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

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
Straube S, et al. (2005) Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: a systematic review of randomized studies. Acta Anaesthesiol Scand 49 (5):

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

7. Methods and Materials:
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

8. Methods and Materials: 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. 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 Reconstruction
meniscectomy
Celecoxib
Placebo
Celecoxi b
No. 34 33 31 32
Age (mean ±SD)
25.8±7.7
26.7±4.9
32.7±8
32.2±9.8
Gender (Male/Female)
6/28
8/25
9/22
12/20
Operation time
40±7
36.7±7
30.3±7
31.7±4
Weight (Kg)
76.6±9.4
74.3±9.9
78.3±6.4
76.2±7.7
BMI
24±2.6
23.6±3.5
24±2.7
23±2.6
Results

11. 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.
Results:

12. Results:
Table2. Pain intensity in subgroups at 6hr and 24hr according to VAS
Follow-up
6hr
24hr
Group
Meniscectomy
(n=57)
ACL
(n=60)
Subgroup C
(n=28) P
(n=29)
(n=31)
VAS
4.3
5.6
5.7
7.5
3.8
6.3
5.3
6.9
Median 4 7 5
P value
<0.0001
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).
Results: Opioid consumption

14. Results: Opioid consumption
Table3. The comparison of opioid consumption between subgroups
Follow-up
6hr
24hr
Group
Meniscectomy
(n=57)
ACL
(n=60)
Subgroup C
(n=28) P
(n=29)
(n=31)
Pethidine
(mg/24hr)
19.2 42 23
35.8
11.4
28.4 26
39.2
Median 25 37 10 30
P value
<0.0001
0.004
0.001
0.02

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 release of several chemical materials
tissue damage
release of several chemical materials
stimulate pain receptors

17. Discussion
Celecoxib effect is dose related and clinical trial studies recommend celecoxib 400 mg to control acute pain (as we applied).
Recart A, et al. (2003) The efficacy of celecoxib premedication on postoperative pain and recovery times after ambulatory surgery: a dose-ranging study. Anesth Analg 96 (6):

18. Discussion
The results of the present study  celecoxib may decrease pain and aopioid consumption.
Ekman et al. / 2006 / partial meniscectomy / 200 patients / significantly reduce morphine consumption
Huang et al. / 2008 / 40 patients / TKA / decreased pain and opioids nd 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):
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:
Boonriong et al. / 102 patients / ACL / reported no significant differences in pain reduction and analgesic consumption between the celecoxib and placebo groups.
Boonriong T, et al. (2010) Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial. BMC Musculoskelet Disord 11:246

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.
Forslund C (2003) BMP treatment for improving tendon repair. Studies on rat and rabbit Achilles tendons. Acta Orthop Scand Suppl 74 (308):I, 1-30

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
recommendation

23. Any suggestions?