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Abstract 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.

Abstract Background For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis. Methods Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated. Results Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159–289] mg/L and the CSF concentration 99 [66–144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163–438] mg/L and 104 [65–269] mg/L. Median CSF penetration was 46 [36–59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L. Conclusion Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.

BackgroundAneurysmal subarachnoid hemorrhage (SAH) presents occasionally with cardiac arrest (CA). The impact of pre-hospital and emergency room (ER) treatment on outcome remains unclear. Therefore, we investigated the impact of pre-hospital treatment, focusing on lay cardiopulmonary resuscitation (CPR), and ER handling on the outcome of SAH patients with out-of-hospital CA (OHCA).MethodsIn this bi-centric retrospective analysis, we reviewed SAH databases for OHCA and CPR from January 2011 to June 2021. Patients were analyzed for general clinical and epidemiological parameters. CPR data were obtained from ambulance reports and information on ER handling from the medical records. Data were correlated with patient survival at hospital discharge as a predefined outcome parameter.ResultsOf 1,120 patients with SAH, 45 (4.0%) were identified with OHCA and CPR, 38 of whom provided all required information and were included in this study. Time to resuscitation was significantly shorter with lay resuscitation (5.3 ± 5.2 min vs. 0.3 ± 1.2 min, p = 0.003). Nineteen patients were not initially scheduled for cranial computed tomography (CCT), resulting in a significantly longer time interval to first CCT (mean ± SD: 154 ± 217 min vs. 40 ± 23 min; p

The measurement of quality indicators supports quality improvement initiatives. The German Interdisciplinary Society of Intensive Care Medicine (DIVI) has published quality indicators for intensive care medicine for the fourth time now. After a scheduled evaluation after three years, changes in several indicators were made. Other indicators were not changed or only minimally. The focus remained strongly on relevant treatment processes like management of analgesia and sedation, mechanical ventilation and weaning, and infections in the ICU. Another focus was communication inside the ICU. The number of 1ndicators remained the same. The development method was more structured and transparency was increased by adding new features like evidence levels or author contribution and potential conflicts of interest. These quality indicators should be used in the peer review in intensive care, a method endorsed by the DIVI. Other forms of measurement and evaluation are also reasonable, for example in quality management. This fourth edition of the quality indicators will be updated in the future to reflect the recently published recommendations on the structure of intensive care units by the DIVI.

Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological disorders. Nitric oxide is generated by nitric oxide synthases from the amino acid L-arginine. L-arginine can also serve as a substrate for arginases or lead to the generation of dimethylarginines, asymmetric dimethylarginine, and symmetric dimethylarginine, by methylation. Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and can lead to endothelial dysfunction. This review discusses the role of L-arginine metabolism in patients suffering from acute and critical neurological disorders often requiring neuro-intensive care treatment. Conditions addressed in this review include intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury. Recent therapeutic advances in the field are described including current randomized controlled trials for traumatic brain injuries and hemorrhagic stroke.

ObjectiveThe influence of preexisting factors on the clinical course of patients with subarachnoid hemorrhage (SAH), such as patient age, arterial hypertension, and aneurysm characteristics, is still a matter of debate. However, the specific impact of the exact aneurysm location has not received adequate attention. Therefore, the aim of this study was to investigate the influence of aneurysm location as a preexisting factor on the clinical course and mortality.MethodsThe data of consecutive patients with aneurysmal SAH who were treated from October 2010 to July 2020 were retrospectively analyzed. We distinguished four aneurysm locations: the anterior complex, internal carotid artery (ICA), middle cerebral artery (MCA), and posterior circulation. Logistic regression analysis and receiver operating characteristics were used to investigate the influence of aneurysm location on the occurrence of acute hydrocephalus, Delayed Cerebral Ischemia (DCI), neurological outcome, and in-hospital mortality. Neurological outcome was assessed 3 months after discharge using the Glasgow Outcome Scale.ResultsA total of 603 patients were included in this study. Patients with MCA aneurysms were 2.52 times less likely to develop acute hydrocephalus compared to patients with anterior complex aneurysms (p = 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm and least frequently in MCA aneurysms (p = 0.014). In ICA aneurysms, mortality was 2.56-fold higher than in patients with aneurysms of the anterior complex (p = 0.006). An additional ROC analysis showed a good prediction for in-hospital mortality when taking the aneurysm's location into account [AUC.855 (CI.817 −0.893)].ConclusionsThe aneurysm's location proved to be a significant predictor of acute hydrocephalus, DCI, and in-hospital mortality, demonstrating the impact of this preexisting biological factor on the course of SAH.

