The effect of nebulized heparin on clinical outcomes in mechanically ventilated patients: a meta-analysis and review of the literature

OBJECTIVE: To determine the relationship between use of nebulized heparin and clinical outcomes in mechanically ventilated patients. METHODS: The Medline, Embase, Web of Science, Cochrane Library, and PubMed databases were searched for relevant randomized controlled trials (RCTs), published between database inception and May 2022. Primary outcomes were intensive care unit (ICU) length of stay and in-hospital mortality; secondary outcomes included duration of mechanical ventilation, ventilator-free days (VFDs) in 28 days, and length of hospitalization. The study protocol was registered on PROSPERO (registration No: CRD42022345533). RESULTS: A total of eight RCTs (651 patients) were included. Nebulized heparin was associated with reduced ICU length of stay (six studies; mean difference [MD] –1.10, 95% confidence interval [CI] –1.87, –0.33, I(2 )= 76%), reduced duration of mechanical ventilation (two studies; MD –2.63, 95% CI –3.68, –1.58, I(2) = 92%) and increased VFDs in 28 days (two studies; MD 4.22, 95% CI 1.10, 7.35, I(2) = 18%), without increased incidence of adverse events, such as bleeding; but was not associated with a reduction in length of hospitalization (three studies; MD –1.00, 95% CI –2.90, –0.90, I(2) = 0%) or in-hospital mortality (five studies; odds ratio 1.10, 95% CI 0.69, 1.77, I(2) = 0%). CONCLUSION: Nebulized heparin reduces ICU length of stay and duration of mechanical ventilation in mechanically ventilated patients, but has no effect on length of hospitalization or mortality.