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Objective Steroids suppress the inflammatory response to cardiopulmonary bypass, but the impact on death at 30 days, myocardial infarction or injury, stroke, renal failure, respiratory failure, new atrial fibrillation, transfusion requirement, infection, and length of intensive care unit (ICU) and hospital stays are uncertain. Design Patient-level data meta-analysis of 2 randomized trials. Setting Eighty-eight cardiac surgical centers in 19 countries. Participants A total of 11,989 participants, from the Steroids in Cardiac Surgery trial and the Dexamethasone in Cardiac Surgery study, undergoing cardiac surgery with the use of cardiopulmonary bypass. Interventions Participants were randomly assigned to steroid or placebo. Measures and Main Results Outcomes assessed were mortality at 30 days, myocardial infarction or injury, stroke, renal failure, respiratory failure, new atrial fibrillation, transfusion requirement, infection, and length of ICU and hospital stays. There was no significant difference in death at 30 days between the steroid and placebo groups (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.72-1.07). Myocardial infarction did not differ significantly (OR, 1.17; 95% CI, 0.93-1.47); however, myocardial injury was higher in the steroid group (OR, 1.25; 95% CI, 1.12-1.40). There were no significant differences for the outcomes of stroke, renal failure, new atrial fibrillation, or transfusion. Steroids significantly reduced respiratory failure (OR, 0.83; 95% CI, 0.75-0.99), infection (OR, 0.80; 95% CI, 0.72-0.89), and length of ICU (p Conclusions This patient-level meta-analysis does not support the routine use of steroids in cardiac surgery. Steroid administration did not decrease the risk of death, myocardial infarction, stroke, renal failure, new atrial fibrillation, or transfusion. Steroids increased the risk of myocardial injury in both the Steroids in Cardiac Surgery and Dexamethasone in Cardiac Surgery trials. Finally, steroids lowered the risk of respiratory failure and infection, and reduced length of ICU and hospital stay.

The glucocorticoid receptor (GR) agonist dexamethasone is frequently used for its anti-inflammatory properties. We recently showed that a single high-dose of dexamethasone had long-lasting protective effects on the development of psychopathology after cardiac surgery and postoperative intensive care unit stay. In this study, we investigated whether common genetic variation in the hypothalamic-pituitary-adrenal (HPA)-axis would influence the susceptibility for PTSD and depression after dexamethasone administration.Participants (n = 996) of the Dexamethasone for Cardiac Surgery (DECS) randomized clinical trial were followed after receiving a single high intraoperative dose of dexamethasone (1 mg/kg), a GR agonist, or placebo. PTSD and depressive symptoms were assessed up to four years after cardiac surgery. We focused primarily on five common single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR). Secondarily, we comprehensively assessed common genetic variation in the FK506 binding protein (FKBP5) and the mineralocorticoid receptor (MR).The protective effects of dexamethasone on postoperative PTSD symptoms were dependent on the GR polymorphisms rs41423247 (p = .009), rs10052957 (p = .003), and rs6189 (p = .002), but not on rs6195 (p = .025) or rs6198, (p = .026) after Bonferroni correction. No genotype-dependent effects were found for postoperative depressive symptoms. Also, no associations of FKBP5 and MR polymorphisms were found on PTSD and depression outcomes.Protective effects of dexamethasone on PTSD symptoms after cardiac surgery and ICU stay seem to depend on common genetic variation in its target receptor, the GR. These effects indicate that pre-operative genetic screening could potentially help in stratifying patients for their vulnerability for developing PTSD symptoms after surgery.

Background The aim of this study was to simulate and compare the healthcare and economic outcomes associated with routine use of intraoperative transoesophageal echocardiography (TOE) in patients undergoing cardiac surgery with those associated with a scenario where TOE is not routinely used. Methods The impact of TOE on surgical decision-making was estimated through a systematic literature review. Individual short-term morbidity and mortality estimates were generated by application of the Society of Thoracic Surgeons risk calculator. Long-term event rates, unit costs, and utility weights were sourced from published literature and expert opinion. A discrete-event simulation model was then constructed to simulate both the in-hospital and post-discharge outcomes for patients undergoing cardiac surgery. Robustness of the base case results was examined through deterministic and probabilistic sensitivity analyses. An incremental cost–effectiveness ratio of €30 000 per quality-adjusted life-year gained was assumed to represent acceptable cost-effectiveness. Results Routine use of intraoperative TOE was associated with lower costs and higher benefits per patient, which indicates that use of TOE is a dominant strategy. The intervention resulted in the avoidance of 299 cardiac complications, 20 strokes, and 11 all-cause deaths per 10 000 patients. Routine intraoperative TOE was associated with an increased occurrence of bleeding owing to more valvular surgery and subsequent long-term anticoagulation. Conclusions Routine intraoperative TOE is a cost-effective procedure for patients undergoing cardiac surgery, leading to lower overall costs. It was associated with a decrease in long-term complications including stroke, cardiac complications, and death, although there was a slight increase in extracranial bleeding events.

BACKGROUND: An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia.METHODS: In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual.FINDINGS: Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI -0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms.INTERPRETATION: Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor.FUNDING: Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.

