ArticleCritical care (London, England)2008
A phase 1 trial of nebulised heparin in acute lung injury.
Article in Critical care (London, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Nebulized anticoagulants for acute lung injury - a systematic review of preclinical and clinical investigations.Critical care (London, England) · 2012Pooled it
- Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.The Lancet. Respiratory medicine · 2021Trial
- Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial.Korean journal of anesthesiology · 2020Trial
- Trial
- Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial.Critical care (London, England) · 2010Trial
- Review
- Heparin Provides Antiviral Activity Against Rhinovirus-16 via an Heparan Sulfate Proteoglycan-Independent Mechanism.International journal of molecular sciences · 2025Article
- Efficacy of inhaled nebulised unfractionated heparin to prevent intubation or death in hospitalised patients with COVID-19: an investigator-initiated international meta-trial of randomised clinical studies.EClinicalMedicine · 2025Article
- COVID-19 and anticoagulation: evidence from a meta-analysis of randomized controlled trials.Journal of thoracic disease · 2025Article
- Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study.Intensive care medicine experimental · 2025Article
- Article
- Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Anticoagulant Treatment in Severe ARDS COVID-19 Patients.Journal of clinical medicine · 2022Review
- Pharmacologic therapies of ARDS: From natural herb to nanomedicine.Frontiers in pharmacology · 2022Review
- Effect of Nebulized Heparin on Weaning off Intubated Patients with Acute Respiratory Distress Syndrome (ARDS) Admitted to Intensive Care Unit (ICU): A Randomized Clinical Trial.Anesthesiology and pain medicine · 2021Article
- Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19.Clinical medicine (London, England) · 2020Article
- Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Thromboinflammation in COVID-19 acute lung injury.Paediatric respiratory reviews · 2020Review
- Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence.Critical care (London, England) · 2020Review
- Future Trends in Nebulized Therapies for Pulmonary Disease.Journal of personalized medicine · 2020Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAnimal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI.
methodsAn open label phase 1 trial of four escalating doses of nebulised heparin was performed. A total of 16 ventilated patients with ALI were studied. The first group was administered a total of 50,000 U/day, the second group 100,000 U/day, the third group 200,000 U/day and the fourth group 400,000 U/day. Assessments of lung function included the PaO2/FiO2 ratio, lung compliance and the alveolar dead space fraction. Monitoring of anticoagulation included the activated partial thromboplastin time (APTT) and the thrombin clotting time. Bronchoalveolar lavage fluid was collected and the prothrombin fragment and tissue plasminogen activator levels were assessed. Analysis of variance was used to compare the effects of dose.
resultsNo serious adverse events occurred for any dose. The changes over time for the PaO2/FiO2 ratio, lung compliance and the alveolar dead space fraction levels were similar for all doses. A trend to increased APTT and thrombin clotting time levels was present with higher doses (P = 0.09 and P = 0.1, respectively). For the highest dose, the APTT reached 64 seconds; following cessation of nebulised heparin, the APTT fell to 39 seconds (P = 0.06). In bronchoalveolar lavage samples a trend to reduced prothrombin fragment levels was present with higher doses (P = 0.1), while tissue plasminogen activator levels were similar for all doses.
conclusionAdministration of nebulised heparin to mechanically ventilated patients with ALI is feasible. Nebulised heparin was not associated with any serious adverse events, and at higher doses it increased APTT levels. Larger trials are required to further investigate the safety and efficacy of nebulised heparin. In these trials due consideration must be given to systemic anticoagulant effects.
trial registrationAustralian Clinical trials registry ACTRN12606000388516.
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