TY - JOUR A1 - Herrmann, Johannes A1 - Adam, Elisabeth Hannah A1 - Notz, Quirin A1 - Helmer, Philipp A1 - Sonntagbauer, Michael A1 - Ungemach-Papenberg, Peter A1 - Sanns, Andreas A1 - Zausig, York A1 - Steinfeldt, Thorsten A1 - Torje, Iuliu A1 - Schmid, Benedikt A1 - Schlesinger, Tobias A1 - Rolfes, Caroline A1 - Reyher, Christian A1 - Kredel, Markus A1 - Stumpner, Jan A1 - Brack, Alexander A1 - Wurmb, Thomas A1 - Gill-Schuster, Daniel A1 - Kranke, Peter A1 - Weismann, Dirk A1 - Klinker, Hartwig A1 - Heuschmann, Peter A1 - Rücker, Viktoria A1 - Frantz, Stefan A1 - Ertl, Georg A1 - Muellenbach, Ralf Michael A1 - Mutlak, Haitham A1 - Meybohm, Patrick A1 - Zacharowski, Kai A1 - Lotz, Christopher T1 - COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study JF - Frontiers in Medicine N2 - Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients. KW - COVID-19 KW - ARDS (acute respiratory distress syndrome) KW - intensive care medicine KW - pandemia KW - Germany Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219834 SN - 2296-858X VL - 7 ER - TY - JOUR A1 - Herrmann, Johannes A1 - Notz, Quirin A1 - Schlesinger, Tobias A1 - Stumpner, Jan A1 - Kredel, Markus A1 - Sitter, Magdalena A1 - Schmid, Benedikt A1 - Kranke, Peter A1 - Schulze, Harald A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study JF - Thrombosis Journal N2 - Background Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) leads to thromboembolic events in a high number of critically ill COVID-19 patients. However, specific diagnostic or therapeutic algorithms for CAC have not been established. In the current study, we analyzed coagulation abnormalities with point-of-care testing (POCT) and their relation to hemostatic complications in patients suffering from COVID-19 induced Acute Respiratory Distress Syndrome (ARDS). Our hypothesis was that specific diagnostic patterns can be identified in patients with COVID-19 induced ARDS at risk of thromboembolic complications utilizing POCT. Methods This is a single-center, retrospective observational study. Longitudinal data from 247 rotational thromboelastometries (Rotem®) and 165 impedance aggregometries (Multiplate®) were analysed in 18 patients consecutively admitted to the ICU with a COVID-19 induced ARDS between March 12th to June 30th, 2020. Results Median age was 61 years (IQR: 51–69). Median PaO2/FiO2 on admission was 122 mmHg (IQR: 87–189), indicating moderate to severe ARDS. Any form of hemostatic complication occurred in 78 % of the patients with deep vein/arm thrombosis in 39 %, pulmonary embolism in 22 %, and major bleeding in 17 %. In Rotem® elevated A10 and maximum clot firmness (MCF) indicated higher clot strength. The delta between EXTEM A10 minus FIBTEM A10 (ΔA10) > 30 mm, depicting the sole platelet-part of clot firmness, was associated with a higher risk of thromboembolic events (OD: 3.7; 95 %CI 1.3–10.3; p = 0.02). Multiplate® aggregometry showed hypoactive platelet function. There was no correlation between single Rotem® and Multiplate® parameters at intensive care unit (ICU) admission and thromboembolic or bleeding complications. Conclusions Rotem® and Multiplate® results indicate hypercoagulability and hypoactive platelet dysfunction in COVID-19 induced ARDS but were all in all poorly related to hemostatic complications.. KW - COVID-19 KW - acute Respiratory Distress Syndrome KW - point of care testing KW - thromboelastometry KW - impedance aggregometry; WHOLE-BLOOD THROMBOELASTOMETRY; DEFINITION; DISEASE Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260739 VL - 19 IS - 1 ER - TY - JOUR A1 - Hottenrott, Sebastian A1 - Schlesinger, Tobias A1 - Helmer, Philipp A1 - Meybohm, Patrick A1 - Alkatout, Ibrahim A1 - Kranke, Peter T1 - Do small incisions need only minimal anesthesia? — anesthetic management in laparoscopic and robotic surgery JF - Journal of Clinical Medicine N2 - Laparoscopic techniques have established themselves as a major part of modern surgery. Their implementation in every surgical discipline has played a vital part in the reduction of perioperative morbidity and mortality. Precise robotic surgery, as an evolution of this, is shaping the present and future operating theatre that an anesthetist is facing. While incisions get smaller and the impact on the organism seems to dwindle, challenges for anesthetists do not lessen and could even become more demanding than in open procedures. This review focuses on the pathophysiological effects of contemporary laparoscopic and