[Climate Crisis: What Gastrointestinal Complications of this Medical Emergency Should We Be Aware Of?] / Klimakrise: Welche gastroenterologischen Folgeerkrankungen dieses medizinischen Notfalls sollten wir kennen?

INTRODUCTION: The climate crisis has serious consequences for many areas of life. This applies in particular to human health - also in Europe. While cardiovascular, pneumological and dermatological diseases related to the climate crisis are often discussed, the crisis' significant gastroenterological consequences for health must also be considered. METHODS: A literature search (Pubmed, Cochrane Library) was used to identify papers with relevance particularly to the field of gastroenterology in (Central) Europe. Findings were supplemented and discussed by an interdisciplinary team. RESULTS: The climate crisis impacts the frequency and severity of gastrointestinal diseases in Europe due to more frequent and severe heat waves, flooding and air pollution. While patients with intestinal diseases are particularly vulnerable to acute weather events, the main long-term consequences of climate change are gastrointestinal cancer and liver disease. In addition to gastroenteritis, other infectious diseases such as vector-borne diseases and parasites are important in the context of global warming, heat waves and floods. DISCUSSION: Adaptation strategies must be consistently developed and implemented for vulnerable groups. Patients at risk should be informed about measures that can be implemented individually, such as avoiding heat, ensuring appropriate hydration and following hygiene instructions. Recommendations for physical activity and a healthy and sustainable diet are essential for the prevention of liver diseases and carcinomas. Measures for prevention and the promotion of resilience can be supported by the physicians at various levels. In addition to efforts fostering sustainability in the immediate working environment, a system-oriented commitment to climate protection is important.

Treatment of mid-trimester preterm premature rupture of membranes (PPROM) with multi-resistant bacteria-colonized anhydramnion with continuous amnioinfusion and meropenem: a case report and literature review.

PURPOSE: Treatment of mid-trimester classic preterm premature rupture of membranes (PPROM) with systemic antibiotics has limited success in the prevention of chorioamnionitis, funisitis and fetal inflammatory response syndrome because of very low transplacental passage. METHODS: Here we report a case of PPROM at 18 weeks gestation with anhydramnion colonized by multi-resistant Escherichia coli (E. coli). A catheter system was implanted at 23/2nd weeks gestation, enabling long-term continuous lavage of the amniotic cavity with Amnion Flush Solution (100 ml/h combined with intraamniotic meropenem application). RESULTS: The patient gave birth to a preterm male infant at 28/3rd without any signs of infection. In a follow-up examination at 24 months, there was no neurological disturbance or developmental delay. CONCLUSION: The classic PPROM with multi-resistant E. coli colonization could be treated with continuous amnioinfusion and meropenem.

[Reduction of Visitor- and Staff-Associated Risk of Infection by Complex Intervention in the Department of Feto-Maternal Medicine]. / Reduktion des Besucher- und Personal- assoziierten Infektionsrisikos durch komplexe Intervention auf perinatologischen Stationen.

AIM: Clinical trial registration of this trial: is to demonstrate in a department of feto-maternal medicine: (a) that a complex intervention improves hand hygiene of visitors, siblings and staff; and (b) that automated voice prompts at disinfectant dispensers improve rate of hand disinfection. STUDY DESIGN: (a) Pre-/post-test follow-up design with control (1-12/2016), intervention (1-12/2017), follow-up-period (1/2018-12/2019); and (b) RCT in quasi crossover design. Primary endpoints: (a) disinfectant consumption (DC) per patient-day, and (b) DC at disinfectant dispenser per passer-by. RESULTS: A multimodal strategy within the intervention period showed a relevant positive effect on hand hygiene compliance (in IP: 26.2% more DC; p=0.088). Voice prompts increased DC by 28.6% (p=0.025). The odds ratio for high positive fingertip testing plates of visiting children (siblings) between control and intervention period was 0.35 (95% CI [0.1074-0.9708] p=0.039). CONCLUSION: Complex intervention and electronic voice prompts on disinfectant dispensers improve hand hygiene behaviour in perinatology. Installation of disinfectant dispensers in a child-friendly position and adequate information material appeal to children. The data represent an important contribution to improve hand hygiene of visitors, siblings and staff in hospitals in a pandemic situation.

Estimation of creatinine clearance using plasma creatinine or cystatin C: a secondary analysis of two pharmacokinetic studies in surgical ICU patients.

