[Perioperative atrial fibrillation : Diagnosis with underestimated relevance]. / Perioperatives Vorhofflimmern : Diagnose mit unterschätzter Relevanz.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults, both in general and perioperatively and is associated with significant morbidity and mortality. The age of the patients is a major risk factor. The prevalence of AF in noncardiac surgery (NCS) varies widely from 0.4% to 30% and for cardiac surgery, especially major combined procedures, up to approximately 50%. Ectopic excitation centers and reentry mechanisms at the atrial level are favored as the main process of uncoordinated electrical atrial activity. The loss of atrial contraction can lead to a reduction in cardiac output of up to 20-25%. The increased risk of thromboembolism due to AF extends beyond the perioperative period. Medication-based prevention strategies have not yet gained widespread acceptance. Treatment strategies include frequency and rhythm control as well as the avoidance of thromboembolisms through anticoagulation.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

[Extracorporeal membrane oxygenation and hemodynamics : Therapy is not only a friend of the heart]. / Extrakorporale Membranoxygenierung und Hämodynamik : Die Therapie ist nicht nur des Herzens Freund.

Extracorporeal support systems for the heart and lungs are employed for cardiac, pulmonary and also cardiopulmonary failure; however, neither the pure lung support by venovenous extracorporeal membrane oxygenation (vvECMO) nor the venoarterial (va) ECMO behave in a hemodynamically inert manner with respect to the patient's own cardiovascular system. The success of ECMO treatment is decisively dependent on monitoring before and during the execution and the pathophysiological understanding of the hemodynamic changes that occur during treatment. This article explicitly elucidates these "concomitant phenomena" and discusses fundamental aspects of cardiovascular physiology and the specific interplay with ECMO treatment.

Ecological effects of selective oral decontamination on multidrug-resistance bacteria acquired in the intensive care unit: a case-control study over 5 years.

PURPOSE: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed. METHODS: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital. Administrative, clinical, and microbiological data which were routinely recorded electronically served as the basis. We analysed differences in the rates and incidence densities (ID, cases per 1000 patient-days) of MDRB associated with SOD use in all patients and stratified by patient origin (outpatient or inpatient). After propensity score matching, health-care infections and ICU mortality were compared. RESULTS: 5034 patients were eligible for the study. 1694 patients were not given SOD. There were no differences in the incidence density of MDRB when SOD was used, except for more vancomycin-resistant Enterococcus faecium (0.72/1000 days vs. 0.31/1000 days, p < 0.01), and fewer ESBL-producing Klebsiella pneumoniae (0.22/1000 days vs. 0.56/1000 days, p < 0.01). After propensity score matching, SOD was associated with lower incidence rates of ventilator-associated pneumonia and death in the ICU but not with ICU-acquired bacteremia or urinary tract infection. CONCLUSIONS: Comparisons of the ICU-acquired MDRB over a 5-year period revealed no differences in incidence density, except for lower rate of ESBL-producing Klebsiella pneumoniae and higher rate of vancomycin-resistant Enterococcus faecium with SOD. Incidence rates of ventilator-associated pneumonia and death in the ICU were lower in patients receiving SOD.

[Proper Perioperative Handling of Continuous Medication in Patients with Cardiac Comorbidities]. / Perioperativer Umgang mit der Dauermedikation bei kardialen Vorerkrankungen.

Cardiac comorbidities place a significant burden on the German population. Every third adult is diagnosed with arterial hypertension (AHT). In 2017 congestive heart failure (CHF) pertained approximately 2,5 million of mandatory health-insured patients. Coronary artery disease (CAD) is diagnosed in 28,3% of men and 19,1% of women older than 65 years.For optimal perioperative care it is important to have a sound knowledge of current treatment strategies of cardiac comorbidities. This helps in gaining an optimal risk stratification of the individual patient. It also ensures an optimal anesthesiological perioperative care for the patient at hand. Recommendations for the perioperative discontinuation or continuation of cardiac active drugs vary between countries and responsible medical societies.This article provides an in-depth review of the current medical therapies for cardiac conditions like AHT, CHF or CAD. The varying recommendations for the perioperative discontinuation/continuation of these therapies are also reviewed.

