麻豆传媒

Iodine-based skin antisepsis appeared better for surgical repair of closed limb fractures but on par with chlorhexidine-based antisepsis when the fracture broke the skin, the PREPARE trial showed.

In closed fractures, surgical-site infection occurred in 2.4% of patients prepped with a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (Duraprep) compared with 3.3% among those prepped with 2% chlorhexidine gluconate in 70% isopropyl alcohol (BD ChloraPrep; OR 0.74, 95% CI 0.55-1.00, P=0.049)

For open fractures, surgical-site infection occurred in numerically but not significantly fewer iodine group patients (6.5% vs 7.3%, OR 0.86, 95% CI 0.58-1.27, P=0.45).

Unplanned reoperation and other outcomes were similar between groups in both open and closed fractures, Sheila Sprague, PhD, of McMaster University in Hamilton, Ontario, and colleagues reported in the .

"Our findings suggest that the use of iodine povacrylex in alcohol as preoperative skin antisepsis could prevent surgical-site infection in thousands of patients with closed fractures," the group noted.

Indeed, the absolute difference in surgical-site infection for that population was almost one infection prevented per 100 surgeries for closed fractures, with an upper limit of the confidence interval of 1.6 percentage points, cited an by Selwyn O. Rogers Jr., MD, MPH, of the University of Chicago Medicine, and Richard P. Wenzel, MD, of the Virginia Commonwealth University in Richmond.

The reason that iodine didn't prove superior across the board could have been that "skin-cleansing procedures may have less effect on open fractures in which contamination may have already occurred in the field," they noted.

PREPARE was the second of two trials performed under the . The first, dubbed , showed no difference in infection risk between two water-based antiseptic solutions -- chlorhexidine and povidone-iodine -- for surgical repair of open limb fractures.

PREPARE now expands the evidence base for the two most commonly used skin antisepsis solutions for the more than 1 million orthopedic trauma surgeries done each year in the U.S.

"Although some guidelines favor antisepsis with chlorhexidine gluconate over an iodophor, all recommendations have recognized a lack of consensus with respect to the most effective agent," said co-author Gerard Slobogean, MD, of the University of Maryland in Baltimore, in a .

The iodine and chlorhexidine solutions have similar price, availability, and directions for use, the researchers noted. "Nevertheless, the possibility that patients will have an allergic reaction to an ingredient in either solution means that hospitals will need to continue to stock both interventions."

The pragmatic trial included 25 hospitals in the U.S. and Canada, cluster randomized to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol or 2% chlorhexidine gluconate in 70% isopropyl alcohol for preoperative antisepsis of limb or pelvic fractures. The hospitals crossed over between treatments every 2 months and had high adherence to both antiseptics.

The trial population comprised 6,785 adults with a closed fracture and 1,700 with an open fracture. Fractures of the proximal femur were most common, accounting for approximately 25% of the trial population.

The primary outcome was surgical-site infection, defined as superficial incisional infection within 30 days and deep incisional or organ-space infection within 90 days after definitive fracture management surgery. For the secondary endpoint -- unplanned reoperation within 365 days after fracture -- the rates in the iodine group and in the chlorhexidine group (5.5% vs 5.9%) were similar.

Serious adverse events were also similar between groups, with no chemical burns or surgical fires reported in either antiseptic group.

One limitation of the trial was lower than expected baseline infection risk in the open-fracture population, which reduced the statistical power for the primary comparison. However, even extending the surveillance period to 1 year did not show a significant difference between antiseptic agents.

Surgeons and patients were aware of the trial-group assignments, but as the editorialists noted, "the central adjudication committee evaluated the trial results in a blinded manner, thus mitigating potential assessment biases of outcomes." Overall, it was a rigorous and well-designed trial, they wrote.

"Given the substantial morbidity and health care costs associated with surgical-site infection, we need more innovative trials testing novel approaches to further lower the infection risk," Rogers and Wenzel argued.

One such strategy might be personalized interventions based on deeper understanding of the individual patient's microbiome, they suggested.

" was able to make a quantum leap to markedly reduce the risk of infection and to lower mortality," they concluded. "We await next-generation innovations to achieve zero surgical-site infections."

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