Stress-related psychopathology after cardiac surgery and intensive care treatment

Objective: Cardiac surgery patients are at risk for psychopathology. Symptoms of post-traumatic stress disorder (PTSD) and depression occur in 10–20% of these patients and affect their quality of life. The aim of this study was to assess factors associated with psychopathology after cardiac surgery. Methods: We followed participants of the multi-center randomized clinical trial Dexamethasone for Cardiac Surgery (DECS), on a single, intravenous dose of dexamethasone (1 mg/kg) or placebo during cardiac surgery, using validated questionnaires to assess PTSD and depressive symptoms after 1.5 to 4 years, as well as childhood trauma, trait anxiety, pre-existing psychopathology, and substance use. Saliva was used for genotyping of the hypothalamic-pituitary-adrenal-axis (HPA axis) glucocorticoid receptor gene. Linear backward regression analysis was performed with these factors, including pre-specified interaction terms of dexamethasone with sex and genotype. Results: Complete data was available for 90% of cases (n = 1111). The model including trait anxiety and the [dexamethasone x female sex] interaction explained 57% of variance in PTSD symptoms (Model fit F (2;4.817)=643.043, p<.001; R2=0 0.57). Similar explained variance was seen for depressive symptoms, where age, trait anxiety and the [dexamethasone x female sex] interaction provided the optimal model (Model fit F (3;4.261)=435,960, p<.001; R2=0.58). Limitations: In this study psychopathology was assessed through validated questionnaires. Variability in data collection detail was present. Conclusion: This study suggests that the occurrence of psychopathology after cardiac surgery is influenced by higher trait anxiety. Female cardiac surgery patients may benefit from intra-operative dexamethasone administration

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial

INTRODUCTION: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. METHODS AND ANALYSIS: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. ETHICS AND DISSEMINATION: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05029050

Paroxysmal autonomic instability with dystonia in a patient with tuberculous meningitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report describes an extremely rare combination of paroxysmal autonomic instability with dystonia and tuberculous meningitis. Paroxysmal autonomic instability with dystonia is normally associated with severe traumatic brain injury.</p> <p>Case presentation</p> <p>A 69-year-old man of Indonesian descent was initially suspected of having a community-acquired pneumonia, which was seen on chest X-ray and computed tomography of the chest. However, a bronchoscopy showed no abnormalities. He was treated with amoxicillin-clavulanic acid in combination with ciprofloxacin. However, nine days after admission he was disorientated and complained of headache. Neurological examination revealed no further abnormalities. A lumbar puncture revealed no evidence of meningitis. He was then transferred to our hospital. At that time, initial cultures of bronchial fluid for <it>Mycobacterium tuberculosis </it>turned positive, as well as polymerase chain reaction for <it>Mycobacterium tuberculosis</it>. Later, during his stay in our intensive care unit, he developed periods with hypertension, sinus tachycardia, excessive transpiration, decreased oxygen saturation with tachypnea, pink foamy sputum, and high fever. This constellation of symptoms was accompanied by dystonia in the first days. These episodes lasted approximately 30 minutes and improved after administration of morphine, benzodiazepines or clonidine. Magnetic resonance imaging showed an abnormal signal in the region of the hippocampus, thalamus and the anterior parts of the lentiform nucleus and caudate nucleus.</p> <p>Conclusions</p> <p>In patients with (tuberculous) meningitis and episodes of extreme hypertension and fever, paroxysmal autonomic instability with dystonia should be considered.</p

The association between frailty and MRI features of cerebral small vessel disease.

