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

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

Evaluation of volatile sedation in the postoperative intensive care of patients recovering from heart valve surgery: protocol for a randomised, controlled, monocentre trial

Introduction Patients undergoing heart valve surgery are predominantly transferred postoperatively to the intensive care unit (ICU) under continuous sedation. Volatile anaesthetics are an increasingly used treatment alternative to intravenous substances in the ICU. As subject to inhalational uptake and elimination, the resulting pharmacological benefits have been repeatedly demonstrated. Therefore, volatile anaesthetics appear suitable to meet the growing demands of fast-track cardiac surgery. However, their use requires special preparation at the bedside and trained medical and nursing staff, which might limit the pharmacological benefits. The aim of our work is to assess whether the temporal advantages of recovery under volatile sedation outweigh the higher effort of special preparation. Methods and analysis The study is designed to evaluate the differences between intravenous sedatives (n=48) and volatile sedatives (n=48) in continued intensive care sedation. This study will be conducted as a prospective, randomised, controlled, single-blinded, monocentre trial at a German university hospital in consenting adult patients undergoing heart valve surgery at a university hospital. This observational study will examine the necessary preparation time, staff consultation and overall feasibility of the chosen sedation method. For this purpose, the continuation of sedation in the ICU with volatile sedatives is considered as one study arm and with intravenous sedatives as the comparison group. Due to rapid elimination and quick awakening after the termination of sedation, closer consultation between the attending physician and the ICU nursing staff is required, in addition to a prolonged setup time. Study analysis will include the required setup time, time from admission to extubation as primary outcome and neurocognitive assessability. In addition, possible operation-specific (blood loss, complications), treatment parameters (catecholamine dosages, lung function) and laboratory results (acute kidney injury, acid base balance (lactataemia), liver failure) as influencing factors will be collected. The study-relevant data will be extracted from the continuous digital records of the patient data management system after the patient has been discharged from the ICU. For statistical evaluation, 95% CIs will be calculated for the median time to extubation and neurocognitive assessability, and the association will be assessed with a Cox regression model. In addition, secondary binary outcome measures will be evaluated using Fisher’s exact tests. Further descriptive and exploratory statistical analyses are also planned. Ethics and dissemination The study was approved by the Institutional Ethics Board of the University of Frankfurt, Germany (#20-1050). Informed consent of all individual patients will be obtained before randomisation. Results will be disseminated via publication in peer-reviewed journals

Association of mortality and early tracheostomy in patients with COVID-19: a retrospective analysis

COVID-19 adds to the complexity of optimal timing for tracheostomy. Over the course of this pandemic, and expanded knowledge of the disease, many centers have changed their operating procedures and performed an early tracheostomy. We studied the data on early and delayed tracheostomy regarding patient outcome such as mortality. We performed a retrospective analysis of all tracheostomies at our institution in patients diagnosed with COVID-19 from March 2020 to June 2021. Time from intubation to tracheostomy and mortality of early (≤ 10 days) vs. late (> 10 days) tracheostomy were the primary objectives of this study. We used mixed cox-regression models to calculate the effect of distinct variables on events. We studied 117 tracheostomies. Intubation to tracheostomy shortened significantly (Spearman’s correlation coefficient; rho = − 0.44, p ≤ 0.001) during the course of this pandemic. Early tracheostomy was associated with a significant increase in mortality in uni- and multivariate analysis (Hazard ratio 1.83, 95% CI 1.07–3.17, p = 0.029). The timing of tracheostomy in COVID-19 patients has a potentially critical impact on mortality. The timing of tracheostomy has changed during this pandemic tending to be performed earlier. Future prospective research is necessary to substantiate these results

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 (±23). The suppression rate was determined to be 14% (±24%). A deep sedation equivalent to the Richmond Agitation and Sedation Scale of −3 to −4 (correlation expected PSI 25–50) 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 < 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

Detecting Sepsis in Patients with Severe Subarachnoid Hemorrhage during Critical Care

