverse Effects
 Metabolic acidosis (propylene glycol
vehicle toxicity)
 Retrograde and anterograde amnesia
 Delirium
Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360.
Wilson KC, et al. Chest. 2005;128(3):1674-1681.
Transitioning to
Delirium Only
OR (95% CI)
P Value
Lorazepam
1.2 (1.1-1.4)
0.003
Midazolam
1.7 (0.9-3.2)
0.09
Fentanyl
1.2 (1.0-1.5)
0.09
Morphine
1.1 (0.9-1.2)
0.24
Propofol
1.2 (0.9-1.7)
0.18
Medication
Delirium Risk
Risk of Delirium With Benzodiazepines
Lorazepam Dose, mg
Pandharipande P, et al. J Trauma. 2008;65:34-41.
Pandharipande P, et al. Anesthesiol. 2006:104:21-26.
GABA Agonist Propofol
Clinical Effects
•
•
•
•
•
•
•
•
Sedation
Hypnosis
Anxiolysis
Muscle relaxation
Mild bronchodilation
Decreased ICP
Decreased cerebral metabolic rate
Antiemetic
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)
Ellett ML. Gastroenterol Nurs. 2010;33(4):284-925.
Lundström S, et al. J Pain Symptom Manage. 2010;40(3):466-470.
Central Mechanisms of Propofol
Monoaminergic pathways
Cholinergic pathways
Lateral hypothalamus neurons
Brown EN, et al. N Engl J Med. 2010;363(27):2638-2650.
Neurotransmitters
ACh
Acetylcholine
DA
Dopamine
GABA
γ-Aminobutyric acid
GAL
Galanin
Glu
Glutamate
His
Histamine
NE
Norepinephrine
5HT
Serotonin
Propofol Has Greater Sedation Efficacy
Than Continuous Midazolam
Efficacy of Sedation*
n = 18 trials
* Avg adequate sedation time
avg total sedation time
Walder B, et al. Anesth Analg. 2001;92:975-983.
Duration of
Adequate Sedation
n = 15 trials
Continuous Midazolam Has Longer
Weaning Time From MV Than Propofol
Data from 8 RCT
Walder B, et al. Anesth Analg. 2001;92:975-983.
Scheduled Intermittent Lorazepam vs Propofol
with Daily Interruption in MICU Patients
Lorazepam
n = 64
Propofol
n = 68
P value
Ventilator days
8.4
5.8
0.04
ICU LOS
10.4
8.3
0.20
APACHE II
22.9
20.7
0.05
Daily sedation
dose
11.5 mg
24.4 mcg/kg/min
_
Morphine dose
(mg/day)
10.7
31.6
0.001
Use of haloperidol
12%
9%
0.80
Carson SS, et al. Crit Care Med. 2006;34:1326-1332.
a2 Agonist Clonidine
Clinical Effects
•
•
•
•
•
Antihypertensive
Analgesia
Sedation
Decrease sympathetic activity
Decreased shivering
Adverse Effects
•
•
•
•
Bradycardia
Dry mouth
Hypotension
Sedation
Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349.
Bergendahl H, et al. Curr Opin Anaesthesiol. 2005;18(6):608-613.
Hossmann V, et al. Clin Pharmacol Ther. 1980;28(2):167-176.
Physiology of a2 Adrenoceptors
a2A
Anxiolysis
a2A
a2C
X
? a2B
a2A
a2B
X
a2A
? a2B
Adapted from Kamibayashi T, Maze M. Anesthesiology. 2000;93:1346-1349.
a2 Agonist Dexmedetomidine
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
Central Mechanisms of
Dexmedetomidine
Neurotransmitters
ACh
DA
GABA
GAL
Glu
His
NE
5HT
Brown EN, et al. N Engl J Med. 2010;363(27):2638-2650.
Acetylcholine
Dopamine
γ-Aminobutyric acid
Galanin
Glutamate
Histamine
Norepinephrine
Serotonin
Maximizing Efficacy of Targeted Sedation and
Reducing Neurological Dysfunction (MENDS)
• Double-blind RCT of dexmedetomidine vs lorazepam
• 103 patients (2 centers)
– 70% MICU, 30% SICU patients (requiring mechanical ventilation >
24 hours)
– Primary outcome: Days alive without delirium or coma
• Intervention
– Dexmedetomidine 0.15–1.5 mcg/kg/hr
– Lorazepam infusion 1–10 mg/hr
– Titrated to sedation goal (using RASS) established by ICU team
• No daily interruption
Pandharipande PP, et al. JAMA. 2007;298:2644-2653.
