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Advanced Sedation Fellows’ Conference 9-26-07

Advanced Sedation Fellows’ Conference 9-26-07. Thao M. Nguyen, MD PEM fellow Emory University Children’s Healthcare of Atlanta. Objectives. Review historical perspective of pain & sedation Review presedation factors Review common agents of procedural sedation

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Advanced Sedation Fellows’ Conference 9-26-07

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  1. Advanced SedationFellows’ Conference9-26-07 Thao M. Nguyen, MD PEM fellow Emory University Children’s Healthcare of Atlanta

  2. Objectives • Review historical perspective of pain & sedation • Review presedation factors • Review common agents of procedural sedation • Review more restricted or up-and-coming agents • Review common complications of sedation

  3. Historical perspective Pain in children are underreported, undertreated, and misunderstood Children do not get the same treatment as adults who have similar painful conditions

  4. Misconceptions • Children…. • cannot experience pain due to a immature CNS • have no memory of pain • cannot quantify or qualify their pain (thereby pain underestimated) • Physicians… • are concerned about masking symptoms • fear adverse effects • cardio-pulmonary decompensation • addiction • lack sedation training

  5. Development Milestones

  6. The old way

  7. The new way

  8. Sedation Goals • Alleviate anxiety • Minimize pain • Minimize negative psychological impact • Maximize amnesia • Control behavior to expedite efficiency and improve quality • Maintain safety and minimize risks • Ensure safe discharge • BETTER OUTCOME

  9. Definitions • Sedation occurs along a continuum… • Analgesia • Relief of pain • Minimal Sedation (anxiolysis) • Responds to verbal commands • Cognitive function and coordination may be impaired • Ventilatory and cardiovascular not affected

  10. Definitions • Moderate • Responds to verbal commands alone or accompanied by touch. Airway, ventilation and cardiovascular maintained • Deep • Cannot be easily aroused but responds to noxious stimuli. May require assistance to maintain airway and adequate ventilation, cardiovascular maintained • General Anesthesia • Patient cannot be aroused. Often requires assistance to maintain airway and positive pressure ventilation. Cardiovascular status may be impaired

  11. Presedation Factors • Factors relating to procedure: • Duration of the procedure • Pain as a side effect of a procedure • Position required for the procedure • Anxiety/Stress/inability to cooperate as a side effect of the procedure • Availability of rescue resources • Factors relating to patient: • Discussed in further slides • Factors relating to provider: • Dedicated sedation monitor • Skills related to depth of sedation • Back-up systems and ability to rescue

  12. ASA Physical Status Classification add E to any of above for emergent procedure

  13. ASA examples • Class I Unremarkable PMHx • Class II Mild asthma, controlled SZ, controlled diabetes, anemia • Class III Moderate to severe asthma, pneumonia, moderate obesity, uncontrolled SZ or DM • Class IV Severe BPD, advanced degrees of pulmonary, cardiac, hepatic, renal, or endocrine insufficiency • Class V Septic shock, severe trauma ASA I and II are usually appropriate candidates ASA III cases should be individually considered ASA IV and V, consult anesthesia or ICU

  14. Presedation evaluation • History • Allergies • Meds • Past History – prior sedation/anesthesia • Last meal • Events • Exam • Airway--Mallampati • Heart • Lungs • Other

  15. Mallampati Class I: soft palate, OP, uvula, pillarsClass II: soft palate, OP, portion of uvulaClass III: soft palate, base of uvulaClass IV: hard palate only

  16. Fasting • ASA Guidelines • 2 hours clears • 4 hours breast milk • 6 hours light meal • 8 full stomach • ACEP • “recent food intake is not a contraindication for administering procedural sedation and analgesia, but should be considered in choosing the timing and target level of sedation”

  17. Informed Consent • Make sure you have discussed it with the parents, signed and in the chart • We have a CHOA sedation video in English and Spanish

  18. Preparations • Expect and be prepared for the worse • You should have the skills to rescue from one level higher than anticipate

  19. Be familiar… • Route • Mechanism of action • How metabolized • Adverse reactions • Time to onset/offset • Avoid dose stacking • Avoid multiple drugs

  20. Common Agents • Chloral Hydrate • Benzodiazepines • Midazolam • Diazepam • Barbiturates • Pentobarbital • Thiopental • Methohexital • Opiates • Morphine • Fentanyl • Ketamine

