Fluid resuscitation associated with elevated angiopoietin-2 and length of mechanical ventilation after cardiac surgery

Background: Fluid restriction in patients with acute respiratory distress syndrome increases ventilator-free days while lowering plasma angiopoietin-2 (Ang-2), a marker of pulmonary endothelial injury. We hypothesised that fluid resuscitation may lead to endothelial injury after cardiac surgery and analysed Ang-2, angiopoietin-1 (Ang-1) and phospholipase A₂ (PLA₂) levels and the impact of fluid management on ventilation time. Methods: Patients enrolled in a single-centre, prospectively randomised interventional study of liberal or conservative fluid resuscitation strategy had plasma Ang-2, Ang-1 and PLA₂ levels measured at baseline (pre-operative), 6 and 24 hours after commencement of cardiopulmonary bypass, and analysed by linear mixed models as liberal v conservative (intention to treat) or high v low fluid group (actual treatment, ≥ 3250 mL of fluid administered), and further subclassified as EuroSCORE (European System for Cardiac Operative Risk Evaluation) II ≥ 0.9 or < 0.9. Results: Over 9 months, 144 patients were randomly allocated to either liberal (n = 74) or conservative (n = 70) fluid. Patients in the liberal fluid arm tended to an increased Ang-2 (P = 0.12) and had higher PLA₂ levels (P = 0.03). Based on actual fluid administered, Ang-2 levels were higher, the Ang-1/Ang-2 ratio lower, and the length of mechanical ventilation and intensive care unit (ICU) stay was longer in the high fluid group (P < 0.001). The highest levels of Ang-2 and corresponding lowest Ang-1/Ang-2 ratio, along with longest length of mechanical ventilation and ICU stay, were found with both the liberal and high fluid groups in patients with a EuroSCORE II ≥ 0.9 (P < 0.01). Conclusion: Liberal fluid resuscitation after cardiac surgery was associated with both pulmonary endothelial injury and prolonged length of mechanical ventilation.