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Nociception monitoring devices are designed to estimate nociception during general anaesthesia. We evaluated the predictive accuracy of heart rate and three nociception indices to predict postoperative pain before emergence from general anaesthesia.In patients undergoing trauma or orthopaedic surgery, HR, Surgical Pleth Index® (SPI), Pupillary Pain Index® (PPI), and Nociception Level® (NOL) were simultaneously recorded for 5 min after the end of surgery but before return of consciousness. After admission to the recovery room, pain scores were assessed regularly for 2 h. HR, SPI, PPI, and NOL were analysed for their predictive accuracy of postoperative pain and opioid consumption with assessment of area under the receiver operating characteristic (AUC) curves, Spearman rank-correlation coefficient, and regression modelling.Data for 60 subjects were analysed. The AUC (95% confidence interval [95% CI]) of the predictive accuracy for moderate-to-severe postoperative pain differed between nociception indices (HR=0.46 [0.29-0.64], P=0.671; SPI=0.46 [0.31-0.61], P=0.621; PPI=0.52 [0.36-0.68], P=0.770; NOL=0.66 [0.51-0.81], P=0.038). In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining NOL values with ASA physical status and information about use of regional anaesthesia (AUC=0.83 [0.72-0.94], P0.001).Heart rate, Surgical Pleth Index, Pupillary Pain Index, and Nociception Level measured before emergence from general anaesthesia do not yet have sufficient diagnostic accuracy for prediction of postoperative pain.NCT05063227.

BACKGROUND: In the absence of lung biopsy there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients that rely on clinical signs, underlying conditions, radiological features, and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e. requiring treatment) and colonization in critically ill patients. In addition, we determined their diagnostic accuracy to detect proven IPA.METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions that were treated in a German quarternary care hospital between 2005 and 2020. Four different diagnostic algorithms were applied to all patients. We compared agreement among the four algorithms to discriminate probable IPA from colonization. In a subgroup of patients with lung tissue histopathology available we determined the sensitivity and specificity of the single algorithms to detect proven IPA. RESULTS: A total number of 684 critically ill patients were included. The mean age of the study population was 63 years (IQR 52-73). Sixty-nine percent (n=472) were medical and 31% (n=212) were surgical ICU patients. Overall, 79% (n=543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n=29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen’s kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue 40% (n=34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]).CONCLUSIONS:In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. The 2021 EORTC/MSGERC ICU working group criteria achieved the highest specificity and sensitivity to detect proven IPA. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonization in critically ill patients remains challenging and may require further optimization.

ZusammenfassungDie Leitlinien des European Resuscitation Council (ERC), die 2021 veröffentlicht wurden, empfehlen eine aktive Temperaturkontrolle zwischen 32 und 36 °C für alle erwachsenen Patient:innen, die nach Wiedererlangen des Spontankreislaufs nach prä- oder innerklinischer Reanimation das Bewusstsein nicht wiedererlangen.Wenige Wochen nach Veröffentlichung der Leitlinien 2021 wurde die TTM2-Studie publiziert, in der kein signifikanter Unterschied im Hinblick auf das Überleben oder das funktionelle Outcome nach sechs Monaten zwischen einer Zieltemperatur von 33 °C und einer Fiebervermeidung nach außerklinischem Herz-Kreislauf-Stillstand festgestellt worden war.Als Antwort auf die zusätzliche Evidenz durch die TTM2-Studie nahm die Advanced Life Support Task Force des International Liaison Committee on Resuscitation (ILCOR) eine Reevaluation der aktuellen Datenlage vor, die in einer überarbeiteten Empfehlung zur Temperaturkontrolle nach Herz-Kreislauf-Stillstand bei Erwachsenen resultierte. Der aktuelle Artikel fasst die aktualisierten Leitlinien zusammen und diskutiert kritische Aspekte der neuen Empfehlungen.

