European Journal of Cardiovascular Medicine

Surgical site infections (SSIs) remain one of the most common healthcare-associated infections worldwide, contributing to prolonged hospital stays, increased treatment costs, and higher morbidity and mortality rates [1]. They account for approximately 20% of all hospital-acquired infections and can occur in up to 2–5% of patients undergoing clean surgical procedures, with higher rates reported in clean-contaminated and contaminated surgeries [2]. The etiology of SSIs is multifactorial, with endogenous skin flora being a predominant source of contamination [3].

Preoperative skin antisepsis plays a critical role in reducing the microbial burden at the surgical site and is considered a fundamental preventive measure in SSI reduction strategies [4]. Among the commonly used antiseptic agents, povidone-iodine and chlorhexidine have been extensively studied for their antimicrobial efficacy. Povidone-iodine, an iodophor, exerts broad-spectrum antimicrobial activity against bacteria, viruses, and fungi by releasing free iodine, which penetrates microbial cell walls and disrupts protein and nucleic acid structure [5]. Its rapid action and minimal systemic absorption make it a widely adopted choice; however, its efficacy may be reduced in the presence of organic matter such as blood or serum [6].

Chlorhexidine, a cationic bisbiguanide, disrupts bacterial cell membranes and precipitates intracellular components, offering persistent residual activity due to its ability to bind to the stratum corneum [7]. Alcohol-based chlorhexidine formulation demonstrate enhanced bactericidal activity, rapid onset, and prolonged antimicrobial effects compared to aqueous formulations and povidone-iodine in certain surgical settings [8]. Several clinical trials and meta-analyses have suggested that chlorhexidine-alcohol preparations may be superior to aqueous povidone-iodine in preventing SSIs, particularly in clean-contaminated surgeries [9].

Despite global guidelines recommending chlorhexidine-alcohol as the preferred agent for preoperative skin preparation, practice variations exist due to differences in availability, cost, surgeon preference, and institutional protocols [10]. In low- and middle-income countries, povidone-iodine remains widely used, partly due to its affordability and historical adoption, even though comparative data in these settings remain limited [11].

Given the ongoing burden of SSIs and the critical importance of optimal preoperative skin preparation, it is essential to generate context-specific evidence to inform practice guidelines. This study was undertaken to compare the effectiveness of 10% povidone-iodine and 2% chlorhexidine in 70% isopropyl alcohol for preoperative skin antisepsis in elective clean and clean-contaminated surgeries, with surgical site infection incidence as the primary outcome measure.

Study Design and Setting
This was a prospective, randomized, controlled study conducted in the Department of General Surgery, Government Siddhartha Medical College & General Hospital, Vijayawada, from July 2024 to June 2025. The study aimed to compare the efficacy of 10% povidone-iodine versus 2% chlorhexidine in 70% isopropyl alcohol for preoperative skin preparation in preventing surgical site infections (SSIs). Approval was obtained from the Institutional Ethics Committee. Written informed consent was obtained from all participants before enrolment.

Study Population
Adult patients (≥18 years) undergoing elective clean or clean-contaminated surgical procedures were eligible.

Inclusion Criteria:

• Patients scheduled for elective clean or clean-contaminated surgeries.
• Willingness to participate and provide informed consent.

Exclusion Criteria:

• Emergency surgeries.
• Known allergy to povidone-iodine or chlorhexidine.
• Contaminated or dirty wounds.
• Patients on systemic antibiotics within 48 hours before surgery (other than standard prophylaxis).

Sample Size Calculation
Based on prior studies reporting SSI incidence of 9% with povidone-iodine and 3% with chlorhexidine, a sample size of 108 patients per group was calculated to achieve 80% power at a 5% significance level. Accounting for a 10% dropout rate, 120 patients were recruited per group, totalling 240 participants.

Randomization and Allocation
Participants were randomized into two groups using a computer-generated block randomization sequence (block size = 4). Allocation was concealed in sequentially numbered, opaque, sealed envelopes opened immediately before skin preparation.

• Group A: Skin preparation with 10% povidone-iodine.
• Group B: Skin preparation with 2% chlorhexidine in 70% isopropyl alcohol.

Intervention Protocol
The operative site was prepared according to group allocation immediately prior to incision, ensuring complete coverage of the surgical field. Skin preparation lasted at least two minutes, allowing drying before draping. All patients received prophylactic antibiotics as per institutional protocol.

Outcome Measures
The primary outcome was the incidence of SSI within 30 days postoperatively, assessed according to CDC criteria (superficial, deep, and organ/space infection).

Secondary outcomes included time to SSI onset, type of SSI, and adverse skin reactions.

Data Collection
Demographic details, comorbidities, body mass index (BMI), wound classification, operative duration, and postoperative SSI data were collected using a structured proforma.

Statistical Analysis
Data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY). Continuous variables were expressed as mean ± standard deviation (SD) and compared using independent t-tests. Categorical variables were presented as frequencies and percentages and compared using the chi-square or Fisher’s exact test. Relative risks (RR) with 95% confidence intervals (CI) were calculated for SSI incidence. A p-value < 0.05 was considered statistically significant.

