Modest Reduction in Risk for Ventilator-Associated Pneumonia in Critically ill Patients Receiving Mechanical Ventilation Following Topical Oral Chlorhexidine

Abstract

The sample (N = 547) included patients older than 18 years (328 men and 219 women from a total population of 10,913) admitted to 3 intensive care units (ICUs) (medical, surgical/trauma, and neuroscience) at Virginia Commonwealth University Medical Center. The sample size required to detect an interaction (ie, the effect of chlorhexidine and toothbrushing in combination) was determined to be larger than that required to detect main effects (ie, chlorhexidine alone or toothbrushing alone) for a test at a given level of significance. The study was designed to detect an interactive effect resulting in a 0.755 difference in mean Clinical Pulmonary Infection Score (CPIS) at a power of 80% and a significance level of .05. An interim analysis was done and a Bonferroni adjustment was used to avoid inflation in the overall significance level related to interim analyses; for this reason, the level of significance for final analysis was .025. This was a randomized controlled clinical trial with a 2 × 2 factorial design. Patients were randomized to treatment within each ICU according to a permuted block design developed by the biostatistician before the start of the study. Staff who performed interventions (oral care) had no knowledge of patients' CPIS. Patients receiving mechanical ventilation were enrolled within 24 hours of intubation and were followed for up to 14 days. Dates of recruitment were not disclosed. Lung infection, resulting from aspiration of potential bacterial pathogens, such as Staphylococcus aureus, Streptococcus pneumoniae, or gram-negative rods that first colonize the oral cavity and oropharynx. Oral topical 0.12 % chlorhexidine gluconate, toothbrushing, or both (applied 4 times per day) were tested to determine their impact, if any, on incidence of lung infection in this cohort. The CPIS was assessed as the primary outcome variable. This score consists of the sum of points assigned to 6 clinical and laboratory variables (yielding a score from 0 to 12): temperature, white blood cell count, tracheal secretions, oxygenation (calculated as PaO2 divided by the fraction of inspired oxygen), findings on chest radiographs (no infiltrate, diffuse infiltrate, localized infiltrate), and results of culturing of tracheal aspirates (microscopic examination and semiquantitative culture of tracheal secretions). Analysis used in this study examined the effect of interventions on both the range of CPIS scores and on dichotomous categories of the presence (CPIS ≥6) or absence (CPIS <6) of VAP. When data on all patients were analyzed together, mixed models analysis indicated no effect of either chlorhexidine (P = .29) or toothbrushing (P = .95); however, chlorhexidine significantly reduced the incidence of pneumonia on day 3 (CPIS ≥6) among patients who had a CPIS less than 6 at baseline (P = .006). Toothbrushing had no effect on CPIS and did not enhance the effect of chlorhexidine. Chlorhexidine oral swabbing was effective in reducing early ventilator-associated pneumonia (VAP) (after 3 days of intervention) in patients in medical, surgical/trauma, and neuroscience ICUs who did not have evidence of lung infection at baseline. This effect was not observed after day 3. Toothbrushing did not reduce the incidence of VAP, and combining toothbrushing and chlorhexidine did not provide additional benefit over use of chlorhexidine alone.