Item does not contain fulltext Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre, randomised, double-blind, placebo-controlled DExamethasone for Cardiac Surgery (DECS) trial were followed up for 12 months after their cardiac surgical procedure. In the DECS trial, patients received a single intra-operative dose of dexamethasone 1 mg.kg(-1) (n = 2239) or placebo (n = 2255). The effects on the incidence of major postoperative events were evaluated. Also, overall costs for the 12-month postoperative period, and cost effectiveness, were compared between groups. Of 4494 randomised patients, 4457 patients (99%) were followed up until 12 months after surgery. There was no difference in the incidence of major postoperative events, the relative risk (95%CI) being 0.86 (0.72-1.03); p = 0.1. Treatment with dexamethasone reduced costs per patient by pound921 [euro1084] (95%CI pound-1672 to -137; p = 0.02), mainly through reduction of postoperative respiratory failure and duration of postoperative hospital stay. The probability of dexamethasone being cost effective compared with placebo was 97% at a threshold value of pound17,000 [euro20,000] per quality-adjusted life year. We conclude that intra-operative high-dose dexamethasone did not have an effect on major adverse events at 12 months after cardiac surgery, but was associated with a reduction in costs. Routine dexamethasone administration is expected to be cost effective at commonly accepted threshold levels for cost effectiveness.

Background Numerous studies have investigated high-dose corticosteroids in cardiac surgery, but with mixed results leading to ongoing variations in practice around the world. DECS-II is a study comparing high-dose dexamethasone with placebo in patients undergoing cardiac surgery. Methods We discuss the rationale for conducting DECS-II, a 2800-patient, pragmatic, multicenter, assessor-blinded, randomized trial in cardiac surgery, and the features of the DECS-II study design (objectives, end points, target population, based on practice preference with post-randomization consent, treatments, patient follow-up and analysis). Conclusions The DECS-II trial will use a novel, efficient trial design to evaluate whether high-dose dexamethasone has a patient-centered benefit of enhancing recovery and increasing the number of days at home after cardiac surgery.

Insa Feinkohl,1,* Gunnar Lachmann,2,* Wolf-Rüdiger Brockhaus,2 Friedrich Borchers,2 Sophie K Piper,3 Thomas H Ottens,4 Hendrik M Nathoe,5 Anne-Mette Sauer,4 Jan M Dieleman,4 Finn M Radtke,6 Diederik van Dijk,7 Tobias Pischon,1,8,9,* Claudia Spies2,* 1Molecular Epidemiology Research Group, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin-Buch, Germany; 2Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 3Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 4Department of Anesthesiology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; 6Department of Anesthesiology, Naestved Hospital, Naestved, Denmark; 7Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; 8Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 9MDC/BIH Biobank, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), and Berlin Institute of Health (BIH), Berlin, Germany *These authors contributed equally to this work Background: Age-related cognitive impairment is rising in prevalence but is not yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate the role of obesity, diabetes and hypertension as candidate risk factors. Methods: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis of cross-sectional associations of diabetes, hypertension, blood pressure, obesity (body mass index [BMI] ≥30 kg/m²) and BMI with presence of cognitive impairment in log-binomial regression analyses. Cognitive impairment was defined as scoring more than 2 standard deviations below controls on at least one of 5–11 cognitive tests. Underweight participants (BMI

Background Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery. Methods We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Results Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71–1.01; P=0.07; I2 = 0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989 patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04–1.31; P=0.008; I2=0%]. New onset atrial fibrillation was lower in the steroid group [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91, 95% CI, 0.86–0.96, P=0.0005, I2=43%]; this beneficial effect was limited to small trials (P for interaction Conclusions After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect.

Background. Cardiac surgery with the use of cardiopulmonary bypass is associated with a systemic inflammatory response. Intraoperative corticosteroids are administered to attenuate this inflammatory response. The recent Dexamethasone for Cardiac Surgery (DECS) trial could not demonstrate a beneficial effect of dexamethasone on major adverse events in cardiac surgical patients. Previous studies suggest that corticosteroids may affect postoperative coagulation and blood loss, and therefore could influence the risk of surgical reinterventions. We investigated the effects of prophylactic intraoperative dexamethasone treatment on the rate of rethoracotomy after cardiac surgery.Methods. We performed a post-hoc additional data collection and analysis in the DECS trial. A total of 4,494 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to intravenous dexamethasone (1.0 mg/kg) or placebo. The primary endpoint for the present study was the incidence of any rethoracotomy within the first 30 postoperative days. Secondary endpoints included the reason for rethoracotomy and the incidence of perioperative transfusion of blood products.Results. In the dexamethasone group, 217 patients (9.7%) underwent a rethoracotomy, and in the placebo group, 165 patients did (7.3%; relative risk 1.32, 95% confidence interval: 1.09 to 1.61, p = 0.005). The most common reason for rethoracotomy was tamponade in both groups: 3.9% versus 2.1%, respectively (relative risk 1.84, 95% confidence interval: 1.30 to 2.61, p Conclusions. Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk. (C) 2015 by The Society of Thoracic Surgeons