The intraoperative dosing of opioids is a challenge in routine anesthesia as the potential effects of intraoperative overdosing and underdosing are not completely understood. In recent years an increasing number of monitors were approved, which were developed for the detection of intraoperative nociception and therefore should enable a better control of opioid titration. The nociception monitoring devices use either continuous hemodynamic, galvanic or thermal biosignals reflecting the balance between parasympathetic and sympathetic activity, measure the pupil dilatation reflex or the nociceptive flexor reflex as a reflexive response to application of standardized nociceptive stimulation. This review article presents the currently available nociception monitors. Most of these monitoring devices detect nociceptive stimulations with higher sensitivity and specificity than changes in heart rate, blood pressure or sedation depth monitoring devices. There are only few studies on the effect of opioid titration guided by nociception monitoring and the possible postoperative benefits of these devices. All nociception monitoring techniques are subject to specific limitations either due to perioperative confounders (e.g. hypovolemia) or special accompanying medical conditions (e.g. muscle relaxation). There is an ongoing discussion about the clinical relevance of nociceptive stimulation in general anesthesia and the effect on patient outcome. Initial results for individual monitor systems show a reduction in opioid consumption and in postoperative pain level. Nevertheless, current evidence does not enable the routine use of nociception monitoring devices to be recommended as a clear beneficial effect on long-term outcome has not yet been proven.

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).

COVID-19-associated ARDS (C-ARDS) is mentioned to express higher analgosedation needs, in comparison to ARDS of other etiologies. The objective of this monocentric retrospective cohort study was to compare the analgosedation needs between C-ARDS and non-COVID-19 ARDS (non-C-ARDS) on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Data were collected from the electronic medical records of all adult patients treated with C-ARDS in our Department of Intensive Care Medicine between March 2020 and April 2022. The control group included patients treated with non-C-ARDS between the years 2009 and 2020. A sedation sum score was created in order to describe the overall analgosedation needs. A total of 115 (31.5%) patients with C-ARDS and 250 (68.5%) with non-C-ARDS requiring VV-ECMO therapy were included in the study. The sedation sum score was significantly higher in the C-ARDS group (p < 0.001). COVID-19 was significantly associated with analgosedation in the univariable analysis. By contrast, the multivariable model did not show a significant association between COVID-19 and the sum score. The year of VV-ECMO support, BMI, SAPS II and prone positioning were significantly associated with sedation needs. The potential impact of COVID-19 remains unclear, and further studies are warranted in order to evaluate specific disease characteristics linked with analgesia and sedation.

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 Diastolic dysfunction is a risk factor for postoperative major cardiovascular events. During anesthesia, patients with diastolic dysfunction might experience impaired hemodynamic function and worsening of diastolic function, which in turn, might be associated with a higher incidence of postoperative complications.We aimed to investigate whether patients with diastolic dysfunction require higher doses of norepinephrine during general anesthesia. Furthermore, we aimed to examine the association between the grade of diastolic dysfunction and the E/e' ratio during anesthesia. A high E/e' ratio corresponds to elevated filling pressures and is an important measure of impaired diastolic function. METHODS We conducted a prospective observational cohort study at a German university hospital from February 2017 to September 2018. Patients aged ≥60 years and undergoing general anesthesia (ie, propofol and sevoflurane) for elective noncardiac surgery were enrolled. Exclusion: mitral valve disease, atrial fibrillation, and implanted mechanical device.The primary outcome parameter was the administered dose of norepinephrine within 30 minutes after anesthesia induction (μg·kg-1 30 min-1). The secondary outcome parameter was the change of Doppler echocardiographic E/e' from ECHO1 (baseline) to ECHO2 (anesthesia). Linear models and linear mixed models were used for statistical evaluation. RESULTS A total of 247 patients were enrolled, and 200 patients (75 female) were included in the final analysis. Diastolic dysfunction at baseline was not associated with a higher dose of norepinephrine during anesthesia (P = .6953). The grade of diastolic dysfunction at baseline was associated with a decrease of the E/e' ratio during anesthesia (P < .001). CONCLUSIONS We did not find evidence for an association between diastolic dysfunction and impaired hemodynamic function, as expressed by high vasopressor support during anesthesia. Additionally, our findings suggest that diastolic function, as expressed by the E/e' ratio, does not worsen during anesthesia.

