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Critical Care

, 16:R70

First Online: 30 April 2012Received: 10 January 2012Revised: 02 April 2012Accepted: 30 April 2012


BackgroundData from interventional trials of systemic anticoagulation for sepsis inconsistently suggest beneficial effects in case of acute lung injury ALI. Severe systemic bleeding due to anticoagulation may have offset the possible positive effects. Nebulization of anticoagulants may allow for improved local biological availability and as such may improve efficacy in the lungs and lower the risk of systemic bleeding complications.

MethodWe performed a systematic review of preclinical studies and clinical trials investigating the efficacy and safety of nebulized anticoagulants in the setting of lung injury in animals and ALI in humans.

ResultsThe efficacy of nebulized activated protein C, antithrombin, heparin and danaparoid has been tested in diverse animal models of direct for example, pneumonia-, intra-pulmonary lipopolysaccharide LPS-, and smoke inhalation-induced lung injury and indirect lung injury for example, intravenous LPS- and trauma-induced lung injury. Nebulized anticoagulants were found to have the potential to attenuate pulmonary coagulopathy and frequently also inflammation. Notably, nebulized danaparoid and heparin but not activated protein C and antithrombin, were found to have an effect on systemic coagulation. Clinical trials of nebulized anticoagulants are very limited. Nebulized heparin was found to improve survival of patients with smoke inhalation-induced ALI. In a trial of critically ill patients who needed mechanical ventilation for longer than two days, nebulized heparin was associated with a higher number of ventilator-free days. In line with results from preclinical studies, nebulization of heparin was found to have an effect on systemic coagulation, but without causing systemic bleedings.

ConclusionLocal anticoagulant therapy through nebulization of anticoagulants attenuates pulmonary coagulopathy and frequently also inflammation in preclinical studies of lung injury. Recent human trials suggest nebulized heparin for ALI to be beneficial and safe, but data are very limited.

AbbreviationsALIacute lung injury

APCactivated protein C

APTTactivated partial thromboplastin time

ARDSacute respiratory distress syndrome


EVLWextravascular lung water



LISlung injury score



MVmechanical ventilation

MeSHmedical subject headings


rhrecombinant human

RCTrandomized controlled trial

TATcthrombin-antithrombin complex

TFtissue factor

TFPItissue factor pathway inhibitor

VCAM-1vascular cell adhesion molecule 1

VILIventilator-induced lung injury.

Electronic supplementary materialThe online version of this article doi:10.1186-cc11325 contains supplementary material, which is available to authorized users.

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Autor: Pieter R Tuinman - Barry Dixon - Marcel Levi - Nicole P Juffermans - Marcus J Schultz


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