Sedation & Analgesia
PICU Resident Talk
Stanford School of Medicine
Pediatric Critical Care Medicine
June 2010
Objectives
After this lesson, the participant will be able to:
• Differentiate between sedation and analgesia.
• Develop an appropriate sedation/analgesia
plan, taking into consideration: airway, depth
of sedation needed, time to onset of drug
effect, duration of sedation/analgesia effect.
• Describe the differences between distribution
half life, elimination half-life and context
sensitive half life.
Questions to ask yourself
• Does patient need pain control or sedation? How
can you tell which one?
• Why does patient need sedation or pain control?
Could the objective be achieved without it?
Might agents for sedation or pain control make
the patient worse (ie delirium)?
• How quickly do you need effect?
• How long do you need effect?
• At what risk to the patient?
• Are you prepared? Airway, BP support
Definitions
• Sedation--Reduction of anxiety, stress,
irritability, or excitement by administration of
a sedative agent or drug
• Analgesia--the relief of pain
Levels of Sedation
• Minimal Sedation (anxiolysis)
– Normal response to verbal stimulus
• Moderate Sedation (conscious sedation)
– Depressed consciousness but response to verbal commands
• Deep Sedation
– Difficult to arouse
– May need assistance w/ airway patency & ventilation
• General Anesthesia
– Not able to arouse even by painful stimulation
– Impaired airway, ventilation & possibly cardiovascular function
Commonly used agents
Analgesics
• Acetaminophen
• NSAIDS/ketorolac
• Opioids (morphine,
fentanyl, dilaudid)
Analgesic and Sedative
Effects
Ketamine
Dexmedetomidine
Remifentanil
Sedatives
• Chloral Hydrate
• Benzodiazepines
(midazolam, lorazepam,
diazapam)
• Propofol
• Barbituates (methohexital,
thiopental, phenobarbital,
pentabarbital)
• Etomidate
Opioids
• Mediate pain by binding to the mu, kappa,
and delta receptors.
• Dose dependent sedative effect via kappa
receptor
• Dose dependent respiratory depression and
decrease in blood pressure
• Reversal agent: Naloxone
Opioids
Agent
Potency
Peak effect
Active
Metabolite
Adverse
reactions
Morphine
1
Peak effect 20
minutes
Yes (Renal)
Histamine
effects
HydroMorphone
5-7
Peak effect
8-10 minutes
No
No Histamine
effects, no rigid
chest
Fentanyl
75-100
Peak effect 5
minutes
No
Rigid chest if
given rapidly
Comparitive Onset of Opioids
Percent of peak effect
site concentration
100
Hydromorphone
Morphine
80
60
Fentanyl
40
20
0
0
5
10
15
Minutes since bolus injection
20
Benzodiazepines
•
•
•
•
GABA agonist
Causes sedation/hypnosis, anxiolysis, amnesia
No analgesia
Dose dependent respiratory depression and
decrease in blood pressure
• Reversal agent: flumazenil
Benzodiazepines
Agent
Potency
Onset
Active
Metabolites
Adverse
Reactions
Midazolam
½ as potent as
lorazepam
1-5 minutes
Yes
Paradoxical
effects
Lorazepam
2 times as
potent as
midazolam
5-15 minutes
No
Paradoxical
effects (less
than
midazolam)
Chloral Hydrate
•
•
•
•
•
•
Sedative-hypnotic
Onset of action: 10-20 minutes
Peak action: 60 minutes
Duration 4-8 hours
No reversal agent
Unreliable in children over 3 years of age
(Krauss Lancet 2006)
Propofol
•
•
•
•
•
•
GABA agonist—binds alpha subunit
Sedative only, no analgesic effects
Rapid onset and offset and no withdrawal
Onset: within 30 seconds
Duration: 3-10 minutes but depends on duration of infusion
PK follows 3 compartment model
– Rapid distribution from blood into tissues
– Rapid metabolic clearance from blood
• Hepatic + extra-hepatic metabolism
– Slow return to blood from peripheral compartment
Propofol
• Propofol infusion syndrome—most often lactic
acidosis, rhabdomyolysis, and circulatory collapse
(Wysowski Anesthesia 2006, Cremer Critical Care
2009)
• Propofol infusion syndrome typically occurs when
high doses (greater than 67-83mcg/kg/min) are
given for long periods of time (greater than 24
hours). (Roberts Critical Care Med 2009, Cremer
Lancet 2001 and Cornfield Pediatrics 2002)
• Not indicated for sedation in the PICU according to
product label
Ketamine
• “Dissociative” anesthetic
• Works at multiple receptors—NMDA receptor antagonist,
opiate receptor agonist
• Bronchodilation effects (Hemmingsen Am J Emerg Med 1994)
• Associated with hemodynamic stability and sometimes
hypertension
• Respiratory effort and airway reflexes maintained
• Onset of action: 30 seconds to 1 minute
• Duration of action: 5-30 minutes
• Adverse effects: increased secretions, dysphoria, pychosis
(may be improved with midazolam premedication)
Dexmedetomidine
• Alpha-2 adrenergic agonist
• Has both sedative and analgesic properties
• Adverse effects: bradycardia, may excacerbate
heart block, hypertension, hypotension
Etomidate
• Sedative-hypnotic
• Used primarily for procedures; doesn’t cause
hemodynamic instability
• Onset of action: 5-30 seconds
• Peak action: 1 minute
• Duration of action: 2-10 minutes
• Adverse effect: Transient adrenal suppression
(Wagner New England Journal 1984)
Barbiturates
• Methohexital, thiopental, pentobarbital
• GABA receptor agonist
• Rarely used in PICU because of hemodynamic
effects and because there is no reversal agent
• Used for seizure burst suppression
Elimination Half Life versus Context
Sensitive Half Life
• Distribution half life (t1/2): the time required for plasma
conc. to drop by 50% due to movement from central to
peripheral compartment
• Elimination half life (t1/2): the time necessary to
metabolize/excrete 50% of the drug from the body after IV
injection
• Context Sensitive half life: Time for plama drug concentration
to decrease by 50% after cessation of an infusion.
Incorporates effects of redistribution into and out of
peripheral compartments (3 compartment model).
Summary of Key Points
• Be prepared to manage adverse effects when
you give a sedative or analgesic drug
• Have a plan! Know what is needed to achieve
your goals.
• Understand the pharmacokinetics
Cases
• 1 year old intubated for ALI and pneumonia
who needs sedation for arterial line
placement.
• 5 year old with elevated WBC count and
mediastinal mass on Chest X-ray and oncology
wants a chest CT.
• 4 year old returns from OR after undergoing
LTR. Needs to be sedated for a week.