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Critical Care

, 12:R64

First Online: 06 May 2008Received: 12 February 2008Revised: 02 April 2008Accepted: 06 May 2008


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.

AbbreviationsALIacute lung injury

APTTactivated partial thromboplastin time

BALbronchoalveolar lavage

ELISAenzyme-linked immunosorbent assay

PaO2-FiO2arterial oxygen partial pressure to inspired oxygen fraction ratio

PTFprothrombin fragments

TCTthrombin clotting time

t-PAtissue plasminogen activator.

Electronic supplementary materialThe online version of this article doi:10.1186-cc6894 contains supplementary material, which is available to authorized users.

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Autor: Barry Dixon - John D Santamaria - Duncan J Campbell

Fuente: https://link.springer.com/

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