Target flow deviations on the cardiopulmonary bypass cause postoperative delirium in cardiothoracic surgery-a retrospective study evaluating temporal fluctuations of perfusion data.

OBJECTIVES: Postoperative delirium (POD) is common, costly and associated with long-term morbidity and increased mortality. We conducted a cohort study to assess the contribution of cardiopulmonary bypass (CPB) to the development of POD by means of algorithm-based data processing. METHODS: A database was compiled from 3 datasets of patients who underwent cardiac surgery between 2014 and 2019: intensive care unit discharge files, CPB protocols and medical quality management records. Following data extraction and structuring using novel algorithms, missing data were imputed. Ten independent imputations were analysed by multiple logistic regression with stepwise deletion of factors to arrive at a minimal adequate model. RESULTS: POD was diagnosed in 456/3163 patients (14.4%). In addition to known demographic risk factors and comorbidities like male sex, age, carotid disease, acute kidney failure and diabetes mellitus, cardiopulmonary parameters like total blood volume at the CPB [adjusted odds ratio (AOR) 1.001; confidence interval (CI) 1.1001-1.002] were independent predictors of POD. Higher values of the minimal blood flow were associated with a lower risk of POD (AOR 0.993; CI 0.988-0.997). Flow rates at least 30% above target did emerge in the minimal adequate model as a potential risk factor, but the confidence interval suggested a lack of statistical significance (AOR 1.819; 95% CI: 0.955-3.463). CONCLUSIONS: CPB data processing proved to be a useful tool for obtaining compact information to better identify the roles of individual operational states. Strict adherence to perfusion limits along with tighter control of blood flow and acid-base balance during CPB may help to further decrease the risk of POD.

Pericardial fluids or Cardiopulmonary Bypass-Is There a Major Culprit for Changes in Coagulation and Inflammation?

BACKGROUND: From the results of a previous study, it remained to be investigated if a perioperative rise of few tested coagulation and inflammation markers is caused by conventional cardiopulmonary bypass (CPB) itself or rather by direct recirculation of pericardial fluids. METHODS: Forty-eight patients operated on with conventional CPB for myocardial revascularization were randomized either for direct recirculation of pericardial suction fluids or for cell saving (CS). RESULTS: Thrombin-antithrombin complexes showed lower values intraoperatively in the CS group (p < 0.0001), and D-dimers tended to remain lower at intensive care unit arrival (p = 0.095). Tests of inflammation markers were less meaningful. CONCLUSION: Direct recirculation of pericardial fluids rather than conventional CPB itself causes major intraoperative changes of some coagulation markers. Pericardial blood loss with direct recirculation should be kept to a minimum to avoid unnecessary activation of coagulation. Inflammation markers need further investigations.

Nonrobotic Total Endoscopic Coronary Artery Bypass Grafting: A Proof-of-Concept Study in 20 Patients.

OBJECTIVE: At present, minimal invasive direct coronary artery grafting is the least invasive nonrobotic surgical approach to revascularize the left anterior descending artery with the left internal mammary artery. Total endoscopic coronary bypass grafting is performed with the help of a telemanipulator ("robot"). A prospective proof-of-concept study was initiated to investigate a nonrobotic total endoscopic coronary bypass grafting approach. METHODS: Twenty patients with significant left anterior descending artery or left main stem lesion were operated on via three or four left thoracic access ports. Under exclusive endoscopic vision, the left internal mammary artery was harvested and anastomosed to the left anterior descending artery manually. Cardiopulmonary bypass and cardioplegic arrest were planned in all cases. RESULTS: In 10 patients, the operation was completed successfully as nonrobotic total endoscopic coronary bypass grafting. Reasons for conversions to minimal invasive direct coronary artery grafting or conventional sternotomy were dense pleural adhesions (3 patients), bleeding of the anastomosis (3), diffuse bleeding during left internal mammary artery harvesting (2), identification problems of the target artery (1), or left internal mammary artery failure (1). Postoperative angiography in five primarily successful nonrobotic total endoscopic coronary bypass grafting patients showed patent anastomoses in four cases. One patient was reoperated on for early anastomotic failure in a 1.0-mm target vessel. Until now, a percutaneous coronary intervention of remaining lesions as staged hybrid procedure was performed in three patients (2 nonrobotic total endoscopic coronary bypass grafting, 1 minimal invasive direct coronary artery grafting). CONCLUSIONS: With a thoroughly surveyed learning curve, nonrobotic total endoscopic coronary bypass grafting procedure could become an alternative to other available treatment options; however, the value of the procedure has to be further investigated.