Objective: Several guidelines recommend oral administration of nimodipine as vasospasm prophylaxis after aneurysmal subarachnoid hemorrhage (SAH). However, in clinical practice, the drug is administered orally and intravenously (i.v.), depending on clinical conditions and local treatment regimens. We have therefore investigated the safety and clinical effects of switching from i.v. to oral nimodipine therapy.Methods: Patients with aneurysmal SAH between January 2014 and April 2018 and initial i.v. nimodipine therapy, which was subsequently switched to oral administration, were included in this retrospective study. Transcranial Doppler sonography (TCD) of the vessels of the anterior circulation was performed daily. The occurrence of vasospasm and infarction during the overall course of the treatment was recorded. Statistical level of significance was set to p < 0.05.Results: A total of 133 patients (mean age 55.8 years, 65% female) initially received nimodipine i.v. after aneurysmal SAH, which was subsequently switched to oral administration after a mean of 12 days. There were no significant increases in mean flow velocities on TCD after the switch from i.v. to oral nimodipine administration regarding the anterior cerebral artery. For the middle cerebral artery, an increase from 62.36 to 71.78 cm/sec could only be detected in the subgroup of patients with infarction. There was no clustering of complicating events such as new-onset vasospasm or infarction during or after the switch.Conclusions: Our results do not point to any safety concerns when switching nimodipine from initial i.v. to oral administration. Switching was neither associated with clinically relevant increases in TCD velocities nor other relevant adverse events.

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The pearl-farming industry depends mostly on the natural recruitment of pearl oysters. Little is known about the relative influence of different ecological processes on the natural recruitment of pearl oysters across biogeographical scales. Spatio-temporal dynamics of bivalve larvae and spats were described at Ahe and Mangareva, 1500 km apart across French Polynesia. We quantified the effect of candidate environmental predictors on the dynamics of larvae. Both lagoons showed similar temporal dynamics with twice more larvae and 6 times more spat in Ahe. Pinctada maculata spat were more abundant than for P. margaritifera at both lagoons. While the temporal dynamics in larvae abundance were best explained by a positive effect of temperature in Ahe, the dynamics in Mangareva were poorly predicted by the environmental variables, meaning bivalve early-life stages perform better in Ahe than Mangareva suggesting a mismatch between the relevant environmental forces driving larval dynamics at these two contrasting lagoons. • Six months of simultaneous surveys of bivalve larvae and spat dynamics in 2 contrasting lagoons. • Higher abundance of larvae and spat associated with higher water temperature and phytoplankton levels in Ahe Atoll. • While temperature was the main driver of larval dynamics in Ahe, no environmental drivers were detected in Mangareva. • Pinctada maculata spats win the competition for space on the collectors in both locations during the 6 months survey. • Mismatch between environmental predictors of larvae dynamics between contrasting atolls. [ABSTRACT FROM AUTHOR]

