Joost M. van der Maaten

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.

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.

The effect of midazolam at two plasma concentrations on hemodynamics and sufentanil requirement in coronary artery surgery

OBJECTIVES In this study, the hemodynamics and sufentanil requirement were compared at two midazolam target plasma concentrations in patients undergoing coronary artery bypass grafting (CABG). DESIGN Prospective, randomized study. SETTING University hospital, single institution. PARTICIPANTS Patients undergoing CABG. INTERVENTIONS Patients were randomly assigned to receive midazolam at a target plasma concentration of 150 ng/mL (group 1; n = 10) or 300 ng/mL (group 2; n = 10). Sufentanil infusion was titrated to maintain hemodynamic stability, defined as mean arterial pressure within 15% of baseline values. All patients received preoperative beta-blocking agents. Arterial blood samples of midazolam and sufentanil were analyzed by high-performance liquid chromatography and radioimmunoassay, respectively. MEASUREMENTS AND MAIN RESULTS The mean dose of sufentanil (7.5 +/- 1.7 microgram/kg in group 1 v 7.2 +/- 2.5 micrograms/kg in group 2) did not differ. There were no significant differences in hemodynamics between the groups in the period before or after cardiopulmonary bypass (CPB). Before CPB, in two patients in each group, hypertension was controlled with sufentanil only. One patient in group 1 required a vasodilator in addition to sufentanil. No ischemic events occurred before CPB. After CPB, one patient in group 2 required a vasodilator to control hypertension. Two patients in group 2 required treatment with nitroglycerin for myocardial ischemia. Stable plasma concentrations of sufentanil and midazolam were obtained during and after CPB. The midazolam infusion was continued in both groups at a rate of 1.25 micrograms/kg/min during the first 4 postoperative hours. The time to awakening did not differ between the groups (100 +/- 58 minutes in group 1 v 173 +/- 147 minutes in group 2) nor did the plasma concentrations of midazolam (96 +/- 28 ng/mL v 108 +/- 42 ng/mL) at the time of awakening. Intraoperative awareness was not reported. CONCLUSION In patients undergoing CABG, good hemodynamic control with a similar incidence of hemodynamic interventions was observed at midazolam target plasma concentrations of 150 and 300 ng/mL when coadministered with sufentanil. The sufentanil requirement was identical in both groups. This study suggests that a midazolam plasma concentration of 150 ng/mL is sufficient to provide satisfactory hemodynamic control and to avoid intraoperative awareness.

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.

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 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.

Risk factors and prognosis of postpericardiotomy syndrome in patients undergoing valve surgery

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.

Computer-guided normal-low versus normal-high potassium control after cardiac surgery: No impact on atrial fibrillation or atrial flutter.

INTRODUCTION This study was designed to determine the effect of 2 different potassium regulation strategies with different targets (within the reference range) on atrial fibrillation (AF) or atrial flutter (AFL) in a cohort of intensive care unit patients after cardiac surgery. METHODS The GRIP-COMPASS study was a prospective double-blinded interventional study in 910 patients after cardiac surgery (coronary artery bypass grafting and/or valvular surgery). Patients were assigned to either the normal-low potassium target (nLP group, 4.0 mmol/L) or the normal-high potassium target (nHP group, 4.5 mmol/L) in alternating blocks of 50 patients. Potassium levels were regulated using a validated computer-assisted potassium replacement protocol (GRIP-II). The primary end point was the incidence of AF/AFL on a 12-lead electrocardiogram during the first postoperative week. RESULTS Of the 910 patients, 447 were assigned to the nLP group; and 463, to the nHP group, with no baseline differences between the 2 groups. The mean daily administered dose of potassium was 30 ± 23 mmol (nLP) versus 52 ± 27 mmol (nHP) (P < .001), which resulted in mean intensive care unit potassium concentration of 4.22 ± 0.36 mmol/L and 4.33 ± 0.34 mmol/L, respectively (P < .001). The incidence of AF/AFL after cardiac surgery did not differ: 38% in the nLP group and 41% in the nHP group. Also in several subgroups (eg, patients not known with prior AF/AFL or with valve surgery), there were no differences. CONCLUSIONS There were no differences in incidence of AF/AFL with 2 potassium regulation strategies with different potassium targets and different amounts of potassium administered in patients after cardiac surgery.