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Advancing specificity in delirium: The delirium subtyping initiative

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

BACKGROUND: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD). METHODS: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery. Diffusion kurtosis imaging metrics were obtained preoperatively, after 3 and 12 months postoperatively. We calculated fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and free water (FW). A structured and validated delirium assessment was performed twice daily. RESULTS: Of 325 patients, 53 patients developed POD (16.3%). Preoperative global MD (standardized beta 0.27 [95% confidence interval [CI] 0.21-0.32] p < 0.001) was higher in patients with POD. Preoperative global MK (-0.07 [95% CI -0.11 to (-0.04)] p < 0.001) and FA (0.07 [95% CI -0.10 to (-0.04)] p < 0.001) were lower. When correcting for baseline diffusion, postoperative MD was lower after 3 months (0.05 [95% CI -0.08 to (-0.03)] p < 0.001; n = 183) and higher after 12 months (0.28 [95% CI 0.20-0.35] p < 0.001; n = 45) among patients with POD. DISCUSSION: Preoperative structural disconnectivity was associated with POD. POD might lead to white matter depletion 3 and 12 months after surgery.The project ‘Biomarker Development for Postoperative Cognitive Impairment in the Elderly’ (BioCog) was supported by the European Community’s FP7 under grant agreement n. 602461

Delirium detection using relative delta power based on 1 minute single-channel EEG : a multicentre study

Background: Delirium is frequently unrecognised. EEG shows slower frequencies (i.e. below 4 Hz) during delirium, which might be useful in improving delirium recognition. We studied the discriminative performance of a brief single-channel EEG recording for delirium detection in an independent cohort of patients. Methods: In this prospective, multicentre study, postoperative patients aged ≥60 yr were included (n=159). Before operation and during the first 3 postoperative days, patients underwent a 5-min EEG recording, followed by a video-recorded standardised cognitive assessment. Two or, in case of disagreement, three delirium experts classified each postoperative day based on the video and chart review. Relative delta power (1–4 Hz) was based on 1-min artifact-free EEG. The diagnostic value of the relative delta power was evaluated by the area under the receiver operating characteristic curve (AUROC), using the expert classification as the gold standard. Results: Experts classified 84 (23.3%) postoperative days as either delirium or possible delirium, and 276 (76.7%) non-delirium days. The AUROC of the relative EEG delta power was 0.75 [95% confidence interval (CI) 0.69–0.82]. Exploratory analysis showed that relative power from 1 to 6 Hz had significantly higher AUROC (0.78, 95% CI 0.72–0.84, P=0.014). Conclusions: Delirium/possible delirium can be detected in older postoperative patients based on a single-channel EEG recording that can be automatically analysed. This objective detection method with a continuous scale instead of a dichotomised outcome is a promising approach for routine detection of delirium. Clinical trial registration: NCT02404181

Delirium detection using relative delta power based on 1 minute single-channel EEG : a multicentre study

Background: Delirium is frequently unrecognised. EEG shows slower frequencies (i.e. below 4 Hz) during delirium, which might be useful in improving delirium recognition. We studied the discriminative performance of a brief single-channel EEG recording for delirium detection in an independent cohort of patients. Methods: In this prospective, multicentre study, postoperative patients aged ≥60 yr were included (n=159). Before operation and during the first 3 postoperative days, patients underwent a 5-min EEG recording, followed by a video-recorded standardised cognitive assessment. Two or, in case of disagreement, three delirium experts classified each postoperative day based on the video and chart review. Relative delta power (1–4 Hz) was based on 1-min artifact-free EEG. The diagnostic value of the relative delta power was evaluated by the area under the receiver operating characteristic curve (AUROC), using the expert classification as the gold standard. Results: Experts classified 84 (23.3%) postoperative days as either delirium or possible delirium, and 276 (76.7%) non-delirium days. The AUROC of the relative EEG delta power was 0.75 [95% confidence interval (CI) 0.69–0.82]. Exploratory analysis showed that relative power from 1 to 6 Hz had significantly higher AUROC (0.78, 95% CI 0.72–0.84, P=0.014). Conclusions: Delirium/possible delirium can be detected in older postoperative patients based on a single-channel EEG recording that can be automatically analysed. This objective detection method with a continuous scale instead of a dichotomised outcome is a promising approach for routine detection of delirium. Clinical trial registration: NCT02404181