Background: Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls., Methods: A prospective observational study was conducted in the intensive care units of the University Medical Center Hamburg-Eppendorf, Germany. IC was used to measure EE on days 2-3, 5-7, and 10-15 post-admission. Urinary catecholamines, metabolites, and urine urea were also measured. Statistical analysis included t -tests, Chi-square tests, and generalized mixed models., Results: We included 110 patients-43 SAH patients (13 with the surgical securing of the aneurysm and 30 with coil embolization of the aneurysm), 22 TBI patients, 23 ICH patients, and 22 controls. The generalized linear mixed model analysis for groups and timepoints including age, height, and weight as covariates revealed a significantly lower EE at timepoint 1 for ICH versus SAH-interventional ( p = 0.003) and versus the control ( p = 0.004), as well as at timepoint 2 for ICH versus SAH-interventional ( p = 0.002) and versus SAH-surgical ( p = 0.013) with a lower EE in ICH patients. No significant differences between groups were found for EE at the other timepoints, or concerning urine urea and measurements of catecholamines in urine., Conclusions: In patients with SAH, ICH, and TBI, no meaningful differences in EE were detected compared to septic critically ill patients, except for a lower EE in ICH patients in the early phase.

Evacuation of chronic subdural hematoma (CSDH) will be one of the most common neurosurgical procedures in the future in the increasingly aging societies. Performing cranial surgery on awake patients may place a psychological burden on them. Aim of this study was to evaluate the psychological distress of patients during awake CSDH relief. Patients with awake evacuation of CSDH via burr hole trepanation were included in our monocentric prospective study. Patient perception and satisfaction were measured using standardized surveys 3-5 days and 6 months after surgery. Among other questionnaires, the Hospital Anxiety and Depression and the Impact of Event Scale, were used to quantify patients' stress. A total of 50 patients (mean age 72.9 years (range 51 - 92)) were included. During surgery, 28 patients reported pain (mean 4.1 (SD 3.3)). Postoperatively, 26 patients experienced pain (mean 2.7 (SD 2.6)). Patients' satisfaction with intraoperative communication was reported with a mean of 8.3 (SD 2.1). There was a significant negative correlation between intraoperatively perceived pain and satisfaction with intraoperative communication (p = 0.023). Good intraoperative communication during evacuation of CSDH in awake patients is associated with positive patient perception and correlates with pain reduction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Aneurysmal subarachnoid hemorrhage (SAH) presents occasionally with cardiac arrest (CA). The impact of pre-hospital and emergency room (ER) treatment on outcome remains unclear. Therefore, we investigated the impact of pre-hospital treatment, focusing on lay cardiopulmonary resuscitation (CPR), and ER handling on the outcome of SAH patients with out-of-hospital CA (OHCA)., Methods: In this bi-centric retrospective analysis, we reviewed SAH databases for OHCA and CPR from January 2011 to June 2021. Patients were analyzed for general clinical and epidemiological parameters. CPR data were obtained from ambulance reports and information on ER handling from the medical records. Data were correlated with patient survival at hospital discharge as a predefined outcome parameter., Results: Of 1,120 patients with SAH, 45 (4.0%) were identified with OHCA and CPR, 38 of whom provided all required information and were included in this study. Time to resuscitation was significantly shorter with lay resuscitation (5.3 ± 5.2 min vs. 0.3 ± 1.2 min, p  = 0.003). Nineteen patients were not initially scheduled for cranial computed tomography (CCT), resulting in a significantly longer time interval to first CCT (mean ± SD: 154 ± 217 min vs. 40 ± 23 min; p  < 0.001). Overall survival to discharge was 31.6%. Pre-hospital lay CPR was not associated with higher survival ( p  = 0.632). However, we observed a shorter time to first CCT in surviving patients ( p  = 0.065)., Conclusions: OHCA in SAH patients is not uncommon. Besides high-quality CPR, time to diagnosis of SAH appears to play an important role. We therefore recommend considering CCT diagnostics as part of the diagnostic algorithm in patients with OHCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pantel, Neulen, Mader, Kurz, Piffko, Fassl, Westphal, Gempt, Ringel and Czorlich.)

