title: Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds.
abstract: After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >105colony forming units on quantitative bacteriology; and healing potential.
  
  
  
  We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders.
  
  
  
  Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization.
  
  
  
  Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser concentrations of inflammatory cytokines and may contribute to a more favorable inflammatory response leading to successful wound healing.
authors.affiliation: Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, MD; Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Lisboa
authors.affiliation: Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, MD; Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bradley
authors.affiliation: Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Hueman
authors.affiliation: Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Schobel
authors.affiliation: Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Gaucher
authors.affiliation: Surgical Critical Care Initiative (SC2i), Bethesda, MD; DecisionQ, Arlington, VA.
authors.forename: Edda L
authors.initials: EL
authors.lastname: Styrmisdottir
authors.affiliation: Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Potter
authors.affiliation: Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, MD; Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Forsberg
authors.affiliation: Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, MD; Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD; Surgical Critical Care Initiative (SC2i), Bethesda, MD. Electronic address: eric.elster@usuhs.edu.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Elster
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001134:Arm Injuries / Q000175:diagnosis / Q000601:surgery*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D003646:Debridement / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007869:Leg Injuries / Q000175:diagnosis / Q000601:surgery*; D016015:Logistic Models; D008297:Male; D008889:Military Personnel; D015999:Multivariate Analysis; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome; D014857:Warfare; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014947:Wounds and Injuries / Q000175:diagnosis / Q000601:surgery
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6