Effect of sonic hedgehog/β-TCP composites on bone healing within the critical-sized rat femoral defect

The creation of entirely synthetically derived bone substitute materials which are as effective as autologous bone grafts is desirable. Osteogenesis involves the concerted action of several proteins within a signaling cascade. Hedgehog proteins act upstream of this cascade, inducing the expression of various bone morphogenetic proteins (BMPs) and promoting physiological bone healing. Therefore, the hypothesis that hedgehog signaling in bone defects improves bone healing more than BMP signaling alone was tested. Recombinant N-terminal sonic hedgehog protein (N-SHh), BMP-2 or a combination of the two was added to β-tricalcium phosphate (β-TCP) and 5-mm femoral midshaft defects in nude rats were filled with these composites. The defects were stabilized with mini-plates. After eight weeks, the animals were sacrificed and the femora were explanted. The radiological evaluation was followed by a three-point bending test and histological examination. BMP-2/β-TCP composites showed a trend of increased stiffness compared with the controls (β-TCP without protein). N-SHh/β-TCP composites had lower stiffness compared with the control group and the N-SHh/BMP-2/β-TCP composites also had lower average stiffness compared with the controls (all not significant). Histomorphometry, however, revealed abundant cartilage and bone core formation in the N-SHh-composite groups. The sum of the new cartilage and bone was highest in the combination group N-SHh/BMP-2 (not significant). The addition of N-SHh to bone substitute materials appears to delay bone healing at the applied concentration and observation time but also showed a trend for higher amounts of ossifying cartilage

Treating patients across European Union borders : an international survey in light of the coronavirus disease-19 pandemic

BACKGROUND In light of the coronavirus disease-2019 (COVID-19) pandemic, how resources are managed and the critically ill are allocated must be reviewed. Although ethical recommendations have been published, strategies for dealing with overcapacity of critical care resources have so far not been addressed. OBJECTIVES Assess expert opinion for allocation preferences regarding the growing imbalance between supply and demand for medical resources. DESIGN A 10-item questionnaire was developed and sent to the most prominent members of the European Society of Anaesthesiology and Intensive Care (ESAIC). SETTING Survey via a web-based platform. PATIENTS Respondents were members of the National Anaesthesiologists Societies Committee and Council Members of the ESAIC; 74 of 80 (92.5%), responded to the survey. MEASUREMENTS AND MAIN RESULTS Responses were analysed thematically. The majority of respondents (83.8%), indicated that resources for COVID-19 were available at the time of the survey. Of the representatives of the ESAIC governing bodies, 58.9% favoured an allocation of excess critical care capacity: 69% wished to make them available to supraregional patients, whereas 30.9% preferred to keep the resources available for the local population. Regarding the type of distribution of resources, 35.3% preferred to make critical care available, 32.4% favoured the allocation of medical equipment and 32.4% wished to support both options. The majority (59.5%) supported the implementation of a central European institution to manage such resource allocation. CONCLUSION Experts in critical care support the allocation of resources from centres with overcapacity. The results indicate the need for centrally administered allocation mechanisms that are not based on ethically disputable triage systems. It seems, therefore, that there is wide acceptance and solidarity among the European anaesthesiological community that local medical and human pressure should be relieved during a pandemic by implementing national and international re-allocation strategies among healthcare providers and healthcare systems

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Volatile isoflurane in critically ill coronavirus disease 2019 patients - a case series and systematic review

Objectives: The ongoing coronavirus pandemic is challenging, especially in severely affected patients who require intubation and sedation. Although the potential benefits of sedation with volatile anesthetics in coronavirus disease 2019 patients are currently being discussed, the use of isoflurane in patients with coronavirus disease 2019–induced acute respiratory distress syndrome has not yet been reported. Design: We performed a retrospective analysis of critically ill patients with hypoxemic respiratory failure requiring mechanical ventilation. Setting: The study was conducted with patients admitted between April 4 and May 15, 2020 to our ICU. Patients: We included five patients who were previously diagnosed with severe acute respiratory syndrome coronavirus 2 infection. Intervention: Even with high doses of several IV sedatives, the targeted level of sedation could not be achieved. Therefore, the sedation regimen was switched to inhalational isoflurane. Clinical data were recorded using a patient data management system. We recorded demographical data, laboratory results, ventilation variables, sedative dosages, sedation level, prone positioning, duration of volatile sedation and outcomes. Measurements & Main Results: Mean age (four men, one women) was 53.0 (± 12.7) years. The mean duration of isoflurane sedation was 103.2 (± 66.2) hours. Our data demonstrate a substantial improvement in the oxygenation ratio when using isoflurane sedation. Deep sedation as assessed by the Richmond Agitation and Sedation Scale was rapidly and closely controlled in all patients, and the subsequent discontinuation of IV sedation was possible within the first 30 minutes. No adverse events were detected. Conclusions: Our findings demonstrate the feasibility of isoflurane sedation in five patients suffering from severe coronavirus disease 2019 infection. Volatile isoflurane was able to achieve the required deep sedation and reduced the need for IV sedation