Introduction: Patients with traumatic brain injury (TBI) regularly require intensive care with prolonged invasive ventilation. Consequently, these patients are at increased risk of pulmonary failure, potentially requiring extracorporeal membrane oxygenation (ECMO). The aim of this work was to provide an overview of ECMO treatment in TBI patients based upon data captured into the TraumaRegister DGU® (TR-DGU)., Methods: A retrospective multi-center cohort analysis of patients registered in the TR-DGU was conducted. Adult patients with relevant TBI (AIS Head ≥3) who had been treated in German, Austrian, or Swiss level I or II trauma centers using ECMO therapy between 2015 and 2019 were included. A multivariable logistic regression analysis was used to identify risk factors for the need for ECMO treatment., Results: 12,247 patients fulfilled the inclusion criteria. The overall rate of ECMO treatment was 1.1% (134 patients). Patients on ECMO had an overall hospital mortality rate of 38% (51/134 patients) while 13% (1523/12,113 patients) of TBI patients without ECMO therapy died. Male gender (p = 0.014), AIS Chest 3+ (p<0.001), higher Injury Severity Score (p<0.001) and packed red blood cell (pRBC) transfusion (p<0.001) were associated with ECMO treatment., Conclusion: ECMO therapy is a potentially lifesaving modality for the treatment of moderate-to-severe TBI when combined with severe chest trauma and pulmonary failure. The in-hospital mortality is increased in this high-risk population, but the majority of patients is surviving., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Acute and chronic hydrocephalus are common pathologies after aneurysmal subarachnoid hemorrhage (SAH). Generally, the presence of acute hydrocephalus is associated with elevated intracranial pressure (ICP) treated with a ventricular drain. Subsequently, however, pronounced hydrocephalus without elevated ICP may develop in some patients with SAH in the postacute phase. This is described as acute low-pressure hydrocephalus (aLPH), and there are very limited data in the literature of this pathology. The aim of this study was to evaluate the rate of and factors associated with aLPH and describe its clinical course., Methods: In this retrospective single-center cohort study, the frequency and clinical characteristics of SAH-associated aLPH were investigated. Acute LPH was defined as an increase in ventricular size as measured by the Evans index, ICP within the normal range (< 5 mm Hg) at the time of ventricular enlargement, and timely neurological improvement after indwelling ventricular CSF drainage with negative pressure up to 5 cm H2O below normal level. Demographic and SAH-specific factors in patients with SAH treated using an external ventricular drain were extracted from the electronic medical chart and further analyzed., Results: From November 2010 to May 2020, 15 (3.7.%) of 406 patients with SAH fulfilled the criteria for aLPH. Acute LPH was diagnosed after an average of 13.1 ± 7.7 days. The presence of IVH and its extension were associated with the occurrence of aLPH. After undergoing the transient phase of aLPH, these patients subsequently developed a chronic, typical malresorptive hydrocephalus requiring a ventriculoperitoneal shunt more often (66.7% vs 17.4%, p < 0.001) and stayed longer in the intensive care unit (27 vs 20.5 days, p = 0.043) and in the hospital (36.4 vs 26.3 days, p = 0.004)., Conclusions: Acute LPH is a rare pathology in patients with SAH and negatively impacts the clinical course. It should be especially considered in patients with a lack of neurological improvement, an increase in ventricular width, and normal ICP values, so that forced CSF drainage is implemented.

Rationale: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH., Aim: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients., Methods and Design: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients., Sample Size Estimates: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21., Study Outcome: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6)., Discussion: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.

