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Papers by Jan Dieleman
Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients
Journal of Affective Disorders, 2016
Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime s... more 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. 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. 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. The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. 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.
Objective: Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidi... more 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. #
The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission
Critical Care Medicine, 2015
Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder ... more 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. Follow-up study of a randomized clinical trial. Five Dutch heart centers. Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. 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. 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
The Annals of Thoracic Surgery, 2015
Cardiac surgery with the use of cardiopulmonary bypass is associated with a systemic inflammatory... more 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. 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. 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). Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk.
Journal of the American Society of Nephrology : JASN, Jan 7, 2015
Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postope... more 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 th...
Long-term neurocognitive deficit, cardiopulmonary bypass and microsphere injection in the rat
Low incidence of early postoperative cerebral edema after coronary artery bypass grafting
Journal of Cardiothoracic and Vascular Anesthesia, 2014
Using magnetic resonance imaging, the authors studied the influence of a single high dose of intr... more 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. 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. A large university hospital in The Netherlands. Twenty adult patients who underwent CABG with cardiopulmonary bypass (CPB) between March and November 2011. Participants received a single intravenous dose of dexamethasone, 1 mg/kg, or placebo, at induction of anesthesia. 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). 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.
Critical Care, 2015
Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are freque... more 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.
Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and posto... more 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.
Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial
Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characteri... more 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.
Life Sciences, 2006
Neurologic and neurocognitive complications after cardiac surgery with cardiopulmonary bypass (CP... more 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-α 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 longterm 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.
Coronary Collaterals are Associated with Less Cognitive Decline after Coronary Artery Bypass Grafting
Journal of Neurosurgical Anesthesiology, 2006
The Effects of Anesthesia on Cognitive Performance in Rats Exposed to Chronic Social Stress
Journal of Neurosurgical Anesthesiology, 2004
The Effects of C1-esterase Inhibition on Cerebral Immune Activation in a Model of Cerebral Embolization in the Rat
Journal of Neurosurgical Anesthesiology, 2004
The Effect of Simultaneous Cardiopulmonary Bypass and Cerebral Embolization on Neurocognitive Outcome in the Rat
Journal of Neurosurgical Anesthesiology, 2004
Journal of Neuroscience Methods, 2009
Background: Cerebral embolization models have been hindered by the fact that delivery is predomin... more 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 microembolization. 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.
Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients
Journal of Affective Disorders, 2016
Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime s... more 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. 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. 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. The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; vulnerability for psychopathology development after cardiac surgery.
Objective: Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidi... more 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. #
The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission
Critical Care Medicine, 2015
Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder ... more 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. Follow-up study of a randomized clinical trial. Five Dutch heart centers. Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology. 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
The Annals of Thoracic Surgery, 2015
Cardiac surgery with the use of cardiopulmonary bypass is associated with a systemic inflammatory... more 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. 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. 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk.
Journal of the American Society of Nephrology : JASN, Jan 7, 2015
Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postope... more 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 th...
Long-term neurocognitive deficit, cardiopulmonary bypass and microsphere injection in the rat
Low incidence of early postoperative cerebral edema after coronary artery bypass grafting
Journal of Cardiothoracic and Vascular Anesthesia, 2014
Using magnetic resonance imaging, the authors studied the influence of a single high dose of intr... more 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. 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. A large university hospital in The Netherlands. Twenty adult patients who underwent CABG with cardiopulmonary bypass (CPB) between March and November 2011. Participants received a single intravenous dose of dexamethasone, 1 mg/kg, or placebo, at induction of anesthesia. 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). 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.
Critical Care, 2015
Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are freque... more 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.
Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and posto... more 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.
Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial
Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characteri... more 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.
Life Sciences, 2006
Neurologic and neurocognitive complications after cardiac surgery with cardiopulmonary bypass (CP... more 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-α 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 longterm 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.
Coronary Collaterals are Associated with Less Cognitive Decline after Coronary Artery Bypass Grafting
Journal of Neurosurgical Anesthesiology, 2006
The Effects of Anesthesia on Cognitive Performance in Rats Exposed to Chronic Social Stress
Journal of Neurosurgical Anesthesiology, 2004
The Effects of C1-esterase Inhibition on Cerebral Immune Activation in a Model of Cerebral Embolization in the Rat
Journal of Neurosurgical Anesthesiology, 2004
The Effect of Simultaneous Cardiopulmonary Bypass and Cerebral Embolization on Neurocognitive Outcome in the Rat
Journal of Neurosurgical Anesthesiology, 2004
Journal of Neuroscience Methods, 2009
Background: Cerebral embolization models have been hindered by the fact that delivery is predomin... more 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 microembolization. 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.