Association Between Dyscapnia, Ventilatory Variables, and Mortality in Patients With Acute Respiratory Distress Syndrome-A Retrospective Cohort Study.

Background: This study aimed to investigate the associations between dyscapnia, ventilatory variables, and mortality. We hypothesized that the association between mechanical power or ventilatory ratio and survival is mediated by dyscapnia. Methods: Patients with moderate or severe acute respiratory distress syndrome (ARDS), who received mechanical ventilation within the first 48 h after admission to the intensive care unit for at least 48 h, were included in this retrospective single-center study. Values of arterial carbon dioxide (PaCO2) were categorized into "hypercapnia" (PaCO2 ≥ 50 mm Hg), "normocapnia" (PaCO2 36-49 mmHg), and "hypocapnia" (PaCO2 ≤ 35 mm Hg). We used path analyses to assess the associations between ventilatory variables (mechanical power and ventilatory ratio) and mortality, where hypocapnia or hypercapnia were included as mediating variables. Results: Between December 2017 and April 2021, 435 patients were included. While there was a significant association between mechanical power and hypercapnia (BEM = 0.24 [95% CI: 0.15; 0.34], P < .01), there was no significant association between mechanical power or hypercapnia and ICU mortality. The association between mechanical power and intensive care unit (ICU) mortality was fully mediated by hypocapnia (BEM = -0.10 [95% CI: -0.19; 0.00], P = .05; BMO = 0.38 [95% CI: 0.13; 0.63], P < .01). Ventilatory ratio was significantly associated with hypercapnia (B = 0.23 [95% CI: 0.14; 0.32], P < .01). There was no significant association between ventilatory ratio, hypercapnia, and mortality. There was a significant effect of ventilatory ratio on mortality, which was fully mediated by hypocapnia (BEM = -0.14 [95% CI: -0.24; -0.05], P < .01; BMO = 0.37 [95% CI: 0.12; 0.62], P < .01). Conclusion: In mechanically ventilated patients with moderate or severe ARDS, the association between mechanical power and mortality was fully mediated by hypocapnia. Likewise, there was a mediating effect of hypocapnia on the association between ventilatory ratio and ICU mortality. Our results indicate that the debate on dyscapnia and outcome after ARDS should consider the impact of ventilatory variables.

Early prediction of ventricular peritoneal shunt dependency in aneurysmal subarachnoid haemorrhage patients by recurrent neural network-based machine learning using routine intensive care unit data.

Aneurysmal subarachnoid haemorrhage (aSAH) can lead to complications such as acute hydrocephalic congestion. Treatment of this acute condition often includes establishing an external ventricular drainage (EVD). However, chronic hydrocephalus develops in some patients, who then require placement of a permanent ventriculoperitoneal (VP) shunt. The aim of this study was to employ recurrent neural network (RNN)-based machine learning techniques to identify patients who require VP shunt placement at an early stage. This retrospective single-centre study included all patients who were diagnosed with aSAH and treated in the intensive care unit (ICU) between November 2010 and May 2020 (n = 602). More than 120 parameters were analysed, including routine neurocritical care data, vital signs and blood gas analyses. Various machine learning techniques, including RNNs and gradient boosting machines, were evaluated for their ability to predict VP shunt dependency. VP-shunt dependency could be predicted using an RNN after just one day of ICU stay, with an AUC-ROC of 0.77 (CI: 0.75-0.79). The accuracy of the prediction improved after four days of observation (Day 4: AUC-ROC 0.81, CI: 0.79-0.84). At that point, the accuracy of the prediction was 76% (CI: 75.98-83.09%), with a sensitivity of 85% (CI: 83-88%) and a specificity of 74% (CI: 71-78%). RNN-based machine learning has the potential to predict VP shunt dependency on Day 4 after ictus in aSAH patients using routine data collected in the ICU. The use of machine learning may allow early identification of patients with specific therapeutic needs and accelerate the execution of required procedures.

