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Pain in the ED: Is Low Dose Ketamine Effective?

Pain in the ED: Is Low Dose Ketamine Effective?. Alyssa Morris, R2 Grand Rounds May 14, 2009 . CASE. 45M MVC, brought in by EMS GCS 15, P= 96, BP= 100/62, O2 94% 2L NP Multiple orthopedic injuries CC of pain. Objectives. Briefly look at pain presentations in the ED

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Pain in the ED: Is Low Dose Ketamine Effective?

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  1. Pain in the ED:Is Low Dose Ketamine Effective? Alyssa Morris, R2 Grand Rounds May 14, 2009

  2. CASE • 45M MVC, brought in by EMS • GCS 15, P= 96, BP= 100/62, O2 94% 2L NP • Multiple orthopedic injuries • CC of pain

  3. Objectives • Briefly look at pain presentations in the ED • How well do we manage patient pain • Ketamine as an analgesic • Pharmacology of its analgesic properties • Evidence for its analgesic effectiveness • Mostly anesthesia literature • Evidence in ED population • Discuss if this is an option in our ED

  4. Pain In ED • Pain is most common reason for ED use • Accounts for up to 78% of visits to EDs • Underuse of analgesia is well documented • “oligoanalgesia” • Many of our patients leave still in pain • Studies show that we have not improved in satisfactorily treating pain in the ED

  5. Pain In ED- How well do we do? Journal of Pain. 2007;8(6):460-466 • Prospective, observational, multicenter, cohort study of 842 pts in US and Canada • 60% were given analgesics • Median wait time for administration was 90 min • 41% of pts pain rating did not change during ED visit • 74% d/c in moderate to severe pain

  6. Pain Control • IV Meds • Fentanyl • Morphine • PO Meds • Tylenol • Ibuprofen • Toradol • Percocet • Morphine • Local anesthetics

  7. Ducharme’s Approach Ketamine • 0.3 mg/kg IV bolus over 10 min • 0.2-0.3 mg/kg/hr infusion

  8. Ketamine- Background • Derived from street drug PCP in 1962 • Been used in clinical practice since 1970s • First used as an anesthetic agent, especially in pediatric population • Became recognized as an analgesic when NMDA R was found to be important in pain response

  9. Ketamine- Effects • Sedation and amnesia • Analgesia (local and systemic) • Cardiac hemodynamically stable agent • +inotropy and chronotropy • Respiratory reflexes usually well preserved • Bronchodilation and increased pulmonary compliance

  10. Ketamine- Adverse Effects • Emesis • Salivary and tracheobronchial secretions • Increase in muscular tone • Emergence rxn • Transient laryngospasm • Respiratory depression

  11. Ketamine- Contraindications ABSOLUTE RELATIVE <12m old Procedures involving stimulation of the posterior pharynx Known or suspected CAD Glaucoma or acute globe injury Uncontrolled HTN Lesions assoc w high ICP • <3m old • Known or suspected psychosis

  12. Ketamine- Pharmacology • Highly lipid soluble • Crosses BBB quickly • Rapid onset of action and recovery • Peak concentration: 1min w IV, 5min w IM • Recover to baseline fxn: 15-30m w IV, 30-90 w IM • Hepatic metabolism • At >1mg/kg = dissociative agent, 0.1-0.5mg/kg = analgesic

  13. Ketamine- MOA • Noncompetitive antagonist of CNS NMDA Receptor • Usually excited by neurotransmitter glutamate • Involved in sensory input at the spinal, thalamic, limbic and cortical levels • Agonist at α and β-adrenergic receptor • Antagonist at muscarinic receptor of the CNS • Blocks reuptake of catecholamines • Agonist at opioid μ and Σ Receptor

  14. Ketamine Anesthesia • Not fully understood and is very complex • Creates a dissociation b/t the cortical and limbic systems • Sensory associative areas of cortex, limbic system and thalamus are directly depressed by ketamine • Higher CNS centers unable to receive or process sensory info • Emotional significance cannot be assessed • Results are anesthesia, analgesia, suppression of fear and anxiety, amnesia