Objective: Using magnetic resonance imaging, the authors studied the influence of a single high dose of intraoperative dexamethasone on the severity of cerebral edema that can occur early after coronary artery bypass grafting (CABG). It was hypothesized that high-dose intraoperative dexamethasone reduces cerebral edema after CABG. Design: Secondary analysis in a subset of participants of the Dexamethasone for Cardiac Surgery (DECS) trial. The DECS trial was a multicenter, randomized, double-blind, placebo-controlled trial in 4,494 cardiac surgery patients, which studied the effect of high-dose dexamethasone on mortality and major complications after cardiac surgery. Setting: A large university hospital in The Netherlands. Participants: Twenty adult patients who underwent CABG with cardiopulmonary bypass (CPB) between March and November 2011. Interventions: Participants received a single intravenous dose of dexamethasone, 1 mg/kg, or placebo, at induction of anesthesia. Measurements and Main Results: Patients underwent magnetic resonance imaging scanning immediately after surgery. The primary outcome was the severity of cerebral edema. Data from 18 patients (9 in each group, median age 69 years in both groups) could be analyzed. Patients in the dexamethasone group were (median, interquartile range 66 (53-99) minutes on cardiopulmonary bypass v 95 (81-105) minutes in the placebo group (p = 0.11). Only 1 patient in the dexamethasone group had slight cerebral edema (0% v11%, p = 1.00), and edema severity did not differ between groups (p = 1.00). Conclusions: Relevant degrees of early postoperative cerebral edema were not observed. The present study findings strongly contrasted with older studies showing cerebral edema early after CABG in most patients. (C) 2015 Elsevier Inc. All rights reserved.

Background/Aims: Older people undergoing surgery are at risk of developing postoperative cognitive dysfunction (POCD), but little is known of risk factors predisposing patients to POCD. Our objective was to estimate the risk of POCD associated with exposure to preoperative diabetes, hypertension, and obesity. Methods: Original data from 3 randomised controlled trials (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis on diabetes, hypertension, baseline blood pressure, obesity (BMI ≥30 kg/m2), and BMI as risk factors for POCD in multiple logistic regression models. Risk estimates were pooled across the 3 studies. Results: Analyses totalled 1,034 patients. POCD occurred in 5.2% of patients in DECS, in 9.4% in SuDoCo, and in 32.1% of patients in OCTOPUS. After adjustment for age, sex, surgery type, randomisation, obesity, and hypertension, diabetes was associated with a 1.84-fold increased risk of POCD (OR 1.84; 95% CI 1.14, 2.97; p = 0.01). Obesity, BMI, hypertension, and baseline blood pressure were each not associated with POCD in fully adjusted models (all p > 0.05). Conclusion: Diabetes, but not obesity or hypertension, is associated with increased POCD risk. Consideration of diabetes status may be helpful for risk assessment of surgical patients.

Background: Postoperative atrial fibrillation (AF) is a common complication after cardiac surgery. Inflammation is believed to play a pivotal role in the etiology of postoperative AF. There is a suggestion from small studies that perioperative treatment with corticosteroids may reduce postoperative AF. The DExamethasone for Cardiac Surgery (DECS) study was a large randomized trial showing no protective effect of dexamethasone on major adverse events. The aim of this study was to investigate the effect of dexamethasone treatment on the occurrence of AF after cardiac surgery. Methods: The DECS study compared intra-operative dexamethasone (1 mg/kg) or placebo treatment in 4494 adult patients undergoing cardiac surgery. AF was defined by the occurrence of any reported AF within 30 days after surgery. We also performed an in-depth analysis of a subset of 1565 patients on new-onset AF. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Results: The incidence of any AF in the main study of 4494 patients was 33.1% in the dexamethasone and 35.2% in the placebo group (RR 0.94, 95% CI: 0.87-1.02, p = 0.14). In the substudy of 1565 patients, the incidence of new-onset AF was 33.0% vs. 35.5% (RR 0.93, 95% CI: 0.81-1.07, p = 0.31), respectively. There was no protective effect of dexamethasone across clinically important patient subgroups. Conclusion: Intraoperative administration of dexamethasone had no protective effect on the occurrence of any or new-onset atrial fibrillation after cardiac surgery. Therefore, the use of dexamethasone for the reduction of postoperative AF should not be recommended. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Background The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic inflammatory response syndrome, during the first 24 h after cardiac surgery. Methods This was a retrospective cohort study, using linked data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database and the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database. Data from patients who underwent coronary artery bypass grafting and/or valve surgery were used. The association between age and postoperative SIRS was analysed using Poisson regression, and corrected for other risk factors. Restricted cubic splines were used to determine relevant age categories. Results are expressed as risk ratios (RR) with 95% confidence intervals (CI). Results Data from 28 513 patients were used. In both univariable and multivariable models, increased patient age was strongly associated with reduced postoperative SIRS prevalence. Using 73–83 yr as the reference category, the RRs (95% CI) for the age categories were 1.38 (1.28–1.49) for ≤43 yr, 1.15 (1.09–1.20) for 44–63 yr, 1.05 (1.00–1.09) for 64–72 yr, and 1.03 (0.94–1.12) for >83 yr, respectively. The predictive value for postoperative SIRS of the final model, however, was moderate (c-statistic: 0.61). Conclusions We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.

Background Cardiovascular disease remains the major contributor to morbidity and mortality. In routine care for patients with an elevated cardiovascular risk or with symptomatic cardiovascular disease information is mostly collected in an unstructured manner, making the data of limited use for structural feedback, quality control, learning and scientific research. Objective The Utrecht Cardiovascular Cohort (UCC) initiative aims to create an infrastructure for uniform registration of cardiovascular information in routine clinical practice for patients referred for cardiovascular care at the University Medical Center Utrecht, the Netherlands. This infrastructure will promote optimal care according to guidelines, continuous quality control in a learning healthcare system and creation of a research database. Methods The UCC comprises three parts. UCC-1 comprises enrolment of all eligible cardiovascular patients in whom the same information will be collected, based on the Dutch cardiovascular management guideline. A sample of UCC-1 will be invited for UCC-2. UCC-2 involves an enrichment through extensive clinical measurements with emphasis on heart failure, cerebral ischaemia, arterial aneurysms, diabetes mellitus and elevated blood pressure. UCC-3 comprises on-top studies, with in-depth measurements in smaller groups of participants typically based on dedicated project grants. All participants are followed up for morbidity and mortality through linkage with national registries. Conclusion In a multidisciplinary effort with physicians, patients and researchers the UCC sets a benchmark for a learning cardiovascular healthcare system. UCC offers an invaluable resource for future high quality care as well as for first-class research for investigators.

Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and postoperative inflammation may contribute to PNAF by inducing atrial dysfunction. Corticosteroids reduce inflammation and may thus reduce atrial dysfunction and PNAF development. This study aimed to determine whether dexamethasone protects against left atrial dysfunction and PNAF in cardiac surgical patients. Cardiac surgical patients were randomised to a single dose of dexamethasone (1 mg.kg(-1)) or placebo after inducing anaesthesia. Transoesophageal echocardiography was performed in patients before and after surgery. Primary outcome was left atrial total ejection fraction (LA-TEF) after sternal closure; secondary outcomes included left atrial diameter and PNAF. 62 patients were included. Baseline characteristics were well balanced. Postoperative LA-TEF was 36.4 % in the dexamethasone group and 40.2 % in the placebo group (difference -3.8 %; 95 % confidence interval (CI) -9.0 to 1.4 %; P = 0.15). Postoperative left atrial diameter was 4.6 and 4.3 cm, respectively (difference 0.3; 95 % CI -0.2 to 0.7; P = 0.19). The incidence of PNAF was 30 % in the dexamethasone group and 39 % in the placebo group (P = 0.47). Intraoperative high-dose dexamethasone did not protect against postoperative left atrial dysfunction and did not reduce the risk of PNAF in cardiac surgical patients.

Background Severe pulmonary complications occur frequently following transthoracic oesophagectomy. An exaggerated immunological response is probably a main driving factor, and this might be prevented by perioperative administration of a glucocorticoid. Objective To determine the clinical benefits and harms of perioperative glucocorticoid during transthoracic oesophagectomy, using pulmonary complications as the primary outcome. Mortality, anastomotic leakage rate and infection were secondary outcomes. Methods A systematic review of interventional trials with a meta-analysis of randomised controlled trials (RCTs). Results The search retrieved seven RCTs and four interventional nonrandomised studies. In total, 367 patients received perioperative glucocorticoid and 415 patients did not. A meta-analysis of the RCTs showed no significant effect of glucocorticoid. For pulmonary complications, the pooled risk ratio was 0.69 [95% confidence interval (CI) 0.26 to 1.79], for anastomotic leakage 0.61 (95% CI 0.23 to 1.61) and for infections 1.09 (95% CI 0.41 to 2.93). A subgroup analysis of RCTs that used weight-dependent dosing within 30 min preoperatively showed a pooled risk ratio of 0.28 (95% CI 0.10 to 0.77) for pulmonary complications compared with placebo. Conclusion In this meta-analysis, perioperative administration of glucocorticoid did not affect the risk of pulmonary complications after transthoracic oesophagectomy, nor did it cause adverse effects. A subgroup analysis showed that a weight-dependent dose of methylprednisolone 10 to 30 mg kg within 30 min preoperatively might be the most promising dosing regimen for further research.

Background: Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characterized by impaired memory function and intellectual ability. The systemic inflammatory response that is induced by major surgery and cardiopulmonary bypass may play an important role in the etiology of POCD. Prophylactic corticosteroids to attenuate the inflammatory response may therefore reduce the risk of POCD. The authors investigated the effect of intraoperative high-dose dexamethasone on the incidence of POCD at 1 month and 12 months after cardiac surgery. Methods: This multicenter, randomized, double-blind, placebo-controlled trial is a preplanned substudy of the DExamethasone for Cardiac Surgery trial. A total of 291 adult patients undergoing cardiac surgery with cardiopulmonary bypass were recruited in three hospitals and randomized to receive dexamethasone 1 mg/kg (n = 145) or placebo (n = 146). The main outcome measures were incidence of POCD at 1- and 12-month follow-up, defined as a decline in neuropsychological test performance beyond natural variability, as measured in a control group. Results: At 1-month follow-up, 19 of 140 patients in the dexamethasone group (13.6%) and 10 of 138 patients in the placebo group (7.2%) fulfilled the diagnostic criteria for POCD (relative risk, 1.87; 95% CI, 0.90 to 3.88; P = 0.09). At 12-month follow-up, 8 of 115 patients in the dexamethasone group (7.0%) and 4 of 114 patients (3.5%) in the placebo group had POCD (relative risk, 1.98; 95% CI, 0.61 to 6.40; P = 0.24). Conclusion: Intraoperative high-dose dexamethasone did not reduce the risk of POCD after cardiac surgery.

Background Postoperative new-onset atrial fibrillation (PNAF) is the most common complication following cardiac surgery. The pathogenesis of PNAF is multifactorial. The concept of the postoperative inflammatory response, as a potential underlying mechanism has been extensively studied. This review aims to provide a comprehensive summary of literature relevant to the association between the inflammatory response following cardiac surgery and PNAF. Design MEDLINE, EMBASE and the Cochrane Central Register were systematically reviewed by two independent investigators for studies published between January 1980 and May 2012, in which an association between serum markers of inflammation and PNAF was evaluated, or the effect of drugs with anti-inflammatory properties on the risk of PNAF. Results Sixty-three studies met selection criteria (39 observational and 24 randomized studies) including 27 363 patients. The mean incidence of PNAF after cardiac surgery was 25! 5%. Elevated levels of various inflammatory mediators were associated with PNAF, and the most consistent association was found between white blood cell count and PNAF. Of the drugs with anti-inflammatory properties, statins gave the best protective effect against PNAF, followed by anti-oxidants, steroids and colchicine. Nonsteroidal anti-inflammatory drugs did not prevent PNAF significantly. Conclusion The postoperative inflammation response may play a role in the pathogenesis of PNAF. However, of the inflammation biomarkers, only elevated white blood cell count reliably predicts PNAF. Pre- and perioperative use of statins and several other drugs with anti-inflammatory properties reduce the incidence of PNAF.

