Predictive markers related to local and systemic inflammation in severe COVID-19-associated ARDS: a prospective single-center analysis.

BACKGROUND: As the COVID-19 pandemic strains healthcare systems worldwide, finding predictive markers of severe courses remains urgent. Most research so far was limited to selective questions hindering general assumptions for short- and long-term outcome. METHODS: In this prospective single-center biomarker study, 47 blood- and 21 bronchoalveolar lavage (BAL) samples were collected from 47 COVID-19 intensive care unit (ICU) patients upon admission. Expression of inflammatory markers toll-like receptor 3 (TLR3), heme oxygenase-1 (HO-1), interleukin (IL)-6, IL-8, leukocyte counts, procalcitonin (PCT) and carboxyhemoglobin (CO-Hb) was compared to clinical course. Clinical assessment comprised acute local organ damage, acute systemic damage, mortality and outcome after 6 months. RESULTS: PCT correlated with acute systemic damage and was the best predictor for quality of life (QoL) after 6 months (r = - 0.4647, p = 0.0338). Systemic TLR3 negatively correlated with impaired lung function (ECMO/ECLS: r = - 0.3810, p = 0.0107) and neurological short- (RASS mean: r = 0.4474, p = 0.0023) and long-term outcome (mRS after 6 m: r = - 0.3184, p = 0.0352). Systemic IL-8 correlated with impaired lung function (ECMO/ECLS: r = 0.3784, p = 0.0161) and neurological involvement (RASS mean: r = - 0.5132, p = 0.0007). IL-6 in BAL correlated better to the clinical course than systemic IL-6. Using three multivariate regression models, we describe prediction models for local and systemic damage as well as QoL. CO-Hb mean and max were associated with higher mortality. CONCLUSIONS: Our predictive models using the combination of Charlson Comorbidity Index, sex, procalcitonin, systemic TLR3 expression and IL-6 and IL-8 in BAL were able to describe a broad range of clinically relevant outcomes in patients with severe COVID-19-associated ARDS. Using these models might proof useful in risk stratification and predicting disease course in the future. Trial registration The trial was registered with the German Clinical Trials Register (Trial-ID DRKS00021522, registered 22/04/2020).

Risks and Benefits of Ultrasound, Nerve Stimulation, and Their Combination for Guiding Peripheral Nerve Blocks: A Retrospective Registry Analysis.

BACKGROUND: Ultrasound, nerve stimulation, and their combination are all considered acceptable ways to guide peripheral nerve blocks. Which approach is most effective and associated with the fewest complications is unknown. We therefore used a large registry to analyze whether there are differences in vascular punctures, multiple skin punctures, and unintended paresthesia. METHODS: Twenty-six thousand seven hundred and thirty-three cases were extracted from the 25-center German Network for Regional Anesthesia registry between 2007 and 2016 and grouped into ultrasound-guided puncture (n = 10,380), ultrasound combined with nerve stimulation (n=8173), and nerve stimulation alone (n = 8180). The primary outcomes of vascular puncture, multiple skin punctures, and unintended paresthesia during insertion were compared with conditional logistic regression after 1:1:1 propensity score matching. Results are presented as odds ratios and 95% CIs. RESULTS: Propensity matching successfully paired 2508 patients with ultrasound alone (24% of 10,380 patients), 2508 patients with a combination of ultrasound/nerve stimulation (31% of 8173 patients), and 2508 patients with nerve stimulation alone (31% of 8180 patients). After matching, no variable was imbalanced (standardized differences <0.1). Compared with ultrasound guidance alone, the odds of multiple skin punctures (2.2 [1.7-2.8]; P < .001) and vascular puncture (2.7 [1.6-4.5]; P < .001) were higher with nerve stimulation alone, and the odds for unintended paresthesia were lower with nerve stimulation alone (0.3 [0.1-0.7]; P = .03). The combined use of ultrasound/nerve stimulation showed higher odds of multiple skin punctures (1.5 [1.2-1.9]; P = .001) and lower odds of unintended paresthesia (0.4 [0.2-0.8]; P = .007) compared with ultrasound alone. Comparing the combined use of ultrasound/nerve stimulation with ultrasound alone, the odds for vascular puncture (1.3 [0.7-2.2]; P = .4) did not differ significantly. Systemic toxicity of local anesthetics was not observed in any patient with ultrasound guidance alone, in 1 patient with the combined use of ultrasound and nerve stimulation, and in 1 patient with nerve stimulation alone. CONCLUSIONS: Use of ultrasound alone reduced the odds of vascular and multiple skin punctures. However, the sole use of ultrasound increases the odds of paresthesia.

