"A phase 1 trial of nebulised heparin in acute lung injury

Critical Care 2008, 12:R64 doi:10.1186/cc6894

Barry Dixon et al

Abstract:

Introduction: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit

damage from fibrin deposition in the alveolar space and microcirculation. To date no human

studies have been undertaken. We assessed the feasibility, safety and potential anti-coagulant

effects of administration of nebulised heparin to patients with ALI.

Methods: An open label phase 1 trial of 4 escalating doses of nebulised heparin. A total of 16

ventilated patients with ALI were studied. The first group was administered a total of 50,000

U/day, the second 100,000 U/day, the third 200,000 U/day and the fourth 400,000 U/day.

Assessments of lung function included the arterial to inspired oxygen ratio (PaO2/FiO2), lung

compliance and the alveolar dead space fraction. Monitoring of anti-coagulation included the

activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT).

Bronchoalveolar lavage (BAL) fluid was collected and prothrombin fragment (PTF) and

tissue plasminogen activator (t-PA) levels were assessed. Analysis of variance was used to

compare the effects of dose.

Results: No serious adverse events occurred for any dose. The changes over time for the

PaO2/FiO2, lung compliance and the alveolar dead space fraction levels were similar for all

doses. A trend to increased APTT and TCT levels was present with higher doses (p = 0.09

and 0.1, respectively). For the highest dose the APTT reached 64 seconds and following

cessation of nebulised heparin fell to 39 seconds (p = 0.06). In BAL samples a trend to

reduced PTF levels was present with higher doses (p = 0.1), while t-PA levels were similar

for all doses.

Conclusions: Administration of nebulised heparin to mechanically ventilated patients with

ALI is feasible. It was not associated with any serious adverse events and at higher doses

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 anti-

coagulant effects."


I have to wonder if this will eventually "pave the way" to nebulize Xigris?

I have heard that ARDSnet is looking into using Xigris---don't know if systemic or nebulized.