ABSTRACT
Previous studies have reported that the use of incisional negative pressure wound therapy (INPWT) might reduce the incidence of wound infections, although its mechanism remains unknown. We designed a prospective study to explore the effects of INPWT on different stages of the wound healing process. After meeting the inclusion criteria, 108 patients were enrolled. Based on exclusion criteria four patients were excluded and 104 patients were randomised into two groups. INPWT was applied after primary closure of the midline sternotomy in the study group (n = 52), while conventional wound dressing was applied in the control group (n = 52). We documented the incidence of deep sternal wound infections and analysed the pre- and postoperative inflammatory biomarkers and scar size in both groups. No wound infections were observed in the study group compared with six cases (11.1%) in the control group, (P = .026). No significant differences were observed in the inflammatory biomarkers between the groups. Scar size was significantly smaller in the study group. We concluded that INPWT has less effect on the inflammatory phase and appears to have more effect on the proliferation phase through pronounced scar formation.
Subject(s)
Negative-Pressure Wound Therapy , Sternotomy , Wound Healing , Aged , Bandages , Cicatrix , Female , Humans , Male , Middle Aged , Prospective Studies , Surgical Wound Infection/prevention & controlABSTRACT
INTRODUCTION AND AIM: Post-sternotomy wound infection is still a major concern and it affects morbidity, mortality, and hospital costs. Reconstruction failure may further increase these risks with significant financial implications. METHOD: Here, we attempted to verify some factors that may significantly influence the success of the surgical treatment. We performed a single-center retrospective analysis of data from 3177 consecutive patients who underwent midline sternotomy. The diagnostic signs of post-sternotomy wound infections were observed in 60 patients (1.9%). These data were thoroughly analyzed. RESULTS: Beside late diagnosis, the positive microbiological culture of the wounds, radical surgical intervention and peripheral vascular disease were found to significantly contribute to the development of surgical reconstruction failure. Radical surgical reconstruction was associated with a higher success rate (81.8 vs. 11.1%), p<0.001. CONCLUSION: Identification of the predictive factors that may lead to treatment failure can assist in developing treatment algorithms and improving the success rates of surgical reconstructions. Orv Hetil. 2018; 159(14): 566-570.
Subject(s)
Cardiac Surgical Procedures/mortality , Sternotomy/mortality , Surgical Wound Infection/mortality , Aged , Cardiac Surgical Procedures/adverse effects , Female , Humans , Male , Middle Aged , Retrospective Studies , Sternotomy/adverse effects , Sternum/surgery , Surgical Wound Infection/etiology , Time FactorsABSTRACT
Low output syndrome significantly increases morbidity and mortality of cardiac surgery and lengthens the durations of intensive care unit and hospital stays. Its treatment by catecholamines can lead to undesirable systemic and cardiac complications. Levosimendan is a calcium sensitiser and adenosine triphosphate (ATP)-sensitive potassium channel (IK,ATP) opener agent. Due to these effects, it improves myocardium performance, does not influence adversely the balance between O2 supply and demand, and possesses cardioprotective and organ protective properties as well. Based on the scientific literature and experts' opinions, a European recommendation was published on the perioperative use of levosimendan in cardiac surgery in 2015. Along this line, and also taking into consideration cardiac surgeon, anaesthesiologist and cardiologist representatives of the seven Hungarian heart centres and the children heart centre, the Hungarian recommendation has been formulated that is based on two pillars: literature evidence and Hungarian expert opinions. The reviewed fields are: coronary and valvular surgery, assist device implantation, heart transplantation both in adult and pediatric cardiologic practice. Orv Hetil. 2018; 159(22): 870-877.
Subject(s)
Cardiac Surgical Procedures/methods , Cardiotonic Agents/therapeutic use , Hydrazones/therapeutic use , Preoperative Care/methods , Pyridazines/therapeutic use , Cardiovascular Diseases/surgery , Humans , Hungary , SimendanABSTRACT
The efficacy of negative pressure wound therapy in the treatment of poststernotomy mediastinitis has been revealed in many reports. The present retrospective observational study examined the efficacy of incisional negative pressure wound therapy in the reconstructive surgery of poststernotomy mediastinitis. We retrospectively examined 1034 consecutive patients, who underwent median sternotomy in the period between October 2013 and September 2015. Mediastinitis developed in 21 patients (2%), who subsequently underwent surgical reconstruction. We applied incisional negative pressure wound therapy (iNPWT) after primary closure of the wound over redon drains in ten patients (iNPWT + redon group). In 11 patients, only redons were used (redons only group). We observed the time between the introduction and removal of redon drains, hospital stay until final wound closure and the rate of failure of treatment. Failure of treatment is defined as the need for further surgical reconstruction. In the iNPWT + redon group, the duration of redon drainage therapy was 6·9 ± 5·2 days versus 13·36 ± 11·58 in the redons only group. Hospital stay was 11·4 ± 8·6 versus 101·64 ± 89·2, and failure of treatment was 10% versus 45·5%, respectively. The primary results of this study appear to support the beneficial effect of iNPWT after radical wound reconstruction.
Subject(s)
Mediastinitis/etiology , Mediastinitis/surgery , Negative-Pressure Wound Therapy/methods , Sternotomy/adverse effects , Sternum/surgery , Surgical Wound Infection/etiology , Surgical Wound Infection/surgery , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Wound HealingABSTRACT
Severe mitral regurgitation due to prolapse of the valve demands early surgical intervention. Recently artificial chord implantation is the prefered solution, which requires cardioplegia and application of cardiopulmonary bypass using the left atrial approach. Transoesophageal echocardiography guided transapical neochord implantation is an emerging new technique for the treatment of mitral regurgitation. It enables the operation through left minithoracotomy on beating heart using a special instrument introduced into the left ventricle. Acute procedural success rates in different centres vary between 86 and 100%. According to reports, 92% of the patients do not require additional intervention at the 3-month follow-up. Continuous integration of data resulting improved outcomes supports the hope that this novel, less-invasive technique will be applied widely for the treatment of mitral regurgitation.
Subject(s)
Heart Rate , Heart Valve Prosthesis Implantation/methods , Mitral Valve Insufficiency/surgery , Mitral Valve/pathology , Mitral Valve/physiopathology , Thoracotomy , Clinical Trials as Topic , Echocardiography, Transesophageal , Equipment Design , European Union , Heart Valve Prosthesis , Humans , Mitral Valve Insufficiency/pathology , Mitral Valve Insufficiency/physiopathology , Multicenter Studies as Topic , Thoracotomy/methods , Treatment OutcomeABSTRACT
Introduction: Low-volume (1-2 U) transfusion affects more than a quarter of cardiac surgical patients. This may increase the incidence of complications, mortality, and blood use, even in low-risk patients. Objective: By analyzing risk factors, we searched for measures to reduce the frequency of low-volume transfusions. Method: The risk factors for transfusion of up to 2 U red blood cells were examined in 1011 patients. We compared data from 276 (27.3%) patients who received low-volume transfusion (study group) with 448 (44.3%) patients who received no transfusion (control group). 287 patients (28,4%), who received more than 2 U red blood cells, were excluded. Multivariate logistic regression analysis of data was performed. Results: The factors affecting low-volume transfusion were female gender (OR= 2.048; p = 0.002), age (OR= 1.033; p = 0.002), body weight (OR= 0.954; p<0.001), preoperative hemoglobin value of <130 g/l (OR = 3.185; p<0.001), preoperative glomerular filtration rate <60 ml/min/1.73 m(2) (OR = 1.750; p = 0.026), off-pump coronary artery bypass surgery (OR = 0.371; p<0.001), combined procedures (OR = 2.432; p = 0.015), perioperative fluid balance (OR = 1.227; p = 0.005), intraoperative bleeding and preoperative clopidogrel treatment (OR = 1.002; p<0.001), postoperative bleeding >1200 ml/24 hours (OR= 2.438; p<0.005). Conclusion: Screening and treatment of preoperative anemia, decreasing operative hemodilution, increasing the number of minimally invasive and off-pump procedures as well as applying a surgical hemostasis protocol could be a solution to avoid low-volume transfusion in cardiac surgery.
Subject(s)
Anemia , Cardiac Surgical Procedures , Blood Transfusion , Female , Hemostasis, Surgical , Humans , Postoperative HemorrhageABSTRACT
INTRODUCTION: Bleeding and transfusions following cardiac surgery significantly increase the rate of complications. Early diagnosis of "surgical" and "coagulopathic" bleeding is a prerequisite for effective treatment. Thromboelastometry with targeted hemostasis therapy can help in setting up the indication for reoperation and reduction of blood loss, transfusions and costs. AIM: We aimed to develop a local "reoperation for bleeding" protocol derived from the data of our former patients. METHOD: Based on data from 1011 cardiac surgical patients (control group), we developed a statistical algorithm to distinguish between "coagulopathic" and "surgical" bleeding. We used viscoelastic coagulation test and risk stratification. In 112 consecutive patients (study group), we examined the reoperations, and the impact of the protocol on the rates of transfusions and treatment costs. RESULTS: There was no difference in the rate of reoperations between the two groups (6.2% vs. 5.4%; p = 0.584). No coagulopathic bleeding occurred in the study group, compared to 12.7% in the control group. In the study group, we experienced reduction in bleeding (p = 0.026), an increased application of fibrinogen (p<0.001), prothrombin complex concentrate (p<0.001), and tranexamic acid (p<0.001). Red blood cell transfusions decreased by 30% (1.7 ± 2.6 E vs. 2.3 ± 3.3 E; p = 0.012). No difference was found in the amounts of fresh frozen plasma or platelet transfusions used. Calculated cost savings were HUF -20,333 per patient. CONCLUSION: Using this algorithm, reoperations were performed only in cases of surgical bleeding. The amount of bleeding, requirement for transfusions and treatment costs were reduced. Orv Hetil. 2020; 161(34): 1414-1422.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Hemostasis, Surgical/methods , Hemostatics/therapeutic use , Molecular Targeted Therapy , Reoperation , Algorithms , Case-Control Studies , Combined Modality Therapy , Humans , Treatment OutcomeABSTRACT
BACKGROUND: Because of its advantages, full midline sternotomy has remained the main approach for cardiac surgery. However, the development of post-sternotomy wound infections is its primary disadvantage. We evaluated the impact of xiphoid process (XIP)-sparing midline sternotomy regarding reducing the risk of deep sternal wound infections (DSWIs). METHODS: Data from 446 patients who underwent coronary artery bypass grafting by one surgeon, from January 2007 through May 2017, were retrospectively analyzed. Patients were divided into preliminary (from 2007-2011; n=202) and contemporary (January 2012-May 2017; n=244) groups. Traditional midline sternotomy was performed in the preliminary group, while xiphoid-sparing midline sternotomy was performed in the contemporary group. To adjust for differences in baseline and operative characteristics, the inverse probability of treatment weighting (IPTW) was applied. The generalized linear model was used to compare xiphoid-sparing and conventional sternotomy regarding the development of sternal wound infections. RESULTS: The sternal infection rates were 0.8% and 4.5% in the xiphoid-sparing and standard sternotomy groups, respectively (P=0.014). After adjustment for the IPTW, the xiphoid-sparing group showed a decreased risk for DSWIs (odds ratio 0.171, 95% confidence interval, 0.036-0.806, P=0.026) compared to the traditional sternotomy group. CONCLUSIONS: XIP-sparing midline sternotomy may be an alternative approach in coronary artery bypass surgery and seemed to reduce the risk of post-sternotomy wound infections in this study.