  15. NMDA R and Pain • Pain is detected by 2 types of peripheral nociceptive neurons • A-delta nociceptors • C-fiber nociceptors • Prolonged firing of C-fiber nociceptors causes release of glutamate which activates NMDA R in spinal cord • spinal cord neurons become more responsive to all of its inputs • Hyperexcitable dorsal root ganglion • Wind-up phenomenon • Pain memory • Decreases neuronal sensitivity to opioid receptor agonists • Tolerance can develop

  16. Ann Emerg Med 2005;46:362-5 • Prospective, convenience cohort • Quantify analgesic effect of a dose of o.1mg/kg IV morphine bolus is ED pts with acute, severe pain • Outcome: %pts whose pain decreased by >50% in 30 min • Results: • N-119 • 67% did not have a 50% reduction in pain

  17. Anesthesiology 2004;100:292-301 Objective: measure the analgesic effect of ketamine with use of MRI • 8 volunteers received noxious thermal and auditory stimuli and then given approx 0.5mg/kg of ketamine and brain areas mapped with MRI • Results: sig reduced pain scores with matched decrease in activity in brain • Concluded that ketamine analgesia occurs thru lower cortical processing in pain-related regions of brain

  18. Anesth Analg 2005;100:169-74. • ASA I/II, age 18-65, major elective open abdo, uro or ortho Sx • Randomized, double-blinded, to receive morphine 3mg Q5m until pain VRS <2 and either placebo (N/S) or Ketamine 10mg IV • End-pt: morphine consumption and time to effective analgesia (VRS<2) and time to return of pain (VRS>2)

  19. Conclusions • Low-Dose bolus of Ketamine improves effects of morphine • 40% Less opiate needed • Less time to analgesic effect • Less analgesic failures • No difference in adverse events

  20. Anest Analg 2003;96:789-95. • RDBCT • ASA I, II, III for abdo, ortho or thoracic Sx • End points: morphine consumption and time to effective analgesia using VAS • Received a bolus of 0.1mg/kg morphine IV • Then allowed 0.03mg/kg boluses of morphine (max of three) • Randomized to saline or ketamine 0.25mg/kg bolus

  21. Conclusions • Low-dose Ketamine bolus decreased the morphine consumption • Low-dose Ketamine decreased the time to effective analgesia • Low-dose ketamine group had better respiratory status and returned to baseline more quickly • Morphine alone group had more adverse events and took much longer to return to baseline hemodynamics

  22. Anesth Analg 2003;97:843-7. • RDBCT of pts needing abdo surgery • Outcome: consumption of morphine and VAS scores • Intervention: morphine boluses until VAS<30 then randomized to either morphine PCA (1mg w 7min lock out) and placebo or ketamine bolus of 0.5mg/kg then 0.12mg/kg/hr infusion

  23. Conclusion • Low dose bolus and then infusion of Ketamine reduces morphine consumption • No difference in VAS pain scores • No difference in side effects

  24. AJEM. 2007;25:385-390. • Prospective, multicenter, RDBCT • Objective: compare ketamine plus morphine to morphine alone • 0.1mg/kg of morphine IV, followed by 3mg Q5min until pain relief obtained (VAS<30/100) • +/- 0.2mg/kg Ketamine IV over 10 mins • Outcomes: morphine consumption and VAS at 30 mins

  25. Inclusion: • Trauma pts with VAS>60/100 • 18-70y.o • SBP>90, GCS 15, no resp distress • Exclusion: • Pts with psych hx • Renal/hepatic/resp failure • Chronic pain pts treated with opioids • N= 73; K=38, P= 35

  26. Conclusion • Ketamine reduced morphine consumption • No difference in hemodynamics • Generalizable to only some of our trauma patients as some are HD unstable • Not enough to change practice, but gives us another option to think about

  27. Summary • Pain is one of the most common ED presentations • Pain is inadequately managed in the ED • Low-dose Ketamine has been shown to be an effective and safe adjunct for pain control • Need more evidence

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