Background: Angiopoietin-2 and vascular endothelial growth factor (VEGF) may impair vascular barrier function while angiopoietin-1 may protect it. It was hypothesised that circulating angiopoietin-2 is associated with pulmonary permeability oedema and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) during septic or non-septic critical illness. Methods: Plasma levels of angiopoietin-1 and angiopoietin-2 were measured in mechanically ventilated patients (24 with sepsis, 88 without sepsis), together with the pulmonary leak index (PLI) for 67-gallium-labelled transferrin and extravascular lung water (EVLW) by transpulmonary thermal-dye dilution as measures of pulmonary permeability and oedema, respectively. ALI/ ARDS was characterised by consensus criteria and the lung injury score (LIS). Plasma VEGF and von Willebrand factor (VWF) levels were assayed. Results: Angiopoietin-2, VWF, PLI, EVLW and LIS were higher in patients with sepsis than in those without sepsis and higher in patients with ALI/ARDS (n = 10/12 in sepsis, n = 19/8 in non-sepsis) than in those without. VEGF was also higher in patients with sepsis than in those without. Patients with high PLI, regardless of EVLW, had higher angiopoietin-2 levels than patients with normal PLI and EVLW. Angiopoietin-2 correlated with the PLI, LIS and VWF levels (minimum r = 0.34, p,0.001) but not with EVLW. Angiopoietin-2 and VWF were predictive for ARDS in receiver operating characteristic curves (minimum area under the curve = 0.69, p = 0.006). Angiopoietin-1 and VEGF did not relate to the permeability oedema of ALI/ ARDS. Conclusion: Circulating angiopoietin-2 is associated with pulmonary permeability oedema, occurrence and severity of ALI/ARDS in patients with and without sepsis.

Pulmonary edema and LIS are not affected by the type of fluid loading in the steep part of the cardiac function curve in both septic and nonseptic patients. Then, pulmonary capillary permeability may be a smaller determinant of pulmonary edema than COP and CVP. Safety factors may have prevented edema during a small filtration pressure-induced rise in pulmonary protein and thus fluid transport.

PurposeTo investigate whether angiopoietin-2, von Willebrand factor (VWF) and angiopoietin-1 relate to surrogate indicators of vascular permeability, pulmonary dysfunction and intensive care unit (ICU) mortality throughout the course of septic shock.MethodsIn 50 consecutive mechanically ventilated septic shock patients, plasma angiopoietin-2, VWF and angiopoietin-1 levels and fluid balance, partial pressure of oxygen/inspiratory oxygen fraction and the oxygenation index as indicators of vascular permeability and pulmonary dysfunction, respectively, were measured until day 28.ResultsAngiopoietin-2 positively related to the fluid balance and pulmonary dysfunction, was higher in non-survivors than in survivors and independently predicted non-survival throughout the course of septic shock. VWF inversely related to the fluid balance and pulmonary dysfunction throughout the course of septic shock, was comparable between survivors and non-survivors and predicted non-survival on day 0 only. Angiopoietin-1 positively related to pulmonary dysfunction throughout the course, but did not differ between survivors and non-survivors.ConclusionsIn contrast to VWF, plasma angiopoietin-2 positively relates to fluid balance, pulmonary dysfunction and mortality throughout the course of septic shock, in line with a suggested mediator role of the protein.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-009-1560-y) contains supplementary material, which is available to authorized users.

In critically ill patients, decreased plasma albumin and transferrin levels parallel increased pulmonary vascular permeability irrespective of underlying disease and fluid status. While normal levels help to exclude acute respiratory distress syndrome, hypoalbuminemia and hypotransferrinemia increase the diagnostic accuracy of the American European Consensus Conference criteria and lung injury score for elevated pulmonary vascular permeability.