ABSTRACT
BACKGROUND: Deep sternal wound infections (DSWIs) are a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. We compared treatment outcomes after conventional sternal rewiring and reconstruction with no sternal rewiring in patients with a sternal wound infection. METHODS: We retrospectively enrolled patients who developed a DSWI after an open-heart procedure with median sternotomy at the Department of Cardiac Surgery, at the St. Rafael Hospital, Zalaegerszeg, Hungary, between 2012 and 2016. All patients received negative pressure wound and antibiotic therapy before surgical reconstruction. Patients were divided into groups determined by the reconstruction technique and compared. Subjects were followed up for 12 months, and the primary end-points were readmission and 90-day mortality. RESULTS: Among 3,177 median sternotomy cases, 60 patients developed a DSWI, 4 of whom died of sepsis before surgical treatment. Fifty-six patients underwent surgical reconstruction with conventional sternal rewiring (23 cases, 41%) or another interventions with no sternal refixation (33 cases, 59%). Eighty-one percent of sternal wound infections followed coronary bypass surgery (alone or combinated with another procedures), and 60% were diagnosed after hospital discharge. Staphylococcus aureus was cultured in 30% of all wounds and, 56.5% of cases reconstructed by sternal rewiring vs. 26.5% with no sternal rewiring, (P=0.022). Hospital readmission occurred in 63.6% of the sternal rewiring group vs. 14.7% of the no sternal rewiring group. The rate of death before wound healing or the 90th postoperative day was 21.7% in the sternal rewiring group vs. 0% in the no sternal rewiring group. The median hospital stay was longer in the sternal rewiring group than in the other group (51 vs. 30 days, P=0.006). CONCLUSIONS: Sternal rewiring may be associated with a higher rate of treatment failure than other forms of treatment for sternal wound infections.
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INTRODUCTION: Experimental studies have demonstrated that dextran-70 reduces the leukocyte-endothelium interaction, but clinical evidence is still lacking. Our objective was to justify the anti-inflammatory effect of dextran-70 following cardiac operations. METHODS: Forty patients undergoing coronary bypass surgery (n = 32) or aortic valve replacement (n = 8) were enrolled in this prospective, randomized, double-blind study. Two groups were formed. In group A (n = 20), dextran-70 infusion was administered at a dose of 7.5 ml/kg before the initiation of cardiopulmonary bypass and at a dose of 12.5 ml/kg after the cessation of cardiopulmonary bypass. Group B served as a control with identical amounts of gelatin infusion (n = 20). The plasma concentration of procalcitonin, C-reactive protein, IL 6, IL 6r, IL 8, IL 10, soluble endothelial leukocyte adhesion molecule-1, soluble intercellular adhesion molecule-1, cardiac troponin-I and various haemodynamic parameters were measured in the perioperative period. Multivariate methods were used for statistical analysis. RESULTS: In group A, lower peak (median) plasma levels of procalcitonin (0.2 versus 1.4, p < 0.001), IL 8 (5.6 versus 94.8, p < 0.001), IL 10 (47.2 versus 209.7, p = 0.001), endothelial leukocyte adhesion molecule-1 (88.5 versus 130.6, p = 0.033), intercellular adhesion molecule-1 (806.7 versus 1,375.7, P = 0.001) and troponin-I (0.22 versus 0.66, p = 0.018) were found. There was no significant difference in IL 6, IL-6r and C-reactive protein values between groups. Higher figures of the cardiac index (p = 0.010) along with reduced systemic vascular resistance (p = 0.005) were noted in group A. CONCLUSION: Our investigation demonstrated that the use of dextran-70 reduces the systemic inflammatory response and cardiac troponin-I release following cardiac operation. TRIAL REGISTRATION NUMBER: ISRCTN38289094.
Subject(s)
Anticoagulants/therapeutic use , Cardiac Surgical Procedures/adverse effects , Dextrans/therapeutic use , Inflammation/drug therapy , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/etiology , Biomarkers/blood , Calcitonin/blood , Calcitonin Gene-Related Peptide , Double-Blind Method , Female , Humans , Intercellular Adhesion Molecule-1/blood , Interleukin-8/blood , Male , Middle Aged , Myocardial Reperfusion Injury/blood , Prospective Studies , Protein Precursors/bloodABSTRACT
INTRODUCTION: The objective of current study is the evaluation of the accuracy and precision of EuroSCORE in the population of those patients undergone cardiac surgery in our department. MATERIAL AND METHODS: We have analyzed the data of 1839 consecutive patients who had their operations between 1/January 2003 and 31/December 2005. We have compared the mortality rates predicted preoperatively by additive and logistic EuroSCORE with the actual 30-day mortality figures. On statistical analysis the discriminative accuracy of the methods has been defined with the use of C-statistics. The calibration and precision of the methods have been checked by the Hosmer-Lemeshow statistics. RESULTS: The overall mortality rate in the above period was 3.3%. Additive and logistic EuroSCORE predicted 4.1 +/- 2.8 and 4.5 +/- 6.1%, consecutively. Based on the C-statistics the area below the Receiver Operating Characteristic curve has measured 0.699 (0.629-0.769) and 0.711 (0.642-0.779). The kappa 2 value for the Hosmer-Lemeshow statistics has proved 6.5 ( p = 0.475) and 12.5 ( p = 0.131). CONCLUSION: Logistic EuroSCORE has appropriate discriminative power and satisfactory precision, whilst the accuracy of additive EuroSCORE only comes near to the acceptable level, but at the same time it has an adequate calibration value. These results suggest that logistic EuroSCORE is more suitable for the preoperative risk assessment of these patients.
