Dexamethasone for Cardiac Surgery: A Practice Preference-Randomized Consent Comparative Effectiveness Trial.

BACKGROUND: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. Our primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. Our secondary aim was to evaluate efficiency, value and impact of the novel trial design. METHODS: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across 7 hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone, 1 mg/kg, or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (>48 h), sepsis, renal failure, myocardial infarction, stroke and death. RESULTS: Of 2093 patients assessed for eligibility, 1951 were randomized (median age 63 years, 80% male). The median number of home days was 23.0 (IQR, 20.1 to 24.1) in the dexamethasone group and 23.1 (IQR, 20.1 to 24.6) in the no dexamethasone group; median difference 0.1 (95% CI, -0.3 to 0.5), P=0.66. The rates of prolonged mechanical ventilation, RR 0.72 (95% CI, 0.48 to 1.08), sepsis, RR 1.02 (95% CI, 0.57 to 1.82), renal failure, RR 0.94 (95% CI, 0.80 to 1.12), myocardial infarction, RR 1.20 (95% CI, 0.30 to 4.82), stroke, RR 1.06 (95% CI, 0.54 to 2.08), and death, RR 0.72 (95% CI, 0.22 to 2.35), were comparable between groups (all P>0.10). Dexamethasone reduced intensive care unit stay, median 29 (IQR, 22 to 50) h vs. 43 (24 to 72) h, P=0.004. Our novel trial design was highly efficient (89.3% enrolment). CONCLUSIONS: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.

Cost-effectiveness of routine transoesophageal echocardiography during cardiac surgery: a discrete-event simulation study.

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.

The Effect of Steroids in Patients Undergoing Cardiopulmonary Bypass: An Individual Patient Meta-Analysis of Two Randomized Trials.

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 < 0.001) and hospital stays (p = 0.006). 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.

Dexamethasone for Cardiac Surgery trial (DECS-II): Rationale and a novel, practice preference-randomized consent design.

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.

Diabetes, but Not Hypertension and Obesity, Is Associated with Postoperative Cognitive Dysfunction.

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.

Determinants of the postpericardiotomy syndrome: a systematic review.

BACKGROUND: Postpericardiotomy 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: A total of 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, seven studies were considered eligible for this review. Lower preoperative interleukin-8 levels and higher postoperative complement conversion products were 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 aetiology of the syndrome. Due to a lack of a uniform definition of PPS in the past, study comparability was poor across the studies.

The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission: Longitudinal Follow-Up of a Randomized Controlled Trial.

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 < 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p < 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology. 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.

Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control: a randomized controlled trial.

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 <0.001 and glucose AUC15 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, 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.

Low incidence of early postoperative cerebral edema after coronary artery bypass grafting.

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% v 11%, 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.

Dexamethasone for the prevention of postpericardiotomy syndrome: A DExamethasone for Cardiac Surgery substudy.

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.

Inflammation in new-onset atrial fibrillation after cardiac surgery: a systematic review.

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.

Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial.

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.

The effect of perioperative administration of glucocorticoids on pulmonary complications after transthoracic oesophagectomy: a systematic review and meta-analysis.

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.

Inflammation risk before cardiac surgery and the treatment effect of intraoperative dexamethasone.

Patients who exhibit high systemic inflammation after cardiac surgery may benefit most from pre-emptive anti-inflammatory treatments. In this secondary analysis (n = 813) of the randomised, double-blind Intraoperative High-Dose Dexamethasone for Cardiac Surgery trial, we set out to develop an inflammation risk prediction model and assess whether patients at higher risk benefit from a single intraoperative dose of dexamethasone (1 mg/kg). Inflammation risk before surgery was quantified from a linear regression model developed in the placebo arm, relating preoperatively available covariates to peak postoperative C-reactive protein. The primary endpoint was the interaction between inflammation risk and the peak postoperative C-reactive protein reduction associated with dexamethasone treatment. The impact of dexamethasone on the main clinical outcome (a composite of death, myocardial infarction, stroke, renal failure, or respiratory failure within 30 days) was also explored in relation to inflammation risk. Preoperatively available covariates explained a minority of peak postoperative C-reactive protein variation and were not suitable for clinical application (R2 = 0.058, P = 0.012); C-reactive protein before surgery (excluded above 10 mg/L) was the most predictive covariate (P < 0.001). The anti-inflammatory effect of dexamethasone increased as the inflammation risk increased (-0.689 mg/L per unit predicted peak C-reactive protein, P = 0.002 for interaction). No treatment-effect heterogeneity was detected for the main clinical outcome (P = 0.167 for interaction). Overall, risk predictions from a model of inflammation after cardiac surgery were associated with the degree of peak postoperative C-reactive protein reduction derived from dexamethasone treatment. Future work should explore the impact of this phenomenon on clinical outcomes in larger surgical populations.

Storage time of red blood cell concentrates and adverse outcomes after cardiac surgery: a cohort study.

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.

Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial.

CONTEXT: Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE: To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. INTERVENTION: Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00293592.

Prophylactic corticosteroids for cardiopulmonary bypass in adults.

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.