Table 1. Demographic characteristics of study participants

Table 2. Primary outcome – incidence of surgical site infections

Table 3. SSI incidence according to wound classification

Table 4. Time to onset of SSI

Table 5. Adverse skin reactions

FIG 1: COMPARISON OF SSI BETWEEN POVIDONE IODINE AND CHLORHEXIDINE

A total of 240 patients were analyzed, with 120 participants in each intervention group. Baseline demographic and clinical characteristics were comparable between the groups (Table 1). The mean age was 44.6 ± 13.2 years in the povidone-iodine group and 45.2 ± 12.7 years in the chlorhexidine group (p = 0.72). Male predominance was similar (56.7% vs 58.3%, p = 0.78), as were mean BMI values (24.8 ± 3.6 vs 24.5 ± 3.4 kg/m², p = 0.54). The prevalence of diabetes mellitus, hypertension, and smoking history showed no statistically significant differences (p > 0.70 for all).

The overall SSI incidence (Table 2, Figure 1) was higher in the povidone-iodine group (12 cases; 9.6%) compared to the chlorhexidine group (4 cases; 3.3%), with a statistically significant difference (p = 0.042). The relative risk of SSI with povidone-iodine was 2.91 (95% CI: 1.01–8.37). Superficial SSIs occurred in 6.7% versus 2.5% of patients (p = 0.12), deep SSIs in 2.5% versus 0.8% (p = 0.34), and organ/space SSIs in 0.8% versus 0.0% (p = 0.32) for povidone-iodine and chlorhexidine, respectively.

When stratified by wound classification (Table 3), SSI rates in clean surgeries were 5.0% for povidone-iodine and 2.6% for chlorhexidine (p = 0.18). In clean-contaminated surgeries, SSI incidence was significantly higher in the povidone-iodine group (14.3%) compared to the chlorhexidine group (4.8%, p = 0.049).

The mean time to onset of SSI (Table 4) was 6.4 ± 2.1 days in the povidone-iodine group and 7.0 ± 1.8 days in the chlorhexidine group (p = 0.52). Median onset was day 6 (IQR: 5–8) and day 7 (IQR: 6–8), respectively.

No adverse skin reactions, including irritation, contact dermatitis, or allergic reactions, were reported in either group (Table 5).

In this randomized prospective study, preoperative skin antisepsis with 2% chlorhexidine in 70% isopropyl alcohol resulted in a lower overall surgical site infection (SSI) rate compared to 10% povidone-iodine (3.3% vs 9.6%, RR 2.91; 95% CI: 1.01–8.37; p = 0.042). The difference was most pronounced in clean-contaminated procedures, where SSIs occurred in 4.8% of patients in the chlorhexidine group versus 14.3% in the povidone-iodine group (p = 0.049), while the rates in clean procedures (2.6% vs 5.0%) were not statistically significant (p = 0.18).

Our findings are consistent with Darouiche et al. [8], who reported SSI rates of 4.0% for chlorhexidine-alcohol and 9.5% for povidone-iodine in clean-contaminated surgeries, corresponding to a relative risk reduction of nearly 58%. Similarly, Noorani et al. [9], in a meta-analysis of over 7,000 patients, demonstrated SSI incidences of 7.4% with chlorhexidine compared to 11.2% with povidone-iodine, yielding a pooled relative risk of 0.65 (95% CI: 0.55–0.77).

In gastrointestinal procedures, Lee et al. [10] found SSI rates of 5.8% in the chlorhexidine group and 12.1% in the povidone-iodine group (p = 0.016), which closely mirrors the magnitude of difference observed in our clean-contaminated subgroup. Paocharoen et al. [11] also reported a lower SSI incidence with chlorhexidine (2.8%) compared to povidone-iodine (6.4%) across mixed surgical populations, reinforcing the superiority trend. Even in studies where statistical significance was not reached for superficial SSIs, such as Swenson et al. [12], the rates favored chlorhexidine (4.9%) over povidone-iodine (7.2%), aligning with the directional consistency in our data for superficial infections (2.5% vs 6.7%).

The mean time to SSI onset in our study was 7.0 days for chlorhexidine and 6.4 days for povidone-iodine, comparable to the median 5–7 days reported by Darouiche et al. [8]. The absence of adverse skin reactions in both groups parallels the safety outcomes documented by Noorani et al. [9] and Paocharoen et al. [11], confirming that both agents are well-tolerated.

Overall, when integrated with consistent international evidence, our findings strengthen the recommendation for chlorhexidine-alcohol as the preferred preoperative antiseptic, particularly in clean-contaminated procedures where the absolute risk reduction is clinically significant.

This prospective randomized study demonstrated that preoperative skin preparation with 2% chlorhexidine in 70% isopropyl alcohol significantly reduced the incidence of surgical site infections compared to 10% povidone-iodine, particularly in clean-contaminated procedures. The overall SSI rate was 3.3% with chlorhexidine versus 9.6% with povidone-iodine, with a relative risk of 2.91 (95% CI: 1.01–8.37; p = 0.042). No adverse skin reactions were observed in either group. These findings, in conjunction with consistent evidence from international literature, support the preferential adoption of chlorhexidine-alcohol formulations for preoperative skin antisepsis to improve postoperative outcomes and reduce healthcare-associated infection burden, especially in resource-limited surgical settings.

Acknowledgement
The authors thank the operating theatre staff and infection control team of the Department of General Surgery, XXXXX, for their invaluable support in conducting this study.

Conflicts of Interest
The authors declare no conflicts of interest.

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