Thomas H. Ottens

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.

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.

Association between delirium and cognitive change after cardiac surgery

Background Previous studies provide inconsistent data on whether postoperative delirium (POD) is a risk factor for postoperative cognitive decline (POCD). We thus investigated the relationship between POD and cognitive change after cardiac surgery and assessed the relationship between preoperative cognitive domain scores and POD. Methods Postoperative delirium was assessed with the Confusion Assessment Method (CAM) adapted for the intensive care unit and the conventional CAM accompanied by chart review. Cognitive function was assessed with a neuropsychological test battery before elective cardiac surgery and 1 month and 1 yr afterwards. Cognitive change was calculated using the Reliable Change Index (RCI). Multiple linear regression was used to adjust for confounding. Results Of the 184 patients who completed baseline assessment, 23 (12.5%) developed POD. At 1 month, the decline in cognitive performance was worse in patients with POD [median composite RCI -1.00, interquartile range (IQR) -1.67 to 0.28] than in patients without POD (RCI -0.04, IQR -0.70 to 0.63, P =0.02). At 1 yr, both groups showed cognitive improvement on average compared with baseline (POD patients median composite RCI 0.25, IQR -0.42 to 1.31, vs non-POD patients RCI 0.92, IQR 0.18-1.53; P =0.08). Correction for differences in age and level of education did not change the results. Patients with POD performed less well than patients without POD on the preoperative Trailmaking test part A ( P =0.03). Conclusions Postoperative delirium is independently associated with cognitive decline 1 month after surgery, but cognitive performance generally recovers in 1 yr. Patients with a predisposition to POD can be identified before surgery by worse performance in an attention task. Clinical trial registration NCT00293592.

TEMPORARY REMOVAL: Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery—2018

Abstract Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non‐cardiac surgery. Other than the inclusion of non‐surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face‐to‐face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM‐5) and National Institute for Aging and the Alzheimer Association (NIA‐AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM‐5 nomenclature. The working group recommends that ‘perioperative neurocognitive disorders’ be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

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.

Brain volume and cognitive function in patients with revascularized coronary artery disease

BACKGROUND The pathogenesis of cognitive dysfunction in patients with CAD remains unclear. CAD is associated with brain atrophy and specific lesions. Detailed knowledge about the association of brain volume measured with MRI, and cognitive function in patients with CAD is lacking. We therefore investigated brain volume and cognitive function in patients with revascularized coronary artery disease (CAD), and controls without CAD. METHODS Brain MRI scans and cognitive tests from patients with CAD were compared with data from control subjects without CAD. Cognitive performance was assessed with the Rey Auditory Verbal Learning (short term memory) and Trailmaking (divided attention) tests. Multivariable regression analysis was used to study associations between CAD, brain volume and cognitive function. RESULTS A total of 102 patients with CAD and 48 control subjects were included. Level of education and age were comparable between the groups. Compared with controls, patients with CAD had smaller total brain volume (expressed as fraction of intracranial volume) [%ICV, mean (SD), 0.78 (0.03) vs 0.80 (0.02), P=0.001] and larger volume of non-ventricular cerebrospinal fluid [%ICV, median (IQR) 0.19 (0.18 to 0.21) vs 0.18 (0.17 to 0.20), P=0.001]. Patients in the CAD group had poorer cognitive function [mean (SD) Z-score -0.16 (0.72) vs 0.41 (0.69), P<0.01]. Multivariable regression showed that CAD, higher age, lower level of education and greater cerebrospinal fluid volume were independent predictors of poorer cognitive function. CONCLUSIONS CAD patients had a smaller total brain volume and poorer cognitive function than controls. Greater volume of cerebrospinal fluid was an independent predictor of poorer cognitive function.

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.

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.