S(+)-ketamine Treatment of Acute and Chronic Pain Marnix Sigtermans, MD  Department of Anesthesiology
Chronic pain <ul><li>19% of 46,394 respondents suffered pain for > 6 months </li></ul><ul><li>61 % were less able or unabl...
Introduction: NMDA receptor antagonists <ul><li>Fencyclidine (PCP) was developed in 1926  </li></ul><ul><li>NMDA-receptor ...
Study objectives <ul><li>Characterization of efficacy and safety </li></ul><ul><li>of ketamine in: </li></ul><ul><li>Healt...
Healthy volunteers
 
<ul><ul><li>Does treatment with ketamine result in pain reduction in chronic pain patients? </li></ul></ul><ul><li>Complex...
CRPS-1: International Association for the Study of Pain <ul><li>Complex Regional Pain Syndrome type 1  (sympathetic reflex...
CRPS type 1: example
Example continued
Flowchart
Infusion period
Time course of analgetic effect P <0.001
Side effects during treatment <ul><li>No changes in: </li></ul><ul><ul><li>Blood pressure </li></ul></ul><ul><ul><li>Liver...
CRPS acute and chronic pain Infusion   phase Elimination phase
Results: n=12
CRPS Experimental pain
CRPS Experimental pain CRPS pain
Conclusion <ul><li>Difference between onset and offset of analgetic action of ketamine </li></ul><ul><ul><li>Pharmacokinet...
Conclusion
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Second life of Ketamine

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Second life of Ketamine

  1. 1. S(+)-ketamine Treatment of Acute and Chronic Pain Marnix Sigtermans, MD Department of Anesthesiology
  2. 2. Chronic pain <ul><li>19% of 46,394 respondents suffered pain for > 6 months </li></ul><ul><li>61 % were less able or unable to work </li></ul><ul><li>19% had lost their job becaus of pain </li></ul><ul><li>40% inadequate pain managment </li></ul>
  3. 3. Introduction: NMDA receptor antagonists <ul><li>Fencyclidine (PCP) was developed in 1926 </li></ul><ul><li>NMDA-receptor antagonist </li></ul><ul><li>Patented 1950 </li></ul><ul><li>Anesthetic drug </li></ul><ul><li>Side effects: hallucinogenic and neurotoxic </li></ul><ul><li>Mid 1960’s ketamine, a new NMDA receptor antagonist </li></ul><ul><li>Anesthetic drug </li></ul><ul><li>Analgesic drug in anesthetic doses </li></ul>
  4. 4. Study objectives <ul><li>Characterization of efficacy and safety </li></ul><ul><li>of ketamine in: </li></ul><ul><li>Healthy volunteers </li></ul><ul><li>CRPS patients </li></ul><ul><ul><li>Efficacy: analgesia (heat pain model) </li></ul></ul><ul><ul><li>Safety: haemodynamic, psychomimetic effects </li></ul></ul>
  5. 5. Healthy volunteers
  6. 7. <ul><ul><li>Does treatment with ketamine result in pain reduction in chronic pain patients? </li></ul></ul><ul><li>Complex Regional Pain Syndrome type 1 </li></ul><ul><li>(posttraumatic dystrophy) </li></ul><ul><ul><li>Affects one or more extremities </li></ul></ul><ul><ul><li>Standard pain management often inadequate </li></ul></ul><ul><ul><li>Relative young patients </li></ul></ul><ul><ul><li>Low quality of life and high costs for society </li></ul></ul>
  7. 8. CRPS-1: International Association for the Study of Pain <ul><li>Complex Regional Pain Syndrome type 1 (sympathetic reflex dystrophy or posttraumatic dystrophy) </li></ul><ul><li>Following a trauma </li></ul><ul><li>Effects the extremities </li></ul><ul><li>Pain and / or dystonic major complaints </li></ul><ul><li>CRITERIA </li></ul><ul><ul><li>Presence of a noxious event, or immobilization </li></ul></ul><ul><ul><li>Continuing pain, allodynia or hyperalgesia, </li></ul></ul><ul><ul><li>(pain disproportionate) </li></ul></ul><ul><ul><li>Edema, changes in skin blood flow </li></ul></ul><ul><ul><li>and/or abnormal sudomotor activity </li></ul></ul><ul><ul><li>No other explanation </li></ul></ul>
  8. 9. CRPS type 1: example
  9. 10. Example continued
  10. 11. Flowchart
  11. 12. Infusion period
  12. 13. Time course of analgetic effect P <0.001
  13. 14. Side effects during treatment <ul><li>No changes in: </li></ul><ul><ul><li>Blood pressure </li></ul></ul><ul><ul><li>Liver function test </li></ul></ul>P < 0.001 P = 0.004 P < 0.001 P = 0.78
  14. 15. CRPS acute and chronic pain Infusion phase Elimination phase
  15. 16. Results: n=12
  16. 17. CRPS Experimental pain
  17. 18. CRPS Experimental pain CRPS pain
  18. 19. Conclusion <ul><li>Difference between onset and offset of analgetic action of ketamine </li></ul><ul><ul><li>Pharmacokinetic driven </li></ul></ul><ul><li>This suggests that apart from an analgesic effect ketamine displays a modulatory effect on the chronic pain process </li></ul>
  19. 20. Conclusion

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