EuroScore and IL-6 predict the course in ICU after cardiac surgery.

BACKGROUND: Despite modern advances in intensive care medicine and surgical techniques, mortality rates in cardiac surgical patients are still about 3%. Considerable efforts were made to predict morbidity and mortality after cardiac surgery. In this study, we analysed the predictive properties of EuroScore and IL-6 for mortality in ICU, prolonged postoperative mechanical ventilation, and prolonged stay in ICU. METHODS: We enrolled 2972 patients undergoing cardiac surgery. The patients either underwent aortic valve surgery (AV), mitral valve surgery (MV), coronary artery bypass grafting (CABG), and combined operations of aortic valve and coronary artery bypass grafting (AV + CABG) or of mitral and tricuspid valve (MV + TV). Different laboratory and clinical parameters were analysed. RESULTS: EuroScore as well as IL-6 were associated with increased mortality after cardiac surgery. Furthermore, a higher EuroScore and elevated levels of IL-6 were predictors for prolonged mechanical ventilation and a longer stay in ICU. Especially, highly significant elevated IL-6 levels and an increased EuroScore showed a strong association. Statistics suggested superiority when both parameters were combined in a single model. CONCLUSION: Our results suggest that EuroScore and IL-6 are helpful in predicting the course in ICU after cardiac surgery, and therefore, the use of intensive care resources. Especially, the combination of highly elevated levels of IL-6 and EuroScore may prove to be excellent predictors for an unfortunate postoperative course in ICU.

Bilirubin and lactate: easy to determine and valuable to predict outcome in cardiac surgery.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery is associated with metabolic changes after operation and results inter alia in increased levels of lactate and bilirubin. Since prediction of the course after operation has become very important for the management of an ICU and the patients themselves, we evaluated easily assessable markers (lactate and bilirubin), regarding their potential to predict mortality 90 days after surgery and the length of stay in ICU. METHODS: All patients within a period of five years undergoing cardiac surgery were enrolled in the study. Among others peak levels of lactate and bilirubin within 48 hours after operation were recorded. A Cox proportional hazard model as well as a logistic regression model were used to predict mortality or rather length of stay in ICU. RESULTS: Increased levels of bilirubin and lactate were associated with a significantly increase in mortality and length of stay in ICU (in a concentration-related manner). Interestingly, creatinine serum levels before operation showed a similar performance. CONCLUSIONS: Three easily assessable and cheap laboratory parameters (bilirubin, lactate, and creatinine) are useful to predict 90-day mortality and length of stay in ICU. These findings might be helpful to give patients a reliable prediction about short and mid-term-survival and to improve the management of an ICU.

Non-invasive evaluation of macro- and microhemodynamic changes during induction of general anesthesia - A prospective observational single-blinded trial.

