Björn Brondén

Incidence, dynamics, and prognostic value of acute kidney injury for death after cardiac surgery.

OBJECTIVE This study relates long-term mortality after cardiac surgery to different methods of measuring postoperative renal function, classified according to the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. The dynamics of acute kidney injury during hospital stay were studied by comparing renal function preoperatively, at its poorest measurement, and at discharge. METHODS A total of 5746 patients undergoing coronary artery bypass grafting were studied in a Cox analysis, over a median follow-up time of 6.0 years (range, 2.5-9.5 years). Renal function was determined using the highest and discharge levels of plasma creatinine by Cockroft-Gault and Modification of Diet in Renal Disease formulae. Acute kidney injury was classified according to the RIFLE criteria. Renal recovery was studied in a 2-dimensional matrix, and the impact of renal function at different time points was related to survival. RESULTS Although the p-creatinine classified most patients in the nonacute kidney injury and Risk class; the Cockroft-Gault and Modification of Diet in Renal Disease formulae classified more patients in Injury and Failure classes; and higher Risk, Injury, and Failure classes were associated with increased long-term mortality. The effect of renal recovery on long-term survival was only in part associated with improved outcome. In addition, the poorest renal function was a stronger predictor of mortality compared with preoperative and discharge levels. CONCLUSIONS Classification using RIFLE criteria seems to be useful because it detects patients with renal impairment that affects long-term survival. The Modification of Diet in Renal Disease method seems to be the most robust method when predicting outcome, and the poorest renal function was the best predictor of outcome. Renal recovery was generally associated with better outcome.

Erythropoietin and protection of renal function in cardiac surgery (the EPRICS Trial).

Background:To date, there are no known methods for preventing acute kidney injury after cardiac surgery. Increasing evidence suggests that erythropoietin has renal antiapoptotic and tissue protective effects. However, recent human studies have shown conflicting results. The authors aimed to study the effect of a single high-dose erythropoietin preoperatively on renal function after coronary artery bypass grafting in patients with preoperative impaired renal function. Methods:This single-center, randomized, double-blind, placebo-controlled study included 75 patients scheduled for coronary artery bypass grafting with preexisting renal impairment estimated glomerular filtration rate based on p-cystatin C (<60 and >15 ml/min). The patients either received a single high-dose erythropoietin (400 IU/kg) or placebo preoperatively. The primary endpoint was renal protection evaluated by p-cystatin C at the third postoperative day compared to the preoperative values. Incidence of acute kidney injury and other renal biomarker changes were among secondary endpoints. Results:There was no statistically significant difference on the third postoperative day for relative p-cystatin C level changes from baseline between the groups, 131 ± 31% (mean ± SD) for the study group and 125 ± 24% for the control group (P = 0.31; 95% CI, −0.6 to 20% for the difference). There were no statistically significant differences in other renal biomarkers or measures between the groups (p-neutrophil gelatinase–associated lipocalin, p-creatinine, p-urea, and estimated glomerular filtration rate). There were no other differences in outcome variables between the groups. Conclusion:Intravenous administration of a single high-dose (400 IU/kg) erythropoietin did not have a renal protective effect on patients with reduced kidney function undergoing coronary artery bypass surgery.

Blood transfusion after cardiac surgery: is it the patient or the transfusion that carries the risk?

Background: The transfusion of red blood cells (RBCs) after cardiac surgery has been associated with increased long‐term mortality. This study reexamines this hypothesis by including pre‐operative hemoglobin (Hb) levels and renal function in the analysis.

Evaluation of cystatin C with iohexol clearance in cardiac surgery.

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery.

Risks Associated With the Transfusion of Various Blood Products in Aortic Valve Replacement.

