BACKGROUND Acute kidney injury (AKI) predicts adverse outcomes after cardiac surgery. The accuracy of using changes in serum creatinine for diagnosis and grading of AKI is limited in the peri-operative cardiac surgical setting and AKI may be underdiagnosed due to haemodilution from cardiopulmonary bypass priming and the need for intra-operative and postoperative volume resuscitation. OBJECTIVES To determine whether the urinary biomarker neprilysin can be used as a marker for the early detection of AKI after cardiac surgery. DESIGN Prospective, observational cohort study. SETTING Austrian tertiary referral centre. PATIENTS 96 Patients undergoing elective cardiac surgery with cardiopulmonary bypass. MAIN OUTCOME MEASURES Differences and discriminatory power of neprilysin levels early after cardiac surgery and on postoperative day 1 between patients with or without AKI, as defined by the Kidney Disease Improving Global Outcomes Group. RESULTS AKI was found in 27% (n=26). The median neprilysin levels on postoperative day 1 were significantly higher in the AKI than in the non-AKI group, 4.0 [interquartile range (IQR): 2 to 6.25] vs. 2.0 ng ml−1 [IQR: 1.0 to 4.5], P = 0.0246, respectively. In addition, the median neprilysin levels at the end of surgery were significantly different between both groups, 5.0 [IQR: 2.0 to 9.0] vs. 2.0 ng ml−1 [IQR: 1.0 to 4.0], P = 0.0055, respectively. The discriminatory power of neprilysin for detecting early AKI corresponded to an area under the curve of 0.77 (95% confidence interval, 0.65 to 0.90). CONCLUSION Urinary neprilysin has potential as a biomarker for the early detection of AKI after cardiac surgery and has comparable discriminatory power to recently studied AKI biomarkers. TRIAL REGISTRATION The trial was registered at ClinicalTrials.gov (NCT03854825, https://clinicaltrials.gov/ct2/show/NCT03854825).

The authors report a case of intraoperative reversal of apixaban with andexanet alfa in a patient supported with venoarterial extracorporeal membrane oxygenation due to low-cardiac-output immediately after surgery for acute type A aortic dissection and massive intraoperative transfusion with administration of procoagulants. In this patient, andexanet alfa's off-label use was not associated with acute thrombotic complications despite being given during extracorporeal life support and after previous administration of prothrombin complex concentrates.

Background Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions. Methods We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS. Results After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62–0.79) in the left lung vs 0.14 (IQR 0.14–0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (Cdyn) of the left lung occurred immediately, whereas Cdyn of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and -8 were increased in both lungs. Conclusions We established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.