Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management?

The current ARDS guidelines highly recommend lung protective ventilation which include plateau pressure (Pplat < 30 cm H2O), positive end expiratory pressure (PEEP > 5 cm H2O) and tidal volume (Vt of 6 ml/kg) of predicted body weight. In contrast, the ELSO guidelines suggest the evaluation of an indication of veno-venous extracorporeal membrane oxygenation (ECMO) due to hypoxemic or hypercapnic respiratory failure or as bridge to lung transplantation. Finally, these recommendations remain a wide range of scope of interpretation. However, particularly patients with moderate-severe to severe ARDS might benefit from strict adherence to lung protective ventilation strategies. Subsequently, we discuss whether extended physiological ventilation parameter analysis might be relevant for indication of ECMO support and can be implemented during the daily routine evaluation of ARDS patients. Particularly, this viewpoint focus on driving pressure and mechanical power.

Randomised controlled studies in Germany and the world during the COVID-19 pandemic: classic or flexible study design?

Summary Background: During the COVID-19 pandemic, platform trials with a flexible, adaptive design have emerged as an important study design for randomised controlled trials (RCTs) to provide timely, robust findings on new interventions based on large numbers of participants. Since Germany has often been criticised for deficits in clinical research during the pandemic, we compared the study landscape of various countries during the pandemic. Method(s): ClinicalTrials.gov, the U.S. National Library of Medicine's central trial registry and the Cochrane COVID-19 trial registry were searched for interventional RCTs and platform studies on COVID-19 up to 8 February 2022. The results on number, status, number of participants and funding of the countries were compared. Result(s): A total of 1,246 interventional RCTs and 45 platform studies were registered in Germany, France, UK, US and Australia until February 2022. Germany coordinated only a small proportion of initiated trials. In Germany, one RCT per 1 million inhabitants has been identified;whereas more than twice as many have been identified in France and the US. About a quarter of the RCTs initiated in Germany with >500 participants were completed. In the US, 99 % were completed. One platform study per 100 million inhabitants was initiated in Germany, six in US, eleven in Australia and UK and 18 in France. Conclusion(s): Compared to other countries, Germany initiated fewer interventional RCTs and platform studies during the pandemic. The results from platform studies formed a relevant basis for evidence-based recommendations on interventions to treat COVID-19. Germany contributed little evidence to COVID-19 guidelines. Copyright © 2022 DIOmed Verlags GmbH. All rights reserved.

External Validation of the 4C Mortality Score and the qSOFA for Different Variants of Concerns of SARS-CoV-2 Using Data of the NAPKON Cross-Sectoral Cohort Platform (SUEP)

Background. Numerous predictive clinical scores with varying discriminatory performance have been developed in the context of the current coronavirus disease 2019 (COVID-19) pandemic. To support clinical application, we test the transferability of the frequently applied 4C mortality score (4C score) to the German prospective Cross-Sectoral Platform (SUEP) of the National Pandemic Cohort Network (NAPKON) compared to the non COVID-19 specific quick sequential organ failure assessment score (qSOFA). Our project aims to externally validate these two scores, stratified for the most prevalent variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in Germany. Methods. A total of 685 adults with polymerase chain reaction (PCR)-detected SARS-CoV-2 infection were included from NAPKON-SUEP. Patients were recruited from 11/2020 to 03/2022 at 34 university and non-university hospitals across Germany. Missing values were complemented using multiple imputation. Predictive performance for in-hospital mortality at day of baseline visit was determined by area under the curve (AUC) with 95%-confidence interval (CI) stratified by VOCs of SARS-CoV-2 (alpha, delta, omicron) (Figure 1). Figure 1: Study flow chart with inclusion criteria and methodological workflow. Results. Preliminary results suggest a high predictive performance of the 4C score for in-hospital mortality (Table 1). This applies for the overall cohort (AUC 0.813 (95%CI 0.738-0.888)) as well as the VOC-strata (alpha: AUC 0.859 (95%CI 0.748-0.970);delta: AUC 0.769 (95%CI 0.657-0.882);omicron: AUC 0.866 (95%CI 0.724-1.000)). The overall mortality rates across the defined 4C score risk groups are 0.3% (low), 3.2% (intermediate), 11.6% (high), and 49.5% (very high). The 4C score performs significantly better than the qSOFA (Chi2-test: p=0.001) and the qSOFA does not seem to be a suitable tool in this context. Table 1: Discriminatory performance of the 4C Mortality Score and the qSOFA score within the validation cohort NAPKON-SUEP stratified by the Variant of Concerns of SARS-CoV- 2. Conclusion. Despite its development in the early phase of the pandemic and improved treatment, external validation of the 4C score in NAPKON-SUEP indicates a high predictive performance for in-hospital mortality across all VOCs. However, since the qSOFA was not specifically designed for this predictive issue, it shows low discriminatory performance, as in other validation studies. Any interpretations regarding the omicron stratum are limited due to the sample size.