  21. Unknown mechanism of action Contraindicated in hepatic or renal disease May have paradoxical excitement Side Effects: Hypotension Cardiopulmonary depression GI upset Dose: 25-100 mg/kg PO/PR Max 1 gram in infants 2 grams in children Onset: 30-60min Duration 4-9 hours 30 hrs in neonate chloral hydrate

  22. Shortest acting benzodiazepine The most commonly used sedation agent in children and adults Provides potent sedation, anxiolysis, and amnesia No analgesia May be given IV, PO, IN, IM, PR Bitter aftertaste so mix in Syrpalta Burns in nose Contraindicated with narrow angle glaucoma and shock PO Dose: 0.5-1 mg/kg, max 20mg Onset: 15 min Duration: 30-90 min Intranasal or Sublingual Dose: 0.2-0.5 mg/kg, max 10 mg Onset: 10-15 minutes Duration: 60 minutes IV Dose: 0.05-0.1mg/kg, max 0.6mg/kg or 10mg Onset: 2-3 min Duration: 60-90 min midazolam (Versed®)

  23. barbiturates drug of choice for head trauma, status epilepticus Side effects: Hypotension Myocardial depression Respiratory depression Bronchospasm- stimulate histamine release Contraindications: liver failure CHF hypotension NO analgesia! Dose: 2-6 mg/kg/dose PO/PR/IM 1-3 mg/kg/dose IV Max dose is 150mg Onset: 15-60 min Duration: 1-4 hours pentobarbital

  24. Opioid Slower onset, longer duration Better for procedures that have a longer duration ( ≥ 30 minutes) Histamine release can cause flushing and itching Side effects Respiratory Depression Hypotension Bradycardia Nausea Urticaria Dose: 0.1-0.2 mg/kg IV/IM/SQ, max 10-15 mg bolus, no ceiling Onset: 5-10 minutes Peak effect: 15-30 minutes IV 30-60 minutes IM ½ life = 2-9 hours (neonates) Duration: 2-4 hours morphine

  25. Synthetic opioid Excellent choice for pain management & sedation with short duration 75-200 times more potent with much shorter half-life than MSO4 Rapid onset, elimination, and lack of histamine release; metabolize in liver chest wall rigidity syndrome associated with doses > 15 mcg/kg and rapid infusion; reverse with naloxone and/or paralytics Respiratory depression may last longer than the period of analgesia Dose is 1-2 mcg/kg over 3-5 minutes Titrate to effect every 3-5 minutes Onset: 1-2 minutes Peak effect: 10 minutes Duration: 30-60 minutes fentanyl

  26. Reversal Agents • Naloxone • Competitive opiate antagonist • 0.1 mg/kg IV/IM/SC/ET (min 0.1 mg & max 2 mg) Q2-3 minutes until response; may repeat Q2-3 min • ½ life = 1-2 hr • 30 minute duration; monitor for re-sedation • Reverses resp depression, sedation, and analgesia • Rebound sedation and apnea may occur • Flumazenil • 0.01mg/kg IV (max 0.2 mg) then 0.005-0.01 mg/kg Q1 min to total max dose 1 mg. May repeat doses in 20 min, max 3 mg in 1hr • Do not use in kids on chronic benzo due to seizure risk • If a reversal agent is required the patient must be observed for an additional 2 hours from the time the reversal agent is given

  27. Provides both analgesia and sedation Releases endogenous catecholamines Preserves respiratory drive and airway protective reflexes Bronchodilator effect (good for asthmatics) Maintains hemodynamic stability Rapid infusion causes respiratory depression and apnea Dose: 1-3 mg/kg IV 3-5mg/kg IM Onset: 1 minute IV 5 minute IM Duration: 60 min for sedation 40 to 45 min for analgesia ketamine

  28. ketamine • COMPLICATIONS • Laryngospasm (1%) • Hypersalivation • Apnea • Vomiting • Agitation/Hallucinations/Emergence Reactions • Older aged population • Hypertension • Increased Intracranial and Intraocular Pressure • Myoclonus

  29. Less common agents • Propofol • Ketofol • Brevital • Etomidate • Dexmedetomidine • Nitrous oxide

  30. Diprivan propofol (Diprivan®)

  31. Ultra short acting sedative No analgesic Dose dependent level of sedation with rapid recovery time (high lipid solubility) Common adverse effects: cardiopulmonary depression, upper airway obstruction, hypoventilation and apnea leading to hypoxemia Attending needs to be present during the entire infusion! Dose: 1-3 mg/kg IV Repeat 0.5mg/kg Q2-3 min Onset: 40 secs Duration: 1-3 mins Contraindicated in patients with egg or soybean allergy. IV site pain: 1% lidocaine propofol