Purpose Surgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We hypothesized that robot-assisted radical prostatectomy with head-down tilt causes impairment of cerebral autoregulation compared with open retropubic radical prostatectomy in the supine position. Methods Patients scheduled for elective radical prostatectomy were included at a tertiary care prostate cancer clinic. Continuous monitoring of the cerebral autoregulation was performed using the correlation method. Based on measurements of cerebral oxygenation with near-infrared spectroscopy and invasive mean arterial blood pressure (MAP), a moving correlation coefficient was calculated to obtain the cerebral oxygenation index as an indicator of cerebral autoregulation. Cerebral autoregulation was measured continuously from induction until recovery from anesthesia. Results There was no significant difference in cerebral autoregulation between robot-assisted and open retropubic radical prostatectomy during induction (p = 0.089), intraoperatively (p = 0.162), and during recovery from anesthesia (p = 0.620). Age (B = 0.311 [95% CI 0.039; 0.583], p = 0.025) and a higher difference between baseline MAP and intraoperative MAP (B = 0.200 [95% CI 0.073; 0.327], p = 0.002) were associated with impaired cerebral autoregulation, whereas surgical technique was not (B = 3.339 [95% CI 1.275; 7.952], p = 0.155). Conclusion Compared with open radical prostatectomy in the supine position, robot-assisted surgery in the extreme Trendelenburg position with capnoperitoneum did not lead to an impairment of cerebral autoregulation during the perioperative period in our study population. Trial registration number: DRKS00010014, date of registration: 21.03.2016, retrospectively registered.

OBJECTIVE To assess the effects of robot-assisted radical prostatectomy in the Trendelenburg position on postoperative neurocognitive outcomes this study compared cognitive function between patients who underwent robot-assisted radical prostatectomy and those who underwent open retropubic radical prostatectomy. METHODS Objective evaluations of pre- and postoperative cognitive function were performed upon admission and before hospital discharge, by using a neuropsychological test battery. We collected self-reported data on cognitive failures at 3 months postoperatively. Binary logistic regression analysis was used to assess the effects of surgical technique on postoperative cognitive performance. RESULTS The pre- and postoperative neuropsychological assessments were completed by 367 patients with a median age of 64 years (range 44-76). The incidence of postoperative cognitive dysfunction was 23.9% after robot-assisted (39/165) and 22.3% after open radical prostatectomy (45/202). There was no significant difference in postoperative cognitive function during the early postoperative period (P = 0.758) and self-reported cognitive failures at 3 months (P = 0.303) between robot-assisted and open surgery. Surgical technique was not associated with early postoperative cognitive dysfunction in multivariable analysis (OR 1.012, 95%CI: 0.608-1.685, P = 0.962). CONCLUSION Compared with open surgery in supine position postoperative neurocognitive disorders do not occur more frequently after robot-assisted radical prostatectomy in the extreme Trendelenburg position. Based on these findings potential adverse effects on cognitive function do not have to be considered in the choice of surgical approach for radical prostatectomy.

The current guidelines of the European Resuscitation Council recommend targeted temperature management to improve functional neurological outcome in comatose survivors after cardiac arrest. With the pathophysiological background of hypothermia-induced neuroprotection for prevention of hypoxic-ischemic encephalopathy, targeted temperature management is a key measure and represents a central aspect in postresuscitation care.In the 2021 guidelines the application of targeted temperature management in postresuscitation care has been recommended for all rhythms and irrespective of the location of cardiac arrest. Targeted temperature management is advocated for adult patients who remain unresponsive following return of spontaneous circulation (ROSC) after either out-of-hospital cardiac arrest or in-hospital cardiac arrest. The body temperature should be maintained at a constant value between 32 °C and 36 °C for at least 24 h. To avoid rebound hyperthermia, fever following targeted temperature management, defined as a temperature above 37.7 °C, should be prevented and treated for at least 72 h after ROSC in persistently comatose patients. The routine use of prehospital cooling by rapid infusion of large volumes of cold i.v. fluid immediately after ROSC is not recommended.Based on a systematic review of the current literature, this article summarizes the results of randomized trials and new findings on targeted temperature management in comatose adult patients after cardiac arrest. The review has a particular focus on the most recent evidence regarding the optimum range of target temperatures. Furthermore, recent data on preclinical management, different patient populations, the duration of targeted temperature management, cooling methods and rebound hyperthermia are discussed.The impact of targeted temperature management on neurological outcome after cardiac arrest has been a matter of controversy. Despite contradictory results and heterogeneity of study designs, the current evidence supports the relevance and the necessity of strict temperature control in postresuscitation care for neuroprotection and improvement in functional neurological outcomes.In den aktuellen Leitlinien des European Resuscitation Council wird das gezielte Temperaturmanagement zur Verbesserung des funktionell-neurologischen Outcome bei komatösen Patient:innen nach Wiedereinsetzten des Spontankreislaufs empfohlen. Mit dem pathophysiologischen Hintergrund der hypothermieinduzierten Neuroprotektion zur Prävention einer hypoxisch-ischämischen Enzephalopathie stellt das gezielte Temperaturmanagement einen zentralen Stellenwert in der Postreanimationsbehandlung dar.Basierend auf einer selektiven Literaturrecherche zeigt dieser Leitthemenbeitrag aktuelle Ergebnisse randomisierter Studien und Erkenntnisse bezüglich des optimalen Temperaturmanagements bei komatösen Patienten nach erfolgreicher Reanimation auf. Besonderer Fokus liegt auf neuer Evidenz hinsichtlich des angestrebten Temperaturzielbereichs. Weiterhin werden Entwicklungen und Änderungen hinsichtlich des präklinischen Managements, der Berücksichtigung unterschiedlicher Patient:innengruppen sowie der Dauer und Anwendung physikalischer Maßnahmen zur Temperaturregulation aufgeführt.In der Zusammenschau der Ergebnisse stellt der Einfluss des gezielten Temperaturmanagements auf das neurologische Outcome weiterhin eine viel diskutierte Kontroverse dar. Trotz der z. T. widersprüchlichen Ergebnisse der letzten Jahre und weiterhin offener Fragen hinsichtlich des optimalen Regimes unterstreichen die aktuellen Ergebnisse jedoch erneut die Relevanz und die Notwendigkeit einer strikten Temperaturkontrolle in den Postreanimationsabläufen.