Influence of 6% Hydroxyethyl Starch 130/0.4 Versus Crystalloid Solution on Structural Renal Damage Markers After Coronary Artery Bypass Grafting: A Post Hoc Subgroup Analysis of a Prospective Trial.

OBJECTIVE: The restriction of hydroxyethyl starch (HES) has mandated changes in volume management based on data of critically ill patients. Reliable data of structural renal damage after HES treatment in cardiac surgical patients are lacking. The influence of 6% HES 130/0.4 was investigated in this study. DESIGN: An exploratory post hoc subgroup analysis of a prospective trial was performed. SETTING: The study was carried out at a university hospital. PARTICIPANTS: Forty-four low-risk cardiac surgical patients were examined. INTERVENTIONS: Twenty-two patients received only crystalloid solutions, and 22 were treated with balanced 6% HES 130/0.4. MEASUREMENTS AND MAIN RESULTS: Functional renal parameters and the structural biomarkers α-glutathione S-transferase, kidney injury molecule-1, liver fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were investigated. Volume balances, vasopressor dosages, blood losses, and coagulation parameters were compared. Most functional and structural renal parameters did not differ between the groups (serum creatinine p = 0.8380). Liver fatty acid-binding protein was transiently higher in the HES group only at 24 hours postoperatively (p = 0.0002). No differences in mortality, acute kidney injury, and need for renal replacement therapy were observed. Blood coagulation was significantly more compromised in the HES group at intensive care unit arrival (factor II, p = 0.0012; factor X, p = 0.0031; thrombocytes, p = 0.0010). Blood losses, and vasopressor dosages tended to be higher in HES-treated patients without significance. CONCLUSION: Overall, the values and time courses of the biomarkers used did not indicate evidence of a mechanism for tubular injury caused by HES.

Extraction of Total RNA from Calcified Human Heart Valves for Gene Expression Analysis.

BACKGROUND: The isolation of high-quality RNA is an important first step in gene expression studies. However, difficult tissue disruption, low cell content and low RNA content makes consistent RNA extraction from human aortic valve tissue a challenging task. METHODS: A protocol has been developed for the successful isolation of high-quality RNA from human aortic valve samples by optimizing RNA extraction protocols based on a comparison of commercial kits. RESULTS: Guanidinium thiocyanate-phenolchloroform extraction was found to be a prerequisite for successful purification. Two protocols based on this extraction were further optimized. RNA quality and quantity were assessed spectrophotometrically, using a Bioanalyzer and by PCR analysis of several housekeeping genes. Optimized parameters included storage in RNAlater™, DNase digestion, the amount of tissue, homogenization time, and freezing of tissue after homogenization. CONCLUSIONS: The modified protocol for fatty and fibrous tissue achieved satisfactory results for gene expression analysis of human aortic valve samples.

Selective venous vasodilator properties of the analgesic metamizole (dipyrone) in a human ex vivo model-implications for postoperative pain management.

Metamizole (dipyrone) is a first-line, non-opioid analgesic used for postoperative pain management. Clinical data and animal experiments indicate a possible vasodilator action of this drug. We investigated the effects of metamizole on human artery and vein tone in an ex vivo model to assess potential contributions to venous pooling. Excess segments of bypass grafts were harvested during coronary artery bypass grafting procedures. Tensions were measured in an organ bath for 120 min after adding metamizole to the preconstricted vessels. Contribution of endothelium was assessed in endothelium-denuded vessels, and indometacin was used to identify cyclooxygenase-mediated effects. Internal mammary arteries (n = 6) constricted after addition of 1, 3, and 10 µM metamizole and remained constricted at the lower doses. Transient constrictions also occurred in saphenous veins (n = 20), but veins relaxed below solvent controls after 20 min at all concentrations. Endothelium removal (n = 12) and cyclooxygenase inhibition (n = 12) suppressed the vasoconstrictor effect but not the vasodilator effect. Metamizole and its metabolites display counteracting effects on blood vessel tone ex vivo. The vasoconstrictor effect is mediated by cyclooxygenase-derived products. The net effect is site-specific, resulting in a selective venous vasodilator action. This may exacerbate unwanted venous pooling during postoperative pain therapy.

