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.