Thromboembolism prophylaxis and anticoagulation in COVID-19 patients - A systematic review and meta analysis

Background: Thromboembolic events are common complications of COVID- 19. Study results on the safety and efficacy of thromboprophylaxis or anticoagulation in COVID-19 are controversial. This review with random-effects meta-analyses systematically summarises the current evidence. Method(s): We included randomised controlled trials (RCTs) published until February 2022 that investigated standard thromboprophylaxis or anticoagulation at any dosage with thromboprophylaxis or no prophylaxis in COVID-19 patients. Relevant outcomes were mortality, clinical status, thrombotic events or death and (severe) bleeding (28 days). Certainty of evidence was assessed according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Result(s): We included 13 RCTs with 7,364 patients. Two studies investigated thromboprophylaxis versus placebo in COVID-19 outpatients;three studies compared intermediate-dose and seven therapeutic-dose anticoagulation with standard thromboprophylaxis in hospitalised COVID-19 patients;one study investigated post-discharge thromboprophylaxis versus no prophylaxis. We are uncertain whether thromboprophylaxis is beneficial over placebo or no thromboprophylaxis in outpatient- or post-discharge-settings. Intermediatedose anticoagulation is not capable of reducing thrombotic events or death (RR 1.03, 95 % CI 0.86 - 1.24), but is associated with an increase of severe bleedings (non-significant) (RR 1.48, 95 % CI 0.53 - 4.15). Therapeutic-dose anticoagulation may decrease thrombotic events or deaths in patients with moderate COVID-19 (RR 0.64, 95 % CI 0.38-1.07;fixed-effect meta-analysis RR 0.72, 95 % CI 0.57 - 0.91) but showed no effect in patients with severe disease (RR 0.98, 95 % CI 0.86 - 1.12). The risk of severe bleeding may increase regardless of disease severity (RR 1.78, 95 % CI 1.15 - 2.74). Conclusion(s): Certainty of evidence is low. Hospitalised, moderately-ill COVID-19 patients may benefit from therapeutic-dose anticoagulation, however, with an increased risk of bleeding. Copyright © 2022 DIOmed Verlags GmbH. All rights reserved.

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid®) plus standard of care compared to standard of care with or without placebo, or any other proven intervention for treating COVID-19 and for preventing SARS-CoV-2 infection.

Pregnant and postpartum women requiring intensive care treatment for COVID-19-first data from the CRONOS-registry

Background Critical illness during pregnancy puts mother and fetus at serious risks. Current literature regarding the effect of coronavirus 2 (SARS-CoV-2) describes an increased risk for maternal mortality as well as high rates of preterm delivery, however data vary and depend on the respective health care system. We aimed to describe maternal characteristics and clinical presentation of SARS-CoV-2 positive pregnant and postpartum women requiring intensive care treatment for COVID-19 in Germany, in order to explore risk factors for severe COVID-19 courses as well as to provide an overview on treatments applied. Methods COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS), an ongoing prospective multicenter registry for SARS-CoV-2 positive pregnant women from 150 centres in Germany was analyzed with respect to intensive care treatment for COVID-19. We extracted information for all women requiring intensive care treatment for COVID-19 and compared maternal characteristics, course of disease, as well as maternal and neonatal outcomes. Results Out of 2445 cases in CRONOS registry, 96 women (4%) had a documented intensive care unit (ICU) stay and were analyzed. While 75 (78%) women were pregnant when receiving ICU treatment, 21 (22%) were admitted post-delivery. Median maternal age was 33 (IQR, 30-36) years. COVID-19 was diagnosed at a median gestational age of 32 (IQR, 28-35) weeks. We observed the following interventions as highest form of treatment required for COVID-19: continuous monitoring of vital signs (n=6 (6%)), insufflation of oxygen (n=32 (33%)), non-invasive ventilation (n=17 (18%)), invasive ventilation (n=29 (30%)) and escalation to extracorporeal membrane oxygenation (ECMO, n=12 (13%)). Maternal characteristics such as maternal age, ethnicity, body mass index at admission, history of smoking, comorbidities and concomitant medication, as well as gestational age were analyzed. No significant differences between patients receiving different forms of respiratory therapy for COVID-19 could be identified. Preterm delivery was observed in 45 women (47%). Two women (2%) died of COVID-19 and four fetuses (4%) were stillborn. Conclusions Our cohort shows that progression of COVID-19 in pregnant and postpartum women requiring ICU treatment is rare. Preterm birth rate is high and COVID-19 requiring respiratory support is not necessarily related to poor maternal or neonatal outcome. But, as one in ten patients admitted to ICU might require ECMO therapy, all pregnant women suffering from COVID-19 should be closely monitored. In future studies, detail about obstetric women requiring intensive care treatment for COVID-19 should be further evaluated.

