Haptoglobin and free haemoglobin during cardiac surgery-is there a link to acute kidney injury?

Acute kidney injury (AKI) is frequently observed after cardiac surgery (CS) with cardiopulmonary bypass (CPB). Multiple mechanisms underlie this phenomenon, including CPB-dependent haemolysis. Haemoglobin is released during haemolysis, and free haemoglobin (frHb) causes tubular cell injury after exceeding the binding capacity of haptoglobin (Hp). The objective of this study was to investigate the influence of perioperative changes in frHb and Hp levels on the incidence of CS-associated (CSA) AKI. After receiving local ethics committee approval and obtaining informed consent from our patients, we analysed the data pertaining to 154 patients undergoing CPB surgery. We recorded frHb and Hp concentrations pre-, intra- and postoperatively and defined AKI using the Kidney Disease Improving Global Outcomes (KDIGO) classification. We observed that frHb levels increased significantly during surgery and then decreased at ten hours thereafter and that Hp levels decreased during surgery and remained at low levels until the first postoperative day. We noted a moderate negative correlation between frHb and Hp levels. AKI was identified in 45.5% of patients; however, there was no significant difference in frHb or Hp levels between patients with and without AKI. We did not observe a relationship between frHb or Hp levels and CSA AKI and thus could not confirm the hypothesis that patients with higher baseline Hp concentrations experience a lower incidence of AKI than patients with lower baseline Hp concentrations.

The effects of residual pump blood on patient plasma free haemoglobin levels post cardiac surgery.

At the end of cardiopulmonary bypass, there are invariably several hundred millilitres of residual pump blood in the reservoir, which can either be re-transfused or discarded. The objective of this prospective observational study was to investigate the quality of the residual pump blood, focusing on plasma free haemoglobin (pfHb) and blood cell counts. Fifty-one consecutive patients were included in the study. Forty-nine units of residual pump blood and 58 units of transfused red blood cell (RBC) concentrates were analysed. The mean preoperative pfHb of the patients was 0.057 ± 0.062 g/l, which increased gradually to 0.55 ± 0.36 g/l on arrival in the intensive care unit postoperatively. On the first postoperative day, the mean pfHb had returned to within the normal range. Our data showed that haemoglobin, haematocrit, and erythrocyte counts of residual pump blood were approximately 40% of the values in standardised RBC concentrates. Plasma free haemoglobin was significantly higher in residual pump blood compared to RBC concentrates, and nearly twice as high as the pfHb in patient blood samples taken contemporaneously. Our findings indicate that residual pump blood pfHb levels are markedly higher compared to patients' blood and RBC concentrates, but that its administration does not significantly increase patients' pfHb levels.

Effects of different proton pump inhibitors on cardiac contractility in isolated human failing myocardium.

AIM: Proton pump inhibitors (PPI), e.g. pantoprazole (PP), esomeprazole (EP) and omeprazole (OP), work as anti-ulcer/gastrointestinal reflux drugs. Also, they are widely used in postoperative care of patients in cardiac surgery to prevent upper gastrointestinal bleeding. Therefore, in western industrial countries they play a major economic role, representing one of the most important drugs in open heart cardiac surgery. METHODS: Intact muscle strips (n=32) were isolated from the right ventricle wall of failing human hearts. In four different groups (PP, EP, OP, control group, each n=8), force amplitudes were recorded at a frequency of 60 beats per minute (bpm) with increasing PPI concentrations (0 to 320 µm/mL). RESULTS: In isometrically contracting muscle strips, significant negative inotropic effects were observed in the presence of all three PPI-groups (PP, EP and OP) with doses of 2.5 µg/mL and higher compared to the control group (p < 0.05 each). With high doses (320 µm/mL), force amplitudes could be almost completely depressed. The half maximal inhibitory concentration (IC50) for EP was 35.7 (confidence interval: 17.3-73.6) vs. OP 29.3 (6.8-126.6) vs. PP 25.1 (14.6-43.1) µg/mL (n.s.). No significant differences were found between the different proton pump inhibitors (PP, EP, OP) throughout the range of all concentrations. Relaxation was impaired in all PPI subgroups with prolonged time to 90% relaxation (RT90%) and maximum relaxation velocity (­df/dt) was reduced, too. These effects were partially reversible after wash-out of the drugs. CONCLUSION: We conclude that proton pump inhibitors show significant negative inotropic effects on isolated human failing myocardium. There is no apparent difference seen in the magnitude of the effects of each PPI-group. Further, in-vivo investigations are necessary to reveal the clinical evidence of PPI's negative inotropic effects, e.g. in cardio-surgical patients with heart failure.