Adaptive servo‐ventilation in heart failure associated with central sleep apnoea. Is it effective in both acute and chronic setting?

Chronic heart failure (CHF) is a highly prevalent disease associated with repeated hospitalisations, and high morbidity and mortality. Patients with CHF often have sleep-disordered breathing (SDB) characterized by either obstructive sleep apnoea (OSA) or central sleep apnoea (CSA). Due to the fact that in these patients the classic breathing Cheyne2Stokes respiration (CSR) often occurs, CSA is called CSR-CSA. Both types, OSA and CSR-CSA, contribute to the progression of CHF and are associated with an increased mortality in patients with CHF. When using the apnoea2hyperpnoea index of .15/h for the diagnosis of SDB, the reported prevalence is 50% in patients with CHF. Although the pathophysiologies of OSA and CSR-CSA are different, the continuous exposure of the heart to nocturnal stress by repeated episodes of apnoea, hypoxia, and arousal from sleep result in a cascade of phenomena including activation of the sympathetic nervous system leading to increased pre-load and afterload and impaired cardiac contractility. Cheyne2Stokes respiration-central sleep apnoea is more common in heart failure patients, but mixed patterns exist. However, OSA may expose the failing heart to greater stress than CSR-CSA because of a different pathophysiology. In short, the generation of negative intrathoracic pressure during obstructive apnoea increases left ventricular (LV) transmural pressure and afterload. Increased venous return contributes to right ventricular distension compromising LV filling by displacement of the interventricular septum during diastole. This results in reduced stroke volume and cardiac output. Cheyne2Stokes respiration-central sleep apnoea is associated with chronic hypocapnia which is related to stimulation of pulmonary vagal irritant receptors by elevated LV filling pressures and volumes. The pulmonary congestion in heart failure contributes to augmented CO2-chemoreceptor sensitivity resulting in chronic hyperventilation which leads by definition to a reduction in PaCO2. This may bring the PaCO2 below the apnoeic threshold resulting in an apnoea. Before starting specific therapy for SDB in patients with CHF, pharmacological treatment for CHF should be optimized. Improvements in cardiac performance have been associated with an improvement of CSR-CSA suggesting that congestive heart failure is a contributing factor for breathing abnormalities. Among the many therapies that have been shown to improve the severity of SDB, only positive pressure ventilation is associated with an improvement in cardiac function. Sleep-disordered breathing can be effectively treated with various forms of positive-pressure ventilation therapy. Adaptive Servo-Ventilation (ASV) has been shown to be more effective than continuous positive airway pressure (CPAP) in reducing CSR-CSA in patients with CHF, while Philippe et al. showed that ASV led to better compliance. Other studies showed improvements in laboratory data (decreased N-terminal prohormone of brain natriuretic peptide), clinical parameters (decreased apnoea2 hypopnoea index, improved daytime sleepiness, improved quality of life), and functional parameters (LV ejection fraction). –11 However, the mechanism of how ASV improves cardiac function in CHF remains unclear. In the current issue of the European Journal of Heart Failure, Haruki et al. evaluate in CHF patients with CSAwhether the impact of ASV on left chamber geometry and function differs in the acute and chronic setting. For the acute setting (30 min after the initiation of ASV therapy) they demonstrated a significant increase in stroke volume and cardiac output at a lower heart rate in conjunction with a reduction of systemic vascular resistance (SVR). Left ventricular end-diastolic volume or echocardiographic parameters of diastolic function including E/e′ remained unchanged. The authors also investigated the impact of chronic ASV therapy on cardiac performance and geometry. Of the 30 patients included in this study, 15 patients tolerated ASV therapy and were compared with 11 patients in the withdrawal group due to poor tolerance (four patients were lost to follow-up). These patients were included in the chronic study and were followed up for a period

Recurrent Mitral Stenosis and an Intra-Atrial Mitral Valve Mass 40 Years After Tubbs Mitral Commissurotomy

Figure 1. (A) Transesophageal echocardiography showed a thickenedmitral valve with an echogenic mass (‘‘band’’) extending from the posterior leaflet to the interatrial septum. (B and C) Intraoperative photographs of the fibrous, thickened, and stenoticmitral valve with a fibrous band extending from segment P1/P2 to the interatrial septum. (D)Microscopic histopathologic photograph of the band and its attachment to the thickened posterior leaflet.