Introduction: Sepsis and septic shock continue to have a very high mortality rate. Therefore, the last consensus-based sepsis guideline introduced the sepsis related organ failure assessment (SOFA) score to ensure a rapid diagnosis and treatment of sepsis. In neurosurgical patients, especially those patients with subarachnoid hemorrhage (SAH), there are considerable difficulties in interpreting the SOFA score. Therefore, our study was designed to evaluate the applicability of the SOFA for critical care patients with subarachnoid hemorrhage. Methods: Our retrospective monocentric study was registered (NCT05246969) and approved by the local ethics committee (# 211/18). Patients admitted to the Department of Neurosurgery at the Frankfurt University Hospital were enrolled during the study period. Results: We included 57 patients with 85 sepsis episodes of which 141 patients had SOFA score-positive results and 243 SIRS positive detections. We failed to detect a correlation between the clinical diagnosis of sepsis and positive SOFA or SIRS scores. Moreover, a significant proportion of sepsis that was incorrectly detected via the SOFA score could be attributed to cerebral vasospasms (p < 0.01) or a decrease in Glasgow Coma Scale (p < 0.01). Similarly, a positive SIRS score was often not attributed to a septic episode (49.0%). Discussion: Regardless of the fact that SAH is a rare disease, the relevance of sepsis detection should be given special attention in light of the long duration of therapy and sepsis prevalence. Among the six modules represented by the SOFA score, two highly modules were practically eliminated. However, to enable early diagnosis of sepsis, the investigator’s clinical views and synopsis of various scores and laboratory parameters should be highlighted. Conclusions: In special patient populations, such as in critically ill SAH patients, the SOFA score can be limited regarding its applicability. In particular, it is very important to differentiate between CVS and sepsis

Entwicklung und Validierung einer Checkliste zur Bewertung von Videos zum Erlernen von Reanimationsmaßnahmen

Hintergrund: Gut durchgeführte Wiederbelebungsmaßnahmen können bei einem Herz-Kreislauf-Stillstand das Outcome verbessern. Um praktische Fähigkeiten zu erlernen, greifen Medizinstudierende oft auf Lehrvideos zurück. Studien zeigen jedoch häufig eine unzureichende Qualität der im Internet zur Verfügung gestellten Videos zu Reanimationsmaßnahmen. Eine Bewertung anhand einer validierten, auf den aktuellen „guidelines“ basierten Checkliste fehlt bisher. Ziel der Arbeit: Entwicklung und Validierung einer Checkliste zur Bewertung von Lehrvideos zur Reanimation. Material und Methoden: In einem Expertenworkshop erfolgte basierend auf den aktuellen „guidelines“ die Formulierung der Checklistenitems. Die Checkliste wurde in einem vierstufigen Reviewprozess von Notärzten getestet. Die Bewertungen wurden analysiert und die Items angepasst und spezifiziert. Nach dem Reviewprozess wurde die Checkliste an 74 Videos zur Reanimation angewendet. Ergebnisse: Die Checkliste umfasst 25 Items in vier Kategorien (initiale Maßnahmen, Thoraxkompression, AED-Nutzung, Atmung), die auf einer 3 stufigen Likert-Skala bewertet werden. 16 NotärztInnen nahmen an der Studie teil. Sie bewerteten jeweils durchschnittlich 9,3 ± 5,7 Videos. Die Reviewer stimmten in 65,1 ± 12,6 % der Fälle überein. Die höchsten Übereinstimmungen wurden im Unterthema AED erzielt, das Item „Beim Schock Patienten nicht berühren“ wies die höchste Übereinstimmung auf. Die Items der Kategorie Thoraxkompression wurden am häufigsten unterschiedlich bewertet. Diskussion: Es konnte erstmalig für den deutschsprachigen Raum eine Checkliste zur Bewertung von Lehrvideos zur Reanimation erstellt und validiert werden