MENDS: Dexmedetomidine vs Lorazepam
P = 0.086
P < 0.001
6
 Differences in 28-day
mortality and delirium-free
days were not significant
2
Dexmedetomidine n = 52
0
Delirium/Coma-Free
Days
 Dexmedetomidine resulted in
more days alive without
delirium or coma (P = 0.01)
and a lower prevalence of
coma (P < 0.001) than
lorazepam
 Dexmedetomidine resulted in
more time spent within
sedation goals than
lorazepam (P = 0.04)
4
Days
8
10
12
P = 0.011
Delirium-Free
Days
Coma-Free
Days
Pandharipande PP, et al. JAMA. 2007;298:2644-2653.
Lorazepam n = 51
MENDS Delirium: All Patients
Pandharipande PP, et al. Crit Care. 2010;14:R38.
MENDS: Survival in Septic ICU Patients
Pandharipande PP, et al. Crit Care. 2010;14:R38.
MENDS Trial: Safety Profile
Outcome
Lorazepam
(n = 50)
Dexmedetomidine
(n = 51)
P-Value
Lowest SBP
97 (88,102)
96 (88,105)
0.58
20%
25%
0.51
0 (0,3)
0 (0,2)
0.72
Sinus bradycardia (< 60/min)
4%
17%
0.03
Heart rate < 40
2%
2%
0.99
Self-extubations
(reintubations)
2 (2)
4 (3)
0.41
Ever hypotensive
(SBP < 80)
Days on vasoactive
meds
Pandharipande PP, et al. JAMA. 2007;298:2644-2653.
SEDCOM:
Dexmedetomidine vs Midazolam
• 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
Outcome
PMidazolam Dexmedetomidine
Value
(n = 122)
(n = 244)
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
93 (76.6%)
132 (54%)
0.001
1.7
2.5
0.002
60 (49%)
153 (63%)
0.02
Delirium prevalence
Delirium-free days
Patients receiving open-label midazolam
Riker RR, et al. JAMA. 2009;301:489-499.
Reduced Delirium Prevalence with
Dexmedetomidine vs Midazolam
SEDCOM
Patients With Delirium, %
100
Dexmedetomidine versus Midazolam, P < 0.001
80
Midazolam
60
Dexmedetomidine
40
20
0
Baseline
1
2
3
4
5
6
57 92
42 60
44 34
Treatment Day
Sample Size
118 229
109 206
Riker RR, et al. JAMA. 2009;301:489-499.
92 175
77 134
SEDCOM Trial:
Safety Outcomes
Outcome
Midazolam
(n = 122)
Dexmedetomidine P(n = 244)
Value
Bradycardia
Bradycardia needing treatment
18.9%
0.8%
42.2%
4.9%
0.001
0.07
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.
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
Haloperidol
X
X
X
X
X
X
X
Tachycardia 1
Bradycardia 1
a2 Agonists
X
morphine
X
fentanyl
*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.
Costs of Drug Therapy
•
•
•
•
•
•
•
•
Acquisition
Waste disposal
Preparation
Distribution
Administration (Nursing time)
Toxicity cost (ADRs)
Monitoring (Time, lab, and diagnostic tests)
Downstream issues (infections, adverse events,
ICU stay, ventilator time, etc)
Dasta JF, Kane-Gill S. Crit Care Clin. 2009;25:571-583.
Drug Acquisition Cost
(70 kg patient, per day)
•
•
•
•
Lorazepam 3 mg/hr:
Midazolam 5 mg/hr
Propofol 30 mcg/kg/min:
Dexmedetomidine 0.5 mcg/kg/hr:
Tufts Medical Center 2009 Pricing
$35
$42
$150
$274
Propofol Is More Cost-Effective Than Lorazepam
Propofol less expensive
Ratio of propofol to lorazepam MV days
2 `
Average duration of MV
Cost of ICU day
0.5
Lorazepam more
effective
Low
High
$1,825
$9,488
75%
5%
Cost of hospital ward day
$1,892
$631
Probability of propofol intolerance
20%
0%c
Probability of lorazepam intolerance
20%
0%
Hospital mortality
Crossover group from propofol
Lorazepam
Physician costs
High
Cost of propofol
$11.37
Daily propofol dose, mg
4,347
Cost of lorazepam
-$30
-$25
Low
$60.77
949
$0.81 $7.82
Daily lorazepam dose, mg
-$35
Midazolam
23 4
-$20
-$15
-$10
-$5
$0
$5
Cost Difference Between Lorazepam and Propofol ($ Thousands)
Cox CE, et al. Crit Care Med. 2008;36:706-714.