Stored red blood cells undergo progressive structural and functional changes over time. Recently, concerns have been raised about the transfusion of older red blood cell (RBC) concentrates after cardiac surgery. The objective of the study was to test the hypothesis that longer storage time of RBCs increases the risk of adverse outcome after cardiac surgery. This is a retrospective cohort study which includes patients who underwent coronary artery bypass surgery and/or valve surgery. All patients were operated in the period from September 2006 to December 2010 and received 1 to 6 units of RBCs intraoperative or after surgery. Patients were divided into two groups according to the storage time of the RBCs. The “younger” group comprised patients who received RBCs ≤14 days old (n = 111) and the “any older” group comprised patients who received RBCs >14 days old (n = 710). Using univariable and multivariable regression analysis, we examined the effect of storage time on the primary composite endpoint of death, myocardial infarction, and stroke (major adverse cardiovascular events). Secondary outcomes were prolonged ICU and hospital stay. Data of 821 patients who received a total of 2,004 RBCs were analyzed. The median storage time for the younger group was 13 ± 2 days, the median storage time for the “any older” group was 21 ± 5 days. The incidence of the primary outcome was 8.6 % in the “any older” group and 4.5 % in the younger group (adjusted odds ratio (OR) 1.68; 95 % confidence interval (CI), 0.65–4.34). Prolonged ICU stay was 12.3 % in the “any older” group and 6.3 % in the younger group (adjusted OR 1.58; 95 % CI, 0.69–3.66). In patients undergoing cardiac surgery, transfusion of RBCs stored for more than 2 weeks was not associated with adverse outcomes.

Cardiac surgery and cardiopulmonary bypass are associated with an intense activation of the immune system. The systemic inflammatory response that develops in many cardiac surgical patients has the potential to lead to significant postoperative morbidity, and even mortality. Intraoperative corticosteroids are often used as prophylaxis for this systemic inflammatory response. This update provides a review of the existing evidence of the effects of corticosteroids on clinical outcomes after cardiopulmonary bypass, and combines this with emerging evidence from a recently published first large clinical trial of dexamethasone in cardiac surgery.

Background Postoperative new-onset atrial fibrillation (PNAF) is the most common complication following cardiac surgery. The inflammatory response, as a potential underlying mechanism, has been extensively studied. In small studies, the white blood cell count (WBC) has been shown to be the only consistent inflammatory marker associated with PNAF. This study aimed to determine the association between perioperative WBC response and PNAF in a larger study cohort. Methods Patients ≥18years, undergoing elective cardiac surgery with a preoperative sinus rhythm were included. WBC was routinely measured preoperatively, and daily during the first four postoperative days. Main outcomes were the difference between peak postoperative WBC and neutrophil/lymphocyte ratio (N/L ratio) and preoperative WBC and N/L ratio (ΔWBC and ΔN/L ratio respectively). Development of PNAF was evaluated in all patients with continuous 12-lead ECG monitoring. Results 657 patients were included and 277 (42%) developed PNAF. Univariable analyses showed a statistically significant relationship between ΔWBC ( P =0.030) and ΔN/L ratio ( P =0.002), and PNAF. In multivariable analysis no significant relationship was found between ΔWBC (OR: 1.14 per 1×10 9 /L increase; 95% CI: 0.65–2.03; P =0.645), ΔN/L ratio (OR: 1.65 per 1×10 9 /L increase; 95% CI: 0.94–2.90; P =0.089), and PNAF. Increasing age (OR: 1.08 per year; 95% CI: 1.01–1.16; P =0.022) and (additional) valve surgery (versus CABG) (OR: 4.96; 95% CI: 2.07–6.91; P ≤0.001) were associated with PNAF. Conclusions The perioperative WBC response and its components were not associated with the development of PNAF.

Background: Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. Methods: Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. Results: PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. Limitations: The unequal distribution of male (78%) and female patients (22%) might limit the general-izability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. Conclusions: In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery. (C) 2016 Elsevier B.V. All rights reserved.

Item does not contain fulltext OBJECTIVE: The study aim was to investigate the long-term prognosis and risk factors of postpericardiotomy syndrome (PPS). METHODS: We performed a single-center cohort study in 822 patients undergoing nonemergent valve surgery. Risk factors of PPS were evaluated using multivariable logistic regression analysis. We also compared the incidence of reoperation for tamponade at 1 year between patients with and without PPS. Main secondary outcomes were hospital stay and mortality. RESULTS: Of the 822 patients, 119 (14.5%) developed PPS. A higher body mass index (odds ratio (OR) per point increase, 0.94; 95% confidence interval (CI), 0.89-0.99) was associated with a lower risk of PPS, whereas preoperative treatment for pulmonary disease without corticosteroids (OR, 2.55; 95% CI, 1.25-5.20) was associated with a higher risk of PPS. The incidence of reoperation for tamponade at 1 year in PPS versus no PPS was 20.9% versus 2.5% (OR, 15.49; 95% CI, 7.14-33.58). One-year mortality in PPS versus no PPS was 4.2% versus 5.5% (OR, 0.68; 95% CI, 0.22-2.08). Median hospital stay was 13 days (interquartile range, 9-18 days) versus 11 days (interquartile range, 8-15 days) (P = .001), respectively. CONCLUSIONS: Despite longer hospital stays and more short-term reoperations for tamponade, patients with PPS had an excellent 1-year prognosis.