Epidural Catheterization in Obstetrics: A Checklist-Based Video Assessment of Free Available Video Material

Epidural catheterization has become an indispensable part of modern pain therapy, for example, in obstetrics. Learning how to master this skill is an important competency. Videos are among the information sources with the highest information content for learning such skills. The present study aims to analyze videos regarding epidural catheter placement provided on the YouTube platform based on a validated checklist. An expert workshop selected crucial items for learning epidural catheterization in obstetrics. Items were identified and optimized in a five-step testing process. Using this checklist, videos from YouTube were evaluated by eleven health care professionals. Sixteen videos were identified and analyzed. Concerning the catheterization-specific part of the checklist, only two videos showed satisfactory quality. In the didactic part, eleven out of 21 items reached a mean score >50% of the points. Regarding interrater reliability, the catheterization-specific checklist was shown to be substantial (Fleiss’ kappa = 0.610), and the didactic part was shown to be fair (Fleiss’ kappa = 0.401). Overall, standard monitoring and appropriate aseptic technique were followed in only 42% and 49% for the procedure. There was a significant correlation between the runtime and the content quality (p < 0.001). No correlation could be found in terms of platform rating parameters. The video quality varied highly in terms of the requirements of this practical skill. The majority appear unsuitable for self-study due to serious errors and deficiencies regarding patient safety. However, there is no quality control on free platforms. Accordingly, it is difficult to identify suitable videos for educational purposes

Rise of public e-learning opportunities in the context of COVID-19 pandemic-induced curtailment of face-to-face courses, exemplified by epidural catheterization on YouTube.

Abstract Background In the context of the coronavirus pandemic, countless face-to-face events as well as medical trainings were cancelled or moved to online courses, which resulted in increased digitalization in many areas. In the context of medical education, videos provide tremendous benefit for visualizing skills before they are practised. Methods Based on a previous investigation of video material addressing epidural catheterization available on the YouTube platform, we aimed to investigate new content produced in the context of the pandemic. Thus, a video search was conducted in May 2022. Results We identified twelve new videos since the pandemic with a significant improvement in the new content in terms of procedural items (p = 0.03) compared to the prepandemic video content. Video content released in the course of the COVID-19 pandemic was more often created by private content creators and were significantly shorter in total runtime than those from university and medical societies (p = 0.04). Conclusion The profound changes in the learning and teaching of health care education in relation to the pandemic are largely unclear. We reveal improved procedural quality of predominantly privately uploaded content despite a shortened runtime compared to the prepandemic period. This might indicate that technical and financial hurdles to producing instructional videos by discipline experts have decreased. In addition to the teaching difficulties caused by the pandemic, this change is likely to be due to validated manuals on how to create such content. The awareness that medical education needs to be improved has grown, so platforms offer specialized sublevels for high-quality medical videos

Therapy and Outcome of Prolonged Veno-Venous ECMO Therapy of Critically Ill ARDS Patients

Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) therapy has become increasingly used and established in many hospitals as a routine treatment. With ECMO-therapy being a resource-demanding procedure, it is of interest whether a more prolonged VV-ECMO treatment would hold sufficient therapeutic success. Our retrospective study included all VV-ECMO runs from 1 January 2020 to 31 June 2022. We divided all runs into four groups (p = 0.15) and increased mortality though a significant correlation between the patients’ age and their probability of survival (p = 0.02). Notably, we found significantly lower interleukin-6 levels with an increase in therapy duration (p < 0.01). Our findings show no association between the duration of ECMO therapy and mortality. Thus, the treatment duration alone may not be used for making assumptions about the prospect of survival. However, attention is also increasingly focused on long-term outcomes, such as post-intensive care syndrome with severe impairments

High sedation needs of critically ill COVID-19 ARDS patients - a monocentric observational study