$10
$15
$20
$25
$30
$35
MENDS Trial: Cost of Care
Component
Lorazepam
Dexmedetomidine
P-value
Pharmacy
20.6 (10,42)
27.4 (16,46)
0.15
2.9 (2,6)
3.5 (2,7)
0.35
59.5 (36,83)
61.4 (37,108)
0.32
Respiratory
ICU cost
$ – Costs represented in thousands, US dollars (Median, IQR)
Pandharipande PP, et al. JAMA. 2007;298:2644-2653.
SEDCOM Cost of Care
DEX
MID
• Median drug costs
• Dex
$1,166
• Midazolam
$60
60,000
50,149
50,000
40,365
Dollars
40,000
• Total ICU patient savings with
40,501 Dex: $9679
36,571
• Reduced ICU stay
• Reduced MV
30,000
20,000
10,885
10,000
P < 0.01
P < 0.05
7,022
P < 0.01
0
Total ICU cost
Dasta JF, et al. Crit Care Med. 2010;38:497-503.
ICU component
Mechanical ventilation
component
Strategies to Reduce the Duration of
Mechanical Ventilation in Patients
Receiving Continuous Sedation
Nurse-Driven Sedation Protocol
•
•
RCT of RN-driven protocol vs non-protocol sedation care in 321 MICU patients
requiring mechanical ventilation
The protocol:
–
–
–
–
–
Assess pain first
Correct other etiologies for agitation
Use a sedation score to titrate sedatives
Use intermittent sedation first
Actively down-titrated sedation even when patient was at “goal”
Brook AD, et al Crit Care Med. 1999;27:2609-2615.
Pharmacist-Driven Sedation Protocol
Median Days of Mechanical
Ventilation
• 156 MICU patients prescribed continuous sedation
• Protocol encouraged 25% down-titration when patients more
sedated than goal
• Before/after design evaluating impact of pharmacist promoting
protocol on at least a daily basis
10
9
8
7
6
5
4
3
2
1
0
P < 0.001
6.9
5.2
Pharmacist-Led
Marshall J, et al. Crit Care Med. 2008;36:427-433.
Control
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 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
• 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.
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
SBT
SAT+SBT
P-value†
12
15
0.02
Successful extubation
7.0
5
0.05
ICU discharge
13
9
0.02
Hospital discharge
19
15
0.04
97 (58%)
74 (44%)
0.01
Coma
3.0
2.0
0.002
Delirium
2.0
2.0
0.50
Outcome*
Ventilator-free days
Time-to-Event, days
Death at 1 year, n (%)
Days of brain dysfunction
*Median, except as noted
†SBT compared with SAT+SBT
Girard TD, et al. Lancet. 2008;371:126-134.
ABC Trial: 1 Year Follow-Up
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.
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
#1 Barrier
Leads to cardiac ischemia
#2 Barrier
#3 Barrier
Leads to PTSD
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.
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.
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.
Animation = Less Delirium
Control
(n = 55)
P-Value
2
4
0.03
Time in ICU with
Delirium
33%
57%
0.02
Time in Hosp. with
Delirium
28%
41%
0.01
Variable
Intervention
(n = 49)
ICU/Hosp Delirium (days)
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
Procedural Sedation
Major Applications
• Surgical
– CV surgery
– Neurosurgery
– Bariatric surgery
• Endoscopic
– Bronchoscopy
– Fiberoptic intubation
– Colonoscopy
Standardized Monitoring
• Hemodynamic
– ECG
– Blood pressure
• Respiration
– Oxygenation (SpO2 by pulse oximetry, supplemental
oxygen)
– Ventilation (end tidal CO2, EtCO2)
• Temperature (risk of hypothermia)
• Higher risk at remote locations
– Inadequate oxygenation/ventilation
– Oversedation
– Inadequate monitoring
Eichhorn V, et al. Curr Opin Anaesthesiol. 2010;23(4):494-499.
Factors Jeopardizing Safety
• Risk of major blood loss
• Extended duration of surgery (> 6 h)
• Critically ill patients (evaluate and document prior to
procedure)
• Need for specialized expertise or equipment (cardiopulmonary bypass, thoracic or intracranial surgery)
• Supply and support functions or resources are limited
• Inadequate postprocedural care
• Physical plant is inappropriate or fails to meet
regulatory standards
Eichhorn V, et al. Curr Opin Anaesthesiol. 2010;23(4):494-499.