BACKGROUND: In ICU patients, glomerular filtration is often impaired, but also supraphysiological values are observed ("augmented renal clearance", >130 mL/min/1.73 m(2)). Renally eliminated drugs (e.g. many antibiotics) must be adjusted accordingly, which requires a quantitative measure of renal function throughout all the range of clinically encountered values. Estimation from plasma creatinine is standard, but cystatin C may be a valuable alternative. METHODS: This was a secondary analysis of renal function parameters in 100 ICU patients from two pharmacokinetic studies on vancomycin and betalactam antibiotics. Estimated clearance values obtained by the Cockcroft-Gault formula (eCLCG), the CKD-EPI formula (eCLCKD-EPI) or the cystatin C based Hoek formula (eCLHoek) were compared with the measured endogenous creatinine clearance (CLCR). Agreement of values was assessed by modified Bland-Altman plots and by calculating bias (median error) and precision (median absolute error). Sensitivity and specificity of estimates to identify patients with reduced (<60 mL/min/1.73 m(2)) or augmented (>130 mL/min/1.73 m(2)) CLCR were calculated. RESULTS: The CLCR was well distributed from highly compromised to supraphysiological values (median 73.2, range 16.8-234 mL/min/1.73 m(2)), even when plasma creatinine was not elevated (≤0.8 mg/dL for women, ≤1.1 mg/dL for men). Bias and precision were +13.5 mL/min/1.73 m(2) and ±18.5 mL/min/1.73 m(2) for eCLCG, +7.59 and ±16.8 mL/min/1.73 m(2) for eCLCKD-EPI, and -4.15 and ±12.9 mL/min/1.73 m(2) for eCLHoek, respectively, with eCLHoek being more precise than the other two (p < 0.05). The central 95% of observed errors fell between -59.8 and +250 mL/min/1.73 m(2) for eCLCG, -83.9 and +79.8 mL/min/1.73 m(2) for eCLCKD-EPI, and -103 and +27.9 mL/min/1.73 m(2) for eCLHoek. Augmented renal clearance was underestimated by eCLCKD-EPI and eCLHoek. Patients with reduced CLCR were identified with good specificity by eCLCG, eCLCKD-EPI and eCLHoek (0.95, 0.97 and 0.91, respectively), but with less sensitivity (0.55, 0.55 and 0.83). For augmented renal clearance, specificity was 0.81, 0.96 and 0.96, but sensitivity only 0.69, 0.25 and 0.38. CONCLUSIONS: Normal plasma creatinine concentrations can be highly misleading in ICU patients. Agreement of the cystatin C based eCLHoek with CLCR is better than that of the creatinine based eCLCG or eCLCKD-EPI. Detection and quantification of augmented renal clearance by estimates is problematic, and should rather rely on CLCR.

Cervical Necrotizing Fasciitis--The Value of the Laboratory Risk Indicator for Necrotizing Fasciitis Score as an Indicative Parameter.

PURPOSE: Cervical necrotizing fasciitis (CNF) is uncommon, difficult to diagnose, and rapidly progressive. The objective of the present study was to determine the predictive value of the laboratory risk indicator for necrotizing fasciitis (LRINEC) score for CNF. MATERIALS AND METHODS: The LRINEC score for 16 consecutive cases of CNF and 595 cases of severe non-necrotizing neck infections was determined over a 6.5-year period in a single-center retrospective cohort study and case report. CNF was confirmed by histologic examination and operative report documentation. RESULTS: Using a cutoff score of 6, the LRINEC score had a sensitivity of 0.94 (95% confidence interval [CI] 0.92 to 0.96) and specificity of 0.94 (95% CI 0.70 to 1.00). The positive predictive value was 0.29 (95% CI 0.17 to 0.44), and the negative predictive value was 0.99 (95% CI 0.99 to 1.00). CONCLUSIONS: The LRINEC score can detect early cases of CNF. Patients with a LRINEC score of ≥6 must be carefully evaluated for the presence of CNF.

When rare becomes common: N2 gene-positive, E gene-negative SARS-CoV-2 PCR results between 2021 and 2022.