Purpose The objective of this study was to determine the influence of postanesthesia care unit (PACU) delirium on self-reported cognitive function and perceived health status 3 months after surgery. Methods This prospective observational cohort study was performed in a PACU at a high-volume prostate cancer center. We used a convenience sample of patients > 60 years undergoing elective radical prostatectomy. Patients with a history of cerebrovascular or neurodegenerative disease were excluded. Fifteen, 30, 45, and 60 following extubation, patients were screened for signs of delirium with the Confusion Assessment Method for the Intensive Care Unit. Three months after surgery self-reported cognitive function was assessed with the Cognitive Failures Questionnaire, and health status was evaluated with the 36-item Short-Form Health Survey (SF-36). Results Signs of PACU delirium were present in 32.4% (n = 72/222) of patients, and 80.2% (n = 178/222) completed the 3-month follow-up. The presence of PACU delirium signs was not significantly associated with self-reported cognitive failures (B = 0.60, 95% CI: −1.72; 2.92, p = 0.61) or SF-36 physical component scores (B = 0.19, 95% CI: 0.02; 0.36, p = 0.03) or SF-36 mental component scores (B = −0.03, 95% CI: −0.18, 0.11, p = 0.66) 3 months after radical prostatectomy. Conclusions In a cohort of educated, highly functioning, elderly male patients who were assessed immediately after surgery and at a 3-month follow-up, we found no association between PACU delirium and self-reported cognitive failures or perceived health status, which implies that PACU delirium may be an event of limited duration and impact. Trial registration The study was registered at ClinicalTrials.gov (Identifier: NCT04168268, Date of registration: November 19, 2019).

Introduction: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. Methods: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18–24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). Results: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948–3,679) and 3,747 (1,301–5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. Conclusion: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53–64) and 52 (39–58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1–5) and 2 (0–5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24–36) vs. 32 (28–41) points (p = 0.009), and SOFA score was 13 (11–14) vs. 12 (8–15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46–78) and 73 (56–104) (p = 0.089); pH was 7.20 (7.16–7.29) and 7.26 (7.18–7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7–27) and 11 (7–20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13–44) and 28 (16–14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.