Psychometric evaluation of the modified quality of recovery score for the postanaesthesia care unit (QoR-PACU2)-A prospective validation study.

BACKGROUND: To date, there is no instrument to adequately assess self-reported quality of recovery (QoR) in the post-anesthesia care unit (PACU). We previously developed the QoR-PACU, a 13-item questionnaire specifically applicable to the PACU. The feasibility, acceptance, and validity of the QoR-PACU were promising. However, measures of reliability were slightly lower than expected. METHODS: We modified the QoR-PACU and evaluated its psychometric properties in a cohort of adult patients scheduled for non-cardiac surgery with general anesthesia. The modified QoR-PACU (termed QoR-PACU2) was administered before surgery and postoperatively in the PACU at the time of the decision to discharge. RESULTS: A total of 307 patients were included in the final analysis. Postoperative QoR-PACU2 sum scores differed across categories of sex, perioperative and surgical risk, and modes of airway management. The duration of anesthesia and surgery, maximum pain intensity and analgesic requirement in the PACU, and length of PACU stay were all inversely correlated with QoR in the PACU. Cronbach's alpha was 0.70 (95%CI: 0.66-0.75). The intra-class correlation coefficient was 0.86 (95%CI: 0.70-0.94, p < 0.001) for intra-rater reliability (n = 24) and 0.94 (95%CI 0.90 to 0.97, p < 0.001) for inter-rater reliability (n = 31). Cohen's effect size was 0.68 and the standardized response mean was 0.57. CONCLUSION: The QoR-PACU2 assesses self-reported QoR after surgery in the PACU. Measures of feasibility, validity, and reliability were consistently high. Measures of responsiveness were moderate, which might be attributable to the heterogeneity of the study population. Future studies should include aspects of ethnicity and cross-cultural applicability.

The impact of cognitive reserve on delayed neurocognitive recovery after major non-cardiac surgery: an exploratory substudy.

Introduction: Delayed neurocognitive recovery is a common and severe complication after surgery and anesthesia with an adverse impact on daily living, morbidity, and mortality. High cognitive reserve may mitigate the development of delayed neurocognitive recovery, however, supporting data is lacking. We aimed to assess the association between cognitive reserve and delayed neurocognitive recovery in the early postoperative period. Methods: This is a substudy of two prospective observational studies. Adult patients undergoing elective major non-cardiac surgery, who were fluent in German, were eligible for study participation. Patients with any pre-existing central nervous system disorders were excluded. Cognitive reserve was assessed using the Cognitive Reserve Index questionnaire. Delayed neurocognitive recovery was defined as a decline in cognitive function compared with baseline assessments and was evaluated with a battery of neuropsychological tests on the day of hospital admission and between day three post procedure and before hospital discharge. Results: A total of 67 patients with a median age of 67 [IQR: (63-73)] years were included in our analysis. We found delayed neurocognitive recovery in 22.4% of patients. There was a significant association between Cognitive Reserve Index questionnaire total score and the occurrence of delayed neurocognitive recovery in the early postoperative period [OR = 0.938, (95% CI, 0.891; 0.988), p = 0.015]. Conclusion: Higher cognitive reserve in elderly patients undergoing major non-cardiac surgery decreases the risk for subsequent delayed neurocognitive recovery in the early postoperative period.