Sedation/Analgesia for Traumatic
Brain Injury
Goal: reduce ICP by decreasing pain, agitation
Agent
Advantages
Considerations
Propofol
• Short acting
• Reduces cerebral
metabolism, O2
consumption
• Improves ICP after 3d
• Propofol infusion syndrome
Barbiturates
• Reduce ICP
• Neuroprotection
• Interfere with neuro exam
• Hypotension, reduced CBF
• OCs not improved with severe TBI
Saiki RL. Crit Care Nurs Clin North Am. 2009;21:549-559.
Fentanyl vs Dexmedetomidine
in Bariatric Surgery
• 20 morbidly obese patients
• Roux-en-Y gastric bypass surgery
• All received midazolam, desflurane to maintain BIS at
45–50, and intraoperative analgesics
– Fentanyl (n = 10) 0.5 µg/kg bolus, 0.5 µg/kg/h
– Dexmedetomidine (n = 10) 0.5 µg/kg bolus, 0.4 µg/kg/h
• Dexmedetomidine associated with
– Lower desflurane requirement for BIS maintenance
– Decreased surgical BP and HR
– Lower postoperative pain and morphine use (up to 2 h)
Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.
Dexmedetomidine in Bariatric Surgery
•
•
•
•
80 morbidly obese patients
Gastric banding or bypass surgery
Prospective dose ranging study
Medication
–
–
–
–
–
Celecoxib
Midazolam
Propofol
Desflurane
Dexmedetomidine
400 mg
20 µg/kg
1.25 mg/kg
4%
0, 0.2, 0.4, 0.8 µg/kg/h
Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.
po
IV
IV
inspired
IV
Dexmedetomidine in Bariatric Surgery:
Results
• More dex 0.8 patients required rescue phenylephrine for
hypotension than control pts (50% vs 20%, P < 0.05)
• All dex groups
–
–
–
–
Required less desflurane (19%–22%)
Had lower MAP for 45’ post-op
Required less fentanyl after awakening (36%–42%)
Had less emetic symptoms post-op
• No clinical difference
–
–
–
–
Emergence from anesthesia
Post-op self-administered morphine and pain scores
Length of stay in post-anesthesia care unit
Length of stay in hospital
Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.
Sedation for Endoscopy
• Desirable qualities
– Permits complete
diagnostic exam
– Safe
– Diminishes memory of
the procedure
– Permits rapid discharge
after procedure
Runza M. Minerva Anestesiol. 2009;75:673-674.
• Risk factors
–
–
–
–
–
–
–
Depth of sedation
ASA status
Medical conditions
Pregnancy
Difficult airway mgt
Extreme age
Rapid discharge time
Propofol vs Combined Sedation
in Flexible Bronchoscopy
• Randomized non-inferiority trial
• 200 diverse patients received propofol or midazolam/hydrocodone
• 1o endpoints
– Mean lowest SaO2
– Readiness for discharge at 1h
• Result
– No difference in mean lowest SaO2
– Propofol group had
• Higher readiness for discharge score (P = 0.035)
• Less tachycardia
• Higher cough scores
• Conclusion: Propofol is a viable alternative to midazolam/ hydrocodone
for FB
Stolz D, et al. Eur Respir J. 2009;34:1024-1030.
Fiberoptic Intubation
Agent
Class
Example
Advantages
Considerations
GABA
agonist
Benzodiazepine
Midazolam
• Quick onset
• Injection not painful
• Short duration
• Not analgesic
• Airway reflexes persist
GABA
agonist
Benzodiazepine
Propofol
• Quick onset
• Respiratory depression
• Unconsciousness
• Decreased bp, cardiac
output
• Increased HR
Opioid
Fentanyl
Remifentanil
• Analgesic
• Cough suppressive
• Respiratory depression
a2 Agonist
Dexmedetomidine
• Pt easily arousable
• Anxiolytic
• Analgesic
• No respir. depression
• Transient hypertension
• Hypotension
• Bradycardia
Summary courtesy of Pratik Pandharipande, MD.
Prevention and Treatment of Delirium
in the ICU
Before Considering a Pharmacologic
Treatment for Delirium…
• Have the underlying causes of delirium been
identified and reversed/treated?
• Have non-pharmacologic treatment strategies been
optimized?
• Does your patient have delirium?