robotic procedures and summarizes anesthetic challenges and strategies for perioperative management. KW - general anesthesia KW - anesthetics KW - perioperative care KW - minimally invasive surgery KW - laparoscopic surgery KW - robotic surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220039 SN - 2077-0383 VL - 9 IS - 12 ER - TY - JOUR A1 - Notz, Quirin A1 - Herrmann, Johannes A1 - Schlesinger, Tobias A1 - Helmer, Philipp A1 - Sudowe, Stephan A1 - Sun, Qian A1 - Hackler, Julian A1 - Roeder, Daniel A1 - Lotz, Christopher A1 - Meybohm, Patrick A1 - Kranke, Peter A1 - Schomburg, Lutz A1 - Stoppe, Christian T1 - Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS JF - Nutrients N2 - The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS. KW - acute respiratory distress syndrome KW - selen KW - zinc KW - critical care KW - oxidative stress KW - nutrient supplementation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241112 SN - 2072-6643 VL - 13 IS - 6 ER - TY - JOUR A1 - Notz, Quirin A1 - Lotz, Christopher A1 - Herrmann, Johannes A1 - Vogt, Marius A1 - Schlesinger, Tobias A1 - Kredel, Markus A1 - Muellges, Wolfgang A1 - Weismann, Dirk A1 - Westermaier, Thomas A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - Severe neurological complications in critically ill COVID‑19 patients JF - Journal of Neurology N2 - No abstract available. KW - COVID-19 KW - neurological complications Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232429 SN - 0340-5354 ER - TY - JOUR A1 - Notz, Quirin A1 - Schmalzing, Marc A1 - Wedekink, Florian A1 - Schlesinger, Tobias A1 - Gernert, Michael A1 - Herrmann, Johannes A1 - Sorger, Lena A1 - Weismann, Dirk A1 - Schmid, Benedikt A1 - Sitter, Magdalena A1 - Schlegel, Nicolas A1 - Kranke, Peter A1 - Wischhusen, Jörg A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study JF - Frontiers in Immunology N2 - Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience. KW - Coronavirus Disease 2019 KW - acute respiratory distress syndrome KW - Severe Acute Respiratory Syndrome Coronavirus 2 KW - cytokines KW - inflammation KW - growth differentiation factor 15 KW - immune response Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212815 SN - 1664-3224 VL - 11 ER - TY - JOUR A1 - Riemer, Manuel A1 - Kranke, Peter A1 - Helf, Antonia A1 - Mayer, Debora A1 - Popp, Maria A1 - Schlesinger, Tobias A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting JF - BMC Anesthesiology N2 - Background: Selective outcome reporting in clinical trials introduces bias in the body of evidence distorting clinical decision making. Trial registration aims to prevent this bias and is suggested by the International Committee of Medical Journal Editors (ICMJE) since 2004. Methods: The 585 randomized controlled trials (RCTs) published between 1965 and 2017 that were included in a recently published Cochrane review on antiemetic drugs for prevention of postoperative nausea and vomiting were selected. In a retrospective study, we assessed trial registration and selective outcome reporting by comparing study publications with their registered protocols according to the ‘Cochrane Risk of bias’ assessment tool 1.0. Results: In the Cochrane review, the first study which referred to a registered trial protocol was published in 2004. Of all 585 trials included in the Cochrane review, 334 RCTs were published in 2004 or later, of which only 22% (75/334) were registered. Among the registered trials, 36% (27/75) were pro- and 64% (48/75) were retrospectively registered. 41% (11/27) of the prospectively registered trials were free of selective outcome reporting bias, 22% (6/27) were incompletely registered and assessed as unclear risk, and 37% (10/27) were assessed as high risk. Major outcome discrepancies between registered and published high risk trials were a change from the registered primary to a published secondary outcome (32%), a new primary outcome (26%), and different outcome assessment times (26%). Among trials with high risk of selective outcome reporting 80% favoured at least one statistically significant result. Registered trials were assessed more often as ‘overall low risk of bias’ compared to non-registered trials (64% vs 28%). Conclusions: In 2017, 13 years after the ICMJE declared prospective protocol registration a necessity for reliable clinical studies, the frequency and quality of trial registration in the field of PONV is very poor. Selective outcome reporting reduces trustworthiness in findings of