Early acute kidney injury and transition to renal replacement therapy in critically ill patients with SARS-CoV-2 requiring veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring veno-venous extracorporeal membrane oxygenation (vv-ECMO) are at risk for acute kidney injury (AKI). Currently, the incidence of AKI and progression to kidney replacement therapy (RRT) in critically ill patients with vv-ECMO for severe COVID-19 and implications on outcome are still unclear. METHODS: Retrospective analysis at the University Medical Center Hamburg-Eppendorf (Germany) between March 1st, 2020 and July 31st, 2021. Demographics, clinical parameters, AKI, type of organ support, length of ICU stay, mortality and severity scores were assessed. RESULTS: Ninety-one critically ill patients with SARS-CoV-2 requiring ECMO were included. The median age of the study population was 57 (IQR 49-64) years and 67% (n = 61) were male. The median SAPS II and SOFA Score on admission were 40 (34-46) and 12 (10-14) points, respectively. We observed that 45% (n = 41) developed early-AKI, 38% (n = 35) late-AKI and 16% (n = 15) no AKI during the ICU stay. Overall, 70% (n = 64) of patients required RRT during the ICU stay, 93% with early-AKI and 74% with late-AKI. Risk factors for early-AKI were younger age (OR 0.94, 95% CI 0.90-0.99, p = 0.02) and SAPS II (OR 1.12, 95% CI 1.06-1.19, p < 0.001). Patients with and without RRT were comparable regarding baseline characteristics. SAPS II (41 vs. 37 points, p < 0.05) and SOFA score (13 vs. 12 points, p < 0.05) on admission were significantly higher in patients receiving RRT. The median duration of ICU (36 vs. 28 days, p = 0.27) stay was longer in patients with RRT. An ICU mortality rate in patients with RRT in 69% (n = 44) and in patients without RRT of 56% (n = 27) was observed (p = 0.23). CONCLUSION: Critically ill patients with severe SARS-CoV-2 related ARDS requiring vv-ECMO are at high risk of early acute kidney injury. Early-AKI is associated with age and severity of illness, and presents with high need for RRT. Mortality in patients with RRT was comparable to patients without RRT.

Impact of Intraoperative Fluctuations of Cardiac Output on Cerebrovascular Autoregulation: An Integrative Secondary Analysis of Individual-level Data.

BACKGROUND: Intraoperative impairment of cerebral autoregulation (CA) has been associated with perioperative neurocognitive disorders. We investigated whether intraoperative fluctuations in cardiac index are associated with changes in CA. METHODS: We conducted an integrative explorative secondary analysis of individual-level data from 2 prospective observational studies including patients scheduled for radical prostatectomy. We assessed cardiac index by pulse contour analysis and CA as the cerebral oxygenation index (COx) based on near-infrared spectroscopy. We analyzed (1) the cross-correlation between cardiac index and COx, (2) the correlation between the time-weighted average (TWA) of the cardiac index below 2.5 L min-1 m-2, and the TWA of COx above 0.3, and (3) the difference in areas between the cardiac index curve and the COx curve among various subgroups. RESULTS: The final analysis included 155 patients. The median cardiac index was 3.16 [IQR: 2.65, 3.72] L min-1 m-2. Median COx was 0.23 [IQR: 0.12, 0.34]. (1) The median cross-correlation between cardiac index and COx was 0.230 [IQR: 0.186, 0.287]. (2) The correlation (Spearman ρ) between TWA of cardiac index below 2.5 L min-1 m-2 and TWA of COx above 0.3 was 0.095 (P=0.239). (3) Areas between the cardiac index curve and the COx curve did not differ significantly among subgroups (<65 vs. ≥65 y, P=0.903; 0 vs. ≥1 cardiovascular risk factors, P=0.518; arterial hypertension vs. none, P=0.822; open vs. robot-assisted radical prostatectomy, P=0.699). CONCLUSIONS: We found no meaningful association between intraoperative fluctuations in cardiac index and CA. However, it is possible that a potential association was masked by the influence of anesthesia on CA.

Antioxidant capacity and inhibition of metabolic syndrome-associated enzymes by Cryptocarya alba fruits.