BACKGROUND: Hypotension and bradycardia are known side effects of general anesthesia, while little is known about further macro- and microhemodynamic changes during induction. Intriguing is furthermore, why some patients require no vasopressor medication to uphold mean arterial pressure, while others need vasopressor support. OBJECTIVE: Determination of macro- and microhemodynamic changes during induction of general anesthesia. METHODS: We enrolled 150 female adults scheduled for gynaecological surgery into this prospective observational, single-blinded trial. Besides routinely measuring heart rate (HR) and mean arterial blood pressure (MAP), the non-invasive technique of thoracic electrical bioimpedance was applied to measure cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume variability (SVV) and index of myocardial contractility (ICON) before induction of anesthesia, 7 times during induction, and, finally, after surgery in the recovery room. Changes in microcirculation were assessed using sidestream dark field imaging to establish the perfused boundary region (PBR), a validated gauge of glycocalyx health. Comparisons were made with Friedman's or Wilcoxon test for paired data, and with Mann-Whitney-U test for unpaired data, with post-hoc corrections for multiple measurements by the Holm-Bonferroni method. RESULTS: 83 patients did not need vasopressor support, whereas 67 patients required therapy (norepinephrine, atropine or cafedrine/theodrenaline) to elevate MAP values to ≥70mmHg during induction, 54 of these receiving norepinephrine (NE) alone. Pre-interventional (basal) values of CO, CI, ICON, SV and SVV were all significantly lower in the group of patients later requiring NE (p < 0.04), whereas HR and MAP were identical for both groups. HR, MAP and CO decreased from baseline to 12 min after induction of general anesthesia in both the patients without and those with NE support. Heart rate decreased significantly by about 25% in both groups (-19 to -21 bpm). The median individual decrease of MAP amounted to -26.7% (19.7/33.3, p < 0.001) and -26.1% (11.6/33.2, p < 0.001), respectively, whereas for CO it was -40.7% (34.1/50.1, p < 0.001) and -43.5% (34.8/48.7). While these relative changes did not differ between the two groups, in absolute values there were significantly greater decreases in CO, CI, SV and ICON in the group requiring NE. Noteably, NE did not restore ICON or the other cardiac parameters to levels approaching those of the group without NE. PBR was measured in a total of 84 patients compiled from both groups, there being no intergroup differences. It increased 6.4% (p < 0.001) from pre-induction to the end of the operation, indicative of damage to microvascular glycocalyx. CONCLUSION: Non-invasive determination of CO provides additional hemodynamic information during anesthesia, showing that induction results in a significant decrease not only of MAP but also of CO and other cardiac factors at all timepoints compared to baseline values. The decrease of CO was greater than that of MAP and, in contrast to MAP, did not respond to NE. There was also no sign of a positive inotropic effect of NE in this situation. Support of MAP by NE must consequently result from an increase in peripheral arterial resistance, posing a risk for oxygen supply to tissue. In addition, general anesthesia and the operative stimulus lead to an impairment of the microcirculation.

Vasopressor Therapy in Cardiac Surgery-An Experts' Consensus Statement.

Hemodynamic conditions with reduced systemic vascular resistance commonly are observed in patients undergoing cardiac surgery and may range from moderate reductions in vascular tone, as a side effect of general anesthetics, to a profound vasodilatory syndrome, often referred to as vasoplegic shock. Therapy with vasopressors is an important pillar in the treatment of these conditions. There is limited guidance on the appropriate choice of vasopressors to restore and optimize systemic vascular tone in patients undergoing cardiac surgery. A panel of experts in the field convened to develop statements and evidence-based recommendations on clinically relevant questions on the use of vasopressors in cardiac surgical patients, using a critical appraisal of the literature following the GRADE system and a modified Delphi process. The authors unanimously and strongly recommend the use of norepinephrine and/or vasopressin for restoration and maintenance of systemic perfusion pressure in cardiac surgical patients; despite that, the authors cannot recommend either of these drugs with respect to the risk of ischemic complications. The authors unanimously and strongly recommend against using dopamine for treating post-cardiac surgery vasoplegic shock and against using methylene blue for purposes other than a rescue therapy. The authors unanimously and weakly recommend that clinicians consider early addition of a second vasopressor (norepinephrine or vasopressin) if adequate vascular tone cannot be restored by a monotherapy with either norepinephrine or vasopressin and to consider using vasopressin as a first-line vasopressor or to add vasopressin to norepinephrine in cardiac surgical patients with pulmonary hypertension or right-sided heart dysfunction.

Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass.

OBJECTIVES: Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass-related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression. DESIGN: In vitro studies with human peripheral blood mononuclear cells. SETTING: Cardiosurgical ICU, University Research Laboratory. PATIENTS: Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018). INTERVENTIONS: Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15 cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested. MEASUREMENTS AND MAIN RESULTS: After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence. CONCLUSIONS: Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass.

Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is an incretin hormone, which gets secreted in response to nutritional stimuli from the gut mediating glucose-dependent insulin secretion. Interestingly, GLP-1 was recently found to be also increased in response to inflammatory stimuli in an interleukin 6 (IL-6) dependent manner in mice. The relevance of this finding to humans is unknown but has been suggested by the presence of high circulating GLP-1 levels in critically ill patients that correlated with markers of inflammation. This study was performed to elucidate, whether a direct link exists between inflammation and GLP-1 secretion in humans. RESEARCH DESIGN AND METHODS: We enrolled 22 non-diabetic patients scheduled for cardiac surgery as a reproducible inflammatory stimulus with repeated blood sampling before and after surgery. RESULTS: Mean total circulating GLP-1 levels significantly increased in response to surgery from 25.5 ± 15.6 pM to 51.9 ± 42.7 pM which was not found in a control population. This was preceded by an early rise of IL6, which was significantly associated with GLP-1 under inflammatory but not basal conditions. Using repeated measure ANCOVA, IL6 best predicted the observed kinetics of GLP-1, followed by blood glucose concentrations and cortisol plasma levels. Furthermore, GLP-1 plasma concentrations significantly predicted endogenous insulin production as assessed by C-peptide concentrations over time, while an inverse association was found for insulin infusion rate. CONCLUSION: We found GLP-1 secretion to be increased in response to inflammatory stimuli in humans, which was associated to parameters of glucose metabolism and best predicted by IL6.

Indocyanine green clearance as an outcome prediction tool in cardiac surgery: a prospective study.

PURPOSE: To evaluate the role of plasma disappearance rate of indocyanine green (PDR-ICG) as an outcome prediction tool in cardiac surgery. PATIENTS AND METHODS: One hundred ninety patients undergoing coronary artery bypass grafting, valve surgery or combined procedures were enrolled. PDR-ICG measurements along with standard lab values were performed preoperative and on postoperative days 1, 2, and on discharge from the intensive care unit. Adverse outcomes were defined as prolonged length of stay in the intensive care unit and/or mortality. Two groups were defined according to length of stay in the intensive care unit (≤ 3 days vs >3 days). RESULTS: PDR-ICG values differed significantly for all time points between the groups. In a multivariate model, in patients over 65 years with a EuroSCORE below 8.5, a preoperative PDR-ICG value below 12.85%/min was the strongest independent predictor for prolonged intensive care unit stay (>3 days). A preoperative PDR-ICG value below 8.2%/min was the strongest independent predictor for mortality in a multivariate analysis including age, cardiac function, and EuroSCORE. CONCLUSIONS: In addition to the established scores, PDR-ICG may provide valuable information for the assessment of perioperative morbidity and mortality in cardiac surgery. Pre- and early postoperative measurements may help to identify patients at risk for developing perioperative complications.

Routine use of corticosteroids to prevent inflammation response in cardiac surgery.

Cardiac surgery, especially if it involves cardiopulmonary bypass, is associated with a severe systemic inflammatory response. It is characterized by complement activation and initiation of coagulation, fibrinolysis and kallikrein cascades. Consecutive activation of immunoregulatory cells results in an extensive release of pro- and anti-inflammatory cytokines. This inflammatory storm is related to organ dysfunction or failure and correlates with postoperative morbidity. In order to attenuate this deleterious inflammatory response in the perioperative period alternative surgical techniques, novel extracorporeal circulation devices and immunomodulatory pharmacological strategies are in focus of contemporary research. Since decades corticosteroids have been used and studied in patients undergoing cardiac surgery. Although it could be shown that glucocorticoids seem to change the pro-inflammatory cytokine profile in a favourable manner, it still remains controversial if this effect translates into a better clinical outcome. Several clinical trials have proclaimed an association between this inflammatory response and the incidence of major complications i.e, myocardial infarction and pulmonary complications, but until now they have failed to show conclusive results. This article describes the different types and recommended dose schemes of corticosteroids in the perioperative period of cardiac surgery along with the discussion of few patents. It will comment on potential side effects and review the effect on the postoperative outcome.

Glucocorticoid-endocannabinoid interaction in cardiac surgical patients: relationship to early cognitive dysfunction and late depression.

BACKGROUND: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid-signaling molecules that are important for adaptation to stressful and aversive situations.They are known to interact with glucocorticoids and other stress-responsive systems. Maladaptation to acute or chronic stress represents a major risk factor for the development of psychiatric disorders. In the present study, we administered stress doses of hydrocortisone ina prospective, randomized, placebo-controlled double blind study in patients undergoing cardiac surgery (CS) to examine the relationship between the use of glucocorticoids, plasma EC levels, and the occurrence of early postoperative cognitive dysfunction (delirium) and of later development of depression. METHODS: We determined plasma levels of the ECs anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone (n=56) and the placebo group(n=55) preoperatively, at postoperative day (POD) 1, at intensive care unit discharge, and at 6 months after CS(n=68). Postoperative delirium was diagnosed according to Diagnostic and Statistical Manual of the American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression was determined by validated questionnaires and a standardized psychological interview (Structured Clinical Interview for DSM-IV). RESULTS: Stress doses of hydrocortisone did not affect plasma EC levels and the occurrence of delirium or depression. However, patients who developed deliriumon POD 1 had significantly lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8 vs. 11.3ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of postoperative delirium (sensitivity=0.70;specificity=0.69; cutoff value=4.9 ng/ml; receiver operating characteristic curve area=0.70; 95 o/o confidence interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had significantly lower anandamide and 2-AG levels during the perioperative period. CONCLUSIONS: A low perioperative EC response may indicate an increased risk for early cognitive dysfunction and long-term depression in patients after CS. Glucocorticoids do not seem to influence this relationship.

Noninvasive mechanical ventilation in patients with acute respiratory failure after cardiac surgery.

OBJECTIVE: To evaluate the feasibility and outcomes of protocol-driven noninvasive mechanical ventilation in patients with acute respiratory failure (ARF) after cardiac surgery. METHODS: From 2001 to 2004, a total of 2428 cardiac surgery patients admitted to our intensive care unit were observed. After exclusion of patients who received tracheostomy or were discharged while still on mechanical ventilation, 2261 patients with spontaneous breathing were further evaluated for ARF. Patients diagnosed with ARF were treated with intermittent noninvasive mechanical ventilation (NIV) if possible. Risk factors for the development of postoperative ARF as well as outcomes in patients with and without ARF were analyzed. RESULTS: In 2261 spontaneously breathing postoperative cardiac surgical patients after primarily successful extubation, 799 patients (35%) were diagnosed with ARF. Fifty-six patients (7%) did not tolerate NIV treatment. In 743 patients (33%) intermittent NIV was performed. In patients with ARF, ejection fraction was lower, combined cardiac surgical procedures were more frequent, postoperative mechanical ventilation time was longer, and the severity of illness score (SAPS II) was higher (P < .05). The duration of catecholamine support was longer, and the transfusion rate was higher in the NIV group (P < .05); however, mortality did not differ between patients with ARF treated by NIV and patients without ARF. CONCLUSION: Our study demonstrates the feasibility of NIV in patients after cardiac surgery. These results might suggest that NIV should be considered as first-line ventilatory support in ARF after cardiac surgery. A large randomized trial is warranted to confirm these findings.

Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: effects on interleukin-6 to interleukin-10 ratio and early outcome.

BACKGROUND: Severe systemic inflammation (systemic inflammatory response syndrome) associated with cardiac surgery often leads to a worse short-term and long-term outcome. Stress doses of hydrocortisone have been successfully used to improve outcome of CS. The interleukin (IL)-6 to IL-10 ratio is associated with outcome after trauma and major surgery. OBJECTIVE: To evaluate immunologic effects (especially IL-6 to IL-10 ratio) of stress doses of hydrocortisone in a high-risk group of patients after cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Cardiovascular intensive care unit of a university hospital. PATIENTS: High-risk patients (n = 36) undergoing CS. INTERVENTION: Stress doses of hydrocortisone or placebo. MAIN OUTCOME MEASURES: IL-6 to IL-10 ratio and other markers of systemic inflammation at predefined time points; short-term clinical outcome. RESULTS: The two study groups did not differ with regard to demographic data. The patients from the hydrocortisone group (n = 19) had significantly lower levels of IL-6 and higher levels of IL-10, resulting in an attenuated change in IL-6/IL-10 ratio (28.7 [6.4/128.7] vs. 292.8 [6.5/534.6] 4 hours after cardiopulmonary bypass; p < 0.001). Patients in the hydrocortisone group had a shorter duration of catecholamine support (1 [1/2] vs. 4 [2/4.5] days; p = 0.02), a shorter length of stay in the intensive care unit (2 [2/3] vs. 6 [4/8] days; p = 0.001), and a lower incidence of postoperative atrial fibrillation (26% vs. 59%; p = 0.04). CONCLUSIONS: Stress doses of hydrocortisone attenuate the evolution of IL-6/IL-10 ratio in patients with systemic inflammatory response syndrome after CS, which seems to be associated with an improved outcome. The immunologic effects of hydrocortisone may thus be both, inhibitory (IL-6) and permissive (IL-10), regarding the immune response.

Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions.

INTRODUCTION: Inflammatory stimuli are causative for insulin resistance in obesity as well as in acute inflammatory reactions. Ongoing research has identified a variety of secreted proteins that are released from immune cells and adipocytes as mediators of insulin resistance; however, knowledge about their relevance for acute inflammatory insulin resistance remains limited. In this study we aimed for a clarification of the relevance of different insulin resistance mediating factors in an acute inflammatory situation. METHODS: Insulin resistance was measured in a cohort of 37 non-diabetic patients undergoing cardiac surgery by assessment of insulin requirement to maintain euglycaemia and repeated measurements of an insulin glycaemic index. The kinetics of cortisol, interleukin 6 (IL6), tumour necrosis factor alpha (TNFalpha), resistin, leptin and adiponectin were assessed by repeated measurements in a period of 48 h. RESULTS: Insulin resistance increased during the observation period and peaked 22 h after the beginning of the operation. IL6 and TNFalpha displayed an early increase with peak concentrations at the 4-h time point. Serum levels of cortisol, resistin and leptin increased more slowly and peaked at the 22-h time point, while adiponectin declined, reaching a base at the 22-h time point. Model assessment identified cortisol as the best predictor of insulin resistance, followed by IL6, leptin and adiponectin. No additional information was gained by modelling for TNFalpha, resistin, catecholamine infusion rate, sex, age, body mass index (BMI), operation time or medication. CONCLUSIONS: Serum cortisol levels are the best predictor for inflammatory insulin resistance followed by IL6, leptin and adiponectin. TNFalpha, and resistin have minor relevance as predictors of stress dependent insulin resistance.

Fibrin glue in coronary artery bypass grafting operations: casting out the Devil with Beelzebub?

OBJECTIVE: Fibrin sealants are frequently used in aortocoronary bypass operations. Although they are considered to be clinically safe, we performed a retrospective analysis of our data to examine the possible side effects of Tissucol fibrin sealant, namely the acute thrombosis of grafts and native coronary arteries resulting in severe myocardial damage and patient deaths. METHODS: The data of 2716 patients (2001 male, 715 female) who received an aortocoronary bypass operation from November 1995 to December 1999 were studied retrospectively. Two groups (group 1: received Tissucol, group 2: no sealant used) were compared with respect to an a priori selected set of demographic and clinical variables and with respect to their effect on the outcome using bivariate tabulation. Multiple exploratory assessments of factors possibly related to fatal outcome were done by multiple logistic regression. RESULTS: Nine hundred ninety patients (group 1) received Tissucol, 1726 patients (group 2) did not receive it. Mean patient age was 64+/-9.1 years. Group 1 had a higher risk of death (7.8% vs 2.8%, p<0.001). The peak values of creatine kinase >500 and creatine kinase-myocardial band >50 were higher in group 1 than in group 2, p<0.001. Adjusted odds ratios for the risk of fatal outcome were: 2.01 for the use of Tissucol, 2.71 for patient age >70 years, 2.02 for aortic cross clamp time >90 min, 3.95 for postoperative ventricular fibrillation, 6.35 for postoperative cardiopulmonary resuscitation, 4.55 for postoperative aortocoronary reoperation. CONCLUSION: In our analysis an increased risk of myocardial injury or even death was found in coronary artery bypass grafting patients when Tissucol fibrin sealant was used intraoperatively.