Background Sedative premedication with benzodiazepines has been linked with prolonged recovery and inadequate emergence during the immediate postoperative period. We aimed to analyze the association between postanesthesia care unit (PACU) delirium and sedative premedication with oral midazolam. Methods We performed a secondary analysis of prospectively collected data before (midazolam cohort) and after (non-midazolam cohort) implementation of a restrictive strategy for oral premedication with midazolam. From March 2015 until July 2018, we included patients 60 years and older, who underwent elective radical prostatectomy for prostate cancer. Exclusion criteria were contraindications to premedication with midazolam, preoperative anxiety, and a history of neurological disorders. Patients, who were scheduled for postoperative admission to the intensive care unit, were excluded. Between 2015 and 2016, patients received 7.5 mg oral midazolam preoperatively (midazolam cohort). Patients included between 2017 and 2018 did not receive any sedative medication preoperatively (non-midazolam cohort). The primary endpoint was the incidence of PACU delirium. Results PACU delirium rates were 49% in the midazolam cohort (n = 214) and 33% in the non-midazolam cohort (n = 218). This difference was not statistically significant on multivariable logistic regression analysis (OR 0.847 [95% CI 0.164; 4.367]; P = 0.842). Age (OR 1.102 [95% CI 1.050; 1.156]; P < 0.001), the cumulative dose of sufentanil (OR 1.014 [95% CI 1.005; 1.024]; P = 0.005), and propofol-sufentanil for anesthesia maintenance (OR 2.805 [95% CI 1.497; 5.256]; P = 0.001) were significantly associated with PACU delirium. Conclusion Midazolam for sedative premedication was not significantly associated with PACU delirium. The reduction in the incidence of PACU delirium throughout the study period may be attributable to improvements in perioperative management other than a more restrictive preoperative benzodiazepine administration.

Purpose: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from removal of inflammatory mediators via hemadsorption.Methods: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 μg/kg/min to maintain a mean arterial pressure ≥ 65 mmHg), IL-6≥500 ng/l and an indication for renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO) were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18–24 hours. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min≥24h). Secondary endpoints included 28-day mortality, SOFA, and reduction of IL-6, PCT, and MR-proADM. Results: Of 242 screened patients, 24 were randomized and assigned to either HT (N=12) or SMT (N=12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p=0.590) and SOFA (17 vs. 16, p=0.551). At randomization, 22 (92%) patients were on RRT and 11 (46%) had vv-ECMO. Median IL-6 levels were 2269 (IQR 948–3679) and 3747 (1301–5415) ng/l in the HT and SMT group at baseline, respectively (p=0.378). Serum IL-6 reduction in the first 24h of treatment compared between both groups was 83% vs. 46% (p=0.235). Shock resolution (primary endpoint) was reached in 33% (4/12) vs. 17% (2/12) in the HT and SMT group, respectively (p=0.640). 28-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p=1.0).Conclusion: HT was associated with a non-significant trend towards clinical improvement within the intervention period including reduction of IL-6 levels and shock resolution. In selected patients, HT might therefore be an option for stabilization and bridge to transfer and decision. (Trial registration: ClinicalTrials.gov: NCT04344080, https://clinicaltrials.gov/ct2/show/NCT04344080, trial registration date 04/14/2020)]

About 20% of ICU patients with COVID-19 require renal replacement therapy (RRT). Mid-regional pro-adrenomedullin (MR-proADM) might be used for risk assessment. This study investigates MR-proADM for RRT prediction in ICU patients with COVID-19.We analysed data of consecutive patients with COVID-19, requiring ICU admission at a university hospital in Germany between March and September 2020. Clinical characteristics, details on AKI, and RRT were assessed. MR-proADM was measured on admission.64 patients were included (49 (77%) males). Median age was 62.5y (54-73). 47 (73%) patients were ventilated and 50 (78%) needed vasopressors. 25 (39%) patients had severe ARDS, and 10 patients needed veno-venous extracorporeal membrane oxygenation. 29 (45%) patients required RRT; median time from admission to RRT start was 2 (1-9) days. MR-proADM on admission was higher in the RRT group (2.491 vs. 1.23 nmol/l;AKI requiring RRT is frequent in ICU patients with COVID-19. MR-proADM on admission was able to predict RRT requirement, which may be of interest for risk stratification and management.

