Sedation, Analgesia and Paralysis
in ICU
Mazen Kherallah, MD, FCCP
ICU Sedation
• ICU sedation is a complex clinical
problem
• Current therapeutic approaches all
have potential adverse side effects
• Agitated patients are often
hypertensive, increase stress hormones,
and require more intensive nursing
care
The Need for Sedation
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Anxiety
Pain
Acute confusional status
Mechanical ventilation
Treatment or diagnostic procedures
Psychological response to stress
Goals of sedation in the ICU
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Patient comfort and
Control of pain
Anxiolysis and amnesia
Blunting adverse autonomic and
hemodynamic responses
Facilitate nursing management
Facilitate mechanical ventilation
Avoid self-extubation
Reduce oxygen consumption
Characteristics of an ideal sedation agents
for the ICU
• Lack of respiratory depression
• Analgesia, especially for surgical patients
• Rapid onset, titratable, with a short
elimination half-time
• Sedation with ease of orientation and
arousability
• Anxiolytic
• Hemodynamic stability
The Challenges of ICU Sedation
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Assessment of sedation
Altered pharmacology
Tolerance
Delayed emergence
Withdrawal
Drug interaction
Sedation
Causes for Agitation
Sedatives
Undersedation
Sedatives
Causes for Agitation
Agitation & anxiety
Pain and discomfort
Catheter displacement
Inadequate ventilation
Hypertension
Tachycardia
Arrhythmias
Myocardial ischemia
Wound disruption
Patient injury
Oversedation
Causes for Agitation
Prolonged sedation
Delayed emergence
Respiratory depression
Hypotension
Bradycardia
Increased protein breakdown
Muscle atrophy
Venous stasis
Pressure injury
Loss of patient-staff interaction
Increased cost
Sedatives
Correctable Causes of Agitation
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Full bladder
Uncomfortable bed position
Inadequate ventilator flow rates
Mental illness
Uremia
Drug side effects
Disorientation
Sleep deprivation
Noise
Inability to communicate
Causes of Agitation Not to be
Overlooked
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Hypoxia
Hypercarbia
Hypoglycemia
Endotracheal tube malposition
Pneumothorax
Myocardial ischemia
Abdominal pain
Drug and alcohol withdrawal
Altered Pharmacology
.
.
T
/
hours
Midazolam and Age
.
.
.
Age (y)
Harper et al. Br J Anesth, 1985;57:866-871
Delayed Emergence
• Overdose (prolonged infusion)
– pK derived from healthy patients
– Drug interaction
– Individual variation
• Delayed elimination
– Liver (Cp450)
– Kidney dysfunction
– Active metabolites
Morphine Metobolism
Morphine
Type title here
80%
Morphine-3-G
Antianalgesic
10%
Normorphine
Neurotoxicity
Morphine-6-G
Analgesic (40X)
Withdrawal
• Withdrawal from preoperative drugs
• Sudden cessation of sedation
– Return of underlying agitation
• Hyperadrenergic syndrome
– Hypertension, tachycardia,sweating
• Opioid withdrawal
– Salivation, yawning, diarrhea
Drug Interactions
Diazepam-Morphine Interaction
Antagonism
Diazepam
Synergism
Morphine
Kissin et al. Anesthesiology. 1989, 70:689-694
ED50 isobologram
Righting reflex
In rats
Strategies for Patient Comfort
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Set treatment goal
Quantitate sedation and pain
Choose the right medication
Use combined infusion
Reevaluate need
Treat withdrawal
Set Treatment Goal
Sedation
