Background

Celecoxib (Celebrex) is a selective inhibitor of cyclooxygenase-2 (COX-2) non-steroidal anti-inflammatory drug (NSAID), and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. The use of Celecoxib, as an adjunct in post-operative analgesia, has been advocated in several research studies 1, 2, 3 with the main benefit of reduction of opioid pain medication intake for analgesia3.  

Recently, an unpublished retrospective study 4, exhibited a high incidence (31%) of delayed surgical wound healing in foot and ankle surgery patients taking a COX-2 selective inhibitor in the perioperative period (AOFAS summer meeting, 2008).

At the Weil Foot & Ankle Institute, Celecoxib is routinely given to patients on the day of surgery one hour prior to the surgical procedure.  Patients are instructed to continue the medication daily, for five days and p.r.n. thereafter for pain.  Those patients with an allergy to sulfa drugs are given a non-selective COX-inhibitor.

In our knowledge, there are no current published studies that address wound healing issues specifically related to foot and ankle surgery.  This study seeks to present dissimilar experience than that of the previously mentioned research study with regards to Celecoxib use in patients undergoing elective foot and ankle surgery.

Materials and Methods

A retrospective review was performed of patients that underwent elective surgery by the senior author (LWJ) at the Foot & Ankle Surgery Center (FASC) from January 2005 to December 2008. 

Over 700 patient operative charts were reviewed. Patients with a history of foot and ankle wounds, chronic ulcers, diabetes and smokers were excluded from the study.  All other patients having undergone invasive foot and ankle surgery and taking an anti-inflammatory medication in the perioperative period were included in the study and two comparative groups were formed:  COX-1 inhibitor and Celecoxib group. 

The  protocol is as follows: One hour prior to surgery, Celecoxib 400 mg is administered with a sip of water and thereafter, 200 mg every 12 h for 3 postoperative days, followed by 200mg taken once daily for 2 days. 

The protocol for the COX-1 group included a loading dose one hour prior to surgery, followed by the standard dose (SD) every 12 h p.c. for 3 postoperative days, followed by the (SD) taken once daily p.c. for 2 days.  The protocol for the COX-1 drug is as follows:  On the day of surgery, a COX-1 drug is administered one hour prior to surgery.  The max dose is then taken daily as instructed for 5 postoperative days.

All patients meeting the inclusion criteria and took a COX-1 medication were included in the  COX-1 group.  Using the inclusion criteria, an age-matched Celecoxib group was then assembled.   Patient charts of both groups were then reviewed up to 3 months after the date of surgery for incidence of surgical wound complications (infection, dehiscence).

Descriptive statistics, including mean and standard deviation, were used to describe the demographic data.  To compare categorical variables, the Fisher Exact Test was used.  Student's t-test was performed to compare normally distributed continuous variables.  Statistical differences were considered to be significant when the p-value was < 0.05.  

Data and Tables

TABLE 1. Celebrex Group Demographics, Surgical Procedures and Complications

	AGE	GENDER	SURGICAL PROCEDURE	COMPLICATIONS
Patient 1	30	F	5th met head resection	None
Patient 2	43	M	Scarf Bunionectomy	None
Patient 3	46	F	Scarf-Akin	None
Patient 4	46	F	Scarf-Akin, Weil Osteotomy 2nd  (WMO), Hammertoe	None
Patient 5	47	F	Peroneal Tendon repair	None
Patient 6	49	F	Hammertoe repair	None
Patient 7	49	F	Scarf bunionectomy	None
Patient 8	50	F	Scarf-Akin, Weil Osteotomy 2nd , plantar plate repair 2nd MTP	YES:  3 wks post-op pain, redness & swelling
Patient 9	52	F	Weil Osteotomy 2nd , plantar plate repair 2nd MTP	None
Patient 10	55	F	Weil Osteotomy 2nd and 3rd	None
Patient 11	57	M	Valenti arthroplasty	None
Patient 12	61	F	Scarf-Akin, Weil Osteotomy 2nd , Hammertoe, plantar plate repair 2nd MTP	None
Patient 13	63	F	Hammertoe repair	None
Patient 14	63	M	Haglund's resection, Tailor's bunionectomy	None
Patient 15	65	F	Hammertoe  repair	None
Patient 16	66	F	Total joint implant 1st MTP	None
Patient 17	66	F	Hammertoe  repair	None
Patient 18	67	F	Scarf bunionectomy	None
Patient 19	68	F	Scarf-Akin, WMO, plantar plate repair, 2nd MTP hammertoe repair	None
Patient 20	76	M	Total joint implant 1st MTP	None

TABLE 2.  COX-1 1nhibitor Group Demographics, Surgical Procedures and Complications

