Table 1.
Pre-clinical studies of nebulised heparin treatment for acute lung injury
| Dosage (Timing) | Species | Model (Sacrifice) | Nebulizer | Outcomes | Side effects | Reference |
|---|---|---|---|---|---|---|
| Animal models of acute lung injury treated with nebulised heparin | ||||||
|
1000 IU/kg (30min before injury and every 6h) |
Rat | it. Streptococcus pneumoniae (40h) | Aeroneb Pro Nebulizer | ↓ Pulmonary coagulation | NR | Hofstra et al, 2009 [104] |
|
1000 IU/kg (30min before, 6h and 12h after injury) |
Rat | iv. LPS (7.5 mg/kg) (16h) | Aeroneb Pro Nebulizer | ↓ Coagulation | NR | Hofstra et al, 2010 [105] |
|
1000 IU/kg (30min before injury and every 6h) |
Rat | it. Pseudomonas aeruginosa (16h) | Aeroneb Pro Nebulizer | = | NR | Cornet et al, 2011 [106] |
|
Dose NR (5 min after injury) |
Mouse | inh. Chlorine (400 ppm for 30min) (6h) | AirLife Brand Misty Max 10 | ↓ Decreased inflammation | No side effects | Zarogiannis et al, 2014 [107] |
|
1000 IU/kg (4h and 8h after injury or 30min before, 4h and 8h after injury) |
Rat | it. LPS (10μg/g) (24h) | Aeroneb Pro Nebulizer | ↓ Pulmonary coagulation and inflammation | NR | Chimenti et al, 2017 [80] |
| Animal models of acute lung injury treated with nebulised heparin and combined with another treatment | ||||||
| 10000 IU (1h after injury, every 4h) | Sheep | Smoke inh. and it. Pseudomonas aeruginosa (24h) | AirLife Brand Misty Max 10 |
↓ Lung injury and airways obstruction ↑ PaO2 |
No side effects | Murakami et al, 2002 [108] |
| 10000 IU (30min after injury, every 4h for 24h) or combined with intravenous 10 mg/kg/h lisofylline | Sheep | Smoke inh. (48h) | AirLife Brand Misty Max 10 |
↓ Need for MV ↑ PaO2 |
No side effects | Tasaki et al, 2002 [109] |
| 10000 IU (2h after injury, every 4h) or combined with nebulized 290 IU recombinant antithrombin | Sheep | Cutaneous burn and smoke inh. (48h) | AirLife Brand Misty Max 10 |
Combination: ↓ Pulmonary inflammation and airways obstruction ↑ PaO2 |
No side effects | Enkhbataar et al, 2007 [110] |
| 10000 IU (1h after injury, every 4h) combined with intravenous 0.34 mg/kg/h recombinant antithrombin | Sheep | Cutaneous burn and smoke inh. (48h) | AirLife Brand Misty Max 10 |
↓ Inflammation, oedema, airways obstruction ↑ PaO2 |
No side effects | Enkhbataar et al, 2008 [111] |
| 10000 IU (2h after injury, every 4h) combined with intravenous 6 IU/kg/h recombinant antithrombin (from 1h after injury until the end of the study) and nebulized 2 mg tissue plasminogen inhibitor (4h after injury, every 4h) | Sheep | Cutaneous burn and smoke inh. (48h) | AirLife Brand Misty Max 10 |
↓ Lung injury, oedema and airways obstruction ↑ PaO2 |
No side effects | Rehberg et al, 2014 [112] |
| 1000 IU/kg (4h, 12h and 28h after injury) combined with nebulized 500 IU/kg antithrombin (4h and 28h after injury) | Rat | it. HCl and LPS (30 μg/g) (72h) | Aeroneb Pro Nebulizer | ↓ Pulmonary coagulation and inflammation | No side effects | Camprubí-Rimblas et al, 2020 [113] |
↓: reduced, ↑: increased, =: equal, inh inhalation, it. intratracheal, iv. intravenous, LPS lipopolysaccharide, MV mechanical ventilation, NR not reported