The fruits of the native tree Cryptocarya alba Mol. (Lauraceae), known as "peumo" were consumed by the Mapuche Amerindians in Chile both raw and after boiling. The aim of this work was to compare the content of phenolic, procyanidins, antioxidant capacity and inhibition of enzymes related with metabolic syndrome (α-glucosidase, α-amylase and pancreatic lipase) from the phenolic enriched extracts (PEEs) of peumo fruits. Fruits were collected during two years in three different places in central Chile and were investigated raw, boiled, and after separation into cotyledons and peel. The water resulting from the fruit decoction was also analyzed. The composition of the PEE was assessed by HPLC-DAD-MS/MS and the main compounds were quantified by HPLC. The strong inhibitory effect on α-glucosidase, with IC50 values below 1 µg/mL for several samples, was related, at least in part, to the content of 3-caffeoylquinic acid, 5-caffeoylquinic acid and (-)-epicatechin. The effect of the PEE on pancreatic lipase is of interest and can be partially explained by the (-)-epicatechin content. PCA analyses showed a clear separation of the samples according to the fruit parts and processing. However, no differences by geographic origin were observed. The activity of peumo PEEs on enzymes related to metabolic syndrome and its antioxidant capacity support further studies on the health promoting properties of this native Chilean food plant.

Comparative analysis of characteristics and outcomes in hospitalized COVID-19 patients infected with different SARS-CoV-2 variants between January 2020 and April 2022 - A retrospective single-center cohort study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the roll-out of vaccines and therapeutic agents, as well as the emergence of novel SARS-CoV-2 variants, have shown significant effects on disease severity. METHODS: Patients hospitalized at our center between January 2020 and April 2022 were attributed to subgroups depending on which SARS-CoV-2 variant was predominantly circulating in Germany: (i) Wild-type: January 1, 2020, to March 7, 2021, (ii) Alpha variant: August 3, 2021, to June 27, 2021, (iii) Delta variant: June 28, 2021, to December 26, 2021, and (iv) Omicron variant: December 27, 2021, to April 30, 2022. RESULTS: Between January 2020 and April 2022, 1500 patients with SARS-CoV-2 infections were admitted to the University Medical Center Hamburg-Eppendorf. The rate of patients who were admitted to the intensive care unit (ICU) decreased from 31.2% (n = 223) in the wild-type group, 28.5% (n = 72) in the Alpha variant group, 18.8% (n = 67) in the Delta variant group, and 13.4% (n = 135) in the Omicron variant group. Also, in-hospital mortality decreased from 20.6% (n = 111) in the wild-type group, 17.5% (n = 30) in the Alpha variant group, 16.8% (n = 33) in the Delta variant group, and 6.6% (n = 39) in the Omicron variant group. The median duration of hospitalization was similar in all subgroups and ranged between 11 and 15 days throughout the pandemic. CONCLUSIONS: In-hospital mortality and rate of ICU admission among hospitalized COVID-19 patients steadily decreased throughout the pandemic. However, the practically unchanged duration of hospitalization demonstrates the persistent burden of COVID-19 on the healthcare system.

Psychometric evaluation of a quality of recovery score for the postanesthesia care unit-A preliminary validation study.

INTRODUCTION: Patients' perception of postoperative recovery is a key aspect of perioperative care. Self-reported quality of recovery (QoR) has evolved as a relevant endpoint in perioperative research. Several psychometric instruments have been introduced to assess self-reported recovery 24 hours after surgery. However, there is no questionnaire suitable for use in the postanesthesia care unit (PACU). We aimed to develop and psychometrically evaluate a QoR questionnaire for the PACU (QoR-PACU). METHODS: The QoR-PACU was developed in German language based on the 40-item QoR-40 questionnaire. Between March and November 2020, adult patients scheduled for elective urologic surgery completed the QoR-PACU preoperatively and during the PACU stay. We evaluated feasibility, validity, reliability, and responsiveness. RESULTS: We included 375 patients. After two piloting phases including 72 and 48 patients, respectively, we administered the final version of the QoR-PACU to 255 patients, with a completion rate of 96.5%. Patients completed the QoR-PACU at a median of 125.0 (83.0; 156.8) min after arrival in the PACU. Construct validity was good with postoperative QoR-PACU sum scores correlating with age (r = 0.23, 95% CI: 0.11 to 0.35, p < 0.001), length of PACU stay (r = -0.15, 95%CI: -0.27 to -0.03, p = 0.02), pain in the PACU (r = -0.48, 95% CI: -0.57 to -0.37, p < 0.001) and piritramide dose administered (r = -0.29, 95% CI: -0.40 to -0.17, p < 0.001). Cronbach's alpha was 0.67 (95% CI: 0.61-0.73) with moderate test-retest reliability (ICC of 0.67, 95% CI: 0.38 to 0.83). Cohen's effect size was 3.08 and the standardized response mean was 1.65 indicating adequate responsiveness. CONCLUSION: The assessment of QoR in the early postoperative period is feasible. We found high acceptability, good validity, adequate responsiveness, and moderate reliability. Future studies should evaluate the psychometric properties of the QoR-PACU in more heterogeneous patient populations including female and gender-diverse patients with varying degress of perioperative risk.