A multitude of pathological and inflammatory processes determine the clinical course after aneurysmal subarachnoid hemorrhage (aSAH). However, our understanding of predictive factors and therapeutic consequences is limited. We evaluated the predictive value of clinically relevant factors readily available in the ICU setting, such as white blood cell (WBC) count and CRP, for two of the leading comorbidities, delayed cerebral ischemia (DCI) and ventriculoperitoneal (VP) shunt dependency in aSAH patients with and without corticosteroid treatment. We conducted a retrospective analysis of 484 aSAH patients admitted to our institution over an eight-year period. Relevant clinical factors affecting the risk of DCI and VP shunt dependency were identified and included in a multivariate logistic regression model. Overall, 233/484 (48.1%) patients were treated with corticosteroids. Intriguingly, predictive factors associated with the occurrence of DCI differed significantly depending on the corticosteroid treatment status (dexamethasone group: Hunt and Hess grade ( p = 0.002), endovascular treatment ( p = 0.016); no-dexamethasone group: acute hydrocephalus ( p = 0.018), peripheral leukocyte count 7 days post SAH (WBC at day 7) ( p = 0.009)). Similar disparities were found for VP shunt dependency (dexamethasone group: acute hydrocephalus ( p = 0.002); no-dexamethasone group: WBC d7 ( p = 0.036), CRP peak within 72 h ( p = 0.015)). Our study shows that corticosteroid-induced leukocytosis negates the predictive prognostic potential of systemic inflammatory markers for DCI and VP shunt dependency, which has previously been neglected and should be accounted for in future studies.

The evolution of intracranial pressure (ICP) of critically ill patients admitted to a neurointensive care unit (ICU) is difficult to predict. Besides the underlying disease and compromised intracranial space, ICP is affected by a multitude of factors, many of which are monitored on the ICU, but the complexity of the resulting patterns limits their clinical use. This paves the way for new machine learning techniques to assist clinical management of patients undergoing invasive ICP monitoring independent of the underlying disease. An institutional cohort (ICP-ICU) of patients with invasive ICP monitoring (n = 1346) was used to train recurrent machine learning models to predict the occurrence of ICP increases of ≥22 mmHg over a long (>2 h) time period in the upcoming hours. External validation was performed on patients undergoing invasive ICP measurement in two publicly available datasets [Medical Information Mart for Intensive Care (MIMIC, n = 998) and eICU Collaborative Research Database (n = 1634)]. Different distances (1-24 h) between prediction time point and upcoming critical phase were evaluated, demonstrating a decrease in performance but still robust AUC-ROC with larger distances (24 h AUC-ROC: ICP-ICU 0.826 ± 0.0071, MIMIC 0.836 ± 0.0063, eICU 0.779 ± 0.0046, 1 h AUC-ROC: ICP-ICU 0.982 ± 0.0008, MIMIC 0.965 ± 0.0010, eICU 0.941 ± 0.0025). The model operates on sparse hourly data and is stable in handling variable input lengths and missingness through its nature of recurrence and internal memory. Calculation of gradient-based feature importance revealed individual underlying decisions for our long short time memory-based model and thereby provided improved clinical interpretability. Recurrent machine learning models have the potential to be an effective tool for the prediction of ICP increases with high translational potential., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological disorders. Nitric oxide is generated by nitric oxide synthases from the amino acid L-arginine. L-arginine can also serve as a substrate for arginases or lead to the generation of dimethylarginines, asymmetric dimethylarginine, and symmetric dimethylarginine, by methylation. Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and can lead to endothelial dysfunction. This review discusses the role of L-arginine metabolism in patients suffering from acute and critical neurological disorders often requiring neuro-intensive care treatment. Conditions addressed in this review include intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury. Recent therapeutic advances in the field are described including current randomized controlled trials for traumatic brain injuries and hemorrhagic stroke., Competing Interests: None