Amnesia
Analgesia
Hypnosis
Anxiolysis
Patient Comfort
Quantitate Sedation & Analgesia
• Subjective measure
• Objective measures
Sedation Scoring Scales
• Ramsay Sedation Scale (RSS)
• Sedation-agitation Scale (SAS)
• Observers Assessment of Alertness/Sedation
Scale (OAASS)
• Motor Activity Assessment Scale (MAAS)
BMJ 1974;2:656-659
Crit Care Med 1999;27:1325-1329
J Clin Psychopharmacol 1990;10:244-251
Crit Care Med 1999;27:1271-1275
The Ramsay Scale
Scale
Description
1
Anxious and agitated or restless, or both
2
Cooperative, oriented, and tranquil
3
Response to commands only
4
Brisk response to light glabellar tap or loud
auditory stimulus
Sluggish response to light glabellar tap or loud
auditory stimulus
No response to light glabellar tap or loud
auditory stimulus
5
6
The Riker Sedation-Agitation Scale
Score Description
Definition
7
Dangerous agitation Pulling at endotracheal tube, trying to strike
at staff, thrashing side to side
6
Very agitated
Does not calm despite frequent verbal
commands, biting ETT
5
Agitated
Anxious or mildly agitated, attempting to sit
4
Calm and
cooperative
Calm, awakens easily, follows commands
3
Sedated
Difficult to arouse, awakens to verbal
stimuli, follows simple commands
2
Very sedated
Arouse to physical stimuli, but does not
communicate spontaneously
1
Unarousable
Minimal or no response to noxious stimuli
The Motor Activity Assessment Scale
Score Description
Definition
6
Dangerous agitation Pulling at endotracheal tube, trying to strike
at staff, thrashing side to side
5
Agitated
Does not calm despite frequent verbal
commands, biting ETT
4
Restless and
cooperative
Anxious or mildly agitated, attempting to sit
3
Calm and
cooperative
Calm, awakens easily, follows commands
2
Responsive to touch Opens eyes or raises eyebrows or turns head
or name
when touched or name is loudly spoken
1
Responsive only to
noxious stimuli
Opens eyes or raises eyebrows or turns head
with noxious stimuli
0
Unresponsive
Does not move with noxious stimuli
What Sedation Scales Do
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Provide a semiquantitative “score”
Standardize treatment endpoints
Allow review of efficacy of sedation
Facilitate sedation studies
Help to avoid oversedation
What Sedation Scales Don’t Do
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Assess anxiety
Assess pain
Assess sedation in paralyzed patients
Predict outcome
Agree with each other
BIS Monitoring
BIS Monitoring
BIS Range Guidelines
BIS
100
80
60
40
20
0
Awake
Responds to normal voice
Axiolysis
Responds to loud commands
or mild prodding/shaking
Moderate
sedation
Low probability to explicit recalls
Unresponsive to verbal stimuli
Burst suppression
Flat line EEG
Deep Sedation
Assess Pain Separately
Pain
Visual Pain Scales
0
No pain
1
2
3
4
5
6
7
8
9
10
Worst possible
pain
Signs of Pain
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Hypertension
Tachycardia
Lacrimation
Sweating
Pupillary dilation
Principles of Pain Management
• Anticipate pain
• Recognize pain
– Ask the patient
– Look for signs
– Find the source
• Quantify pain
• Treat:
– Quantify the patient’s perception of pain
– Correct the cause where possible
– Give appropriate analgesics regularly as required
• Remember, most sedative agents do not provide
analgesia
• Reassess
Nonpharmacologic Interventions
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Proper position of the patient
