Skin Antisepsis before Surgical Fixation of Extremity Fractures

N Engl J Med. 2024 Feb 1;390(5):409-420. doi: 10.1056/NEJMoa2307679.


Background: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture).

Methods: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications.

Results: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups.

Conclusions: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE number, NCT03523962.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • 2-Propanol / administration & dosage
  • 2-Propanol / adverse effects
  • 2-Propanol / therapeutic use
  • Anti-Infective Agents, Local* / administration & dosage
  • Anti-Infective Agents, Local* / adverse effects
  • Anti-Infective Agents, Local* / therapeutic use
  • Antisepsis / methods
  • Canada
  • Chlorhexidine* / administration & dosage
  • Chlorhexidine* / adverse effects
  • Chlorhexidine* / therapeutic use
  • Cross-Over Studies
  • Ethanol
  • Extremities / injuries
  • Extremities / microbiology
  • Extremities / surgery
  • Fracture Fixation*
  • Fractures, Bone* / surgery
  • Humans
  • Iodine* / administration & dosage
  • Iodine* / adverse effects
  • Iodine* / therapeutic use
  • Preoperative Care / adverse effects
  • Preoperative Care / methods
  • Skin / microbiology
  • Surgical Wound Infection* / etiology
  • Surgical Wound Infection* / prevention & control
  • United States


  • 2-Propanol
  • Anti-Infective Agents, Local
  • Chlorhexidine
  • chlorhexidine gluconate
  • Ethanol
  • Iodine

Associated data