Subject(s)
Cardiac Surgical Procedures/mortality , Cardiology Service, Hospital/statistics & numerical data , Adult , Aged , Europe , Female , Humans , Hungary/epidemiology , Logistic Models , Male , Middle Aged , ROC Curve , Risk Assessment , Risk FactorsABSTRACT
INTRODUCTION: Since its introduction in 1968, the Bentall procedure has been the primary surgical solution for aneurysms of the aortic root. However, many surgeons have reported serious procedural complications such as detachment of coronary ostia and pseudoaneurysm formation at anastomosis sites. Therefore, the Bentall procedure has undergone several modifications to eliminate those complications. Partial or total detachment of the proximal anastomosis is rarely reported. PRESENTATION OF CASE: We report a total detachment of the proximal anastomosis after a Bentall operation with emphasis on the possible practical mechanisms, which might have led to the development of this very rare complication. The diagnosis was confirmed at a routine follow up examination and urgent surgery was performed. We also report our operative solution and review other possible surgical solutions that might be considered in this setting. DISCUSSION: The Bentall procedure and its modifications continue to be considered the gold standard for treating aneurysms involving the aortic root. Various modifications can serve as optimal solutions for procedure-related complications. CONCLUSION: Surgeons performing the Bentall procedure must be familiar with all existing modifications because they are complementary to the original surgical procedure. In the absence of endocarditis left ventricle outflow tract elongation may be an acceptable surgical solution to deal with total detachment of the proximal anastomosis.
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INTRODUCTION: Iatrogenic ventricular septal defect is a rare complication after the surgical replacement of cardiac valves. Small defects may have no hemodynamic significance or remain unremarked at the end of the surgical procedure. Understanding of the valvular anatomy alone is not always enough to avoid such complications, especially in the hands of young surgeons. PRESENTATION OF CASE: We present a case of iatrogenic ventricular septal defect that developed early after the surgical closure of a hemodynamically significant mitral paravalvular leak. Although the patient's critical state did not allow surgical intervention and he died, we think the lessons drawn from this case could be helpful to avoid such horrible complications in the future. DISCUSSION: This case documents a rare disastrous complication after imperfect surgical closure of a mitral paravalvular leak. Despite the unfortunate end, in reporting this case we try to direct the light to the possible mechanisms that led to the development of this injury focusing on the embryological and anatomical background. CONCLUSION: Understanding the anatomical and embryological structure of the cardiac fibrotic skeleton should keep cardiac surgeons more vigilent in detecting iatrogenic ventricle septal defects before the development of a devastating hemodynamic state.
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BACKGROUND: Surgical repair of ischemic mitral regurgitation (IMR) associated with chordal rupture in patients with ischemic cardiomyopathy is challenging as it aims to correct several structural pathologies at once. There are ongoing studies evaluating multiple approaches, however long term results are still scarce. METHODS AND RESULTS: 19 patients with IMR underwent mitral valve repair with interpapillary polytetrafluoroethylene (PTFE) bridge and neochordae formation at the Zala County Teaching Hospital. Concomitant coronary artery bypass grafting was performed in all patients. Post-procedural Transesophageal Echocardiogram (TEE) showed no mitral regurgitation (MR) in eighteen (94.7%) patients, with a leaflet coaptation mean height of 8 ± 3 mm. No operative mortality was observed. At the follow up (mean 17.7 ± 4.6 months; range 9 to 24 months), 17 (89%) patients showed no leakage and 2 had regurgitation grade ≤1, with documented NYHA functional class I or II in all patients. CONCLUSION: This retrospective study presents the first results of a novel surgical approach to treating ischemic mitral regurgitation. The interpapillary PTFE bridge formation is a safe and feasible surgical procedure that is reproducible, time sparing and effectively eliminates mitral valve regurgitation with promising long-term results.
