Inhaled Heparin to Shorten Antibiotic Duration in Ventilator‐Associated Pneumonia: A Randomized Double‐Blind Controlled Trial
Abstract
ABSTRACT 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; p < 0.001). Baseline characteristics were similar except for higher mean APACHE II in the control group (18.8 vs. 15.2). After adjusting for baseline APACHE II imbalance, the treatment effect remained significant (adjusted mean difference −2.9 days; 95% CI: −4.5 to −1.3; p = 0.001). Heparin also reduced duration of mechanical ventilation (mean difference −1.47 days; p = 0.01), ICU LOS (− 3.5 days; p = 0.02),…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 82 participants or records.
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