Sedation & Analgesia

PICU Resident TalkStanford School of Medicine

Pediatric Critical Care MedicineJune 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)

Sedatives• Chloral Hydrate• Benzodiazepines

(midazolam, lorazepam, diazapam)

• Propofol• Barbituates (methohexital,

thiopental, phenobarbital, pentabarbital)

• Etomidate

Analgesic and Sedative Effects

KetamineDexmedetomidineRemifentanil

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

OpioidsAgent Potency Peak effect Active

MetaboliteAdverse reactions

Morphine 1 Peak effect 20 minutes

Yes (Renal) Histamine effects

Hydro- Morphone

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

Minutes since bolus injection0 5 10 15 20

Per

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0

20

40

60

80

100

Fentanyl

Hydromorphone

Morphine

Comparitive Onset of Opioids

Benzodiazepines

• GABA agonist• Causes sedation/hypnosis, anxiolysis, amnesia• No analgesia• Dose dependent respiratory depression and

decrease in blood pressure• Reversal agent: flumazenil

BenzodiazepinesAgent Potency Onset Active

MetabolitesAdverse 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.