Bacterial Contamination of the Anesthesia Workplace and Efficiency of Routine Cleaning Procedures: A Prospective Cohort Study.

In this prospective cohort study, 200 decontamination (cleaning and disinfection) procedures of the anesthesia workplace either by anesthesia nurses or by specially trained housekeeping staff were monitored. Time used by housekeeping staff was shorter (1.2 ± 0.1 vs 2.6 ± 0.2 minutes on average, data are mean ± SEM; P < 0.0001) with less visible marker spots (14.4 ± 0.68 [55%] vs 17.3 ± 0.75 [66.7%] on average, data are mean ± SEM; P = 0.0041), and the bacterial load showed a decrease (≅67%, P < 0.0001) compared with anesthesia nurses. Specially trained housekeeping staff outperformed anesthesia nurses in cleaning the anesthesia workplace. Specific training for anesthesia workplace cleaning is supported by these findings.

Incidence of spinal haematoma after epidural puncture: analysis from the German network for safety in regional anaesthesia.

CONTEXT: The incidence of epidural haematoma after epidural anaesthesia is uncertain. OBJECTIVE: To quantify epidural haematoma after epidural anaesthesia in 2008 and 2009 in a network for safety in regional anaesthesia in Germany. DESIGN: Analysis of data systematically documented within the German network for safety in regional anaesthesia. SETTING: A regional anaesthesia register for clinics recording their clinical practice was set up according to a consented protocol. After checking the registry for the presence of epidural haematoma, all participating centres were asked for the number of epidural haematoma and the number of neuraxial procedures performed during the 2 years. Patient-specific information regarding procedures and outcome were requested. MAIN OUTCOME MEASURES: The incidence of epidural haematoma in the network with comorbidities, coagulation status and time from first symptoms, also the performance of MRI and laminectomy. RESULTS: During a period of 2 years, 33,142 non-obstetric epidural blocks were performed. Five thoracic epidural and one cranial haematoma occurred. DISCUSSION: The incidence of spinal haematoma was 1: 6 628 in this general surgical population. When local anaesthetics are continuously applied, progressive motor block should increase the level of suspicion. When accompanied by pain or paraesthesia, progression to diagnosis by MRI is mandatory.

Expression of HO1 and PER2 can predict the incidence of delirium in trauma patients with concomitant brain injury.

Intensive care unit (ICU)-acquired delirium is associated with adverse outcome in trauma patients with concomitant traumatic brain injury (TBI), but diagnosis remains challenging. Quantifying circadian disruption by analyzing expression of the circadian gene period circadian regulator 2 (PER2) and heme oxygenase 1 (HO1), which determines heme turnover, may prove to be potential diagnostic tools. Expression of PER2 and HO1 was quantified using qPCR from blood samples 1 day and 7 days after trauma. Association analysis was performed comparing mRNA expression levels with parameters of trauma (ISS-injury severity score), delirium, acute kidney injury (AKI) and length of ICU stay. 48 polytraumatized patients were included (equal distribution of TBI versus non-TBI) corrected for ISS, age and gender using a matched pairs approach. Expression levels of PER2 and HO1 were independent of age (PER2: P = 0.935; HO1: P = 0.988), while expression levels were significantly correlated with trauma severity (PER2: P = 0.009; HO1: P < 0.001) and longer ICU length of stay (PER2: P = 0.018; HO1: P < 0.001). High expression levels increased the odds of delirium occurrence (PER2: OR = 4.32 [1.14-13.87]; HO1: OR = 4.50 [1.23-14.42]). Patients with TBI showed a trend towards elevated PER2 (OR = 3.00 [0.84-9.33], P = 0.125), but not towards delirium occurrence (P = 0.556). TBI patients were less likely to develop AKI compared to non-TBI (P = 0.022). Expression levels of PER2 and HO1 correlate with the incidence of delirium in an age-independent manner and may potentially improve diagnostic algorithms when used as delirium biomarkers.Trial registration: German Clinical Trials Register (Trial-ID DRKS00008981; Universal Trial Number U1111-1172-6077; Jan. 18, 2018).

Navigating hospitals safely through the COVID-19 epidemic tide: Predicting case load for adjusting bed capacity.