Nucleocapsid gene-positive, envelope gene-negative (N2+/E-) SARS-CoV-2 PCR results obtained with the Cepheid Xpert Xpress SARS-CoV-2 assay are an infrequent phenomenon. We assessed the validity of the N2+/E- cases with an indirect approach by analyzing their occurrence in relation to overall positive PCR rates and absolute number of PCR tests (24,909 samples, collected June 2021 to July 2022). Additionally, 3022 samples were analyzed with the Xpert Xpress CoV-2-plus assay in August/September 2022. The incidence of monthly N2+/E- cases closely followed the overall frequency of positive tests (p < 0.001), while there was no correlation with the monthly number of PCR test. The observed distribution of N2+/E- cases implicates, that they are not merely artefacts, but rather represent samples with a very low viral load. This phenomenon will persist with the Xpert Xpress SARS-CoV-2 plus assay, which also produced more than 10% results where only one target gene replicated with a very high Ct value.

Monitoring Antibiotic Consumption in Pediatrics. How Close to Reality Are Days of Therapy and Recommended Daily Dose Methods?

BACKGROUND: Hospitals are advised to monitor antibiotic use. Several approximation methods do exist to perform this task. Adult cohorts can easily be monitored using the defined daily dose method, or its German adaption recommended daily doses (RDD) method, that seems inapplicable in pediatric cohorts due to body weight variations. Guidelines recommend the days of therapy (DOT) method in pediatrics. Still, there is a need for more detailed analysis regarding the performance of both methods. METHODS: Based on data from 4½ years of our fully computerized patient care data managing system in a combined neonatal and pediatric intensive care unit, we compare the results for DOT and RDD per 100 patient days with exact measurement of antibiotic consumption (individual daily dose per 100 patient days) as internal reference. RESULTS: The DOT method reflected antibiotic consumption in our cohort on the level of total consumption, subgroups, and agents with almost always high accuracy (correlation with individual daily dose between 0.73 and 1.00). The RDD method showed poor correlation on the level of total consumption (r = 0.21) and fluctuating results on more detailed levels (correlation, 0.01-0.94). A detailed analysis of body weight distribution and ordered packaging sizes of single agents revealed that RDD seems to work well when only one package size of the agent was ordered in our pharmacy. CONCLUSION: The DOT method is superior to RDD for monitoring antibiotic drug consumption in pediatric cohorts. RDD seems to work satisfactory well for selected antibiotic agents that are administered with little variation in packaging size.

Hypoactive delirium after cardiac surgery as an independent risk factor for prolonged mechanical ventilation.

OBJECTIVE: The authors' intention was to evaluate the incidence of the three subtypes of delirium, the risk factors of the subtypes in cardiac surgery, and the impact of the subtypes on clinical outcomes. DESIGN: A prospective study. SETTING: A university hospital. PARTICIPANTS: A total population of 506 patients undergoing cardiac surgery was screened for delirium. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients undergoing cardiac surgery were screened by using the Intensive Care Delirium Screening Checklist (ICDSC) and the Richmond Agitation and Sedation Scale (RASS). Patients with hypoactive delirium were compared with nondelirious patients. Outcomes measured were the duration of mechanical ventilation and the length of stay in the intensive care unit. The overall delirium incidence was 11.6%, whereas the incidence of the hypoactive subtype was 9%. Age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.09, p = 0.02), a history of depression (OR = 3.57; 95% CI, 1.04-10.74; p = 0.03), preoperative therapy with diuretics (OR = 2.85; 95% CI, 1.36-6.35; p < 0.01), aortic clamping times (OR = 1.01; 95% CI, 1.00-1.02; p < 0.01) and blood transfusions (OR = 1.18; 95% CI, 1.05-1.34; p < 0.01) were predictors for the development of hypoactive delirium. Preoperative therapy with ß-blockers (OR = 0.32; 95% CI, 0.16-0.65; p < 0.01) and higher hemoglobin before surgery (OR = 0.73; 95% CI, 0.60-0.91; p < 0.01) were associated with a lower prevalence of hypoactive delirium. Hypoactive delirium is an independent predictor for prolonged mechanical ventilation time (OR = 1.56; 95% CI, 1.25-1.92; p < 0.01) and the length of stay in the ICU (OR = 1.42; 95% CI, 1.22-1.65, p < 0.01). CONCLUSION: Hypoactive delirium itself is a strong predictor for a longer ICU stay and a prolonged period of mechanical ventilation. Some of the risk factors related to the intraoperative and postoperative setting are suitable for preventive action.

[West-Nile-Virus Infection acquired in Germany in a Kidney Transplant Recipient]. / In Deutschland erworbene West-Nil-Virusinfektion bei einem nierentransplantierten Patienten.