Impact of COVID-19 on Sedation Requirements during Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

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.

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit.

BACKGROUND: Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown. METHODS: We retrospectively analyzed data collected during a single-center observational study (March 2020-November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity. RESULTS: Patients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors. CONCLUSIONS: Our study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.

History of cerebrovascular disease but not dementia increases the risk for secondary vascular events during SARS-CoV-2 infection with presumed Omicron variant: a retrospective observational study.

BACKGROUND AND PURPOSE: This study aimed to investigate if pre-existing neurological conditions, such as dementia and a history of cerebrovascular disease, increase the risk of severe outcomes including death, intensive care unit (ICU) admission and vascular events in patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2022, when Omicron was the predominant variant. METHODS: A retrospective analysis was conducted of all patients with SARS-CoV-2 infection, confirmed by polymerase chain reaction test, admitted to the University Medical Center Hamburg-Eppendorf from 20 December 2021 until 15 August 2022. In all, 1249 patients were included in the study. In-hospital mortality was 3.8% and the ICU admission rate was 9.9%. Ninety-three patients with chronic cerebrovascular disease and 36 patients with pre-existing all-cause dementia were identified and propensity score matching by age, sex, comorbidities, vaccination status and dexamethasone treatment was performed in a 1:4 ratio with patients without the respective precondition using nearest neighbor matching. RESULTS: Analysis revealed that neither pre-existing cerebrovascular disease nor all-cause dementia increased mortality or the risk for ICU admission. All-cause dementia in the medical history also had no effect on vascular complications under investigation. In contrast, an increased odds ratio for both pulmonary artery embolism and secondary cerebrovascular events was observed in patients with pre-existing chronic cerebrovascular disease and myocardial infarction in the medical history. CONCLUSION: These findings suggest that patients with pre-existing cerebrovascular disease and myocardial infarction in their medical history may be particularly susceptible to vascular complications following SARS-CoV-2 infection with presumed Omicron variant.

Oscillatory and aperiodic neuronal activity in working memory following anesthesia.

OBJECTIVE: Anesthesia and surgery are associated with cognitive impairment, particularly memory deficits. So far, electroencephalography markers of perioperative memory function remain scarce. METHODS: We included male patients >60 years scheduled for prostatectomy under general anesthesia. We obtained neuropsychological assessments and a visual match-to-sample working memory task with simultaneous 62-channel scalp electroencephalography 1 day before and 2 to 3 days after surgery. RESULTS: Twenty-six patients completed both pre- and postoperative sessions. Compared with preoperative performance, verbal learning deteriorated after anesthesia (California Verbal Learning Test total recall; t25 = -3.25, p = 0.015, d = -0.902), while visual working memory performance showed a dissociation between match and mismatch accuracy (match*session F1,25 = 3.866, p = 0.060). Better verbal learning was associated with an increase of aperiodic brain activity (total recall r = 0.66, p = 0.029, learning slope r = 0.66, p = 0.015), whereas visual working memory accuracy was tracked by oscillatory theta/alpha (7 - 9 Hz), low beta (14 - 18 Hz) and high beta/gamma (34 - 38 Hz) activity (matches: p < 0.001, mismatches: p = 0.022). CONCLUSIONS: Oscillatory and aperiodic brain activity in scalp electroencephalography track distinct features of perioperative memory function. SIGNIFICANCE: Aperiodic activity provides a potential electroencephalographic biomarker to identify patients at risk for postoperative cognitive impairments.

