Jan M. Dieleman

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.

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

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.

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.

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.

Intraoperative hypotension and delirium after on-pump cardiac surgery

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 <60 mm Hg threshold was 1.04 (99% confidence interval: 0.99-1.10) for each 1000 mm Hg(2) min(2) AUC(2) increase. IOH, as defined according to the other three definitions, was not associated with postoperative delirium either. Deep and prolonged IOH seemed to increase the risk of delirium, but this was not statistically significant. CONCLUSIONS Independent of the applied definition, IOH was not associated with the occurrence of delirium after cardiac surgery.

Dexamethasone for the prevention of postoperative atrial fibrillation

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 (1mg/kg) or placebo treatment in 4494 adult patients undergoing cardiac surgery. AF was defined by the occurrence of any reported AF within 30days 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.

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.

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.

Presence of coronary collaterals is associated with a decreased incidence of cognitive decline after coronary artery bypass surgery

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 outcome at both 3 months (odds ratio (OR) 0.30; 95% confidence interval (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.

Intraoperative High-Dose Dexamethasone in Cardiac Surgery and the Risk of Rethoracotomy

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 < 0.001). CONCLUSIONS Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk.