Table 2 Clinical studies of nebulised heparin treatment for acute lung injury
Dosage (Timing) | Patients | n | Nebulizer | Outcomes | Reference |
|---|---|---|---|---|---|
Clinical studies of acute respiratory distress syndrome with nebulised heparin | |||||
 50000-400000 IU/day (two days) | MV ARDS Open-label phase 1 trial | 16 | Aeroneb Pro Nebulizer | ↓systemic coagulation (↓ pulmonary coagulation, 400000 IU) | Dixon et al, 2008 [114] |
 25000 IU (every 4h or 6h, max 14 days) | > 48h MV RCT | 50 | Aeroneb Pro Nebulizer | ↓systemic coagulation ↑ Free days MV | Dixon et al, 2010 [100] |
 5000 IU (four times a day until cease MV or discharge from the UCI) | > 48h MV Phase 2 RCT | 214 | Aeroneb Pro Nebulizer | = | Bandeshe et al, 2016 [115] |
 50000 IU (one day) | Elective cardiac surgery RCT | 40 | Aeroneb Pro Nebulizer | ↓ alveolar dead space fraction and tidal volumes | Dixon et al, 2016 [101] |
 25000 IU (every 6h, 10 days) | MV ARDS RCT | 256 | Aeroneb Pro Nebulizer | ↓Lung injury ↑ 60 day survivors at home | Dixon et al, 2020 (submitted for publication) |
Clinical studies of acute respiratory distress syndrome with nebulised heparin and combined with another treatment | |||||
 5000 IU combined with N-acetylcysteine and bronchodilator (every 4h for 7 days) | Burn patients paediatric Retrospective | 90 (children) | NR | ↓atelectasis, reintubation and mortality | Desai et al, 1999 [116] |
 5000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) | Burn patients Retrospective | 150 (children/adults) | NR | = | Holt et al, 2008 [117] |
 10000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) | Burn patients Retrospective | 30 | NR | ↓ lung injury ↓ mortality ↑ oxygenation | Miller et al, 2009 [118] |
 5000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) | Burn patients Retrospective | 63 | NR | = | Yip et al, 2011 [119] |
 5000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) | Burn patients Retrospective | 40 | NR | = | Kashefi et al, 2014 [120] |
 10000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) | Burn patients Retrospective | 72 | NR | ↑ free days MV | McIntire et al, 2017 [121] |
 25000 IU (every 4h for 14 days) | Burn patients RCT (terminated, insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication) | 160 | Aeroneb Pro Nebulizer | Not available | Glas et al, 2014 [122] |
Clinical studies of COVID-19 with nebulised heparin | |||||
 25000 IU (every 6h for 10 days) | SARS CoV 2 infection, on MV | RCT ACTRN: 12620000517976 | Aeroneb Pro Nebulizer | On-going | Dixon et al, 2020 [123] |
 25000 IU (every 6h up to 21 days) | SARS CoV 2 infection, pre-ICU | RCT EudraCT: 2020-001736-95 | Aeroneb Pro Nebulizer | On-going | ACCORD-2 (NHS UK) |