Similarity of coagulation and inflammation despite different surgical revascularization strategies - a prospective randomized trial.

BACKGROUND:: Supposedly, minimized extracorporeal circulation or off-pump revascularization as alternatives to conventional extracorporeal circulation (ONCAB) reduce inflammation and coagulation disturbances. METHODS:: One hundred and twenty coronary artery bypass graft (CABG) patients were prospectively randomized for three surgical techniques. Coagulation and inflammation markers were measured up to 72 hours postoperatively. RESULTS:: Coagulation factors I, II, V, X, antithrombin III and C-reactive protein did not differ perioperatively between the groups and increased, as did several other markers, 12 to 72 hours postoperatively. Compared to its alternatives, ONCAB showed the most obvious transient increase in thrombin-antithrombin complexes (p<0.0001), D-dimers (p=0.0059), tissue factor pathway inhibitor (p=0.0005), factor VIII (p=0.0041) and tumor necrosis factor α (p=0.0300) during the operation and up to 12 hours postoperatively. Furthermore, ONCAB generated lower leukocyte and platelet counts and higher values of soluble P-selectin and soluble intercellular adhesion molecule 1 at some time points. CONCLUSIONS:: With similarity in pivot coagulation factors, a specific detrimental influence of ONCAB on common coagulation pathways was excluded. Higher perioperative concentrations of products from the coagulation cascade most likely indicate activation of pericardial blood - recirculated only in ONCAB. Furthermore, with only temporary differences in markers of inflammation, the alternatives to ONCAB altogether were without advantage at 72 hours postoperatively. In the general answer to surgical trauma, the part of modern extracorporeal circulation is possibly overestimated. The study is registered at the German Clinical Trial Registry. Registration number DRKS00007580. URL: https://drks-neu.uniklinik-freiburg.de/drks_web/ URL: http://apps.who.int/trialsearch/.

Renal Function and Urinary Biomarkers in Cardiac Bypass Surgery: A Prospective Randomized Trial Comparing Three Surgical Techniques.

Background Cardiopulmonary bypass procedure is associated with an increased risk of renal impairment. To which extent structural damage causes functional decline is unknown. We evaluated perioperative kidney injury and function in patients treated with conventional extracorporeal circulation (CECC), minimized extracorporeal circulation (MECC), and off-pump coronary artery bypass grafting (OPCAB). Methods Blood and urine samples, collected at baseline and up to 72 hours after surgery from patients of the HEPCON trial (DRKS00007580, 120 patients randomized for heparin management and for surgical technique), were analyzed for differences in renal injury and function. Neutrophil gelatinase-associated lipocalin, α glutathione S-transferase, liver fatty acid-binding protein, and kidney injury molecule-1 were measured as urinary protein markers of renal tubular injury. Serum creatinine, blood urea levels, and estimated glomerular filtration rate were determined to monitor renal function. Results Markers of tubular injury differed significantly between surgical technique groups early after surgery, indicating the most detrimental effect in CECC. Hemolysis and hemodilution correlated with these early changes. A late rise did not show intergroup differences. Time courses of renal function parameters, as well as the development of acute kidney injury in 15 patients (13.5%), were irrespective of surgical technique. Heparin management did not influence renal parameters. Conclusion During coronary artery bypass grafting, CECC temporarily induces more tubular injury than MECC or OPCAB. However, late changes of renal function parameters occur irrespective of extracorporeal perfusion mode and even in off-pump surgery.

On-Pump Nonrobotic Total Endoscopic Coronary Artery Bypass Grafting: An Animal Study.