  32. propofol • Lidocaine 1% 1 cc in PIV (use with tourniquet) 1 minute prior to propofol • INDUCTION • Draw up 3-5 mg/kg • Give 1-1.5 mg/kg initially over 30-60 secs, then increments of 0.5 mg/kg • Babies < 6mos or pts with CNS pathology usually require higher dose (at least 5 mg/kg) • Bigger kids start @ 1 mg/kg then 0.5 mg/kg • INFUSION • Infusion 5 mg/kg/hr, titrate by 1-2 mg/kg/hr increments, max 18 • Concurrent opioid therapy can be associated with an increased risk of respiratory depression and hypotension

  33. Why is propofol so restricted in the pediatric population, especially in the PICU settings?

  34. propofol infusion syndrome • 1992, report of 5 children with croup or bronchiolitis in an ICU, sedated with propofol and subsequently died of metabolic acidosis and myocardial failure - Bray - • 1998, 18 critically ill pediatric pts experienced bradycardia, asystole, severe metabolic acidosis, lipemia, hepatomegaly and rhabdomyolysis - CMAJ 2001 • 2001 FDA noted of higher death rates in PICU pts given propofol for sedation in a randomized controlled trial. - Medwatch 2001

  35. propofol infusion syndrome • Cornfield & Tegtmeyer • “Continuous Propofol Infusion in 142 Critically Ill Children” • Retrospective review of a case series • 18 mo period; PICU & BMT; age 2 mo – 18 yo • Propofol infusion < 50 mcg/kg/min = 3 mg/kg/h • Additional bolus of 1 mg/kg Q1h • RESULTS • Median infusion 16.5 hrs; longest < 20 hrs • Adequate sedation (no extubation or CVL dislodgement) • Not assoc with metabolic acidosis or hemodynamic compromise • Conclusion: continuous infusion of propofol for extended periods of time should not exceed 67 mcg/kg/min = 4 mg/kg/h Pediatrics 2002;110(6):1177-1181

  36. propofol infusion syndrome • Described in critically ill children given long term propofol infusion • Severe metabolic acidosis and rhabdomyolysis associated with hepatomegaly, lipemia, myocardial failure and hyperkalemia • Relative absence in adults • Not associated with brief procedural sedation • Limited use to the physicians on the sedation team

  37. ketofol • 1:1 mixture of ketamine 10 mg/ml and propofol 10 mg/ml • In theory, the opposing hemodynamic & respiratory effects of each drug might be complementary and minimize overall adverse effects • Prospective study of 114 procedural sedation and analgesia events for orthopedic procedures; effective & safe; fast recoveries (median 15 minutes) - Willman 2007 Dose: 1-3 mg/kg IV slow push, usually 1-1.5 mg/kg Onset: < 1 min Duration: 15-20 min

  38. Rapid, ultra short-acting barbiturate anesthetic Indication similar to propofol and with egg or soy allergies; $$$ Contraindicated in porphyria, temporal seizures Rapid infusion can lead to transient hypotension & tachycardia; respiratory depression/apnea Associated with hiccups, coughing, muscle twitching & rigidity, salivation, emergence delirium Metabolism in the liver Dose: IV 1-2 mg/kg induction of 1%; 3 mg/kg/hr infusion, titrate by 1.5 IM 6.6-10 mg/kg of 5% sol’n PR 25 mg/kg, 10%, max 500 mg Contraindicated in pts < 1 mo Onset: 30 secs IV 2-10 mins IM 5-15 mins PR Duration: 5-10 mins IV methohexital (Brevital®)

  39. Ultra short acting sedative-hypnotic Unknown mechanism of action Rapid IV induction Minimal respiratory depression or hemodynamic instability No histamine release Myocardial & cerebral protection No analgesia Adverse Reactions Nausea and vomiting – 5% Local burning infusion pain Myoclonic movements Inhibits steroid synthesis Contraindications: Seizure disorder Children < 2 y/o Dose: 0.2-0.5 mg/kg IV Induction 0.3 mg/kg IV over 30-60 sec Duration: 5-10 min Full recovery in 30 min Re-dose with 0.1mg/kg every 5-10 minutes as needed Lidocaine 1% for iv site pain etomidate

