What was the rationale for the study by Widmer and colleagues comparing povidone iodine and chlorhexidine gluconate (antiseptics) for preventing surgical site infections (SSIs)?

Rationale for the Widmer Study Comparing Antiseptic Solutions

The controversy about whether the efficacy of chlorhexidine gluconate versus povidone iodine differs for the prevention of surgical site infections (SSIs) was the primary rationale for the Widmer study.

Background on Antiseptic Agents

Surgical site infections remain a significant cause of postoperative morbidity and mortality. Preoperative skin antisepsis is a critical step in preventing SSIs, with chlorhexidine gluconate and povidone iodine (both typically in alcohol-based solutions) being the two most commonly used agents.

Historical Context

Prior to the Widmer study, there was conflicting evidence regarding the superiority of these antiseptic agents:

• A 2010 landmark study by Darouiche et al. found that chlorhexidine-alcohol was superior to povidone-iodine for preventing SSIs after clean-contaminated surgery (9.5% vs. 16.1% infection rate) 1
• Multiple guidelines recommended both agents but with varying preferences:
  • The 2012 ERAS Society guidelines noted that "skin preparation with a scrub of chlorhexidine-alcohol has recently been claimed to be superior to povidone-iodine in preventing surgical-site infections" 2
  • The 2023 ERAS Society guidelines for liver surgery stated that "skin preparation with chlorhexidine-alcoholic solution is associated with a lower rate of surgical site infections, compared to povidone-iodine solution" 2

The Controversy in Evidence

The controversy stemmed from several factors:

1. Inconsistent findings across studies:

   • A 2020 systematic review and meta-analysis found chlorhexidine to be superior to povidone-iodine in preventing SSIs (RR 0.65; 95% CI 0.55-0.77) 3
   • However, some studies showed no significant difference between the agents in specific surgical contexts 4, 5

2. Methodological limitations in previous research:

   • Many studies had small sample sizes or were single-center designs
   • Different formulations (aqueous vs. alcoholic) were used across studies
   • Varying surgical populations made comparisons difficult

3. Lack of high-quality evidence for specific surgical populations:

   • Most guidelines acknowledged the limited evidence specific to certain surgical specialties
   • The 2020 World Journal of Emergency Surgery guidelines stated "there are insufficient data to determine the role of saline or povidone irrigation of incisional wounds before closure to prevent SSI" 2

The Widmer Study Design and Purpose

The Widmer study (2024) was designed specifically to address this controversy through:

1. A multicenter, cluster-randomized, investigator-masked, crossover, noninferiority trial
2. Large sample size (3,360 patients)
3. Focus on both cardiac and abdominal surgery populations
4. Standardized application protocols for both antiseptic agents
5. Rigorous follow-up (30 days for abdominal surgery and 1 year for cardiac surgery)

The study aimed to determine whether povidone iodine in alcohol was noninferior to chlorhexidine gluconate in alcohol for preventing SSIs 6.

Clinical Implications

The controversy about antiseptic efficacy was particularly important because:

1. Both agents are widely available and commonly used
2. Cost considerations exist but are secondary to efficacy
3. Some patients have allergies or sensitivities to one agent
4. Standardizing preoperative protocols requires evidence-based decisions

The Widmer study ultimately found that povidone iodine in alcohol was noninferior to chlorhexidine gluconate in alcohol in preventing SSIs after cardiac or abdominal surgery (5.1% vs. 5.5% infection rate) 6, providing important evidence to resolve the controversy that had existed in the literature.