Publications by authors named "Patrick Meybohm"

256 Publications

[Anesthesiology Seminar in Times of COVID-19: a Hybrid Model evolving from Digital and Virtual Lessons].

Anasthesiol Intensivmed Notfallmed Schmerzther 2021 Dec 24;56(11-12):782-790. Epub 2021 Nov 24.

On March 14, 2020, the first Bavaria-wide exit restriction was imposed and university teaching in its familiar form was drastically restricted. For intensive care physicians and anesthetists, there was a special area of tension in many places due to the extraordinary demand for the treatment of critically ill patients and the restructuring and maintenance of teaching. We report on the realignment of the anesthesia seminar in an online flipped classroom and the development towards a hybrid model. As such, an adequate transfer of knowledge could take place under difficult conditions and at the same time the teaching concept could be further developed.
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http://dx.doi.org/10.1055/a-1543-2913DOI Listing
December 2021

[COVID-19 in obstetric anesthesia : Prospective surveillance of peripartum infections with SARS-CoV-2 and peripartum course of disease in affected women].

Anaesthesist 2021 Nov 23. Epub 2021 Nov 23.

Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Universitätsklinikum Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Deutschland.

Background: In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected.

Objective: This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV‑2 pandemic in Germany.

Material And Methods: As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV‑2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV‑2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV‑2 positive pregnant women.

Results: A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV‑2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV‑2 infection.

Conclusion: The number of pregnant women infected with SARS-CoV‑2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients.
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http://dx.doi.org/10.1007/s00101-021-01068-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609991PMC
November 2021

Patient Blood Management in intensive care patients.

Curr Opin Crit Care 2021 12;27(6):709-716

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt.

Purpose Of Review: Patients admitted to ICUs are a heterogeneous group, displaying multiple anaemia risk factors and comorbidities. Clinicians should therefore take all possible measures to identify modifiable risks. Patient Blood Management (PBM) is an approach promoting the timely application of evidence-based interventions designed to maintain patients own blood mass.

Recent Findings: Within ICU-patients, anaemia is highly prevalent. Generally, anaemia is associated with impaired outcome and need of blood transfusion. Currently, with ICUs working at full capacity and the global blood reserves exhausted, the SARS-CoV-2 pandemic reinforces the need for PBM implementation. For instance, implementation of a comprehensive coagulation management and measures to avoid iatrogenic blood loss may prevent bleeding-associated complications and adherence to blood transfusion guidelines may reduce adverse events associated with transfusion.

Summary: Critically ill patients display various morbidities often requiring individualized treatment. PBM offers patient-centred measures to improve outcome any time during hospital stay.
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http://dx.doi.org/10.1097/MCC.0000000000000880DOI Listing
December 2021

Estimate of exposure to SARS-CoV-2 and performance of high-risk interventions by European anaesthesiologists: A Pan-European cross-sectional survey.

Eur J Anaesthesiol 2021 12;38(12):1293-1295

From the Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg (BS, PM, MS, MP, PK), Department of Pediatrics, University Hospital Wuerzburg, Wuerzburg (KH), Immunization Unit, Robert Koch-Institute, Berlin, Germany (SMS), Department of Anaesthesiology and Perioperative Medicine, University Hospital Gent, Gent, Belgium (SDH), Department of Anaesthesia and Intensive Care, Cochin University Hospital, Paris, France (CMS), Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital Frankfurt, Frankfurt/Main, Germany (KZ) and European Society of Anaesthesiology and Intensive Care, Bruxelles, Belgium (KZ).

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http://dx.doi.org/10.1097/EJA.0000000000001541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635072PMC
December 2021

Removal of EpCAM-positive tumor cells from blood collected during major oncological surgery using the Catuvab device- a pilot study.

BMC Anesthesiol 2021 10 29;21(1):261. Epub 2021 Oct 29.

Trion Research GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany.

Background: Intraoperative blood salvage (IBS) is regarded as an alternative to allogeneic blood transfusion excluding the risks associated with allogeneic blood. Currently, IBS is generally avoided in tumor surgeries due to concern for potential metastasis caused by residual tumor cells in the erythrocyte concentrate.

Methods: The feasibility, efficacy and safety aspects of the new developed Catuvab procedure using the bispecific trifunctional antibody Catumaxomab was investigated in an ex-vivo pilot study in order to remove residual EpCAM positive tumor cells from the autologous erythrocyte concentrates (EC) from various cancer patients, generated by a IBS device.

Results: Tumor cells in intraoperative blood were detected in 10 of 16 patient samples in the range of 69-2.6 × 10 but no residual malignant cells in the final erythrocyte concentrates after Catuvab procedure. IL-6 and IL-8 as pro-inflammatory cytokines released during surgery, were lowered in mean 28-fold and 52-fold during the Catuvab procedure, respectively, whereas Catumaxomab antibody was detected in 8 of 16 of the final EC products at a considerable decreased and uncritical residual amount (37 ng in mean).

