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Cerebral blood flow is tightly regulated by cerebrovascular autoregulation (CVA), and intraoperative impairment of CVA has been linked with perioperative neurocognitive disorders. We aim to assess whether impairment of CVA during major oncologic surgery is associated with delayed neurocognitive recovery (DNCR) postoperatively. We performed a secondary analysis of prospectively collected data. Patients were included if they had undergone complete pre- and postoperative neuropsychological assessments, continuous intraoperative measurement of CVA, and major oncologic surgery for visceral, urological, or gynecological cancer. Intraoperative CVA was measured using the time-correlation method based on near-infrared-spectroscopy, and DNCR was assessed with a neuropsychological test battery. A decline in cognitive function before hospital discharge compared with a preoperative baseline assessment was defined as DNCR. One hundred ninety-five patients were included in the analysis. The median age of the study population was 65 years (IQR: 60–68); 11 patients (5.6%) were female. Forty-one patients (21.0%) fulfilled the criteria for DNCR in the early postoperative period. We found a significant association between impaired intraoperative CVA and DNCR before hospital discharge (OR = 1.042 [95% CI: 1.005; 1.080], p = 0.028). The type of surgery (radical prostatectomy vs. other major oncologic surgery; OR = 0.269 [95% CI: 0.099; 0.728], p = 0.010) and premedication with midazolam (OR = 3.360 [95% CI: 1.039; 10.870], p = 0.043) were significantly associated with the occurrence of DNCR in the early postoperative period. Intraoperative impairment of CVA is associated with postoperative neurocognitive function early after oncologic surgery. Therefore, intraoperative monitoring of CVA may be a target for neuroprotective interventions. The initial studies were retrospectively registered with primary clinical trial registries recognized by the World Health Organization (ClinicalTrials.gov Identifiers: DRKS00010014, 21.03.2016 and NCT04101006, 24.07.2019).

BackgroundAnaesthesia and surgery can lead to cognitive decline, especially in the elderly. However, to date, the neurophysiological underpinnings of perioperative cognitive decline remain unknown.MethodsWe included male patients, who were 60 years or older scheduled for elective radical prostatectomy under general anaesthesia. We obtained neuropsychological (NP) tests as well as a visual match-to-sample working memory (WM) task with concomitant 62-channel scalp electroencephalography (EEG) before and after surgery.ResultsA total number of 26 patients completed neuropsychological assessments and EEG pre- and postoperatively. Behavioural performance declined in the neuropsychological assessment after anaesthesia (total recall; t-tests: t25 = -3.25, Bonferroni-corrected p = 0.015 d = -0.902), while WM performance showed a dissociation between match and mis-match accuracy (rmANOVA: match*session F1,25 = 3.866, p = 0.060). Distinct EEG signatures tracked behavioural performance: Better performance in the NP assessment was correlated with an increase of non-oscillatory (aperiodic) activity, reflecting increased cortical activity (cluster permutation tests: total recall r = 0.66, p = 0.029, learning slope r = 0.66, p = 0.015), while WM accuracy was tracked by distinct temporally-structured oscillatory theta/alpha (7 – 9 Hz), low beta (14 – 18 Hz) and high beta/gamma (34 – 38 Hz) activity (cluster permutation tests: matches: p < 0.001, mis-matches: p = 0.022).ConclusionsOscillatory and non-oscillatory (aperiodic) activity in perioperative scalp EEG recordings track distinct features of perioperative cognition. Aperiodic activity provides a novel electrophysiological biomarker to identify patients at risk for developing perioperative neurocognitive decline.

Background The aim of this study was to investigate the influence of mild therapeutic hypothermia (MTH) on the incidence of and recovery from acute kidney injury (AKI). Methods Patients who had undergone successful cardiopulmonary resuscitation (CPR) were included. Serum creatinine and cystatin C were measured at baseline, daily up to 5 days and at ICU discharge. AKI was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. MTH was applied for 24 h targeting a temperature of 33 °C. Neurological outcome was assessed with the Cerebral Performance Categories score at hospital discharge. Results 126 patients were included in the study; 73 patients (58%) developed AKI. Patients treated with MTH had a significantly lower incidence of AKI as compared to normothermia (NT) (44 vs. 69%; p = 0.004). Patients with less favourable neurological outcomes had a significantly higher rate of AKI, although when treated with MTH the occurrence of AKI was reduced (50 vs. 80%; p = 0.017). Furthermore, MTH treatment was accompanied by significantly lower creatinine levels on day 0–1 and at ICU discharge (day 0: 1.12 (0.90–1.29) vs. 1.29 (1.00–1.52) mg/dl; p = 0.016) and lower cystatin C levels on day 0–3 and at ICU discharge (day 0: 0.88 (0.77–1.10) vs. 1.29 (1.06–2.16) mg/l; p