Objective:Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission.Design:Follow-up study of a randomized clinical trial.Setting:Five Dutch heart centers.Patients:Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial.Interventions:A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way.Measurements and Main Results:Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p Conclusions:Overall, our findings suggest that exogenous administration of the glucocorticoid receptor agonist dexamethasone-compared with placebo-during cardiac surgery does not positively or negatively affect the prevalence of posttraumatic stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present.

van den Berg et al1 investigated the association between the type of anesthesia and clinical outcome in a cohort of patients who were included in a clinical trial evaluating endovascular treatment for acute ischemic stroke. This is an important topic as it has been previously suggested that general anesthesia worsens the outcome after endovascular treatment for stroke, compared with procedures under conscious sedation or awake procedures.2 In their post hoc analysis, van den Berg et al1 reported a good clinical outcome, defined as a modified Rankin Scale score of 2 or less, in 10 of the 70 patients (14%) who received general anesthesia, compared with 72 of the 278 patients (26%) who …

BACKGROUND: Delirium is a common complication after cardiac surgery and may be as a result of inadequate cerebral perfusion. We studied delirium after cardiac surgery in relation to intraoperative hypotension (IOH). METHODS: This observational single-centre, cohort study was nested in a randomized trial, on a single intraoperative dose of dexamethasone vs placebo during cardiac surgery. During the first four postoperative days, patients were screened for delirium based on the Confusion Assessment Method (CAM) for Intensive Care Unit on the intensive care unit, CAM on the ward, and by inspection of medical records. To combine depth and duration of IOH, we computed the area under the curve for four blood pressure thresholds. Logistic regression analyses were performed to investigate the association between IOH and the occurrence of postoperative delirium, adjusting for confounding and using a 99% confidence interval to correct for multiple testing. RESULTS: Of the 734 included patients, 99 patients (13%) developed postoperative delirium. The adjusted Odds Ratio for the Mean Arterial Pressure

Neurologic and neurocognitive complications after cardiac surgery with cardiopulmonary bypass (CPB) have been reported repeatedly. To better understand its etiology and design protective strategies, an appropriate animal model may prove useful. Although impaired short-term neurocognitive function has been recently demonstrated after CPB in rats, the demonstration of persistent long-term neurocognitive changes would be more relevant from a clinical perspective. We hypothesized that CPB results in long-term impairment of neurocognitive performance in rats. Male rats were exposed to either 60 min of normothermic non-pulsatile CPB, using a roller-pump and a neonatal membrane oxygenator, or to cannulation only (sham animals). Long-term neurocognitive function was assessed at 4 to 7 weeks after CPB (Can test), and again after 12 weeks (Morris water maze) in both operated groups and in a non-operated control group, followed by histologic evaluation of the hippocampus. In separate groups of CPB and sham animals, we also measured TNF-alpha and IL-6 in plasma. There were no significant differences in long-term neurocognitive performance or histological outcome between the three groups. Cytokine patterns were also similar in both operated groups. We conclude that CPB did not appear to cause long-term neurocognitive dysfunction in this model of CPB in young healthy rats. The lack of long-term deficits may be due to the absence of clinically important etiologic factors such as atheromatous and gaseous embolization in this model. Similar cytokine patterns in both operated groups suggest that surgical trauma rather than exposure of blood to extra-corporeal circuit was probably responsible for the inflammatory response.

Background Post Pericardiotomy Syndrome (PPS) is a common complication following cardiac surgery, however the exact pathogenesis remains uncertain. Identifying risk factors of PPS might help to better understand the syndrome. The aim of this study was to provide an overview of existing literature around determinants of PPS in adult cardiac surgery patients. Material and methods Two independent investigators performed a systematic search in MEDLINE, EMBASE and the Cochrane Central Register. The search aimed to identify studies published between January 1950 and December 2015, in which determinants of PPS were reported. Results 19 studies met the selection criteria. In these studies, 14 different definitions of PPS were used. The median incidence of PPS was 16%. After quality assessment, 7 studies were considered eligible for this review. Lower preoperative Interleukin-8 levels and higher postoperative complement conversion products where associated with a higher risk of PPS. Among other clinical factors, a lower age, transfusion of red blood cells and lower preoperative platelet and haemoglobin levels were associated with a higher risk of PPS. Colchicine use decreased the risk of PPS. Conclusion We found that both the inflammatory response and perioperative bleeding and coagulation may play a role in the development of PPS, suggesting a multifactorial etiology of the syndrome. Due to a lack of a uniform definition of PPS in the past, study comparability was poor across the studies. This article is protected by copyright. All rights reserved.

Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characterized by impaired memory function and intellectual ability. The systemic inflammatory response that is induced by major surgery and cardiopulmonary bypass may play an important role in the etiology of POCD. Prophylactic corticosteroids to attenuate the inflammatory response may therefore reduce the risk of POCD. The authors investigated the effect of intraoperative high-dose dexamethasone on the incidence of POCD at 1 month and 12 months after cardiac surgery.This multicenter, randomized, double-blind, placebo-controlled trial is a preplanned substudy of the DExamethasone for Cardiac Surgery trial. A total of 291 adult patients undergoing cardiac surgery with cardiopulmonary bypass were recruited in three hospitals and randomized to receive dexamethasone 1 mg/kg (n = 145) or placebo (n = 146). The main outcome measures were incidence of POCD at 1- and 12-month follow-up, defined as a decline in neuropsychological test performance beyond natural variability, as measured in a control group.At 1-month follow-up, 19 of 140 patients in the dexamethasone group (13.6%) and 10 of 138 patients in the placebo group (7.2%) fulfilled the diagnostic criteria for POCD (relative risk, 1.87; 95% CI, 0.90 to 3.88; P = 0.09). At 12-month follow-up, 8 of 115 patients in the dexamethasone group (7.0%) and 4 of 114 patients (3.5%) in the placebo group had POCD (relative risk, 1.98; 95% CI, 0.61 to 6.40; P = 0.24).Intraoperative high-dose dexamethasone did not reduce the risk of POCD after cardiac surgery.

Background: Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characterized by impaired memory function and intellectual ability. The systemic inflammatory response that is induced by major surgery and cardiopulmonary bypass may play an important role in the etiology of POCD. Prophylactic corticosteroids to attenuate the inflammatory response may therefore reduce the risk of POCD. The authors investigated the effect of intraoperative high-dose dexamethasone on the incidence of POCD at 1 month and 12 months after cardiac surgery. Methods: This multicenter, randomized, double-blind, placebo-controlled trial is a preplanned substudy of the DExamethasone for Cardiac Surgery trial. A total of 291 adult patients undergoing cardiac surgery with cardiopulmonary bypass were recruited in three hospitals and randomized to receive dexamethasone 1 mg/kg (n = 145) or placebo (n = 146). The main outcome measures were incidence of POCD at 1- And 12-month follow-up, defined as a decline in neuropsychological test performance beyond natural variability, as measured in a control group. Results: At 1-month follow-up, 19 of 140 patients in the dexamethasone group (13.6%) and 10 of 138 patients in the placebo group (7.2%) fulfilled the diagnostic criteria for POCD (relative risk, 1.87; 95% CI, 0.90 to 3.88; P = 0.09). At 12-month follow-up, 8 of 115 patients in the dexamethasone group (7.0%) and 4 of 114 patients (3.5%) in the placebo group had POCD (relative risk, 1.98; 95% CI, 0.61 to 6.40; P = 0.24). Conclusion: Intraoperative high-dose dexamethasone did not reduce the risk of POCD after cardiac surgery.

Background The postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery. The pathophysiology remains unclear, although evidence exists that surgical trauma and the use of cardiopulmonary bypass provoke an immune response leading to PPS. We hypothesized that an intraoperative dose of dexamethasone decreases the risk of PPS, by reducing this inflammatory response. Methods We performed a subanalysis of the DECS study, which is a multicenter, double-blind, placebo-controlled, randomized trial of 4,494 patients undergoing cardiac surgery with use of cardiopulmonary bypass. The aim of the DECS study was to investigate whether a single intraoperative dose of 1 mg/kg dexamethasone reduced the incidence of a composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. In this substudy, we retrospectively analyzed the occurrence of PPS in 822 patients who were included in the DECS trial and underwent valvular surgery. Postpericardiotomy syndrome was diagnosed if 2 of 5 listed symptoms were present: unexplained fever, pleuritic chest pain, pericardial or pleural rub, new or worsening pericardial or pleural effusion. All medical charts, x-rays, and echocardiograms were reviewed. Secondary end point was the occurrence of complicated PPS, defined as PPS with need for evacuation of pleural effusion, pericardiocentesis, and tamponade requiring intervention or hospital readmission for PPS. This is a blinded, single-center, post hoc analysis. Results Postpericardiotomy syndrome occurred in 119 patients (14.5%). The incidence of PPS after dexamethasone compared with placebo was 13.5% vs 15.5% (relative risk 0.88, 95% CI 0.63-1.22). For complicated PPS, the incidence was 3.8% versus 3.2% (relative risk 1.17, 95% CI 0.57-2.41, P = .66), respectively. Conclusion In patients undergoing valvular cardiac surgery, high-dose dexamethasone treatment had no protective effect on the occurrence of PPS or complicated PPS.

Background High-dose prophylactic corticosteroids are often administered during cardiac surgery. Their use, however, remains controversial, as no trials are available that have been sufficiently powered to draw conclusions on their effect on major clinical outcomes. Objectives The objective of this meta-analysis was to estimate the effect of prophylactic corticosteroids in cardiac surgery on mortality, cardiac and pulmonary complications. Search strategy Major medical databases (CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science) were systematically searched for randomised studies assessing the effect of corticosteroids in adult cardiac surgery. Database were searched for the full period covered, up to December 2009. No language restrictions were applied. Selection criteria Randomised controlled trials comparing corticosteroid treatment to either placebo treatment or no treatment in adult cardiac surgery were selected. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more end-points. Data collection and analysis The processes of searching and selection for inclusion eligibility were performed independently by two authors. Also, quality assessment and data-extraction of selected studies were independently performed by two authors. The primary endpoints were mortality, cardiac and pulmonary complications. The main effect measure was the Peto odds ratio comparing corticosteroids to no treatment/placebo. Main results Fifty-four randomised studies, mostly of limited quality, were included. Altogether, 3615 patients were included in these studies. The pooled odds ratio for mortality was 1.12 (95% CI 0.65 to 1.92), showing no mortality reduction in patients treated with corticosteroids. The odds ratios for myocardial and pulmonary complications were 0.95, (95% CI 0.57 to 1.60) and 0.83 (95% CI 0.49 to 1.40), respectively. The use of a random effects model did not substantially influence study results. Analyses of secondary endpoints showed a reduction of atrial fibrillation and an increase in gastrointestinal bleeding in the corticosteroids group. Authors' conclusions This meta-analysis showed no beneficial effect of corticosteroid use on mortality, cardiac and pulmonary complications in cardiac surgery patients.