Sorption processes control the solubility of toxic thallium (Tl) in soils and thereby its potential leaching into groundwater or uptake by plants. Micaceous clay minerals and Mn oxides are considered to be key sorbents for Tl in soils. We studied the sorption and speciation of Tl in 36 geogenically Tl-rich topsoil materials from the Swiss Jura Mountains by combining chem-ical extractions, isotope exchange experiments, adsorption experiments, X-ray absorption spectroscopy (XAS), and sorption modelling. We demonstrate that the relation between exchangeable and soluble Tl determined in batch extractions of soils with only geogenic and with freshly spiked Tl matches adsorption isotherms of freshly spiked Tl, and that this relation can be described with a published 3-site cation exchange model for Tl adsorption onto illite. Complemented with XAS data, the results show that micaceous clay minerals control the short-term solubility of Tl via cation exchange, but also the long-term sequestration of most geogenic soil Tl (>90%) via structural fixation. Adsorption competition with K+ and NH4+ at the frayed edges of micaceous clay minerals greatly affects Tl solubility. Increases in the dissolved concentrations of K and NH4 in soil pore water may therefore lead to the release of Tl into solution. The fractions of geogenic Tl associated with Mn oxides were about half as high as the fractions of exchangeable Tl. This Mn-associated Tl is not readily mobilized by cation exchange, but could be released during periodic water logging and soil reduction. In (periodically) reducing environments, the potential of Mn oxides for long-term Tl sequestration is therefore limited. In conclusion, the results from this study high-light the importance of micaceous clay minerals for Tl cycling in soils and sediments, and suggest that concepts developed to assess the sorption of (radio)caesium onto micaceous clay minerals in soils and sediments are transferable to Tl., Geochimica et Cosmochimica Acta, 288, ISSN:0016-7037, ISSN:1872-9533

Background Despite advances in the management of bloodstream infections (BSI) caused by Candida spp., the mortality still remains high in critically ill patients. The worldwide epidemiology of yeast-related BSI is subject to changing species distribution and resistance patterns, challenging antifungal treatment strategies. The aim of this single-center study was to identify predictors of mortality after 28 and 180 days in a cohort of mixed surgical and medical critically ill patients with candidemia. Methods Patients, who had been treated for laboratory-confirmed BSI caused by Candida spp. in one of 12 intensive care units (ICU) at a University hospital between 2008 and 2017, were retrospectively identified. We retrieved data including clinical characteristics, Candida species distribution, and antifungal management from electronic health records to identify risk factors for mortality at 28 and 180 days using a Cox regression model. Results A total of 391 patients had blood cultures positive for Candida spp. (incidence 4.8/1000 ICU admissions). The mortality rate after 28 days was 47% (n = 185) and increased to 60% (n = 234) after 180 days. Age (HR 1.02 [95% CI 1.01–1.03]), a history of liver cirrhosis (HR 1.54 [95% CI 1.07–2.20]), septic shock (HR 2.41 [95% CI 1.73–3.37]), the Sepsis-related Organ Failure Assessment score (HR 1.12 [95% CI 1.07–1.17]), Candida score (HR 1.25 [95% CI 1.11–1.40]), and the length of ICU stay at culture positivity (HR 1.01 [95% CI 1.00–1.01]) were significant risk factors for death at 180 days. Patients, who had abdominal surgery (HR 0.66 [95% CI 0.48–0.91]) and patients, who received adequate (HR 0.36 [95% CI 0.24–0.52]) or non-adequate (HR 0.31 [95% CI 0.16–0.62]) antifungal treatment, had a reduced mortality risk compared to medical admission and no antifungal treatment, respectively. Conclusions The mortality of critically ill patients with Candida BSI is high and is mainly determined by disease severity, multiorgan dysfunction, and antifungal management rather than species distribution and susceptibility. Our results underline the importance of timely treatment of candidemia. However, controversies remain on the optimal definition of adequate antifungal management.

Background This RCT investigated the effect of opioid titration by three different nociception monitoring devices or clinical signs during general anaesthesia. Methods Ninety-six patients undergoing radical retropubic prostatectomy with propofol/remifentanil anaesthesia were randomised into one of four groups to receive remifentanil guided by one of three nociception monitoring devices (surgical pleth index [SPI], pupillary pain index [PPI], or nociception level [NOL]) or by clinical judgement (control). Intraoperative remifentanil requirement was the primary endpoint, whereas recovery parameters and stress hormone levels were secondary endpoints. Results The mean [95% confidence interval {CI}] remifentanil administration rate differed between the groups: control 0.34 (0.32–0.37), SPI 0.46 (0.38–0.55), PPI 0.07 (0.06–0.08), and NOL 0.16 (0.12–0.21) μg kg−1 min−1(P Conclusions The nociception monitoring devices and clinical signs reflect the extent of nociception differently, leading to dissimilar doses of remifentanil. Very low remifentanil doses were associated with an increase and higher remifentanil doses were accompanied by a decrease in serum cortisol concentrations. Use of nociception monitoring devices for guiding intra-operative opioid dosing needs further validation. Clinical trial registration NCT03380949.

