1. Are Opioids the Worse Pain Killers? Xavier Capdevila M.D.,Ph.D. Head of Department Department of Anesthesiology and Critical Care Medicine Lapeyronie University Hospital and Montpellier School of Medicine Montpellier, France Conflicts of interest: Pajunk B Braun GE Healthcare Baxter Janssen Abbott

3. Nineteen articles; 603 patients

5. Ilfeld et al Anesthesiology 2008 Patients given 4 days of perineural ropivacaine attained the 3 discharge criteria in a median (25th-75th centiles) of 25 ( 21-47)h compared with 71 (46-89)h in the selected center. Decrease in time until discharge readiness of 46h Ilfeld et al Pain 2010 Patients given 4 days of perineural ropivacaine attained the 3 discharge criteria in a median (25th-75th centiles) of 47 ( 29-69)h compared with 62 (45-79)h in that multicentric trial. Decrease in time until discharge readiness of 15h

6. A Comprehensive Anesthesia Protocol that Emphasizes Peripheral Nerve Blockade for Total Knee and Total Hip Arthroplasty JAMES R. HEBL, SANDRA L. KOPP, MIR H. ALI, TERESE T. HORLOCKER, JOHN A. DILGER, MD, ROBERT L. LENNON, BRENT A. WILLIAMS, ARLEN D. HANSSEN AND MARK W. PAGNANO THE JOURNAL OF BONE & JOINT SURGERY ·VOLUME 87-A · SUPPLEMENT 2 · 2005

11. Cumulative 24 h consumption of i.v. morphine (in milligrams) for break- through pain after operation Pain intensity (0–10-point scale, ranging from 0, no pain, to 10, maximum pain) at rest at 2, 4, 12, and 24 h after operation All surgeries

12. « Respiratory depression remains a major safety concern »

13. Postoperative sedation Nausea and vomiting

15. 0 minutes 5 D +15 0 4 hours D +7 D0D0 Naloxone 0 100 200 300 400 500 600 Pain inflammation Carrageenan Time (days) Paw pressure (g) Inflammation + Fentanyl or Fentanyl NaCl Naive rats * *

16. Angst M.S, Koppert W., Pain 2003

17. // 24816 0.5 24 0 20 40 60 80 100 // * * 1 Desflurane Remifentanil Post - extubation time (h) Guignard et al. Anesthesiology 2000 Visual Analog Scale (mm)

18. Remifentanil vs. desflurane based anesthesia Guignard et al. Anesthesiology 2000 0 20 40 60 0.510412 20 / 2 / / / / / Morphine (mg) Post - extubation time (h) Desflurane Remifentanil P < 0.05 vs. desflurane

19. Opiates Stress Surgery Opiates Hypnotics

20. OPIOIDS

21. CAM: cellular adhesivity molecul CMH: histocompatibility major complex KIR: killer inhibitor-receptor μ3

22. Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study. Shavit Y, Ben-Eliyahu S, Zeidel A, Beilin B. Shavit YBen-Eliyahu SZeidel ABeilin B Neuroimmunomodulation. 2004;11(4):255-60 Fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can be critical for metastases. Acute administration of a moderate dose of opiates during surgery should be applied cautiously in cancer patients Forty patients were included : half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases. Blood samples were collected during the perioperative period.

23. Morphine in clinically relevant doses promotes tumor neovascularization in a human breast tumor xenograft model in mice leading to increased tumor progression.

24. 24 British Journal of Cancer (2007) 97, 1523 – 1531 Morphine during two weeks Association M+C: better analgesia, better survival

25. 25 Anesth Analg 2010;110:1630–5 319 Patients

27. Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia.

28. Nowadays, opioids are useful in the perioperative period as first line analgesics in very painfull surgeries, however regional techniques should be often preferred in order to limit adverse events and immunomodullary dysfunctions.

29. Anesthesia and Analgesia June 2010 Volume 110 Number 6 « Even though the evidence is inconclusive and at times conflicting, we ignore the possibility that anesthesia may contribute to the recurrence of cancer, months or even years after cancer surgery. So what should we do? An obvious choice is to use regional anesthesia when feasible, alone or in combination with general anesthesia, to minimize the amount of opioid administered, and to consider using NSAIDs, especially specific COX-2 inhibitors. Of course, what we really need are good prospective, randomized,and controlled clinical trials ».