BACKGROUND: West-Nile-Virus (WNV) is a widely distributed flavivirus that is mainly transmitted between birds through different mosquito species (e. g. Culex, Aedes), but may also be transmitted to mammals including humans. WNV causes a spectrum of disease, ranging from asymptomatic infection to encephalitis in a minority of cases. Risk factors for severe disease are older age, cardiovascular disease and an immunocompromised state. MEDICAL HISTORY AND CLINICAL EXAMINATION: Here we report about a 60-year-old male patient who was referred to the University Hospital of Halle (Saale) with severe fever two years after kidney transplantation due to hypertensive nephropathy. No infection focus could be found and by day 6 in the course of his illness the patient developed neurologic symptoms and viral encephalitis was suspected. TREATMENT AND COURSE: The patient was initially treated with aciclovir. After initial reduction of immunosuppression, coincident graft dysfunction was treated with methylprednisolon. WNV-infection was suspected due to recent emerging human cases in the nearby area of the city of Leipzig. WNV lineage 2 was detected in the patient's urine by RT-PCR and seroconversion with presence of anti WNV IgM and IgG could be demonstrated. Consecutively, aciclovir treatment was stopped. The patient fully recovered and the transplanted kidney regained adequate function. Kidney biopsy did not reveal gross rejection of the transplant. CONCLUSION: This case highlights the need to consider rarer causes of illness like WNV-infection particularly in risk groups for more severe outcomes of infectious disease. WNV may be detected by PCR in the blood and cerebrospinal fluid early in the course of infection but it is also excreted for a prolonged period of time in the urine. Seroconversion to anti WNV IgG and IgM may be shown but serologic cross-reactivity among members of the flaviviridae family must be considered.

The risk of indoor sports and culture events for the transmission of COVID-19.

Nearly all mass gathering events worldwide were banned at the beginning of the COVID-19 pandemic, as they were suspected of presenting a considerable risk for the transmission of SARS-CoV-2. We investigated the risk of transmitting SARS-CoV-2 by droplets and aerosols during an experimental indoor mass gathering event under three different hygiene practices, and used the data in a simulation study to estimate the resulting burden of disease under conditions of controlled epidemics. Our results show that the mean number of measured direct contacts per visitor was nine persons and this can be reduced substantially by appropriate hygiene practices. A comparison of two versions of ventilation with different air exchange rates and different airflows found that the system which performed worst allowed a ten-fold increase in the number of individuals exposed to infectious aerosols. The overall burden of infections resulting from indoor mass gatherings depends largely on the quality of the ventilation system and the hygiene practices. Presuming an effective ventilation system, indoor mass gathering events with suitable hygiene practices have a very small, if any, effect on epidemic spread.

Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock.

In this prospective, randomized animal study, the role of proinflammatory cytokines in the pathogenesis sepsis-induced circulatory failure with downregulation of angiotensin-II-type-I-(AT(1))-receptors was investigated. Sepsis in wild-type mice and in mice with deficiencies for TNF-alpha, IL-1beta, IFN-gamma or IL-6 was induced by cecal ligation and puncture (CLP) and wild-type mice were injected with cytokines. Animals were treated with glucocorticoids or small interfering RNA (siRNA) targeting single or multiple cytokines or NF-kappaB. Vascular smooth muscle cells (VSMCs) were incubated with cytokines. CLP resulted in circulatory failure and a significant downregulation of AT(1)-receptors. Injection of single proinflammatory cytokines also strongly downregulated AT(1)-receptors paralleled by a markedly endogenous liberation of further cytokines, whereas, simultaneous blockade of these endogenously activated cytokines by dexamethasone prevented downregulation of AT(1)-receptors. Furthermore, inhibition of multiple but not single cytokines by treatment with siRNA against multiple cytokines or NF-kappaB significantly attenuated CLP-induced AT(1)-receptor downregulation and prevented septic circulatory failure. Our data demonstrate that downregulation of AT(1)-receptors during sepsis is due to multiple but not single cytokines and define a relevant role for NF-kappaB in the pathogenesis of septic shock.

Radial oxygen gradients over rat cortex arterioles.

