1. In the name of God

2. Celecoxib as a pre-emptive analgesia in arthroscopic knee surgery; a triple blinded randomized controlled trial Mohsen Mardani-Kivi, M.D. Orthopedic Department, Guilan University Of Medical Sciences

4. Background pre-emptive analgesia not only controls pain but also may result in the reduction of opioid consumption and related side effects following orthopedic surgeries.

5. Background COX-2 inhibitors  inhibitory effects in PG synthesis, & reduce hyperalgesia status following surgical traumas Celecoxib  no side effects such as anti- PLT function, increased risk of GIB, Increased risk of CAD

6. The purpose of the study celecoxib arthroscopic knee surgeriesTo examine the effects of celecoxib in reducing pain following the arthroscopic knee surgeries: ACL reconstruction and partial meniscectomy.

7. a triple blinded randomized placebo-controlled clinical trial patients undergoing knee arthroscopic (isolated ACL reconstruction or partial meniscectomy) / GA anesthesia Exclusion criteria: Simultaneous ACL and meniscus tear, accompanied chondral lesions Intervention: receiving 400mg Celecoxib or receiving identical Placebo pill Methods and Materials :

8. primary and secondary outcome Pain intensity based on Visual Analogue Scale (VAS) Opioid consumption during the 24 hours post operation Side effects (nausea, vomiting, sedation and dizziness) Variables were assessed at: 6 hour post-op, and 24 hour post- op

9. Flowchart of the study

10. Results The patients were similar in both groups with respect to demographic characteristics (such as age, gender, operation time, weight and BMI) (P>0.05). ACL Reconstructionmeniscectomy CelecoxibPlaceboCelecoxibPlacebo No. 34333132 Age (mean ±SD) 25.8±7.726.7±4.932.7±832.2±9.8 Gender (Male/Female) 6/288/259/2212/20 Operation time 40±736.7±730.3±731.7±4 Weight (Kg) 76.6±9.474.3±9.978.3±6.476.2±7.7 BMI 24±2.623.6±3.524±2.723±2.6

11. Results : Patients in Celecoxib group experienced less pain than Placebo group (p<0.0001). Such significant difference was also observed in both ACL and M subgroups.

12. Follow- up 6hr24hr Group Meniscectomy (n=57) ACL (n=60) Meniscectomy (n=57) ACL (n=60) Subgrou p C (n=28) P (n=29) C (n=29) P (n=31) C (n=28) P (n=29) C (n=29) P (n=31) VAS4.35.65.77.53.86.35.36.9 Median47574757 P value<0.0001 Table2. Pain intensity in subgroups at 6hr and 24hr according to VAS Results : C: Celecoxib group P: Placebo group

13. Results : Opioid consumption analgesics used in celecoxib group was significantly lower than in placebo group (P<0.05).

14. Results : Opioid consumption Follow-up6hr24hr Group Meniscectomy (n=57) ACL (n=60) Meniscectomy (n=57) ACL (n=60) Subgroup C (n=28) P (n=29) C (n=29) P (n=31) C (n=28) P (n=29) C (n=29) P (n=31) Pethidine (mg/24hr) 19.2422335.811.428.42639.2 Median2537254210253042 P value<0.00010.0040.0010.02 Table3. The comparison of opioid consumption between subgroups

15. Results : adverse effects All of the observed adverse effects were similar in both groups. –Nausea was observed among 12 cases (21.1%) in Celecoxib and 21 patients (35%) in placebo group at 24hr follow-up (p=0.11). –The drowsiness and dizziness scores were not significantly different between the two groups.

16. Discussion tissue damage release of several chemical materials stimulate pain receptors

17. Discussion dose related celecoxib 400 mgCelecoxib effect is dose related and clinical trial studies recommend celecoxib 400 mg to control acute pain (as we applied).

18. Discussion The results of the present study  celecoxib may decrease pain and opioid consumption. Ekman et al. / 2006 / partial meniscectomy / 200 patients / significantly reduce morphine consumption Huang et al. / 2008 / 40 patients / TKA / decreased pain and opioids and side effects. Ekman EF, et al. (2006) Analgesic efficacy of perioperative celecoxib in ambulatory arthroscopic knee surgery: a double-blind, placebo-controlled study. Arthroscopy 22 (6):635-642. Huang YM, et al. (2008) Perioperative celecoxib administration for pain management after total knee arthroplasty - a randomized, controlled study. BMC Musculoskelet Disord 9:77.

19. Discussion On the contrary: noBoonriong et al. / 102 patients / ACL / reported no significant differences in pain reduction and analgesic consumption between the celecoxib and placebo groups.

20. Discussion Celecoxib potential adverse effects  on bone growth by interfering in bone morphogenetic protein (BMP) signaling system. BMP may also plays certain role in early tendon formation and any interference in its signaling system during post operation time may also delay tendon repair.

21. Discussion Celecoxib as a pre-emptive analgesia Less post- op pain shorter hospital stay? Fewer opioids’ side effects Returning faster to routine activities? Less PONV? Lower socio- economic burden?

22. recommendation a larger population vast range of different side effects further long term follow-up research studies investigating the conclusive evidence of the effects of COX-2 inhibitors on bone formation and tendon repair

23. Any suggestions?