– Hyperactive
– Hypoactive
– Mixed hyperactive-hypoactive
Inouye SK, et al. N Engl J Med. 1999;340:669-676.
Dopamine Antagonist Haloperidol
Clinical Effects
• Hypnotic agent with antipsychotic
properties1
– For treatment of delirium in
critically ill adults1
• Does not cause respiratory
depression1
Adverse Effects
• Dysphoria2
• Adverse CV effects include QT
interval prolongation
• Extrapyramidal symptoms,
neuroleptic malignant syndrome
(rare)1
• Metabolism altered by drug-drug
interactions2
1. Harvey MA. Am J Crit Care. 1996;5:7-16.
2. Crippen DW. Crit Care Clin. 1990;6:369-392.
Use of Haloperidol Is an Independent
Predictor for Prolonged Delirium
Pisani MA, et al. Crit Care Med. 2009;37:177-183.
Potential Advantages of Atypical Antipsychotics
vs Conventional Antipsychotics
• Decreased
extrapyramidal effects
• Little effect on the QTc
interval (with the
exception of ziprasidone)
• Less hypotension/fewer
orthostatic effects
• Less likely to cause
neuroleptic malignant
syndrome
• Unlikely to cause
laryngeal dystonia
• Lower mortality when
used in the elderly to treat
agitation related to
dementia
Tran PV, et al. J Clin Psychiatry. 1997;58:205-211.
Lee PE, et al. J Am Geriatr Soc. 2005;53:1374-1379.
Wang PS, et al. N Engl J Med. 2005;353:2235-2341.
Use of Atypical Antipsychotic
Therapy Is Increasing
90
80
70
60
50
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.
2001
2007
Antipsychotic Therapy
Rule Out Dementia
• Elderly patients with dementia-related psychosis treated with
conventional or atypical antipsychotic drugs are at an increased risk
of death
• Antipsychotic drugs are not approved for the treatment of dementiarelated psychosis. Furthermore, there is no approved drug for the
treatment of dementia-related psychosis
• Physicians who prescribe antipsychotics to elderly patients with
dementia-related psychosis should discuss this risk of increased
mortality with their patients, patients’ families, and caregivers
http://www.canhr.org/ToxicGuide/Media/Articles/FDA%20Alert%20on%20Antipsychotics.pdf
Drug Specificity:
Comparative Receptor Binding Profiles
Quetiapine
Olanzapine
D1D2
D1
5HT2A
D2
5HT1A
5HT2A
M
A1
H1
A1
A2
A2
H1
Ziprasidone
A1
5HT1A
Risperidone
A2 H1
D2 D1
Haloperidol
D1 D2
D1
A1
A1
5HT1A
5HT1A
5HT2A
5HT2A
5HT2A
Adapted from Gareri P, et al. Clin Drug Invest. 2003;23:287-322.
D2
Rationale-based Pharmacotherapy
Important Principles
Receptors
Effects of Receptor Blockade
H1
Sedation, weight gain, postural dizziness
D2
EPS, prolactin elevation, antipsychotic
5-HT2C
Satiety blockade
5-HT2A
Anti-EPS?
α1-adrenergic
Hypotension
M1
Deficits in memory and cognition, dry
mouth, constipation, tachycardia, blurred
vision
Adapted from Weiden P, et al. J Clin Psychiatry. 2007;68:5-46.
Modifying the Incidence of Delirium (MIND) Trial
• Design: Double-blind, placebo-controlled, randomized trial
• Setting: 6 tertiary medical centers
• Intervention:
– Haloperidol (5 mg) vs ziprasidone (40 mg) vs placebo
– Max 14 days
– Dose interval increased if CAM-ICU negative
– Could give IM if NPO up to max 8 doses
– Oversedation: ↓dose frequency when RASS ≥ 2 levels above target
(after holding sedation therapy)
– If delirium reoccurred after d/c of study drug then restarted at last
effective dose (and weaned again as per above)
• Primary outcome:
– Number of days patient alive without delirium or coma during the 21-day
study period
• Delirium = + CAM-ICU
• Coma = RASS (-4) [ie, responsive to physical but not verbal stimulation] or RASS
(-5) [ie, not responsive to either]
Girard TD, et al. Crit Care Med. 2010;38:428-437.