Systemic platelet exhaustion in critically-ill COVID-19 patients

Background : Infection with SARS-CoV-2 leads to an altered hemostatic system and Covid-19 associated coagulopathy (CAC). Platelet counts remain overall unaltered, but thromboembolic events are frequently reported. Studies on the contribution of platelets to CAC are emerging but still lacking precise cohort comparison and broad analyses of platelet markers. Aims : We aimed to analyze platelet receptor expression and function on platelets and biomarkers in platelet-poor plasma to investigate the role of platelets in the onset of critical progression of CAC. Methods : Extensive platelet function analyses were performed on 34 critically-ill patients with Covid-19 and data was compared to sepsis patients ( n = 24) and non-SARS-CoV-2 acute infection ( n = 18). Tests included PFA-200, aggregometry, flow cytometry and whole mount TEM. Plasma levels of TPO, sCD62P and sGPVI were determined by ELISA. For all patients, relatives, and for healthy controls ( n = 10) informed consent was obtained. Results : While platelet counts in patients of our Covid-19 cohort were expectably unaltered, platelet function was severely impaired in multiple assays. Platelets failed to aggregate in response to ADP or TRAP-6 and could not activate integrin response or release α-granules. The amount of platelet-leukocyte aggregates was markedly elevated, indicating previous platelet activation in line with higher levels of sCD62P and sGPVI. Remarkably, we observed platelet exhaustion in Covid-19 patients using whole mount TEM by means of a lack of dense granules corroborating with impaired uptake of mepacrine. Conclusions : Our data imply that SARS-CoV-2 infection leads to a sub-threshold activation of platelets in a way that they become activated already before critical disease progression, without being cleared from the circulation, which is in striking contrast to sepsis. The platelet pool appears to be exhausted with detrimental consequences for thrombus stability and the risk of thromboembolic events. The mere platelet count in Covid-19 does thus not reflect progression to CAC, whereas platelet function is of high prognostic relevance.

Gallium-68-CXCR4-PET/CT chemokine receptor-targeting imaging in acute SARS-Cov-2 infection: A case report

Ziel/Aim Single-patient report on the pattern of CXCR4 expression in a patient presenting with acute respiratory SARS-Cov-2 (COVID-19) infection after hybrid imaging with Ga-68-pentixafor-PET/non-ceCT (CXCR4-PET). Methodik/Methods 37-year-old man presenting with pneumonia, severe ARDS, requiring mechanical ventilation and acute supportive therapy. Later diagnose of bacterial superinfection with septic shock, persistent high fever (>40 °C) and elevated inflammation markers, non-responsive to wide-spectrum antibiotics. 178 MBq of Ga-68-pentixafor then administered in accordance with the responsible regulatory body after obtaining informed consent. Whole-body imaging followed on a dedicated PET-scanner 1h post-injection. Low-dose CT scans for attenuation correction were acquired (top of the skull to proximal tibias). Ergebnisse/Results CRCX4-PET showed only faint pulmonary uptake in parallel with significantly enhanced, diffuse tracer-uptake in the bone marrow (spine, thorax and pelvis) as well as in the spleen. Increased CXCR4-expression in the pharyngeal/palatine tonsils, CXCR4-positive lymph nodes in the neck/thorax as well as abdominal/inguinal regions was also reported. Focal soft-tissue uptake was detected in the distal right thigh, showing a characteristic peripheral tracer distribution strongly suggestive of intramuscular inflammatory focus. Schlussfolgerungen/Conclusions Ga-68-pentixafor-PET/low-dose-CT hybrid imaging showed foci of increased CXCR4-expression other than the lungs in a SARS-Cov-2 patient presenting with persistent high fever. Although lacking validation data, this single case suggests a role of CXCR4-targeted hybrid imaging in acute inflammatory conditions such as COVID-19 infections and warrants further prospective studies to evaluate its potential role in guiding clinical management in a more complex setting of systemic, multi-organ infectious/inflammatory disease.

Surgery in times of COVID-19-recommendations for hospital and patient management.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeons have had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. PURPOSE: To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safely accommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergency surgery and oncological patients or jeopardizing the well-being of hospital staff. CONCLUSIONS: The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life while maintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards and operating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidently and successfully undertake their respective clinical duties.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.

[Anesthesia and intensive care ventilators: differences and usability in COVID-19 patients]. / Anästhesie- und Intensivbeatmungsgeräte: Unterschiede und Nutzbarkeit bei COVID-19-Patienten.

The current coronavirus disease 2019 (Covid-19) pandemia is a highly dynamic situation characterized by therapeutic and logistic uncertainties. Depending on the effectiveness of social distancing, a shortage of intensive care respirators must be expected. Concomitantly, many physicians and nursing staff are unaware of the capabilities of alternative types of ventilators, hence being unsure if they can be used in intensive care patients. Intensive care respirators were specifically developed for the use in patients with pathological lung mechanics. Nevertheless, modern anesthesia machines offer similar technical capabilities including a number of different modes. However, conceptual differences must be accounted for, requiring close monitoring and the presence of trained personnel. Modern transport ventilators are mainly for bridging purposes as they can only be used with 100% oxygen in contaminated surroundings. Unconventional methods, such as "ventilator-splitting", which have recently received increasing attention on social media, cannot be recommended. This review intends to provide an overview of the conceptual and technical differences of different types of mechanical ventilators.