BACKGROUND: The pressures exerted by the coronavirus disease 2019 (COVID-19) pandemic pose an unprecedented demand on healthcare services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. OBJECTIVE: We describe methods used by a university hospital to forecast case loads and time to peak incidence. METHODS: We developed a set of models to forecast incidence among the hospital catchment population and to describe the COVID-19 patient hospital-care pathway. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care-pathway model according to expert opinion (ie, the static model). Once sufficient local data were available, trends for the time-dependent effective reproduction number were fitted, and the care pathway was reparameterized using hazards for real patient admission, referrals, and discharge (ie, the dynamic model). RESULTS: The static model, deployed before the epidemic, exaggerated the bed occupancy for general wards (116 forecasted vs 66 observed), ICUs (47 forecasted vs 34 observed), and predicted the peak too late: general ward forecast April 9 and observed April 8 and ICU forecast April 19 and observed April 8. After April 5, the dynamic model could be run daily, and its precision improved with increasing availability of empirical local data. CONCLUSIONS: The models provided data-based guidance for the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when the population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty.

[Patient care according to the latest state of the science--implications of evidence-based medicine]. / Patientenversorgung nach dem neuesten Stand der Wissenschaft - Was bedeutet Evidence-based Medicine?

Evidence-based medicine implies that recommendations ideally exist for each clinical question based on a systematic data search in the current literature, a data extraction, a summary and critical appraisal. Over the last fifty years evidence-based medicine has been growing rapidly. Systematic reviews and randomised controlled trials are of high impact in this field. However, the question remains: in which way is daily clinical practice affected? In an era of time- and cost-pressures as well as manpower shortages, the complex process of evidence-based medicine is difficult. Examples from perioperative pain therapy are provided to demonstrate how evidence-based medicine could be feasible and incorporated into daily practice.

Subcutaneous Enoxaparin Safely Facilitates Bedside Sustained Low-Efficiency Hemodialysis in Hypercoagulopathic Coronavirus Disease 2019 Patients-A Proof-of-Principle Trial.

OBJECTIVES: Renal replacement therapy in coronavirus disease 2019 patients is complicated by increased activation of the coagulation system. This may worsen the quality of hemodialysis and contribute to a shortage of dialysis machines as well as plastic disposables during the pandemic. This study describes a simple and safe protocol of anticoagulation with low-molecular-weight heparin in combination with bedside sustained low-efficiency hemodialysis in coronavirus disease 2019 patients. DESIGN: Monocentric observational cross-over trial investigating sustained low-efficiency hemodialysis with unfractionated heparin following sustained low-efficiency hemodialysis with low-molecular-weight heparin. SETTING: Coronavirus disease 2019-ICU in a German Tertiary Care University Hospital. PATIENTS: Three consecutive severe coronavirus disease 2019 patients receiving nine sustained low-efficiency hemodialysis therapies with unfractionated heparin followed by 18 sustained low-efficiency hemodialysis therapies with low-molecular-weight heparin. INTERVENTIONS: Switch from IV unfractionated heparin to subcutaneous low-molecular-weight heparin enoxaparin in therapeutic doses for patients receiving bedside sustained low-efficiency hemodialysis. MEASUREMENTS AND MAIN RESULTS: Nine renal replacement therapy sessions in patients anticoagulated with high doses of unfractionated heparin had to be discontinuated prematurely because of clotting of tubes or membrane and poor quality of hemodialysis. In the same patients, the switch to anticoagulation with therapeutic doses of the low-molecular-weight heparin enoxaparin allowed undisturbed bedside sustained low-efficiency hemodialysis for at least 12 hours. Quality of hemodialysis was excellent, no bleeding event was observed. CONCLUSIONS: Systemic anticoagulation with subcutaneous enoxaparin provides an effective and safe renal replacement procedure in critically ill patients with coronavirus disease 2019 and hypercoagulability. The protocol reduces the risk of filter clotting, blood loss, and poor dialysis quality and may also prevent systemic thromboembolism.

[COVID-19-Response - Strategies of the Task-Force Coronavirus and experiences upon implementation in the management of 115 cases at the University Medical Center Freiburg]. / COVID-19-Versorgung ­ Strategien der Taskforce Coronavirus und Erfahrungen von den ersten 115 Fällen am Universitätsklinikum Freiburg.