BACKGROUND: Total endoscopic coronary artery bypass grafting (TECAB) is currently performed exclusively with the help of a telemanipulator. After extensive practice in a biomechanical model, the operation was performed as a nonrobotic approach in an animal study. METHODS: Six large domestic pigs were anesthetized and intubated. Port access and endoscopic vision were used exclusively during the intrathoracic procedure. In five animals, an internal mammary artery was harvested, extracorporeal circulation was established via peripheral vessel access, and the ascending aorta occluded with an intraluminal balloon. In cardioplegic arrest, an anastomosis of internal mammary artery and left anterior descending coronary artery was performed with shortened 7-0 monofil thread running suture. As a terminal study, the animals were humanely killed and the quality of the anastomoses was checked. RESULTS: After a steady learning curve, the fifth animal was operated on successfully and a satisfactory anastomosis was documented. CONCLUSION: Despite demanding differences to humans as shape of thoracic cavity and size of peripheral access vessels, the viability of the nonrobotic TECAB concept was documented in a living animal model.

A step toward nonrobotic total endoscopic coronary bypass grafting: 40 coronary anastomoses in a biomechanical beating heart model.

OBJECTIVE: Nonrobotic total endoscopic coronary bypass grafting is commonly considered as technically too difficult. After endoscopic practicing in a simple box model, we questioned this statement in a more sophisticated training model. METHODS: In a handmade chest model containing a mechanically actuated porcine heart, anastomoses between homologous vein and shunted anterior coronary artery were performed using Prolene 7-0 sutures or U-clips in 20 anastomoses each. Commercially available endoscopic instruments and exclusive two-dimensional endoscopic vision were used. As quality control, the procedures were recorded, flow was measured, indocyanine green dye angiograms were performed, vinylpolysiloxane endocasts were produced, and finally the anastomoses were assessed from the endothelial side. Three-dimensional computed tomographic reconstruction was explored for cast measuring. RESULTS: All anastomoses were completed successfully in a time of 51 ± 14 minutes (Prolene) and 48 ± 10 minutes (U-clips). Despite suboptimal equipment, a reproducible sequence of the procedure was established and documented. Improving surgical performance was reflected in a reduction in anastomotic leakage and time requirement. The quality assessment protocol showed a learning curve and problems itself, which are briefly discussed. CONCLUSIONS: A beating heart model is an adamant requirement of training for the technically demanding procedure of nonrobotic total endoscopic coronary bypass grafting. Refinement of the model and quality assessment as well as expansion of training to other regions of the heart should prepare for a cost-effective, broad-based clinical application of nonrobotic endoscopic techniques in coronary surgery. Available high-definition three-dimensional vision systems and the development of appropriate (articulating) instruments will make the procedure safer and quicker and will cut the learning curve.

Minimally invasive direct coronary artery bypass as a primary strategy for reoperative myocardial revascularization.

OBJECTIVE: : Conventional reoperative coronary artery bypass grafting is associated with risk of sternal re-entry, injury to patent grafts, and embolization from diseased grafts. Sternal sparing minimally invasive direct coronary artery bypass (MIDCAB) avoids such risks in cases where it is technically feasible. We sought to examine in-hospital outcomes of reoperative MIDCAB surgery. METHODS: : We recorded prospective standardized data from the New York Cardiac Surgical Reporting System database of 369 reoperative MIDCAB cases from 1996 to 2006 and compared with 822 primary MIDCAB patients in the same time period. We compared the preoperative risk profile and postoperative in-hospital outcomes and length of stay for both groups. RESULTS: : There was a significantly higher risk profile typical of the reoperative patient population (P < 0.001 for stroke, peripheral/cerebrovascular disease, extensive aortic calcification, renal failure, and left ventricular ejection fraction <40%) compared with the primary MIDCAB group. Despite this fact, there was no difference in the in-hospital outcomes and length of hospital stay between the two groups. CONCLUSIONS: : Reoperative MIDCAB provides targeted coronary revascularization and avoids hazards of sternal re-entry, graft injury and manipulation, and deleterious effects of cardiopulmonary bypass. This hastens recovery and provides excellent early outcomes equivalent to primary MIDCAB procedures.

Off-pump Coronary Bypass Surgery in Patients With Low Ejection Fraction: Is There a Long-Term Survival Advantage?