PURPOSE: We present the results of the visualisation of radial oxygen gradients in rats' cortices and their potential use in neurocritical management. METHODS: PO2 maps of the cortex of ten sedated, intubated and controlled ventilated Wistar rats were obtained with a camera (SensiMOD, PCO, Kelheim, Germany). Those pictures were analysed and edited by a custom-made software. A virtual matrix, designed to evaluate the cortical O2 partial pressure, was placed vertically to the artery under investigation, and afterwards multiple regions of interest were measured (width 10 pixels, length 15-50 pixels). The results showed a map of the cerebral oxygenation, which allowed us to calculate radial oxygen gradients over arterioles. Three groups were defined according to the level of the arterial pO2: PaO2 < 80, PaO2 80-120 and PaO2 > 120. Gradients were analysed from the middle of the vessel to its border (1), from the border into the parenchyma next to the vessel (2) and a combination of both (3). RESULTS: Gradient 1 showed significantly different cortical pO2 values between the three different groups. The mean pO2 values were 2.62, 5.29 and 5.82 mmHg/mm. Gradient 2 measured 0.56, 0.90 and 1.02 mmHg/mm respectively. Gradient 3 showed significant results between the groups with values of 3.18, 6.19 and 6.84 mmHg/mm. CONCLUSION: Using these gradients, it is possible to describe and compare the distribution of oxygen to the brain parenchyma. With the presented technique, it is possible to detect pO2 changes in the oxygen supply of the brain cortex.

Circulatory arrest and deep hypothermia for the treatment of complex intracranial aneurysms--results from a single European center.

BACKGROUND: Vascular neurosurgery faces the controversial discussion about the need for deep hypothermia and circulatory arrest (dh/ca) for the treatment of complex cerebral aneurysms. In this retrospective analysis, we present our experience in the treatment of 26 giant and large cerebral aneurysms under profound hypothermia and circulatory arrest. METHODS: All patients were treated surgically under dh/ca. Seventeen patients had aneurysms of the anterior circulation, and nine patients had aneurysms of the posterior circulation. Thrombosis or calcification was found in ten patients. Eleven patients presented with subarachnoid hemorrhage. The seven patients with the longest circulation arrest time were analyzed in detail. RESULTS: Subarachnoid hemorrhage led to hospital admission in 42% (n = 11) of cases. The overall mortality was 11.5%, and the overall morbidity was 15%. Ten patients deteriorated transiently but fully recovered. The mean age, Glasgow Coma Score, Fisher, and Hunt and Hess Score correlated significantly with the long-term outcome. Circulation arrest time correlated significantly to the neurological outcome on discharge. All patients with prolonged circulation arrest times had wide aneurysmal necks, and four had adjacent vessels to the dome or the parent vessel included in the neck. We observed a significant increase of neurological deficits immediately postoperatively, but this neurological deterioration resolved over time. CONCLUSIONS: We observed neurological deterioration immediately postoperatively in 13 patients, but all patients fully recovered within 6 months except for four patients. A long cardiac arrest time reflected complex pathoanatomical conditions. We conclude that the clipping procedure under deep hypothermia and circulatory arrest remains a pivotal armament in complex vascular neurosurgery.

Determinants of cerebral oximetry in patients undergoing off-pump coronary artery bypass grafting: an observational study.

BACKGROUND AND OBJECTIVE: The present study investigated whether positioning of the heart during off-pump coronary artery bypass grafting leads to changes in regional cerebral oxygen saturation measured by near infrared spectroscopy. METHODS: In 35 consecutive patients undergoing elective off-pump coronary artery bypass grafting, cerebral oxygen saturation was measured by near infrared spectroscopy. A 20% decrease from baseline values was considered to be cerebral hypoperfusion. Mean arterial pressure, cardiac index, arterial carbon dioxide partial pressure, central venous pressure, haemoglobin concentration, and body temperature were determined simultaneously. Each value was recorded at the following time points: at baseline; after positioning the heart for distal anastomoses of the left anterior descending artery, the circumflex, and the right coronary artery; after repositioning the heart; and after chest closure. Significant changes in each parameter from baseline were detected using repeated-measures analysis of variance. Determinants of cerebral oxygen saturation during surgery were analysed by means of generalized estimation equations. RESULTS: Cerebral oxygen saturation remained constant during grafting of the left anterior descending artery and decreased significantly during grafting of the circumflex (P = 0.001) and the right coronary artery (P < 0.001). Cerebral hypoperfusion was found in seven (20%) patients. Changes in haemoglobin concentration (P = 0.014), arterial CO2 partial pressure (P = 0.001), cardiac output (P < 0.001), and central venous pressure (P = 0.014) determined alterations in cerebral oxygen saturation. CONCLUSION: Positioning of the heart during off-pump coronary artery bypass grafting leads to a decrease in regional cerebral oxygen saturation. This decrease is associated with changes in cardiac output, haemoglobin concentration, arterial CO2 partial pressure, and central venous pressure.