Conclusion: The preliminary study results indicate efficacy and feasibility of the new medical device Catuvab allowing potentially the reinfusion of autologous erythrocyte concentrates (EC) produced by IBS device during oncological high blood loss surgery. An open-label, multicenter clinical study on the removal of EpCAM-positive tumor cells from blood collected during tumor surgery using the Catuvab device is initiated to validate these encouraging results.
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http://dx.doi.org/10.1186/s12871-021-01479-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555247PMC
October 2021

[Pro: liberalisation of fluid fasting before elective surgery? : Old habits die hard].

Anaesthesist 2021 Oct 28. Epub 2021 Oct 28.

Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Universitätsklinikum Würzburg, Oberdürrbacher Straße 6, 97080, Würzburg, Deutschland.

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http://dx.doi.org/10.1007/s00101-021-01060-0DOI Listing
October 2021

Antibiotics for the treatment of COVID-19.

Cochrane Database Syst Rev 2021 10 22;10:CD015025. Epub 2021 Oct 22.

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

Background: The effect of antibiotics with potential antiviral and anti-inflammatory properties are being investigated in clinical trials as treatment for COVID-19. The use of antibiotics follows the intention-to-treat the viral disease and not primarily to treat bacterial co-infections of individuals with COVID-19. A thorough understanding of the current evidence regarding effectiveness and safety of antibiotics as anti-viral treatments for COVID-19 based on randomised controlled trials (RCTs) is required.

Objectives: To assess the efficacy and safety of antibiotics compared to each other, no treatment, standard of care alone, placebo, or any other active intervention with proven efficacy for treatment of COVID-19 outpatients and inpatients.  SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (including MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv, CENTRAL), Web of Science and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 14 June 2021.

Selection Criteria: RCTs were included that compared antibiotics with each other, no treatment, standard of care alone, placebo, or another proven intervention, for treatment of people with confirmed COVID-19, irrespective of disease severity, treated in the in- or outpatient settings. Co-interventions had to be the same in both study arms. We excluded studies comparing antibiotics to other pharmacological interventions with unproven efficacy.

Data Collection And Analysis: We assessed risk of bias of primary outcomes using the Cochrane risk of bias tool (ROB 2) for RCTs. We used GRADE to rate the certainty of evidence for the following primary outcomes: 1. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening defined as new need for intubation or death, clinical improvement defined as being discharged alive, quality of life, adverse and serious adverse events, and cardiac arrhythmias; 2. to treat outpatients with asymptomatic or mild COVID-19: mortality, clinical worsening defined as hospital admission or death, clinical improvement defined as symptom resolution, quality of life, adverse and serious adverse events, and cardiac arrhythmias.

Main Results: We included 11 studies with 11,281 participants with an average age of 54 years investigating antibiotics compared to placebo, standard of care alone or another antibiotic. No study was found comparing antibiotics to an intervention with proven efficacy. All studies investigated azithromycin, two studies investigated other antibiotics compared to azithromycin. Seven studies investigated inpatients with moderate to severe COVID-19 and four investigated mild COVID-19 cases in outpatient settings. Eight studies had an open-label design, two were blinded with a placebo control, and one did not report on blinding. We identified 19 ongoing and 15 studies awaiting classification pending publication of results or clarification of inconsistencies. Of the 30 study results contributing to primary outcomes by included studies, 17 were assessed as overall low risk and 13 as some concerns of bias. Only studies investigating azithromycin reported data eligible for the prioritised primary outcomes. Azithromycin doses and treatment duration varied among included studies.  Azithromycin for the treatment of COVID-19 compared to placebo or standard of care alone in inpatients We are very certain that azithromycin has little or no effect on all-cause mortality at day 28 compared to standard of care alone (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.90 to 1.06; 8600 participants; 4 studies; high-certainty evidence). Azithromycin probably has little or no effect on clinical worsening or death at day 28 (RR 0.95; 95% CI 0.87 to 1.03; 7311 participants; 1 study; moderate-certainty evidence), on clinical improvement at day 28 (RR 0.96; 95% CI 0.84 to 1.11; 8172 participants; 3 studies; moderate-certainty evidence), on serious adverse events during the study period (RR 1.11; 95% CI 0.89 to 1.40; 794 participants; 4 studies; moderate-certainty evidence), and cardiac arrhythmias during the study period (RR 0.92; 95% CI 0.73 to 1.15; 7865 participants; 4 studies; moderate-certainty evidence) compared to placebo or standard of care alone. Azithromycin may increase any adverse events slightly during the study period (RR 1.20; 95% CI 0.92 to 1.57; 355 participants; 3 studies; low-certainty evidence) compared to standard of care alone. No study reported quality of life up to 28 days. Azithromycin for the treatment of COVID-19 compared to placebo or standard of care alone in outpatients Azithromycin may have little or no effect compared to placebo or standard of care alone on all-cause mortality at day 28 (RR 1.00 ; 95% CI 0.06 to 15.69; 876 participants; 3 studies; low-certainty evidence), on admission to hospital or death within 28 days (RR 0.94 ; 95% CI 0.57 to 1.56; 876 participants; 3 studies; low-certainty evidence), and on symptom resolution at day 14 (RR 1.03; 95% CI 0.95 to 1.12; 138 participants; 1 study; low-certainty evidence). We are uncertain whether azithromycin increases or reduces serious adverse events compared to placebo or standard of care alone (0 participants experienced serious adverse events; 454 participants; 2 studies; very low-certainty evidence). No study reported on adverse events, cardiac arrhythmias during the study period or quality of life up to 28 days. Azithromycin for the treatment of COVID-19 compared to any other antibiotics in inpatients and outpatients One study compared azithromycin to lincomycin in inpatients, but did not report any primary outcome. Another study compared azithromycin to clarithromycin in outpatients, but did not report any relevant outcome for this review.