Objectives: In difficult-to-treat infections such as nosocomial ventriculitis, meropenem exposure in the infected compartment is often uncertain but crucial for antibacterial effects. The aim of this study was to investigate the cerebrospinal fluid (CSF) penetration of meropenem in patients with nosocomial ventriculitis and to derive a nomograph to predict effective meropenem doses as a function of clinical parameters., Methods: Retrospective patient data including meropenem serum and CSF levels as well as CSF inflammation markers were analyzed using NONMEM to assess the general pharmacokinetics and CSF penetration. Monte Carlo simulations were used to evaluate different meropenem dosing regimens. Probability of target attainment (PTA) in CSF was assessed, and a nomograph to achieve a target twice the minimal inhibitory concentration (MIC) during the dosing interval (100 %fT  > 2x MIC ) was developed., Results: A one-compartment model with meropenem clearance dependent on the estimated glomerular filtration rate (CKD-EPI eGFR, p < 0.001) best described meropenem serum pharmacokinetics of 51 critically ill patients. CSF penetration ratio was correlated with the amount of protein in CSF (p < 0.001), with higher CSF protein levels accounting for higher penetration ratios. Preserved renal function (CKD-EPI eGFR >50 mL/min/1.73 m 2 ) and low CSF protein levels (<500 mg/L) resulted in 80% PTA 100 %fT  > 2x MIC ) for a meropenem dose of 6 g/24 h., Discussion: High interindividual variability in meropenem CSF concentration was observed in patients with nosocomial ventriculitis. A nomograph to predict the daily meropenem dose required for target attainment for a given eGFR and CSF protein count was developed., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The role of pelvic circumferential compression devices (PCCD) is to temporarily stabilize the pelvic ring, reduce its volume and to tamponade bleeding. The purpose of this study was to evaluate the effect of PCCDs on mortality and bleeding in severely injured trauma patients, using a large registry database. Methods: We performed a retrospective analysis of all patients registered in the Trauma Register DGU® between 2015 and 2016. The study was limited to directly admitted patients who were alive on admission, with an injury severity score (ISS) of 9 or higher, with an Abbreviated Injury Scale AIS pelvis of 3-5, aged at least 16, and with complete status documentation on pelvic circular compression devices (PCCD) and mortality. A cohort analysis was undertaken of patients suffering from relevant pelvic fractures. Data were collected on mortality and requirements for blood transfusion. The observed outcome was compared with the expected outcome as derived from version II of the Revised Injury Severity Classification (RISC II) and adjusted accordingly. A Standardized Mortality Ratio (SMR) was also calculated. Results: A total of 9,910 patients were included. 1,103 of 9,910 patients suffered from a relevant pelvic trauma (AIS pelvis = 3-5). Only 41% (454 cases) of these received a PCCD. PCCD application had no significant effect on mortality and did not decrease the need for blood transfusion in the multivariate regression analysis. However, in this cohort, the application of a PCCD is a general indicator for a critical patient with increased mortality (12.0% no PCCD applied vs. 23.2% PCCD applied prehospital vs. 27.1% PCCD applied in the emergency department). The ISS was higher in patients with PCCD (34.12 ± 16.4 vs. 27.9 ± 13.8; p < 0.001). Conclusion: PCCD was applied more often in patients with severe pelvic trauma according to ISS and AIS pelvis as well with deterioration in circulatory status. PCCDs did not reduce mortality or reduce the need for blood transfusion. Trial registration: TR-DGU ID 2017-003, March 2017; German clinical trial register DRKS00024948.

