Reversal of apixaban induced alterations in haemostasis by different coagulation factor concentrates in patients after hip or knee replacement surgery.

BACKGROUND: Apixaban is a direct oral anticoagulant (DOAC) with a specific inhibition of activated factor X (FXa). In case of bleeding or need of urgent surgery a direct antidote is not yet available. Off-label application of non-specific haemostatic agents, such as prothrombin complex concentrate (PCC) and recombinant FVIIa (rFVIIa), has been reported to reverse the effects of apixaban in in vitro and animal studies. The aim of this study is to measure the reversal potential of PCC and rFVIIa in patients with prophylactic apixaban concentrations. MATERIAL AND METHODS: Whole blood from patients under prophylactic therapy with apixaban was spiked with two doses of PCC or rFVIIa. Thromboelastometry (ROTEM®), prothrombin time (PT), and activated partial prothrombin time (aPTT) were performed. RESULTS: Prolongations in PT and aPTT were corrected by the different concentrates with variable efficacies (PCC

Stress induced IL-10 does not seem to be essential for early monocyte deactivation following cardiac surgery.

An increase in circulating levels of IL-10 is believed to contribute to immunosuppression caused by major surgery. Cortisol and catecholamines have been shown to be important costimulatory factors for IL-10 secretion in humans. As thoracic epidural block (TEB) should blunt the perioperative increases in cortisol and catecholamines we investigated whether IL-10 secretion is influenced by TEB. Twenty-six patients undergoing coronary artery bypass graft surgery using cardiopulmonary bypass were randomized to receive either general anesthesia (GA) or GA plus TEB. Sensory and pain levels were measured to demonstrate clinical effectiveness. Plasma concentrations of epinephrine, norepinephrine, cortisol, IL-6 and IL-10 as well as monocyte surface expression of HLA-DR and their ex vivo capacity to release TNF-alpha after LPS stimulation were measured perioperatively. TEB was clinically effective and patients receiving TEB showed decreased circulating levels of IL-10. However, this decrease was independent of decreased levels of cortisol or epinephrine. No influence of TEB on IL-6 levels, monocyte capacity to ex vivo release TNF-alpha upon LPS stimulation or their expression of HLA-DR was found. In conclusion, high TEB reduces antiinflammatory immune suppressing mediators including IL-10 and stress mediators. At least in cardiac surgery patients the monocyte functional depression is not related to systemic release of IL-10 and the influence of cortisol or epinephrine is less important for early monocyte deactivation than what in vitro and animal models have suggested.

Low-dose prostacyclin preserves renal function in high-risk patients after coronary bypass surgery.

OBJECTIVE: Renal failure after bypass is still a threatening problem prolonging hospital care and reducing overall survival. The following pilot study was aimed to analyze whether perioperative low-dose prostacyclin infusion is able to preserve renal function in a selected group of patients who according to a poor cardiac function were stratified as high risk for the development of renal failure after bypass. DESIGN: Prospective randomized study. SETTING: Tertiary care university medical center. PATIENTS: Thirty-four patients scheduled for primary cardiac bypass surgery were included in the study (prostacyclin n = 17, control n = 17). Inclusion criteria were normal renal function before surgery and a cardiac ejection fraction <40%. INTERVENTIONS: Low-dose prostacyclin (2 ng/kg/min) was added to the standard anesthetic protocol. Infusion was started immediately before surgery and was continued for a maximum of 48 MEASUREMENTS AND MAIN RESULTS: Significant differences in the endogenous creatinine clearance were found between the prostacyclin and the control group. Whereas there was a significant drop in the creatinine clearance at 6 hrs after surgery in the control group with a prolonged recovery period, values in the prostacyclin group remained stable. Creatinine clearance before intervention was 100 +/- 22 mL/min in the control group and 91 +/- 22 mL/min in the prostacyclin group, values at 24 hr were 68 +/- 34 mL/min vs. 103 +/- 37 mL/min, respectively (p < .01). Significant findings in favor for the prostacyclin group were also found for urine output and the fractional excretion rate of sodium. CONCLUSION: This first pilot study indicates that low-dose prostacyclin may be of substantial value for preserving renal function in high-risk patients after coronary bypass surgery.