Validation of three nociception indices to predict immediate postoperative pain before emergence from general anaesthesia: a prospective double-blind, observational study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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], P<0.001). CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: NCT05063227.

Sotrovimab in Hospitalized Patients with SARS-CoV-2 Omicron Variant Infection: a Propensity Score-Matched Retrospective Cohort Study.

In vitro data suggest the monoclonal antibody sotrovimab may have lost inhibitory capability against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. We aimed to provide real-life data on clinical outcomes in hospitalized patients. We retrospectively analyzed patients who were treated at the University Medical Center Hamburg-Eppendorf, Germany, between December 2021 and June 2022. Out of all 1,254 patients, 185 were treated with sotrovimab: 147 patients received sotrovimab monotherapy, and 38 received combination treatment with sotrovimab and remdesivir. We compared in-hospital mortality for the different treatment regimens for patients treated on regular wards and the intensive care unit separately and performed propensity score matching by age, sex, comorbidities, immunosuppression, and additional dexamethasone treatment to select patients who did not receive antiviral treatment for comparison. No difference in in-hospital mortality was observed between any of the treatment groups and the respective control groups. These findings underline that sotrovimab adds no clinical benefit for hospitalized patients with SARS-CoV-2 Omicron variant infections. IMPORTANCE This study shows that among hospitalized patients with SARS-CoV-2 Omicron variant infection at risk of disease progression, treatment with sotrovimab alone or in combination with remdesivir did not decrease in-hospital mortality. These real-world clinical findings in combination with previous in vitro data about lacking neutralizing activity of sotrovimab against SARS-CoV-2 Omicron variant do not support sotrovimab as a treatment option in these patients.

Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial.

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.

Outcomes of critically ill coronavirus disease 2019 patients requiring kidney replacement therapy: A retrospective cohort study.

Background: Coronavirus disease 2019 (COVID-19) has resulted in high hospitalization rates worldwide. Acute kidney injury (AKI) in patients hospitalized for COVID-19 is frequent and associated with disease severity and poor outcome. The aim of this study was to investigate the incidence of kidney replacement therapy (KRT) in critically ill patients with COVID-19 and its implication on outcome. Methods: We retrospectively analyzed all COVID-19 patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf (Germany) between 1 March 2020 and 31 July 2021. Demographics, clinical parameters, type of organ support, length of intensive care unit (ICU) stay, mortality and severity scores were assessed. Results: Three-hundred critically ill patients with COVID-19 were included. The median age of the study population was 61 (IQR 51-71) years and 66% (n = 198) were male. 73% (n = 219) of patients required invasive mechanical ventilation. Overall, 68% (n = 204) of patients suffered from acute respiratory distress syndrome and 30% (n = 91) required extracorporeal membrane oxygenation (ECMO). We found that 46% (n = 139) of patients required KRT. Septic shock (OR 11.818, 95% CI: 5.941-23.506, p < 0.001), higher simplified acute physiology scores (SAPS II) (OR 1.048, 95% CI: 1.014-1.084, p = 0.006) and vasopressor therapy (OR 5.475, 95% CI: 1.127-26.589, p = 0.035) were independently associated with the initiation of KRT. 61% (n = 85) of patients with and 18% (n = 29) without KRT died in the ICU (p < 0.001). Cox regression found that KRT was independently associated with mortality (HR 2.075, 95% CI: 1.342-3.208, p = 0.001) after adjusting for confounders. Conclusion: Critically ill patients with COVID-19 are at high risk of acute kidney injury with about half of patients requiring KRT. The initiation of KRT was associated with high mortality.

