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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.

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.

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.

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.

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Cultured pearls are human creations formed by inserting a nucleus and a small piece of mantle tissue into a living shelled mollusc, usually a pearl oyster. Although many pearl observations intuitively suggest a possible rotation of the nucleated pearl inside the oyster, no experimental demonstration of such a movement has ever been done. This can be explained by the difficulty of observation of such a phenomenon in the tissues of a living animal. To investigate this question of pearl rotation, a magnetometer system was specifically engineered to register magnetic field variations with magnetic sensors from movements of a magnetic nucleus inserted in the pearl oyster. We demonstrated that a continuous movement of the nucleus inside the oyster starts after a minimum of 40 days post-grafting and continues until the pearl harvest. We measured a mean angular speed of 1.27° min−1 calculated for four different oysters. Rotation variability was observed among oysters and may be correlated to pearl shape and defects. Nature's ability to generate so amazingly complex structures like a pearl has delivered one of its secrets.