  40. etomidate • Synthesized in 1964 • 1972 clinical practice in Europe • 1983 approved for use in the US; promoted as a safe agent for continuous sedation in mechanically ventilated pts. • Trend toward increased mortality reported in critically ill, multi-trauma pts receiving continuous infusion etomidate in the ICU; 25% vs 44%- Ledingham and Watt • Retrospective review of 428 multi-trauma pts from 1969-1982 • increased mortality 28% vs 47%; p< 0.05 • More pronounced with ↑ MV duration and means of sedation (benzos 28% vs 77% etomidate; p< 0.0005) • All showed at least one subnormal level of serum cortisol • Long-term use of etomidate fell into disfavor • Package insert for etomidate: “this formulation is not intended for administration by prolonged infusion.”

  41. etomidate • Adrenal suppression • Single induction dose • ↓ cortisol & aldosterone levels (30 mins) • transient < 24 hrs • Inhibits conversion of cholesterol to cortisol by a reversible & concentration- dependent blockade of 11ß-hydroxylase >> 17α-hydroxylase

  42. etomidate controversy • Ideal first-line induction agent for select ED pts requiring RSI intubation; stability and predictability • Etomidate single use in septic shock • Adrenal insufficiency is transient and clinically not relevant VS • Etomidate should be abandoned altogether in the ICU • increased the risk of adrenal insufficiency by 12X; • transient effect prolonged in critically ill pts; • poor prognosis associated with adrenal insufficiency in critical illness - Annane 2005 • Meta-analyses support the use of low-dose steroid replacement among pressor dependent septic shock pts

  43. etomidate controversy • 3 approaches to the use of etomidate in septic shock pts: • eliminate etomidate use altogether in this subgroup • Ketamine? • use a lower dose of etomidate in conjunction with lower doses of other induction agents • routinely administer concomitant corticosteroids with etomidate • Annane study showed 94% (68/72) were nonresponders to high-dose cosyntropin stimulation test • Mortality cost of adrenal suppression by etomidate offset by corticosteroid administration

  44. Relatively selective α2-adrenoceptor agonist with sedative properties preserves cardiorespiratory function maintained RR & oxygenation less concurrent opiate use not approved in children adverse effects hypotension bradycardia Dose: infusion 1 mcg/kg over 10 min infusion 0.4 mcg/kg/h (0.2-0.7) Onset: 6 mins t½ : 2 hrs dexmedetomidine (Precedex®)

  45. sweet smelling inorganic gas by Priestly in 1772 late 1800s dental procedures analgesic & sedative properties 20% N2O = morphine rapid onset and recovery 30-80% N2O  LOC suitable for use when short acting analgesia/sedation required for brief procedures adverse reactions: CNS depression Cardiorespiratory depression Exacerbate existing airway obstruction Worsened existing pneumothorax Megaloblastic anemia  affects vitamin B12 metabolism nitrous oxide

  46. nitrous oxide • 2 large prospective studies • 0.35% (27 of 7679 children) major adverse events • O2 desats, airway obstruction, apnea, bradycardia, oversedation • All resolved within minutes of discontinuation • Higher adverse event in pts < 1 yo (2.3%) and received additional psychotropic drugs • 5% minor adverse events: euphoria, nausea, vomiting, dizziness, parasthesia - Pena 1999 - Gall 2001

  47. nitrous oxide • Entonox • fixed concentration of 50% N2O / 50% O2 • self-administered via a demand valve system with a weighted mask • oversedation less likely; young children cannot use • The Matrix Quantiflex nitrous oxide delivery system • Variable delivery of N2O (0-70%) with oxygen administered via a constant gas flow system that does not require patient effort to trigger • oversedation & respiratory depression more likely • Need constant monitor

  48. Common Problems • Inadequate sedation • Assessment/reassessment • Evaluation of efficacy and duration • Timely intervention • Excessive sedation/narcosis • Special circumstances (shock, airway, CNS and concurrent medications) • Most common causes of death • Hypoxemia • Airway obstruction • Cardiovascular collapse (myocardial depression, vasodilation, bradycardia, hypotension, arrhythmias)

  49. Hypoxemia • Is the airway patent? • Upper airway obstruction common, especially in patients predisposed to obstructive sleep apnea (pre-existing obstruction, macroglossia, micrognathia, etc) • Don’t merely give additional oxygen, but evaluate for obstruction, and intervene as needed…

  50. Sniffing position

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