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INTRODUCTION: Nimesulid (Mesulid) is a non-steroid anti-inflammatory drug (NSAID), acting by the selective inhibition of the Cyclooxygenase-2 (COX-2) isoenzyme. In this study the efficacy of nimesulid following cardiac surgery has been investigated in comparison with that of a COX-1 isoenzyme inhibitor drug. PATIENTS AND METHODS: 200 cardiac surgical patients operated on cardiopulmonary bypass have been involved in this prospective study. 100 patients received 100 mg. nimesulid bd. routinely in the postoperative period (group M). Another 100 patients were given 275 mg naproxen bd. (group A). In both groups the White Blood Cell (WBC), the blood sedimentation (We), the C-Reactive Protein (CRP) levels were determined from venous blood samples before the operation and on the first five postoperative days. Venous blood samples of 20 patients of each group in the same period were used to determine the Interleukin-6 (IL-6), and the Soluble Tumour Necrosis Factor Receptor-I (sTNF-RI) levels. Postoperative complications related to the use of the investigated drugs as well as the side effects have been compared in the two groups. A visual analogue pain scale was used before and after drug administration. Kruskal Wallis and student t tests were used for the statistical analysis. RESULTS: No serious complication related to the use of the investigated drugs has developed in either group. In group A gastrointestinal side effect were recorded in 7 cases (7%) whilst in group M no such complaints were found. Drug doses defined in the study protocol had to be raised or another drug had to be added in 11 and 3 cases in group A and M respectively. Neither the laboratory findings, nor the visual pain scale results have not shown any significant difference between the groups. CONCLUSION: The efficacy of nimesulid in postoperative inflammatory inhibition and pain relief has proved equal to that of the investigated COX-1 inhibitor drug, however less gastrointestinal side effects have been related to its administration.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cardiac Surgical Procedures/adverse effects , Cyclooxygenase Inhibitors/therapeutic use , Pain, Postoperative/drug therapy , Sulfonamides/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , C-Reactive Protein/metabolism , Cyclooxygenase 1 , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Female , Humans , Interleukin-6/blood , Isoenzymes/antagonists & inhibitors , Leukocyte Count , Male , Membrane Proteins , Middle Aged , Naproxen/therapeutic use , Pain Measurement , Pain, Postoperative/blood , Pain, Postoperative/etiology , Prospective Studies , Prostaglandin-Endoperoxide Synthases , Receptors, Tumor Necrosis Factor/blood , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiology , Treatment OutcomeABSTRACT
AIM: In this retrospective study the authors have investigated the occurrence and the possible risk factors of renal failure following heart surgery on CPB. PATIENTS AND METHODS: 52 perioperative variables of 536 consecutive patients undergoing cardiac surgery have been analysed. Types of surgery were as follows: coronary-bypass: 266 (49.6%), combined coronary-bypass: 62 (11.5%), valve replacement: 171 (31.9%), adult repair of congenital: disease 24 (4.4%), aortic dissection: 6 (1.1%), others 7 (1.3%). In the past medical history those patients involved in the study chronically impaired renal function could be found in 2.2%, whilst kidney stone and chronic pyelonephritis appeared in 2.4% and 1.2% respectively. Postoperative renal failure developed in 31 patients (5.8%), 3 of them required haemodialysis (0.6%). For the statistical analysis chi 2 test, t-test, Levine-test, Mann-Whitney-test and logistic regression analysis were applied using the SPSS software. RESULTS: On the basis of the performed multivariable logistic regression analysis the risk factors of renal failure following open heart surgery are as follows: age, duration of anaesthesia, chronic pyelonephritis in past medical history, preoperative serum creatinine level and low cardiac output syndrome.