Objective: The influence of preexisting factors on the clinical course of patients with subarachnoid hemorrhage (SAH), such as patient age, arterial hypertension, and aneurysm characteristics, is still a matter of debate. However, the specific impact of the exact aneurysm location has not received adequate attention. Therefore, the aim of this study was to investigate the influence of aneurysm location as a preexisting factor on the clinical course and mortality., Methods: The data of consecutive patients with aneurysmal SAH who were treated from October 2010 to July 2020 were retrospectively analyzed. We distinguished four aneurysm locations: the anterior complex, internal carotid artery (ICA), middle cerebral artery (MCA), and posterior circulation. Logistic regression analysis and receiver operating characteristics were used to investigate the influence of aneurysm location on the occurrence of acute hydrocephalus, Delayed Cerebral Ischemia (DCI), neurological outcome, and in-hospital mortality. Neurological outcome was assessed 3 months after discharge using the Glasgow Outcome Scale., Results: A total of 603 patients were included in this study. Patients with MCA aneurysms were 2.52 times less likely to develop acute hydrocephalus compared to patients with anterior complex aneurysms ( p = 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm and least frequently in MCA aneurysms ( p = 0.014). In ICA aneurysms, mortality was 2.56-fold higher than in patients with aneurysms of the anterior complex ( p = 0.006). An additional ROC analysis showed a good prediction for in-hospital mortality when taking the aneurysm's location into account [AUC.855 (CI.817 -0.893)]., Conclusions: The aneurysm's location proved to be a significant predictor of acute hydrocephalus, DCI, and in-hospital mortality, demonstrating the impact of this preexisting biological factor on the course of SAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Göttsche, Piffko, Pantel, Westphal, Dührsen, Czorlich and Sauvigny.)

Extracorporeal membrane oxygenation (ECMO) is potentially lifesaving for patients with acute respiratory distress syndrome (ARDS) but may be accompanied by serious adverse events, including intracranial hemorrhage (ICRH). We hypothesized that ICRH occurs more frequently in patients with COVID-19 than in patients with ARDS of other etiologies. We performed a single-center retrospective analysis of adult patients treated with venovenous (vv-) ECMO for ARDS between January 2011 and April 2021. Patients were included if they had received a cranial computed tomography (cCT) scan during vv-ECMO support or within 72 h after ECMO removal. Cox regression analysis was used to identify factors associated with ICRH. During the study period, we identified 204 patients with vv-ECMO for ARDS, for whom a cCT scan was available. We observed ICRH in 35.4% ( n = 17/48) of patients with COVID-19 and in 16.7% ( n = 26/156) of patients with ARDS attributable to factors other than COVID-19. COVID-19 (HR: 2.945; 95%; CI: 1.079-8.038; p = 0.035) and carboxyhemoglobin (HR: 0.330; 95%; CI: 0.135-0.806; p = 0.015) were associated with ICRH during vv-ECMO. In patients receiving vv-ECMO, the incidence of ICRH is doubled in patients with COVID-19 compared to patients suffering from ARDS attributable to other causes. More studies on the association between COVID-19 and ICRH during vv-ECMO are urgently needed to identify risk patterns and targets for potential therapeutic interventions.

Objective: Several guidelines recommend oral administration of nimodipine as vasospasm prophylaxis after aneurysmal subarachnoid hemorrhage (SAH). However, in clinical practice, the drug is administered orally and intravenously (i.v.), depending on clinical conditions and local treatment regimens. We have therefore investigated the safety and clinical effects of switching from i.v. to oral nimodipine therapy. Methods: Patients with aneurysmal SAH between January 2014 and April 2018 and initial i.v. nimodipine therapy, which was subsequently switched to oral administration, were included in this retrospective study. Transcranial Doppler sonography (TCD) of the vessels of the anterior circulation was performed daily. The occurrence of vasospasm and infarction during the overall course of the treatment was recorded. Statistical level of significance was set to p < 0.05. Results: A total of 133 patients (mean age 55.8 years, 65% female) initially received nimodipine i.v. after aneurysmal SAH, which was subsequently switched to oral administration after a mean of 12 days. There were no significant increases in mean flow velocities on TCD after the switch from i.v. to oral nimodipine administration regarding the anterior cerebral artery. For the middle cerebral artery, an increase from 62.36 to 71.78 cm/sec could only be detected in the subgroup of patients with infarction. There was no clustering of complicating events such as new-onset vasospasm or infarction during or after the switch. Conclusions: Our results do not point to any safety concerns when switching nimodipine from initial i.v. to oral administration. Switching was neither associated with clinically relevant increases in TCD velocities nor other relevant adverse events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Göttsche, Schweingruber, Groth, Gerloff, Westphal and Czorlich.)