MIND Trial Results
Outcome
Haloperidol,
n = 35
Ziprasidone,
n = 30
Placebo,
n = 36
P-value
Delirium/coma-free days
14.0
15.0
12.5
0.66
Delirium days
4
4
4
0.93
23 (77)
21 (58)
0.28
Delirium resolution on study drug, n(%) 24 (69)
Coma days
2
2
2
0.90
% of days accurately sedated
70
64
71
0.91
Ventilator-free days
7.8
12.0
12.5
0.25
Length of stay, days
ICU
Hospital
21-day mortality, n (%)
11.7
13.8
9.6
13.5
7.3
15.4
0.70
0.68
4 (11)
4 (13)
6 (17)
0.81
0
0
0
0.56
Average extrapyramidal symptoms
score
Girard TD, et al. Crit Care Med. 2010;38:428-437.
Quetiapine for Delirium
Study Design
• Double-blind, placebo-controlled, randomized trial
• 3 academic medical centers
• Intervention
– Quetiapine 50 mg PO/NGT twice daily titrated to a maximum of 200
mg twice daily) vs placebo
– PRN IV haloperidol protocolized and encouraged in each group
– Oversedation: hold study drug when SAS ≤ 2 (after holding sedation
therapy)
• Primary outcome
– Time to first resolution of delirium (ie, first 12-hour period when
ICDSC ≤ 3)
Devlin JW, et al. Crit Care Med. 2010;38:419-427.
258 patients with delirium (ICDSC ≥ 4) tolerating enteral nutrition
222 patients excluded
36 subjects randomized
Quetiapine 50 mg NG bid
(n = 18)
Placebo 50 mg NG bid
(n = 18)
As-needed haloperidol, usual sedation and analgesia
therapy at physician’s discretion
Dose Titration
Increase quetiapine or placebo dose by 50 mg every 12 hours daily
if the subject received ≥ 1 dose of as needed haloperidol in prior 24 hours.
(Maximum dose = 200 mg every 12 hours)
Discontinuation of study drug
1. No signs of delirium
2. 10 days of therapy had elapsed
3. ICU discharge prior to 10 days of therapy
4. Serious adverse event potentially attributable to the study drug
Devlin JW, et al. Crit Care Med. 2010;38:419-427.
Proportion of Patients with Delirium
Patients with First Resolution of 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.
The Interaction Between Sedation,
Critical Illness and Sleep in the ICU
Sleep Abnormalities in the ICU
% time in light sleep increased
(NREM stages 1 and 2)
% time in deep sleep decreased
[slow wave sleep (SWS) and
REM sleep)
Sleep fragmentation increased
Friese R. Crit Care Med. 2008;36:697-705.
Weinhouse GL, Watson PL. Crit Care Clin. 2009;25:539-549.
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.
Strategies to Boost Sleep Quality in the ICU
•
•
•
•
Optimize environmental strategies
Avoid benzodiazepines
Consider dexmedetomidine
Zolpidem and zopiclone are GABA receptor agonists
but do not decrease SWS like the benzodiazepines
• Sedating antidepressants (eg, trazodone) or
antipsychotics may offer an option in non-intubated
patients
• Melatonin may improve sleep of COPD patients in
medical ICU (1 small RCT)
• Don’t disturb sleeping patients at night
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.
American College of Critical Care
Medicine (ACCM) Guidelines
• Clinical practice guidelines for the sustained use of
sedatives and analgesics in the critically ill adult
• Pertains to patients older than 12 years during M V
• Areas of focus
– Assessment for pain, delirium
– Physiological monitoring
– Pharmacologic tools
• Most recommendations grade B or C
Jacobi J, et al. Crit Care Med. 2002;30:119-141.
Conclusions
• Oversedation in the ICU is common; associated with
negative sequelae
• Monitor and treat pain and delirium prior to administering
sedation therapy
• Analgosedation has been shown to improve outcomes;
consider sedation only if necessary
• Titrate all sedative medications using a validated
assessment tool to keep patients comfortable and
arousable if possible
• Monitor for adverse events
Conclusions
• ICU sedation should use protocols that include a downtitration and/or daily interruption strategy coupled with a
spontaneous breathing trial
• Multiple sedatives are available
• Propofol and dexmedetomidine will liberate patients from
mechanical ventilation faster than benzodiazepine therapy
(even when administered intermittently) and are associated
with less delirium
• Use of benzodiazepines should be minimized
Conclusions
• Cost of care calculations should consider the overall
costs, not just drug acquisition costs
• Early mobility in ICU patients decreases delirium and
improves functional outcomes at discharge
• Consider non-pharmacological management of
delirium and reduce exposure to risk factors
• Typical and atypical antipsychotic medications may
be used to treat delirium if non-pharmacological
interventions are not adequate