Accuracy of stroke volume variation compared with pleth variability index to predict fluid responsiveness in mechanically ventilated patients undergoing major surgery.

BACKGROUND AND OBJECTIVE: Accurate assessment of a patient's volume status is an important goal for an anaesthetist. However, most variables assessing fluid responsiveness are either invasive or technically challenging. This study was designed to compare the accuracy of arterial pressure-based stroke volume variation (SVV) and variations in the pulse oximeter plethysmographic waveform amplitude as evaluated with the noninvasive calculated pleth variability index (PVI) with central venous pressure to predict the response of stroke volume index (SVI) to volume replacement in patients undergoing major surgery. METHODS: We studied 20 patients scheduled for elective major abdominal surgery. After induction of anaesthesia, all haemodynamic variables were recorded immediately before (T1) and subsequent to volume replacement (T2) by infusion of 6% hydroxy-ethyl starch (HES) 130/0.4 (7 ml kg) at a rate of 1 ml kg min. RESULTS: The volume-induced increase in SVI was at least 15% in 15 patients (responders) and less than 15% in five patients (nonresponders). Baseline SVV correlated significantly with changes in SVI (DeltaSVI; r = 0.80; P < 0.001) as did baseline PVI (r = 0.61; P < 0.004), whereas baseline values of central venous pressure showed no correlation to DeltaSVI. There was no significant difference between the area under the receiver operating characteristic curve for SVV (0.993) and PVI (0.973). The best threshold values to predict fluid responsiveness were more than 11% for SVV and more than 9.5% for PVI. CONCLUSION: Although arterial pressure-derived SVV revealed the best correlation to volume-induced changes in SVI, the results of our study suggest that both variables, SVV and PVI, can serve as valid indicators of fluid responsiveness in mechanically ventilated patients undergoing major surgery.

Hospital-wide ELectronic medical record evaluated computerised decision support system to improve outcomes of Patients with staphylococcal bloodstream infection (HELP): study protocol for a multicentre stepped-wedge cluster randomised trial.

INTRODUCTION: Staphylococci are the most commonly identified pathogens in bloodstream infections. Identification of Staphylococcus aureus in blood culture (SAB) requires a prompt and adequate clinical management. The detection of coagulase-negative staphylococci (CoNS), however, corresponds to contamination in about 75% of the cases. Nevertheless, antibiotic therapy is often initiated, which contributes to the risk of drug-related side effects. We developed a computerised clinical decision support system (HELP-CDSS) that assists physicians with an appropriate management of patients with Staphylococcus bacteraemia. The CDSS is evaluated using data of the Data Integration Centers (DIC) established at each clinic. DICs transform heterogeneous primary clinical data into an interoperable format, and the HELP-CDSS displays information according to current best evidence in bacteraemia treatment. The overall aim of the HELP-CDSS is a safe but more efficient allocation of infectious diseases specialists and an improved adherence to established guidelines in the treatment of SAB. METHODS AND ANALYSIS: The study is conducted at five German university hospitals and is designed as a stepped-wedge cluster randomised trial. Over the duration of 18 months, 135 wards will change from a control period to the intervention period in a randomised stepwise sequence. The coprimary outcomes are hospital mortality for all patients to establish safety, the 90-day disease reoccurrence-free survival for patients with SAB and the cumulative vancomycin use for patients with CoNS bacteraemia. We will use a closed, hierarchical testing procedure and generalised linear mixed modelling to test for non-inferiority of the CDSS regarding hospital mortality and 90-day disease reoccurrence-free survival and for superiority of the HELP-CDSS regarding cumulative vancomycin use. ETHICS AND DISSEMINATION: The study is approved by the ethics committee of Jena University Hospital and will start at each centre after local approval. Results will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00014320.

The accuracy of jugular bulb venous monitoring in detecting cerebral ischemia in awake patients undergoing carotid endarterectomy.