The impact of spinal anaesthesia on perioperative opioid consumption, postoperative pain and oncological outcome in radical retropubic prostatectomy-a retrospective before-and-after effectiveness study.

BACKGROUND: Spinal anaesthesia preceding general anaesthesia has been conducted for open radical retropubic prostatectomy (RRP) to decrease immediate postoperative pain for many years. Nevertheless, the effectiveness of spinal anaesthesia to reduce postoperative opioid requirements remains unknown. The aim of the present study was to determine the effect of spinal anaesthesia preceding general anaesthesia on opioid requirements, postoperative pain and biochemical cancer-free survival. METHODS: This before-and-after effectiveness study investigated effects of two different anaesthesia techniques in 636 patients with RRP. Three hundred eighteen consecutive patients in the SPA group (spinal anaesthesia preceding general anaesthesia) were compared with 318 patients in the GA group (general anaesthesia alone). The primary endpoint of the study was opioid consumption in the post-anaesthesia care unit. Secondary endpoints were intraoperative opioid consumption, postoperative pain, postoperative recovery time, the length of hospital-stay, persistence of pain 1 year after surgery and cancer-free survival. Differences between the groups were analysed by a two-sided t-test, χ2-test, Fisher's exact test and Mann-Whitney U test and the influence of possible confounders on opioid consumption with a general linear model. Cancer-free survival was determined by Kaplan-Meier curves and group differences by log-rank tests and multivariable Cox regression analyses. RESULTS: The total amount of morphine equivalent administered postoperatively was 7.5 [6.9; 8.1] mg in the SPA group and 6.0 [5.5; 6.5] mg in the GA group (mean [95% CI], p < 0.001). The amount of intraoperative sufentanil was 56.9 [55.1; 58.7] µg in the SPA group and 84.5 [82.5; 86.5] µg in the GA group (mean [95% CI], p < 0.001). There was no difference found in the postoperative pain level, length of hospital-stay and pain level 1 year after surgery. Biochemical cancer-free survival was highly related to TNM stage (p < 0.001, pT3 vs. pT2 hazard ratio 5.4 [95%CI 3.3; 9.2]) but not to the type of anaesthesia (p = 0.29). CONCLUSIONS: Spinal anaesthesia preceding general anaesthesia for RRP is associated with increased postoperative opioid consumption compared to general anaesthesia alone. Postoperative pain level and the oncological outcome are not affected by the adjunctive use of spinal anaesthesia. Thus, the addition of spinal anaesthesia to general anaesthesia has no advantage in RRP. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03565705.

Left Ventricular Diastolic Dysfunction Is Not Associated With Pulmonary Edema in Septic Patients. A Prospective Observational Cohort Study.

Purpose: We aimed to investigate whether left ventricular diastolic dysfunction (LVDD) is associated with pulmonary edema in septic patients. Methods: We conducted a prospective cohort study in adult septic patients between October 2018 and May 2019. We performed repeated echocardiography and lung ultrasound examinations within the first 7 days after diagnosis of sepsis. We defined LVDD according to the 2016 recommendations of the American Society of Echocardiography and-for sensitivity analysis-according to an algorithm which has been validated in septic patients. We quantified pulmonary edema using the lung ultrasound score (LUSS), counting B-lines in four intercostal spaces. Results: We included 54 patients. LVDD was present in 51 (42%) of 122 echocardiography examinations. The mean (±SD) LUSS was 11 ± 6. There was no clinically meaningful association of LVDD with LUSS (B = 0.55 [95%CI: -1.38; 2.47]; p = 0.571). Pneumonia was significantly associated with higher LUSS (B = 4.42 [95%CI: 0.38; 8.5]; p = 0.033). Conclusion: The lack of a clinically meaningful association of LVDD with LUSS suggests that LVDD is not a major contributor to pulmonary edema in septic patients. Trial Registration: NCT03768752, ClinicalTrials.gov, November 30th, 2018 - retrospectively registered.