Objective: Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidity, usually manifested as cognitive decline or stroke. The underlying mechanism leading to cognitive decline is still unclear. Presence of coronary collateral arteries, which may reflect an overall better cardiovascular condition, recently appeared to relate to a better cardiac outcome after CABG. In this study, we investigated the hypothesis that presence of coronary collaterals is associated with less cognitive decline after coronary artery bypass grafting. Methods: Data from 281 patients undergoing first-time coronary artery bypass grafting were used. Presence of coronary collaterals was determined on the preoperative angiogram. Cognitive function was evaluated before the operation, at 3 and 12 months and 5 years thereafter by standardised neuropsychological assessment. Cognitive decline in individuals was determined by calculating the reliable change score, a cognitive change score corrected for natural testing variability and practice effects. Results: Cognitive decline was found in 19 (8%) patients at 3 months, in 31 (12%) patients at 12 months and in 82 (34%) at 5 years follow-up. Presence of coronary collaterals was independently associated with a better cognitive outcomeat both 3 months (odds ratio (OR) 0.30; 95% confidenceinterval (CI) 0.09—0.95;p = 0.04) and 12 months(OR 0.42; 95% CI 0.18— 0.97; p = 0.04) after coronary artery bypass grafting. At 5 years, the OR was 0.57 (95% CI 0.31—1.05; p = 0.07). Conclusions: In patients undergoing first-time coronary artery bypass grafting, presence of coronary collaterals is associated with a decreased risk of cognitive decline at both 3 and 12 months of follow-up. This trend persists at 5-year follow-up. Preoperative differences in the cardiac vascular condition may therefore predict cognitive outcome in patients undergoing coronary artery bypass grafting. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background Cerebral embolization models have been hindered by the fact that delivery is predominantly one-sided and cannot be quantified easily. We have developed a model for bilateral cerebral micro-embolization. By using holmium microspheres, it is possible to quantify intracerebral delivery using MRI. Methods To validate the quantification of holmium microspheres a phantom study was performed in which concentration of microspheres in solution was compared with the number of holmium-induced artifacts on MRI. After that identical microspheres were administered by unilateral injection in the carotid artery, while the opposite carotid artery was clamped. On post-injection MRI scans, intracerebral delivery and right/left distribution of the microspheres was determined. Results In the phantom study it was shown that quantification by MRI is possible and that MRI artifacts represent single microspheres. In the rat brain, about one-third of the injected dose was consistently located on the contralateral side. The administration was reproducible regarding distribution and number of microspheres. Conclusions The use of holmium microspheres enables quantification of delivered dose as single microspheres induce artifacts on MRI. By clamping the contralateral carotid artery, one-third of the dose is diverted to the contralateral hemisphere.

Background Age and diabetes mellitus have been identified as independent risk factors for cognitive decline after cardiac surgery with cardiopulmonary bypass (CPB). We tested the effects of CPB on cognitive function in aged and diabetic rats utilizing the Morris water maze (MWM). Methods Aged rats (26 months) were randomized into a sham group (cannulation but no CPB, n = 11) and a 90 min CPB group (n = 11). In addition, young rats (n = 14) were made diabetic with streptozotocin 9 weeks before experimentation and randomized to a sham or 90 min CPB group. Cytokine release [interleukin (IL-6)] and short-term MWM performance (days 8–14 after operation) were assessed in all animals. Long-term MWM performance (8 weeks after operation) was assessed in aged rats only. Results There were no differences between the aged groups in short-term (P = 0.58) or long-term MWM performances (P = 0.69). The diabetic animals also showed no differences between the sham and CPB groups in MWM performance (P = 0.64). IL-6 assays showed an increased inflammatory response after CPB in the diabetic animals, but not in the elderly groups. Conclusions Ninety minutes of normothermic CPB had no deleterious effect on neurocognitive outcome in elderly or chronically diabetic animals, suggesting that CPB in itself is not a sufficient stressor of the rat central nervous system.

Introduction Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. Methods The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol—Glucose Regulation for Intensive care Patients (GRIP)—was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC15). ICU length of stay and mortality were observed as well. Results The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC15 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P 15 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). Conclusions Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. Trial registration ClinicalTrials.gov NCT00293592. Registered 16 February 2006.

ICU survivors are at risk for post-traumatic stress disorder (PTSD) and depression. The development of psychopathology depends partially on stable personality factors such as trait anxiety. Among ICU patients a high level of trait anxiety is relatively common and associated with intrusions, a symptom of PTSD. Independently, childhood trauma and stress exposure throughout life have been associated with depression. In cardiac surgery patients admitted to the ICU postoperatively, the effect of trait anxiety on the relationship between cumulative life stress and stress-related psychopathology remains unknown. Therefore we aimed to assess the mediating or moderating role of trait anxiety in this at-risk patient population.