Background: Therapy of severely affected coronavirus patient, requiring intubation and sedation is still challenging. Recently, difficulties in sedating these patients have been discussed. This study aims to describe sedation practices in patients with 2019 coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS). Methods: We performed a retrospective monocentric analysis of sedation regimens in critically ill intubated patients with respiratory failure who required sedation in our mixed 32-bed university intensive care unit. All mechanically ventilated adults with COVID-19-induced ARDS requiring continuously infused sedative therapy admitted between April 4, 2020, and June 30, 2020 were included. We recorded demographic data, sedative dosages, prone positioning, sedation levels and duration. Descriptive data analysis was performed; for additional analysis, a logistic regression with mixed effect was used. Results: In total, 56 patients (mean age 67 (±14) years) were included. The mean observed sedation period was 224 (±139) hours. To achieve the prescribed sedation level, we observed the need for two or three sedatives in 48.7% and 12.8% of the cases, respectively. In cases with a triple sedation regimen, the combination of clonidine, esketamine and midazolam was observed in most cases (75.7%). Analgesia was achieved using sufentanil in 98.6% of the cases. The analysis showed that the majority of COVID-19 patients required an unusually high sedation dose compared to those available in the literature. Conclusion: The global pandemic continues to affect patients severely requiring ventilation and sedation, but optimal sedation strategies are still lacking. The findings of our observation suggest unusual high dosages of sedatives in mechanically ventilated patients with COVID-19. Prescribed sedation levels appear to be achievable only with several combinations of sedatives in most critically ill patients suffering from COVID-19-induced ARDS and a potential association to the often required sophisticated critical care including prone positioning and ECMO treatment seems conceivable

Electroencephalogram-Based Evaluation of Impaired Sedation in Patients with Moderate to Severe COVID-19 ARDS

The sedation management of patients with severe COVID-19 is challenging. Processed electroencephalography (pEEG) has already been used for sedation management before COVID-19 in critical care, but its applicability in COVID-19 has not yet been investigated. We performed this prospective observational study to evaluate whether the patient sedation index (PSI) obtained via pEEG may adequately reflect sedation in ventilated COVID-19 patients. Statistical analysis was performed by linear regression analysis with mixed effects. We included data from 49 consecutive patients. None of the patients received neuromuscular blocking agents by the time of the measurement. The mean value of the PSI was 20 (&plusmn;23). The suppression rate was determined to be 14% (&plusmn;24%). A deep sedation equivalent to the Richmond Agitation and Sedation Scale of &minus;3 to &minus;4 (correlation expected PSI 25&ndash;50) in bedside examination was noted in 79.4% of the recordings. Linear regression analysis revealed a significant correlation between the sedative dosages of propofol, midazolam, clonidine, and sufentanil (p &lt; 0.01) and the sedation index. Our results showed a distinct discrepancy between the RASS and the determined PSI. However, it remains unclear to what extent any discrepancy is due to the electrophysiological effects of neuroinflammation in terms of pEEG alteration, to the misinterpretation of spinal or vegetative reflexes during bedside evaluation, or to other causes

Associated Factors of High Sedative Requirements within Patients with Moderate to Severe COVID-19 ARDS

The coronavirus pandemic continues to challenge global healthcare. Severely affected patients are often in need of high doses of analgesics and sedatives. The latter was studied in critically ill coronavirus disease 2019 (COVID-19) patients in this prospective monocentric analysis. COVID-19 acute respiratory distress syndrome (ARDS) patients admitted between 1 April and 1 December 2020 were enrolled in the study. A statistical analysis of impeded sedation using mixed-effect linear regression models was performed. Overall, 114 patients were enrolled, requiring unusual high levels of sedatives. During 67.9% of the observation period, a combination of sedatives was required in addition to continuous analgesia. During ARDS therapy, 85.1% (n = 97) underwent prone positioning. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) was required in 20.2% (n = 23) of all patients. vv-ECMO patients showed significantly higher sedation needs (p &lt; 0.001). Patients with hepatic (p = 0.01) or renal (p = 0.01) dysfunction showed significantly lower sedation requirements. Except for patient age (p = 0.01), we could not find any significant influence of pre-existing conditions. Age, vv-ECMO therapy and additional organ failure could be demonstrated as factors influencing sedation needs. Young patients and those receiving vv-ECMO usually require increased sedation for intensive care therapy. However, further studies are needed to elucidate the causes and mechanisms of impeded sedation