To evaluate the prognostic potential of serum C-terminal provasopressin (CT-proAVP or Copeptin) and midregional pro-A-type natriuretic peptide (MR-proANP) to predict neurological outcome following resuscitation from cardiac arrest.In this prospective observational study, we employed novel ultra sensitive immunoassay technology to examine serial serum samples from 134 cardiac arrest patients. Patients were either allocated to mild therapeutic hypothermia using an endovascular device or normothermia. Serial blood samples were obtained from resuscitated cardiac arrest survivors during their first 7 days in an intensive care unit, and serum Copeptin and MR-proANP were measured. Cerebral function assessments were made using cerebral performance categorization (CPC) at discharge from hospital. Copeptin and MR-proANP data were analyzed using dichotomized CPC scores (1-2 versus 3-5).Sixty-nine patients (51%) had a poor outcome (CPC 3-5) at hospital discharge. MR-proANP and Copeptin peaked on day 1 (i.e. 0-24h) with the medians being 249.3pmol/L and 77.2pmol/L, respectively. In the first 48h maximum levels of MR-proANP and Copeptin showed an AUC in the ROC of 0.743 (95% CI: 0.658-0.828) and 0.677 (95% CI: 0.583-0.771). Binary logistic regression revealed MR-proANP and Copeptin within 48h after ROSC being significantly associated with functional outcome (p0.05). Copeptin within 48h was also associated with outcome in the hypothermia group (p0.05).Systemic levels of MR-proANP and Copeptin peak early in cardiac arrest patients in the 48h post-resuscitation period. MR-proANP and Copeptin were highly predictive for poor outcome in comatose resuscitated patients.

Background Microvesicles (MV) are extracellular vesicles known to be associated with cellular activation and inflammation. Hemofiltration is an effective blood purification technique for patients with renal failure and possibly also eliminates inflammatory mediators in the setting of sepsis. On the other hand, proinflammatory stimuli are induced by blood contacting the artificial membrane during extracorporeal blood purification. In chronic dialysis patients a systemic increase in MV has been described. The aim of the study was to investigate whether hemofilter passage of blood in continuous veno-venous hemofiltration (CVVH) alters MV composition and levels in critically ill patients with sepsis. Methods Pre- and postfilter bloods as well as ultrafiltrate samples from intensive care unit patients with severe sepsis were obtained during CVVH with regional citrate anticoagulation. MV subtypes in blood were analyzed by high-sensitivity flow cytometry. Additionally, tissue factor (TF) levels and MV-associated TF activities as well as MV activities were quantified. All parameters were corrected for hemoconcentration applied during CVVH. Results Twelve patients were analyzed. A significant increase in presumably mostly leukocyte-derived CD31+/CD41− MV (1.32 (1.09–1.93)-fold [median (25th–75th quartiles)], p = 0.021) was observed post- to prefilter, whereas platelet-derived MV as well as AnnexinV-binding MV were unaltered. Increments of AnnexinV+, CD42b+ and CD31+/CD41− MV post- to prefilter correlated with filtration fraction (FF) (all p

The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR.This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge.A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3-5) than in patients with good neurological outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p0.001; 24-48 h: 45 (24-77) vs. 23 (16-39) fmol/ml, p0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946). When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome prediction could be reached.SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results.

Purpose: Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT. Materials and Methods: A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected. Results: The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime. Conclusion: RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation. i 2014 S. Karger AG, Basel

PURPOSE Endothelial pathology is considered to play a key role in septic shock. Since endothelial-derived microvesicles (MV) are elevated in various diseases associated with endothelial pathology, they are considered surrogate markers of the endothelial state. By analyzing the signature of circulating MV with high-sensitivity flow cytometry (hsFC), we wanted to test the hypothesis whether endothelial-derived MV are increased in septic shock. METHODS MV in blood from healthy volunteers and patients with septic shock treated in a medical intensive care unit were quantified by hsFC, which has an improved detection limit of approximately 0.3 μm. RESULTS Patients with septic shock (n = 30) showed 3-fold higher levels of CD31+/CD41- MV (58.5 (26.4-101.2) [median (25th-75th percentile)] vs. 19.5 (12.8-25.4) MV/μL; P

Recent evidence suggests low-flow extracorporeal CO2 removal (ECCO2-R) systems as safe and promising adjunctive therapy to avoid endotracheal intubation and the related negative consequences in subjects with severe hypercapnic respiratory failure [1]. in high-flow extracorporeal membrane oxygenation systems heterogeneous coagulation disorders are a well-known complication. However, to date there is little evidence for the influence of pump-driven low-flow veno-venous ECCO2-R on the coagulation system.

About the effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation little data exists. From animal and human studies it is known that renal function might be impaired, which is not reflected by serum creatinine levels if creatinine production is reduced.

Endothelial dysfunction, activation and apoptosis are considered key features of sepsis. Microvesicles (MV) can be released by cells either constitutively, upon stimulation or apoptosis. Since endothelial derived microvesicles (EMV) were found to be elevated in diseases associated with endothelial activation and damage [1] they seem to be a promising diagnostic tool to assess the state of the endothelium.