BACKGROUND: The new pandemic coronavirus SARS-CoV-2 causing coronavirus disease-2019 (COVID-19) poses immense challenges to health care systems worldwide. In the current manuscript we summarize the strategies, organisational approaches and actions of the Task-force Coronavirus at the University Medical Center Freiburg. We also report on experiences with implementation of these approaches and treatment outcomes in the first 115 COVID patients. METHODS: Retrospective, narrative process description and analysis of the time period between end of January and beginning of April 2020, performed by representatives of the involved departments and institutes. Additionally a retrospective observational cohort study with descriptive analysis of epidemiological and clinical data of COVID patients admitted until March 31st was performed. RESULTS: A multidisciplinary Task-force Coronavirus initiated measures concerning outpatient testing and counseling, reorganisation and separation of patient flow processes alongside with substantial escalation of inpatient capacities on regular wards and intensive care units. Within the framework of the resulting dynamic care model, 115 patients suffering from COVID could be treated without shortages in staff or bed capacities. DICUSSION: In the upcoming pandemic, adequate COVID management and care could be secured by a collaborative approach with inclusion of administrative departments, clinical disciplines and theoretical institutes of the University Medical Center Freiburg.

[A German network for regional anaesthesia of the scientific working group regional anaesthesia within DGAI and BDA]. / Das Netzwerk Regionalanästhesie des wissenschaftlichen Arbeitskreises Regionalanästhesie der DGAI und des BDA.

Regional anaesthesia generally is considered to be safe. However, reports of complications with different severities are also well known. The scientific working group of regional anaesthesia of the DGAI has founded a network in conjunction with the BDA. With the aid of a registry, we are now able to describe risk profiles and associations in case of a complication. Moreover, a benchmark has been implemented in order to continuously improve complication rates.

Propofol or benzodiazepines for short- and long-term sedation in intensive care units? An economic evaluation based on meta-analytic results.

PURPOSE: This evaluation compares propofol and benzodiazepine sedation for mechanically ventilated patients in intensive care units (ICUs) in order to identify the potential economic benefits from different payers' perspectives. METHODS: The patient-level simulation model incorporated efficacy estimates from a structured meta-analysis and ICU-related costs from Italy, Germany, France, UK, and the USA. Efficacy outcomes were ICU length of stay (LOS), mechanical ventilation duration, and weaning time. We calculated ICU costs from mechanical ventilation duration and ICU LOS based on national average ICU costs with and without mechanical ventilation. Three scenarios were investigated: 1) long-term sedation >24 hours based on results from randomized controlled trials (RCTs); 2) long-term sedation based on RCT plus non-RCT results; and 3) short-term sedation <24 hours based on RCT results. We tested the model's robustness for input uncertainties by deterministic (DSA) and probabilistic sensitivity analyses (PSA). RESULTS: In the base case, mean savings with propofol versus benzodiazepines in long-term sedation ranged from €406 (95% confidence interval [CI]: 646 to 164) in Italy to 1,632 € (95% CI: 2,362 to 880) in the USA. Inclusion of non-RCT data corroborated these results. Savings in short-term sedation ranged from €148 (95% CI: 291 to 2) in Italy to €502 (95% CI: 936 to 57) in the USA. Parameters related to ICU and mechanical ventilation had a stronger influence in the DSA than drug-related parameters. In PSA, propofol reduced costs and ICU LOS compared to benzodiazepines in 94%-100% of simulations. The largest savings may be possible in the UK and the USA due to higher ICU costs. CONCLUSION: Current ICU sedation guidelines recommend propofol rather than midazolam for mechanically ventilated patients. This evaluation endorses the recommendation as it may lead to better outcomes and savings for health care systems, especially in countries with higher ICU-related costs.

Carbon monoxide releasing molecule-2 CORM-2 represses global protein synthesis by inhibition of eukaryotic elongation factor eEF2.

