COX-2 Inhibitors and Early Failure of Free Vascular Flaps
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《新英格兰医药杂志》
To the Editor: We wish to report our clinical experience with the use of cyclooxygenase-2 (COX-2) inhibitors to control pain in patients treated with free vascular flaps after undergoing ablative surgery to resect an oral cancer. From January 1997 to February 2004, all patients who underwent ablative surgery at Helsinki University Central Hospital to resect a cancer, followed by surgical reconstruction of the maxillofacial skeleton with the use of a free vascular flap, received 2000 IU of dalteparin per kilogram of body weight twice daily and opioid medications, without the use of selective COX-2 inhibitors, as approved by the institutional review board at the hospital. Our success rate in the use of free vascular flaps was 93 percent (Table 1), which is in line with accepted standards for the surgical repair of similar defects.1,2 Beginning in March 2004, the COX-2 inhibitor valdecoxib (Bextra, Pfizer) and its intravenous prodrug parecoxib (Dynastat, Pfizer) were used postoperatively to minimize gastrointestinal side effects. The patients received an initial intravenous dose of 40 mg of parecoxib during surgery (day 1), followed by the same dose for 7 to 14 days; 40 mg of oral valdecoxib then replaced the intravenous dose and was continued for another 5 to 10 days. The drug was stopped in December 2004 after a decrease in the flap success rate to 71 percent (Table 1). From January 2005 to October 2005, after the cessation of the drug, our success rate returned to that observed before February 2004 (Table 1). The same heparin regimen was used throughout the study period, and the use of COX-2 inhibitors was the only variant that we could identify that could have resulted in the decreased success rate. COX-2 inhibitors not only lack the antiplatelet effects of aspirin but also, by inhibiting the production of prostacyclin, disable one of the primary defenses of the endothelium against platelet aggregation, increasing the risk of venous clot formation.3,4
Table 1. Failure of Free Vascular Flaps.
In conclusion, the use of COX-2 inhibitors was associated with an increased incidence of the failure of free vascular flaps, which arouses concern about the use of these drugs in such circumstances. However, these findings are based on a secular trend analysis, and such an approach cannot prove that graft failure is definitely caused by valdecoxib or parecoxib.
Jehad Al-Sukhun, Ph.D.
Anu Koivusalo, M.D., Ph.D.
Jyrki T?rnwall, M.D., Ph.D.
Christian Lindqvist, M.D., Ph.D.
Helsinki University Central Hospital
00029 HUS Helsinki, Finland
jalsukhun@hotmail.com
References
Finical SJ, Doubek WG, Yugueros P, Johnson CH. The fate of free flaps used to reconstruct defects in recurrent head and neck cancers. Plast Reconstr Surg 2001;107:1363-1366.
Varvares MA, Lin D, Hadlock T, et al. Success of multiple, sequential, free tissue transfers to the head and neck. Laryngoscope 2005;115:101-104.
Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002;360:1071-1073.
Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005;352:1081-1091.
Table 1. Failure of Free Vascular Flaps.
In conclusion, the use of COX-2 inhibitors was associated with an increased incidence of the failure of free vascular flaps, which arouses concern about the use of these drugs in such circumstances. However, these findings are based on a secular trend analysis, and such an approach cannot prove that graft failure is definitely caused by valdecoxib or parecoxib.
Jehad Al-Sukhun, Ph.D.
Anu Koivusalo, M.D., Ph.D.
Jyrki T?rnwall, M.D., Ph.D.
Christian Lindqvist, M.D., Ph.D.
Helsinki University Central Hospital
00029 HUS Helsinki, Finland
jalsukhun@hotmail.com
References
Finical SJ, Doubek WG, Yugueros P, Johnson CH. The fate of free flaps used to reconstruct defects in recurrent head and neck cancers. Plast Reconstr Surg 2001;107:1363-1366.
Varvares MA, Lin D, Hadlock T, et al. Success of multiple, sequential, free tissue transfers to the head and neck. Laryngoscope 2005;115:101-104.
Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002;360:1071-1073.
Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005;352:1081-1091.