Stabilization of fractures
Elimination of irritating stimulation
Proper positioning of the ventilator tubing
to avoid traction on endotracheal tube
Choose the Right Drug
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Benzodiazepines
Propofol
Opioids
-2 agonists
Choose the Right Drug
Sedation
Amnesia
Analgesia
Hypnosis
Benzodiazepines
Anxiolysis
Benzodiazepines
Onset
Peaks
Duration
Diazepam
2-5 min
5-30 min
>20 hr
Midazolam
2-3 min
5-10 min
30-120
min
Lorazepam
5-20 min
30 min
10-20 hr
Choose the Right Drug
Sedation
Amnesia
Analgesia
Hypnosis
Propofol
Anxiolysis
Propofol
Propofol
Onset
Peaks
Duration
30-60 sec
2-5 min
short
Propofol Dosing
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3-5 g/kg/min antiemetic
5-20 g/kg/min anxiolytic
20-50 g/kg/min sedative hypnotic
>100 g/kg/min anesthetic
Choose the Right Drug
Sedation
Amnesia
Analgesia
Hypnosis
Anxiolysis
Opioids
Pharmacology of Selected Analgesics
Agent
Dose (iv)
Half-life
Metabolic pathway Active
metabolites
Fentanyl
200 g
1.5-6 hr
Oxidation
None
Hydromorphone
1.5 mg
2-3 hr
Glucuronidation
None
Morphine
10 mg
3-7 hr
Glucuronidation
Yes (Sedation
in RF)
Meperidine
75-100
mg
3-4 hr
Demethylation &
hydroxylation
Yes
(neuroexcitation
in RF)
Codeine
120 mg
3 hr
Demethylation &
Glucuronidation
Yes (
analgesia,
sedation)
Remifentanil
3-10 min
Plasma esterase
None
Keterolac
2.4-8.6 hr
Renal
None
Opioids
Lipid
Histamine
Solubility Release
Morphine
Hydromorphone
Fentanyl
Potency
+/-
+++
1
+
+
5
+++
-
50
Opioids
Onset
Peaks
Duration
Morphine
2 min
20 min
2-7 hr
Fentanyl
30 sec
5-15 min 30-60 min
Problems with Current Sedative Agents
Prolonged weaning
Respiratory depression
Severe hypotension
Tolerance
Hyperlipidemia
Increased infection
Constipation
Lack of orientation and
cooperation
Midazolam
X
X
X
X
X
Propofol Opioids
X
X
X
X
X
X
X
X
X
Choose the Right Drug
Sedation
Amnesia
Analgesia
Hypnosis
Anxiolysis
-2 agonists
Alpha-2 Receptors
Brain
(locus ceruleus)
Spinal Cord
Peripheral
vasculature
Sedation
Anxiolysis
Sympatholysis
Analgesia
Vasoconstriction
DEX: Dosing
Loading infusion
0.25-1 g/kg
(10-20 min)
Maintenance infusion
0.2-0.7 g/kg/hr
Use Continuous and Combined Infusion
Load
Maintenance
Plasma
Level
Repeated Bolus
Plasma
levels
Opioid + Hypnotic Infusion
Fentanyl + Midazolam or Propofol
Analgesia
Amnesia
Anxiolysis
Hypnosis
Continuous Infusion Regimens
Fentanyl
Midazolam
Propofol
25-250 g/h
0.5-5 mg/hr
15-50 g/kg/min
Choose the Right Drug
Sedation
Amnesia
Primary
Adjunct
sedation
Analgesia
Hypnosis
-2 agonists
Propofol
Anxiolysis
Choose the Right Drug
Sedation
Amnesia
Primary
Adjunct
sedation
Analgesia
Hypnosis
-2 agonists
Midazolam
Anxiolysis
Choose the Right Drug
Sedation
Amnesia
Primary
Adjunct
analgesia
Analgesia
Hypnosis
Anxiolysis
-2 agonists
Morphine
Choose the Right Drug
Sedation
Amnesia
Primary
Adjunct
analgesia
Analgesia
Hypnosis
Anxiolysis
-2 agonists
Fentanyl
Reassess Need
• Use sedation score as endpoint
• Initiate sedation incrementally to desired
level
• Periodically (q day) titrate infusion rate
down until the patient begins to emerge
• Gradually increase infusion rate again to
desired level of sedation
Barr, Donner. Crit Care Clin. 1995;11827
Treat Withdrawal
• Acute management
– Resume sedation
– Beta-blockade, dexmedetomidine
• Prolonged management
– Methadone 5-10 mg VT bid
– Clonidine 0.1-0.2 mg VT q8h
– Lorazepam 1-2 mg IV q8h