Carbon monoxide (CO) is an endogenous gaseous transmitter that exerts antiproliferative effects in many cell types, but effects of CO on the translational machinery are not described. We examined the effects of the carbon monoxide releasing molecule-2 (CORM-2) on critical steps in translational signaling and global protein synthesis in pancreatic stellate cells (PSCs), the most prominent collagen-producing cells in the pancreas, whose activation is associated with pancreatic fibrosis. PSCs were isolated from rat pancreatic tissue and incubated with CORM-2. CORM-2 prevented the decrease in the phosphorylation of eukaryotic elongation factor 2 (eEF2) caused by serum. By contrast, the activation dependent phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1) was inhibited by CORM-2 treatment. The phosphorylation of eukaryotic initiation factor 2α (eIF2α) and eukaryotic initiation factor 4E (eIF4E) were not affected by CORM-2 treatment. In consequence, CORM-2 mediated eEF2 phosphorylation and inactivation of 4E-BP1 suppressed global protein synthesis. These observations were associated with inhibition of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling and increased intracellular calcium and cAMP levels. The CORM-2 mediated inhibition of protein synthesis resulted in downregulation of cyclin D1 and cyclin E expression, a subsequent decline in the phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and cell growth arrest at the G(0)/G(1) phase checkpoint of the cell cycle. Our results suggest the therapeutic application of CO releasing molecules such as CORM-2 for the treatment of fibrosis, inflammation, cancer, or other pathologic states associated with excessive protein synthesis or hyperproliferation. However, prolonged exogenous application of CO might also have negative effects on cellular protein homeostasis.

Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2(nd) Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006-2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3(rd) Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade "A" (very strong recommendation), Grade "B" (strong recommendation) and Grade "0" (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3(rd) Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

The effect of high thoracic epidural anesthesia on systolic and diastolic left ventricular function in patients with coronary artery disease.

In patients with coronary artery disease, vasoconstriction is induced through activation of the sympathetic nervous system. Both alpha1- and alpha2-adrenergic epicardial and microvascular constriction are potent initiators of myocardial ischemia. Attenuation of ischemia has been observed when sympathetic nervous system activity is inhibited by high thoracic epidural anesthesia (HTEA). However, it is still a matter of controversy whether establishing HTEA may correspondingly translate into an improvement of left ventricular (LV) function. To clarify this issue, LV function was quantified serially before and after HTEA using a new combined systolic/diastolic variable of global LV function (myocardial performance index [MPI]) and additional variables that more specifically address systolic (e.g., fractional area change) or diastolic function (e.g., intraventricular flow propagation velocity [Vp]). High thoracic epidural catheters were inserted in 37 patients scheduled for coronary artery surgery, and HTEA was administered in the awake patients. Echocardiographic and hemodynamic measures were recorded before and after institution of HTEA. HTEA induced a significant improvement in diastolic LV function (e.g., Vp changed from 45.1 +/- 16.1 to 53.8 +/- 18.8 cm/s; P < 0.001), whereas indices of systolic function did not change. The change in the diastolic characteristics caused the MPI to improve from 0.51 +/- 0.13 to 0.35 +/- 0.13 (P < 0.001). We conclude that an improvement in cardiac function was due to improved diastolic characteristics.

Transient hemiplegia in posterior instrumentation of scoliosis.

STUDY DESIGN: A case of transient hemiplegia during posterior correction and instrumentation of scoliosis in an 18-year-old woman. OBJECTIVE: To present a case of transient hemiplegia most probably resulting from an arteriovenous fistula. SUMMARY OF BACKGROUND DATA: Neurologic impairment in spinal surgery is a feared complication. Common reasons are direct or indirect trauma to neural elements, intraoperative hypotension, ischemia, bleeding, metabolic dysbalances, or drug effects. Review of the literature did not reveal any case of transient hemiplegia similar to the presented one in which none of the mentioned pathologies could be found. CASE SUMMARY: An 18-year-old woman with a right long thoracic lordoscoliosis measuring 67 degrees Cobb angle and a marfanoid phenotype underwent posterior correction and transpedicular instrumentation from T3 to L2. After uneventful correction of the deformity through rod rotation, the wake-up test revealed a right-sided hemiplegia without facial asymmetry or other neurologic abnormalities affecting structures above the spinal cord. The rods were removed, the pedicle screws left in place, and the patient was turned on her back. Within 30 minutes after extubation, the neurologic deficits disappeared completely. Extensive diagnostic workup, including magnetic resonance angiography, did not show any pathologic findings explaining the transient hemiplegia. Two weeks later, the surgical correction was completed. After rod rotation again, right-sided hemiplegia was found in the wake-up test. Leaving the correction and after finalizing surgery, the patient was turned on her back and a 5 x 3-cm mass became apparent in her right sternocleidomastoid region. Color-coded duplex sonography revealed an arteriovenous fistula between the right external carotid artery and the right internal jugular vein. After extubation, the mass disappeared and within minutes all neurologic functions returned to normal again. CONCLUSIONS: Spine surgeons should be aware of arteriovenous malformations as a potential cause of neurologic disturbances.