A multicenter, randomized trial conducted across eight French hospitals has found that chlorhexidine-alcohol is not superior to povidone-iodine-alcohol in reducing reoperation and surgical site infection (SSI) rates following major cardiac surgery. The study, involving over 3,200 patients undergoing heart or aortic surgery via sternotomy, challenges the prevailing recommendations that favor chlorhexidine-alcohol for preoperative skin antisepsis.
The trial, known as CLEAN 2, was designed to compare the efficacy of 2% chlorhexidine in 70% isopropanol (chlorhexidine-alcohol) with 5% povidone-iodine in 69% ethanol (povidone-iodine-alcohol) in reducing the rates of reoperation and SSI within 90 days of surgery. Patients were randomized to receive one of the two antiseptic solutions for skin disinfection at all surgical sites. The primary outcome was re-sternotomy within 90 days of surgery or reoperation at the saphenous vein/radial artery site within 30 days of surgery.
Key Findings
The results, published in a Springer Medicine article, indicated no statistically significant difference between the two antiseptic solutions in terms of the primary outcome. A total of 125 patients (7.7%) in the chlorhexidine-alcohol group and 121 patients (7.5%) in the povidone-iodine-alcohol group required reoperation (risk difference 0.25, 95% CI -1.58 to 2.07, P=0.74). Secondary outcomes, including mediastinitis rates, deep or superficial incisional SSI, length of hospital stay, hospital readmission rates, and mortality, were also similar between the two groups.
Specifically, mediastinitis occurred in 37 patients (2.3%) in the chlorhexidine-alcohol group and 39 patients (2.4%) in the povidone-iodine-alcohol group (risk difference -0.12, 95% CI -1.17 to 0.92, P=0.81). The incidence of surgical site infections was 4% and 3.3% in the chlorhexidine-alcohol and povidone-iodine-alcohol groups, respectively (risk difference 0.74, 95% CI -0.55 to 2.03, P=0.26).
Study Design and Patient Population
The CLEAN 2 trial enrolled adult patients scheduled for major cardiac surgery (valve, coronary artery bypass graft, ascending aorta, or combined surgery) via sternotomy. Exclusion criteria included known allergies to chlorhexidine, povidone-iodine, isopropanol, or ethanol; heart transplant surgery or thoracic infection; signs of inflammation or sternal instability; and a history of cardiac surgery within the preceding three months.
Patients received either chlorhexidine-alcohol or povidone-iodine-alcohol for skin disinfection, administered according to local practices, which included either a one-step or two-step procedure with or without skin scrubbing using antiseptic soap. All patients received care following the guidelines of the French Society for Hospital Hygiene, including preoperative showers, hair removal with clippers, antibiotic prophylaxis, and maintenance of normoglycemia.
Implications and Context
The findings challenge the World Health Organization (WHO) and the UK National Institute for Health and Care Excellence (NICE) guidelines, which recommend chlorhexidine-alcohol as the first-line antiseptic agent for surgical site preparation. The authors suggest that these recommendations should be modified, considering the similar efficacy and potential cost differences between the two antiseptic solutions.
"Our results do not support claims of superiority of chlorhexidine-alcohol over povidone-iodine-alcohol for reducing reoperation and SSI rates after major cardiac surgery," the researchers stated. "We suggest that WHO and NICE recommendations should be modified accordingly."
While the study did not find a difference in efficacy, it did note that local reactions at surgical sites were reported in 5 (0.3%) and 12 (0.7%) patients in the chlorhexidine-alcohol and povidone-iodine-alcohol groups, respectively (risk difference −0.43 [95% CI −0.93–0.07], P = 0.09).
Limitations
The authors acknowledged several limitations, including a lack of standardization of antiseptic strategies across centers, differences in antiseptic application methods due to the availability of applicators, and the premature termination of the study due to the COVID-19 pandemic and funding constraints. However, they noted that the overall number of primary outcomes was higher than expected, ensuring sufficient statistical power.
Despite these limitations, the CLEAN 2 trial provides valuable evidence for healthcare professionals and policymakers in making informed decisions about surgical site preparation in cardiac surgery.