clinical trials. Investigators and clinicians should be aware that only following a properly registered protocol and transparently reporting of predefined outcomes, regardless of the direction and significance of the result, will ultimately strengthen the body of evidence in the field of PONV research in the future. KW - clinical trial KW - postoperative nausea and vomiting KW - selective outcome reporting KW - systematic review KW - trial registration Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265518 VL - 21 ER - TY - JOUR A1 - Schlesinger, Tobias A1 - Weibel, Stephanie A1 - Steinfeldt, Thorsten A1 - Sitter, Magdalena A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - Intraoperative management of combined general anesthesia and thoracic epidural analgesia: A survey among German anesthetists JF - Acta Anaesthesiologica Scandinavica N2 - Background Evidence concerning combined general anesthesia (GA) and thoracic epidural analgesia (EA) is controversial and the procedure appears heterogeneous in clinical implementation. We aimed to gain an overview of different approaches and to unveil a suspected heterogeneity concerning the intraoperative management of combined GA and EA. Methods This was an anonymous survey among Members of the Scientific working group for regional anesthesia within the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) conducted from February 2020 to August 2020. Results The response rate was 38%. The majority of participants were experienced anesthetists with high expertise for the specific regimen of combined GA and EA. Most participants establish EA in the sitting position (94%), prefer early epidural initiation (prior to skin incision: 80%; intraoperative: 14%) and administer ropivacaine (89%) in rather low concentrations (0.2%: 45%; 0.375%: 30%; 0.75%: 15%) mostly with an opioid (84%) in a bolus-based mode (95%). The majority reduce systemic opioid doses intraoperatively if EA works sufficiently (minimal systemic opioids: 58%; analgesia exclusively via EA: 34%). About 85% manage intraoperative EA insufficiency with systemic opioids, 52% try to escalate EA, and only 25% use non-opioids, e.g. intravenous ketamine or lidocaine. Conclusions Although, consensus seems to be present for several aspects (patient's position during epidural puncture, main epidural substance, application mode), there is considerable heterogeneity regarding systemic opioids, rescue strategies for insufficient EA, and hemodynamic management, which might explain inconsistent results of previous trials and meta-analyses. KW - analgesics KW - enhanced recovery after surgery KW - multimodal treatments KW - perioperative care KW - epidural analgesia Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258286 VL - 65 IS - 10 ER - TY - JOUR A1 - Schlesinger, Tobias A1 - Weißbrich, Benedikt A1 - Wedekink, Florian A1 - Notz, Quirin A1 - Herrmann, Johannes A1 - Krone, Manuel A1 - Sitter, Magdalena A1 - Schmid, Benedikt A1 - Kredel, Markus A1 - Stumpner, Jan A1 - Dölken, Lars A1 - Wischhusen, Jörg A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Lotz, Christpher T1 - Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study JF - PLoS One N2 - Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100% of the cases, oropharyngeal swabs only in 77%. Blood samples were positive in 26% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity. KW - viral load Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231348 VL - 15, 2020 IS - 11 ER - TY - JOUR A1 - Weibel, Stephanie A1 - Pace, Nathan L. A1 - Schaefer, Maximilian S. A1 - Raj, Diana A1 - Schlesinger, Tobias A1 - Meybohm, Patrick A1 - Kienbaum, Peter A1 - Eberhart, Leopold H. J. A1 - Kranke, Peter T1 - Drugs for preventing postoperative nausea and vomiting in adults after general anesthesia: An abridged Cochrane network meta-analysis JF - Journal of Evidence-Based Medicine N2 - Objective In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form. Methods We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia. Results 585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies’ overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK1 receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing. Conclusions There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation. KW - systematic review, KW - antiemetics KW - network meta-analysis KW - postoperative nausea and vomiting KW - vomiting Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259470 VL - 14 IS - 3 ER -