Oropharyngeal Interventions in Intubated Patients for Preventing Ventilator Associated Pneumonia: A Systematic Review and Multi-Variate Network Meta-Analysis Evaluating Pharmacological Agents.

Background: Ventilator-associated pneumonia (VAP) is a prevalent and serious complication of invasive mechanical ventilation (MV), contributing to significant mortality and increased healthcare resource utilization. While numerous oropharyngeal interventions exist, their comparative efficacy across critical outcomes remains uncertain due to a lack of direct comparisons in clinical trials. Methods: We conducted a systematic review and network meta-analysis (NMA) with a comprehensive search of MEDLINE, EMBASE, and Cochrane CENTRAL up to September 2025 for randomized and non-randomized studies comparing topical oral interventions in intubated patients. The primary outcome was VAP incidence; secondary outcomes were intensive care unit (ICU) mortality, duration of MV, and ICU length of stay (LOS). Pairwise and network meta-analyses were performed, and the certainty of evidence was assessed. The effect estimates were odds ratios (OR) for categorical outcomes and mean difference (MD) for numerical outcomes represented with 95% confidence intervals (95% CI). Results: Ninety-six studies (20,650 patients) were included, evaluating 44 interventions. For VAP prevention, several interventions were superior to reference/control, including Antimicrobial combinations (OR: 0.21, 95% CI: 0.05-0.39), Povidone-iodine (OR: 0.47, 95% CI: 0.21-0.98), and Chlorhexidine (OR 0.61, 95% CI 0.39-0.95). However, only Chlorhexidine plus toothbrushing significantly reduced mortality (OR: 0.74, 95% CI: 0.58-0.93). For resource utilization, only antimicrobial combinations significantly reduced the duration of MV (MD: -5.55 days, 95% CI: -10.75--1.7) and ICU LOS (MD: -7.74 days, 95% CI: -13--4). Evidence certainty (GRADE) was moderate for chlorhexidine and very low for other comparisons. Conclusions: This NMA demonstrates that while multiple oropharyngeal interventions are effective for VAP prevention, their benefits are outcome specific. The choice of intervention should be guided by clinical priorities, as the most effective strategy for preventing VAP may not concurrently reduce mortality or resource use. These findings can inform guideline development and underscore the need for standardized, multi-faceted oral care protocols in the ICU.