Chlorhexidine within a standardized oral-care bundle for the prevention of ventilator-associated pneumonia: a pragmatic cluster-randomized crossover trial in six medical intensive care units

Chlorhexidine (CHX) has been a long-standing component of oral-care bundles for preventing ventilator-associated pneumonia (VAP), but recent evidence has questioned its benefit in non-cardiac-surgery ICU. We evaluated whether adding 0.12% CHX to standardized oral-care bundle provides incremental benefit in a mixed medical ICU. We conducted a prospective, pragmatic cluster-randomized crossover (AB/BA) trial in six adult medical ICUs of a single tertiary-care academic hospital in Bhubaneswar, India. ICUs were randomized as three ICUs of two Period of 9 months with the multicomponent oral-care bundle without chlorhexidine and three with the same bundle plus 0.12% chlorhexidine with a 1-month wash-in and re-training interval. Consecutive adults ventilated for ≥ 48 h were included. The primary outcome was VAP incidence density (Clinical Pulmonary Infection Score (CPIS) > 6) as per 1,000 ventilator-days. Secondary outcomes were 28-day all-cause mortality, duration of mechanical ventilation, ICU length of stay, 28- day ventilator-free days, Beck Oral Assessment Scale (BOAS) and Critical-Care Pain Observation Tool (CPOT) scores. The primary model was a population-averaged Poisson generalized estimating equation (GEE) and adjustment for treatment, period, sequence, age, sex, APACHE II, and SOFA. A total of 1,035 patients (637 No CHX, 398 CHX) accrued 10,024 ventilator-days (5,918 vs. 4,106). Groups were well balanced at baseline (mean age ≈ 55 years; APACHE II ≈ 19.6; SOFA ≈ 13.4). VAP occurred in 100/5,918 ventilator-days (16.9 per 1,000) vs. 77/4,106 (18.8 per 1,000) (No CHX vs. CHX). The adjusted Poisson incidence rate ratio was 1.08 (95% CI 0.84–1.38; p = 0.56). 28-day mortality was 28.7% vs. 26.4% (no CHX vs. CHX) (adjusted OR 0.87, 95% CI 0.65–1.15; p = 0.33). ICU length of stay was longer in the CHX arm (adjusted mean difference + 0.89 days, 95% CI + 0.19 to + 1.58; p = 0.013). BOAS and CPOT scores did not differ. In this trial, adding 0.12% chlorhexidine to a standardized oral-care bundle did not reduce VAP incidence density or 28-day mortality and was associated with a modest increase in ICU length of stay. Routine CHX use provided no clear incremental benefit in a mixed medical ICU population. Clinical Trials Regisrty- India (CTRI) identifier [CTRI/2024/02/062201], registered [01 February 2024].