To investigate the accuracy of jugular bulb venous monitoring in detecting cerebral ischemia, we performed ipsilateral jugular bulb venous monitoring in 48 patients undergoing carotid surgery under regional anesthesia. Cerebral ischemia was assumed when neurologic deterioration occurred. During carotid clamping, the maximal arterial-jugular venous oxygen content difference [AJDO2 (max)], the minimal jugular venous oxygen saturation [SjO2 (min)], the maximal arterial-jugular venous lactate content difference [AJDL (max)], the maximal lactate oxygen index [LOI (max)], and the maximal modified LOI [mLOI (max)] were determined. To quantify the selectivity of each parameter, we performed receiver operating characteristic analysis and determined the area under the curve. The cutoff points providing the highest accuracy and the corresponding sensitivity (Se) and specificity (Spec) were determined. Neurologic deterioration occurred in 12 patients. All parameters, except AJDO2 (max), showed significant ability to distinguish between ischemic and nonischemic patients. The area under the curve for AJDL (max) was 0.840, for SjO2 (min) 0.766, for LOI 0.745, for mLOI 0.748, and for AJDO2 (max) 0.672. We found cutoff points of > or =0.16 mmol/L for AJDL (max) (Se=67%; Spec=86%) and < or =55% for SjO2 (Se=75%; Spec=83%). In conclusion, the present investigation shows that AJDL, SjO2, LOI, and mLOI provide the ability to detect cerebral hypoperfusion. The highest accuracy was found for AJDL. Neither the calculation of LOI nor of mLOI showed improved results.

Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients.

Continuous infusion of meropenem is a candidate strategy for optimization of its pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are difficult to predict in critically ill patients. Steady-state concentrations of meropenem were determined prospectively during continuous infusion in 32 surgical ICU patients (aged 21-85 years, body weight 55-125 kg, APACHE II 5-29, measured creatinine clearance 22.7-297 mL/min). Urine was collected for the quantification of renal clearance of meropenem and creatinine. Cystatin C was measured as an additional marker of renal function. Population pharmacokinetic models were developed using NONMEM(®) , which described total meropenem clearance and its relationship with several estimates of renal function (measured creatinine clearance CLCR , Cockcroft-Gault formula CLCG , Hoek formula, 1/plasma creatinine, 1/plasma cystatin C) and other patient characteristics. Any estimate of renal function improved the model performance. The strongest association of clearance was found with CLCR (typical clearance = 11.3 L/h × [1 + 0.00932 × (CLCR - 80 mL/min)]), followed by 1/plasma cystatin C; CLCG was the least predictive covariate. Neither age, weight, nor sex was found to be significant. These models can be used to predict dosing requirements or meropenem concentrations during continuous infusion. The covariate CLCR offers the best predictive performance; if not available, cystatin C may provide a promising alternative to plasma creatinine.

The prognostic value of NSE and S100B from serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage.

Neuron-specific enolase (NSE) and S100B protein have been shown to be increased in cerebrospinal fluid (CSF) and serum of patients suffering from subarachnoid hemorrhage. This study was designed to evaluate the accuracy of NSE and S100B from CSF and serum for the prognosis of outcome and the detection of cerebral infarction, vasospasm and intracranial hypertension. In 55 patients with spontaneous subarachnoid hemorrhage and requiring external ventricular drainage the concentrations of NSE and S100B were determined daily from the serum and the CSF from admission until day 8. At ICU discharge patients' outcome was assessed by the Glasgow outcome scale and occurrence of cerebral infarction, vasospasm and intracranial hypertension were registered. Mean and peak values of each parameter for each patient were calculated. For accuracy assessment receiver operating characteristics were used. Bad outcome (Glasgow outcome scale 1 to 3) was found in 33 patients. Cerebral infarction, vasospasm, and intracranial hypertension were found in 31 (56%), 34 (62%), and 36 (65%) patients. Mean and peak values of NSE CSF (P<0.001), S100B CSF (P<0.001), and S100B serum (P<0.001) but not of NSE serum provided the ability to distinguish between patients with good and bad outcome. The accuracy of NSE CSF and S100B CSF did not differ significantly from that of S100B serum. NSE CSF (P<0.001), S100B CSF (P<0.001), and S100B serum (P<0.001) allowed the detection of cerebral infarction and intracranial hypertension. Cerebral vasospasm was detected by none of the parameters. In conclusion, NSE CSF, S100B CSF, and S100B serum provide similar prognostic values for outcome, intracranial hypertension and cerebral infarction. Significantly lower accuracy was found for NSE serum.