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A phase 1 trial of nebulized heparin in acute lung injury

Introduction

Animal studies of acute lung injury (ALI) suggest nebulized heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. We therefore undertook a trial to assess the safety and tolerability of nebulized heparin in patients with ALI.

Methods

An open-label phase 1 trial of four escalating doses of nebulized heparin was administered over 2 days. A total of 16 ventilated patients with ALI were studied. Each dose was assessed in four patients. The first group was administered 50,000 U/day, the second 100,000 U/day, the third 200,000 U/day and the fourth 400,000 U/day. We measured the arterial to inspired oxygen ratio (PaO2/FiO2), lung compliance, the alveolar dead space fraction, the blood thrombin clotting time and the activated partial thromboplastin time (APTT). Bronchoalveolar lavage (BAL) fluid was collected and the prothrombin fragment and tissue plasminogen activator levels assessed.

Results

There was no difference between groups in the PaO2/FiO2, lung compliance or the alveolar dead space fraction over the study period. A trend to reduced prothrombin fragment levels in BAL fluid was present with higher doses of nebulized heparin (P = 0.1). Nebulized heparin did not increase tissue plasminogen activator levels in BAL fluid. A trend to increased blood thrombin clotting time and APTT levels was present with higher doses of nebulized heparin (P = 0.1 and P = 0.09, respectively). For the highest dose, the APTT reached 64 seconds.

Conclusion

Nebulized heparin can be administered safely to ventilated patients with ALI. At higher doses, nebulized heparin may limit coagulation activation in the lungs and increase systemic APTT levels.

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Dixon, B., Santamaria, D., Campbell, J. et al. A phase 1 trial of nebulized heparin in acute lung injury. Crit Care 12, P211 (2008). https://doi.org/10.1186/cc6432

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Keywords

  • Acute Lung Injury
  • Partial Thromboplastin Time
  • Activate Partial Thromboplastin Time
  • Inspire Oxygen
  • Alveolar Space