BACKGROUND The aim of this study was to compare the incidence of early postoperative delirium in the postanesthesia care unit (PACU) between robot-assisted radical prostatectomy (RARP) in the extreme Trendelenburg position and open retropubic radical prostatectomy (ORP) in supine position. METHODS Patients were screened for delirium signs 15, 30, 45, and 60 minutes following extubation. RESULTS PACU delirium was present in 39.3% of RARP (64/163) patients and 41.8% of ORP (77/184) patients. Higher age (OR 1.072, 95%CI: 1.034-1.111, P

Neuroprotection through targeted temperature management is currently investigated in patients with severe brain injury in multiple trials. Feedback devices have been shown to precisely reach and maintain target temperature by constantly adjusting cooling activity. We analyzed the association between cooling activity expressed as cool bath temperatures and functional neurological outcome.Data were retrospectively analyzed from a prospective randomized trial on controlled prophylactic normothermia (i.e., 36.5 °C) in patients with severe cerebrovascular disease. Body core temperature of patients who had been randomized to the endovascular group, was controlled using an endovascular cooling device. Cool bath temperature was analyzed over a period of 168 h. Functional neurological outcome was evaluated at 180 days using the modified Rankin Scale.51 of 102 patients included were randomized to the endovascular group. Cool bath temperature data were available from 47/51 patients. Patients with lower cool bath temperatures reflecting high cooling activity had a more favorable neurological outcome at 180 days (mRS 0-2) than patients with low cooling activity (p0.05). We did not find a significant correlation between cool bath temperature and inflammatory markers.High cooling activity of an endovascular feedback device is associated with favorable outcome in patients with severe cerebrovascular disease.

Background Nosocomial infections are common in patients with spontaneous subarachnoid hemorrhage (SAH). The aim of this retrospective cohort study was to determine the incidence of infections during SAH and to evaluate the course of inflammation parameters and its implications for long term outcome. Objective Ninety-nine consecutive coiled SAH patients were included. Laboratory and clinical parameters as well as culture positive infections were followed over the disease course. Long-term outcome was assessed at 6-month by the Glasgow Outcome score (GOS) and dichotomized in favorable (GOSg3) and unfavorable outcome (GOS≤3). Results The most frequent infections were pulmonary (30.3%) urinary tract (25.3%), blood stream infections (20.2%) and ventriculitis (5.1%). The incidence of infections did not significantly differ between outcome groups. In contrast, patients with unfavorable outcome had a higher incidence of sepsis (46.7% versus 24.6%). C-reactive protein (CRP) and leukocytes were significantly higher in patients with unfavorable outcome. A CRP increase of 6 mg/dl or more in the first 3 days after SAH was independently associated with unfavorable outcome (OR 7.19 CI 1.7-30.52; p=0.008). Patients with an early CRP increase were more frequently treated with antimicrobial therapy in the first 3 days after admission which led to a significantly lower incidence of culture positive infections in the later course. Conclusion A sharp CRP-increase in the acute phase of SAH could potentially aid the intensivist in the early identification of patients at high risk for neurological morbidity. Early antimicrobial treatment reduces the rate of patients showing culture positive infections in the course of the disease.

Introduction: Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in patients with poor grade aSAH. Methods: Prospectively collected data from 26 consecutive poor-grade aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD) were retrospectively analyzed. IL-6 and TAU-protein levels were analyzed using ELISA from a single CMD-sample every 24 hours and correlated with brain metabolic and hemodynamic parameters. Patients were dichotomized to high-grade (N=10) or low-grade (N=16) neuroinflammation according to their median CMD-IL-6 levels. Data were analyzed using generalized estimating equations to account for multiple within-subject measurements. Results: Perilesional probe location (P=0.02) and aSAH related intracerebral hemorrhage (aICH) volume (P=0.003) at admission were associated with high-grade neuroinflammation. Brain extracellular TAU-protein levels (P=0.001), metabolic distress and delayed cerebral infarction (DCI; P=0.001) were linked to high-grade neuroinflammation. Relative or absolute phosphor-TAU levels were not correlated with CMD-IL-6 levels. High-grade neuroinflammation was a predictor for worse outcome three months after ictus, independently from probe location, initial Hunt&Hess grade and age (P=0.01). Conclusions: Neuroinflammation after aSAH is associated with intraparenchymal bleeding, deranged cerebral metabolism and TAU-protein release. The impact of potential anti-inflammatory treatment strategies on secondary brain injury after aSAH has to be investigated in future studies.