Preop skin antiseptic in fracture fixation: Which is better?

In patients undergoing fixation of a closed lower limb or pelvic fracture, iodine povacrylex in alcohol appears to be a better option than chlorhexidine gluconate (CHG) in alcohol as preoperative skin antiseptic to prevent surgical site infection (SSI). Among those with open upper limb or lower limb fracture, outcomes were similar for both solutions, the PREPARE* trial suggests.

“To determine the most effective skin antisepsis solution for limb fracture surgery … we compared the two most common skin antiseptics used in the US and Canada,” said the researchers. They specifically sought to establish superiority of either the iodine- or CHG-based alcohol solution for SSI prevention in patients undergoing closed fracture (CF) or open fracture (OF) fixation.

The study employed a multiple-period, cluster-randomized, crossover design and included participants from 25 hospitals in the US and Canada. Most of the participants had a CF (n=6,785; mean age 53.9 years, 51 percent women), while the rest had an OF (n=1,700; mean age 44.6 years, 64 percent men) warranting surgical fixation. Patients in the OF subgroup must have received surgical debridement within 72 hours post injury.

Participants in each subgroup were randomized 1:1 to 0.7% iodine povacrylex in 74% isopropyl alcohol or 2% CHG in 70% isopropyl alcohol as preoperative antiseptic for surgery to repair the fractures. The hospitals alternated interventions every 2 months. [N Engl J Med 2024;390:409-420]

In the CF cohort, SSI** risk was lower in the iodine vs CHG group (2.4 percent vs 3.3 percent; odds ratio [OR], 0.74; p=0.049).

“[T]he lower SSI risk in the iodine group may have resulted more from the sustained protection of iodine by the povacrylex copolymer than from the potential superiority of iodine over CHG,” the researchers explained.

Conversely, SSI risk did not differ significantly between the iodine and CHG groups in the OF cohort (6.5 percent vs 7.3 percent; OR, 0.86; p=0.45).

The researchers attributed the contrasting findings to several factors. First, wound irrigation in the OF cohort early in the debridement phase of surgery could have watered down the protective effect of povacrylex.

“Second, OF wounds are exposed to heterogeneous environmental contamination and prolonged bacterial exposure before surgery. At the time of injury, bacteria can reach the deep tissues and begin early biofilm formation several hours before skin antisepsis is performed in the operating room,” they added.

“For surgical fixation of OFs, it is plausible that the choice of antiseptic solution does not have a strong enough effect to measurably alter the risk of infection, whereas antiseptic reduction of skin flora immediately before fixation of a CF can significantly reduce infection,” they continued.

Regarding the secondary outcome*** of unplanned reoperation within 365 days after fracture for fracture healing complications, the rates between the iodine and CHG groups were similar, both in the CF (5.5 percent vs 5.9 percent; OR, 0.96) and OF populations (16.1 percent vs 14.5 percent; OR, 1.16).

There were also similar incidences of serious adverse events between groups. No chemical burns or surgical fires were reported.

Novel antiseptic approaches still warranted

In an accompanying editorial, Dr Selwyn Rogers from the University of Chicago Medicine, Chicago, Illinois, US and Dr Richard Wenzel from Virginia Commonwealth University, Richmond, Virginia, US, pointed out that in PREPARE, the investigators were not able to examine nonskin sources of organisms that may cause SSIs. [N Engl J Med 2024;390:466-467]

“Skin antisepsis cannot address any silent migration of organisms from [nonskin] areas to the wound as potential sources of SSIs. Furthermore, skin-cleansing procedures may have less effect on OFs in which contamination may have already occurred in the field,” they commented.

“[As such,] given the substantial morbidity and healthcare costs associated with SSI, we need more innovative trials testing novel approaches to further [reduce] infection risk. Moreover, a deeper understanding of the individual patient’s microbiome may allow for tailored interventions to further decrease the incidence of infection,” added Rogers and Wenzel.

“In the dawn of the germ theory of infection, British surgeon Dr Joseph Lister applied a bactericidal agent, carbolic acid, to the wounds of patients undergoing limb amputation,” they noted. “Lister was able to make a quantum leap to markedly reduce infection risk and to lower mortality. We await next-generation innovations to achieve zero SSIs.”