OBJECTIVE: : Long-term survival after off-pump surgery in patients with low ejection fraction was investigated. METHODS: : Three hundred forty-six patients with ejection fraction 30% or less with isolated off-pump coronary artery bypass surgery (OPCAB) were compared with a propensity matched historical group operated on-pump (ONCAB) and with data from literature after percutaneous coronary intervention and OPCAB surgery. RESULTS: : The lower invasiveness of OPCAB contributed to a significantly better 30-day survival, shorter postoperative length of stay, and fewer in-hospital complications. Incomplete revascularization of the posterior and lateral territories of the heart correlated with higher 1-year mortality. The probability of survival for 8 years after OPCAB was 50.1% (n = 76) versus 49.7% (n = 82) for ONCAB without comparable data from literature for OPCAB or percutaneous coronary intervention in these high-risk patients. CONCLUSIONS: : OPCAB surgery in patients with low ejection fraction is a viable alternative but so far without demonstrable long-term survival advantage to ONCAB.

Long-Term Survival After Minimal Invasive Direct Coronary Artery Bypass (MIDCAB) Surgery in Patients With Low Ejection Fraction.

OBJECTIVE: : The long-term survival after minimal invasive direct coronary artery bypass (MIDCAB) surgery to any coronary territory in patients with ejection fraction of ≤30% was investigated for the first time in literature. METHODS: : Seventy-three patients with primary MIDCAB and 89 patients with reoperative MIDCAB were studied including preoperative risk factors, operative details, early postoperative complications, and survival up to 10 years postoperatively. RESULTS: : Despite the high-risk profile of the patients, the MIDCAB approach for targeted revascularization resulted in excellent short-term results. Ventricular arrhythmia contributed to four of six early deaths. Survival at 5 years postoperatively was 62.5% for primary MIDCAB and 43.2% for reoperative MIDCAB and at 10 years was 36.9% and 29.5%, respectively. Functionally complete vascularization correlates with significantly better long-term survival particularly in primary MIDCAB procedures. CONCLUSIONS: : MIDCAB is a valuable option for targeted revascularization in high-risk patients with low ejection fraction and reoperation.

Non-typhoid Salmonellae and prosthetic valve endocarditis: more than a rare coincidence? A review of the literature.

Non-typhoid Salmonellae (NTS) commonly cause gastroenteritis but are rarely found pathogens in prosthetic heart valve endocarditis. The details of two patients from the authors' institution and 15 published cases are reviewed in terms of their risk factors, clinical findings and outcomes. Only two of eight patients with paravalvular leakage or abscess--the most serious local complications--survived, both with surgery. It appears that NTS bacteremia in patients with prosthetic valves and concomitant risk factors should be treated early with high-dose antimicrobials for up to six weeks in order to minimize the risk of endocarditis.

A postoperative Gerbode defect in aortic prosthesis endocarditis with non-typhoid Salmonella.

The Gerbode defect is a congenital shunt from the left ventricle to the right atrium. The type I defect (2) results in a direct shunt through a portion of the membranous septum, while a type II (indirect) defect occurs if the membranous septal defect lies below the attachment of the septal leaflet of the tricuspid valve. The shunt is directed towards the right atrium through a cleft or perforations of the septal leaflet. Acquired Gerbode defects have been identified in endocarditis, after mitral or aortic valve surgery, or may be post-traumatic. The case is presented of a 69-year-old woman with a postoperative Gerbode defect in association with aortic prosthetic endocarditis caused by non-typhoid Salmonella.

The antiphospholipid syndrome and heart valve surgery.

The antiphospholipid syndrome (APLS) is a complex autoimmune disease often connected to systemic lupus erythematodes. Main features are thromboses, fetal loss and specific antibodies. The involved autoantibodies are directed against plasma proteins such as beta2glycoprotein1 (beta2GPI) or prothrombin which depend on negatively charged phospholipids. Direct antibodies against phospholipids are of no importance for APLS. Clotting tests such as activated partial thromboplastin time or diluted Russell's viper venom test (dRVVT) can show a prolonged time for coagulation despite a prothrombotic state in vivo but the investigator needs awareness about disturbing phospholipid sources and other influential factors. Enzyme linked immuno sorbent assay tests for antibodies against cardiolipin, beta2GPI and prothrombin are valuable solid phase tests with different specificity. Antiphospholipid, anticardiolipin or lupus anticoagulant are misnomers in connection with APLS. They are preserved as a reminiscence of the pioneering work on the way to the still not exactly revealed basics of APLS. Valve operations in APLS patients seem to be rare; a meta-analysis of 57 cases proves that the perioperative management is, at the moment, an empirical approach with high morbidity and mortality in these young patients.