	AGE	GENDER	NSCI	SURGICAL PROCEDURE	COMPLICATIONS
Patient 1	30	F	Meloxicam 15mg	Scarf bunionectomy	None
Patient 2	44	F	Meloxicam 15mg	Scarf Akin, Weil Osteotomy 2nd	None
Patient 3	45	F	Meloxicam 15mg	Partial met head resection 2, 3, 5.  1st MTP arthrodesis	None
Patient 4	45	F	Meloxicam 15mg	Excision heel spur, Excision of ganglion cyst	None
Patient 5	47	F	Meloxicam 15mg	Hammertoe repair, Condylectomy	None
Patient 6	49	F	Meloxicam 15mg	Osteotomy of 2nd, 3rd, & 4th.  Excision of Morton's neuroma	None
Patient 7	50	F	Meloxicam 15mg	Scarf bunionectomy, Hammertoe repair	None
Patient 8	51	F	Diclofenac 50mg	Scarf Bunionectomy, Hammertoe repair	None
Patient 9	52	F	Diclofenac 50mg	Hammertoe repair	None
Patient 10	54	F	Limbrel 500mg	Subtalar Joint Arthrodesis, Scarf Bunionectomy	YES:  Heel wound dehiscence
Patient 11	57	F	Limbrel 500mg	Scarf Akin, Weil Osteotomy 2nd	None
Patient 12	60	F	Ibuprofen 800mg	Condylectomy, Skin plasty	None
Patient 13	63	F	Meloxicam 15mg	Scarf bunionectomy	None
Patient 14	64	F	Meloxicam 15mg	Hammertoe repair	None
Patient 15	64	F	Meloxicam 15mg	Hammertoe repair	None
Patient 16	65	F	Diclofenac 50mg	Scarf bunionectomy, Mallet Toe repair	None
Patient 17	65	F	Diclofenac 50mg	Scarf Akin	None
Patient 18	67	F	Meloxicam 15mg	Removal of deep implant	None
Patient 19	69	F	Meloxicam 15mg	1st MTP Arthrodesis	None
Patient 20	76	F	Meloxicam 15mg	2nd met head resection	YES:  Wound drainage on post-op visit 2.  Revision of incision 4 weeks post-op.

 

Results

There were 20 patients in each the Celecoxib and COX-1 group.  Average age was 55.95±10.83 in the Celecoxib   group and 55.85±10.77 in the COX-1 group (p = 0.789).  There were 4 (20%) males and 16 (80%) females in the Celecoxib group.  There were 20 (100%) females in the COX-1 group.  There was no statistical difference between gender in the groups (p = 0.106).

In the COX-1 group, 13 (65%) patients took meloxicam, 4 (20%) of patients took diclofenac, 2 (10%) patients took flavocoxid, and 1 (5%) patient took ibuprofen.

Only one (5%) patient in the Celecoxib group had a postoperative wound healing issue. Two (10%) patients in the COX-1 group had incidence of a wound dehiscence.   There was no statistical difference noted in wound healing incidence between the two groups (p = 1.000).

Discussion and Conclusions

Since the removal of Vioxx (Rofecoxib) and Bextra (Valdecoxib) from the U.S. pharmaceutical market, Celecoxib is the only remaining COX-2 selective inhibitor.  The main advantage of this class of drugs is its' ability to selectively block the COX-2 enzyme which directly impedes the release of prostaglandins correlated with arthritic pain and inflammation, while not affecting the gastrointestinal system as much as the COX-1 drugs.

Although studies exist over the adverse effect of long term use of NSAID drugs in fracture healing, one limited study has correlated wound healing issues with the perioperative use of Celecoxib.  

Our results illustrate that there was no increased incidence of wound healing issues with the perioperative and postoperative use of Celecoxib compared to non-selective COX inhibitors.

In this pilot study, we conclude that Celecoxib is not directly linked to foot and ankle wound healing issues and can be safely used as an adjunct to postoperative analgesia.

Limitations of this study are the lack of a control group that did not take any COX inhibitors in the perioperative and postoperative setting.

References

1. Post discharge complications and rehabilitation after ambulatory surgery. Rawal N.  Curr Opin Anaesthesiol. 2008 Dec;21(6):736-42.     Review.
   
   
2. A prospective randomized trial on the role of perioperative celecoxib administration for total knee arthroplasty: improving clinical outcomes.  Reuben SS, Buvenandran A, Katz B, Kroin JS. Anesth Analg. 2008 Apr;106(4):1258-64
   
   
3. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial.  Buvanendran A, Kroin JS, Tuman KJ, Lubenow TR, Elmofty D, Moric M, Rosenberg AG. JAMA. 2003 Nov 12;290(18):2411-8.
   
   
4. Lamoreaux C, Santrock RD and Deemer J. COX-2 inhibitors and wound healing complications. Presented at the American Orthopaedic Foot and Ankle Society 24th Annual Summer Meeting. June 26-28, 2008. Denver.