BACKGROUND Patients undergoing cardiac operations often require transfusions of red blood cells, plasma, and platelets. From a statistical point of view, there is a significant collinearity between the components, but they differ in indications for use and composition. This study explores the relationship between the transfusion of different blood components and long-term mortality in patients undergoing aortic valve replacement alone or combined with revascularization. METHODS A retrospective single-center study was performed including 1,311 patients undergoing aortic valve replacement. Patients who received more than 7 units of red blood cells, those who died early (7 days), and emergency cases were excluded. Patients were monitored for up to 9.5 years. A broad selection of potential risk factors were analyzed using Cox proportional hazards regression, where transfusion of red blood cells, plasma, and platelets were forced to remain in the model. RESULTS The transfusion of red blood cells was not associated with decreased long-term survival (hazard ratio [HR], 1.01; p = 0.520) nor was the transfusion of platelets (HR, 0.946; p = 0.124); however, the transfusion of plasma was (HR, 1.041; p < 0.001). All HRs are per unit of blood product transfused. No increased risk was found for patients undergoing a combined procedure. CONCLUSIONS No significant risk for long-term mortality was associated with transfusion of red blood cells during the study period. However, the transfusion of plasma was associated with increased mortality.

The kinetics of lipid micro-emboli during cardiac surgery studied in a porcine model.

Objective. To study the kinetics of lipid micro-emboli during cardiac surgery. Design. Eleven pigs were studied. Seven of these were put on extracorporeal circulation. A shed blood phantom consisted of blood, saline and radioactive triolein was added to the circuit. Both venous and arterial blood samples were taken at short intervals. Four animals were used to study renal kinetics without extracorporeal circulation. The same kind of shed blood phantom was infused into the ascending aorta. Samples were taken from the renal artery and vein. All samples were analyzed for radioactivity by scintillation counting. Results. A median 130-fold increase in radioactivity was seen in the blood and was quickly eliminated. Systemic first-pass wedging was found to be 62%. The first-pass elimination in the kidney was 77%. No radioactivity was found in urine. Conclusions. This study shows that the turnover of lipid micro-emboli is fast, and that the majority of the emboli are trapped on their first passage through the capillary system. No evidence was found of a renal excretion of these lipid emboli.

Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS): a study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study

Introduction Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia–reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia–reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI. Methods and analysis Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15–90 mL/min/1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury. Ethics and dissemination The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study. Trial registration number NCT02397213; Pre-results.

Lipid emboli distribution in cardiac surgery is dependent on the state of emulsification

Objective. Lipid embolizations from retransfused shed blood during cardiac surgery have been shown to enter the circulation and end up in different organs. The purpose of this investigation was to evaluate differences in the kinetics and deposition between emulsified and non-emulsified lipid emboli in a porcine model. Design. Twelve animals were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom (6 animals given emulsified and 6 given non-emulsified lipids) was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Arterial and venous blood samples were taken at short intervals. Tissue samples were taken post-mortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used to measure lipid emboli content in blood and tissue. Results. Emulsified lipid emboli generated a 5-fold higher embolic load in the arterial and a 12-fold higher in the venous circulation, compared with non-emulsified lipid emboli. Emulsified lipid micro emboli resulted in a 2–15-fold higher tissue deposition in investigated organs compared with non-emulsified lipid micro emboli. Conclusions. This study shows that the state of emulsion significantly alter the kinetics and tissue deposition of lipid emboli. Emulsified lipid emboli give higher embolic load in the arterial and venous circulation, and higher tissue deposition versus non-emulsified lipid emboli. In both groups, the embolic load was higher in the arterial circulation than on the venous side.

Comparison between transcranial Doppler and coulter counter for detection of lipid micro embolization from mediastinal shed blood reinfusion during cardiac surgery.

Introduction: Lipid micro embolization (LME) from re-transfused shed blood has been postulated to be a potential reason for short- and long-term cognitive dysfunction after cardiac surgery. The purpose of this investigation was to evaluate if transcranial Doppler (TCD) has the capacity to detect LME. Methods: Thirteen patients undergoing cardiopulmonary bypass surgery were investigated. Each patient’s cerebral circulation was monitored with transcranial Doppler during the first two minutes after re-transfusion of shed blood and blood was simultaneously sampled and characterised by a Coulter counter. Results: Strong correlation was found between embolic loads, as measured by transcranial Doppler and Coulter counter (r=0.79, P<0.005). Conclusions: This pilot study shows that non-invasive monitoring by transcranial Doppler could be a potential tool to monitor LME during cardiopulmonary bypass surgery.

Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial

Background: Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation–induced ischemia–reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia–reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. Methods: The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min–1 · 1.73 m–2 were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. Results: All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. Conclusions: Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month.