Inhaled Heparin to Shorten Antibiotic Duration in Ventilator-Associated Pneumonia: A Randomized Double-Blind Controlled Trial.

Background and Aims: Prolonged antibiotic therapy in ventilator-associated pneumonia (VAP) contributes to antimicrobial resistance. Inhaled heparin has pleiotropic anti-inflammatory and mucolytic properties. This trial evaluated whether adjunctive nebulized heparin reduces antibiotic duration in VAP using a procalcitonin (PCT)-guided discontinuation algorithm. Methods: In this single-center, double-blind, randomized controlled trial, 82 mechanically ventilated adults with VAP (CPIS ≥ 6) were assigned to standard care plus nebulized heparin (10,000 IU every 6 h) or placebo (sterile distilled water). Both groups followed a PCT-guided antibiotic discontinuation algorithm (≤ 0.2 µg/L or ≥ 90% reduction from peak, plus clinical stability). Primary outcome: antibiotic duration (days). Secondary outcomes: duration of mechanical ventilation, ICU/hospital length of stay (LOS), serial CPIS, CRP, PCT, SOFA, APACHE II, adverse events, and 28-day mortality rate. Results: Antibiotic duration was significantly shorter with heparin (mean difference -3.2 days; 95% CI: -4.8 to -1.6; Conclusion: Adjunctive nebulized heparin (40,000 IU/day) significantly shortens antibiotic duration and improves clinical recovery in VAP without increasing adverse events. However, given the single-center design and modest sample size, our results require confirmation in future multicenter trials with optimum heparin doses and comprehensive biomarker panels to better elucidate the mechanisms of action and establish the definitive role of inhaled heparin in antimicrobial stewardship.