Authors' Conclusions: We are certain that risk of death in hospitalised COVID-19 patients is not reduced by treatment with azithromycin after 28 days. Further, based on moderate-certainty evidence, patients in the inpatient setting with moderate and severe disease probably do not benefit from azithromycin used as potential antiviral and anti-inflammatory treatment for COVID-19 regarding clinical worsening or improvement. For the outpatient setting, there is currently low-certainty evidence that azithromycin may have no beneficial effect for COVID-19 individuals. There is no evidence from RCTs available for other antibiotics as antiviral and anti-inflammatory treatment of COVID-19. With accordance to the living approach of this review, we will continually update our search and include eligible trials to fill this evidence gap. However, in relation to the evidence for azithromycin and in the context of antimicrobial resistance, antibiotics should not be used for treatment of COVID-19 outside well-designed RCTs.
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http://dx.doi.org/10.1002/14651858.CD015025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536098PMC
October 2021

Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting.

BMC Anesthesiol 2021 10 19;21(1):249. Epub 2021 Oct 19.

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Oberduerrbacher Str. 6, 97080, Wuerzburg, Germany.

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.
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http://dx.doi.org/10.1186/s12871-021-01464-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524993PMC
October 2021

[Update on PONV-What is new in prophylaxis and treatment of postoperative nausea and vomiting? : Summary of recent consensus recommendations and Cochrane reviews on prophylaxis and treatment of postoperative nausea and vomiting].

Anaesthesist 2021 Oct 1. Epub 2021 Oct 1.

Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Universitätsklinikum Würzburg, Würzburg, Deutschland.

The prophylaxis and treatment of postoperative pain to enhance patient comfort has been a primary goal of anesthesiologists for the last decades; however, avoiding postoperative nausea and vomiting (PONV) is, from a patient's perspective, a highly relevant and equally important goal of anesthesia. Recent consensus-based guidelines suggest the assessment of risk factors including female gender, postoperative opioid administration, non-smoking status, a history of PONV or motion sickness, young patient age, longer duration of anesthesia, volatile anesthetics and the type of surgery and reducing the patient's baseline risk (e.g. through the use of regional anesthesia and administration of non-opioid analgesics as part of a multimodal approach). In general, a liberal PONV prophylaxis is encouraged for adult patients and children, which should also be administered when no risk assessment is made. The basis for every adult patient should be a standard prophylaxis with two antiemetics, such as dexamethasone in combination with a 5-HT receptor antagonist. In patients at high risk, this should be supplemented by a third and potentially a fourth antiemetic prophylaxis with a different mechanism of action. A recently published comprehensive Cochrane meta-analysis comparing available antiemetic prophylaxes reported the highest effectiveness to prevent PONV for the NK receptor antagonist aprepitant (relative risk, RR 0.26), followed by ramosetron (RR 0.44), granisetron (RR 0.45), dexamethasone (RR 0.51) and ondansetron (RR 0.55), thereby revising the dogma that every antiemetic is equally effective. Adverse events of antiemetics were generally rare and reported in less than half of the included studies, yielding a low quality of evidence for these end points. In general, combinations of different antiemetics were more effective than single prophylaxes. In children above 3 years of age, the same principles should be applied as in adults. For these patients, there is a high degree of evidence for the combination of dexamethasone and 5‑HT receptor antagonists. When PONV occurs, the consensus guidelines suggest that antiemetics from a class different than given as prophylaxis should be administered. To decrease the incidence of PONV and increase the quality of care, the importance of the implementation of institutional-level guidelines and protocols as well as assessment of PONV prophylaxis and PONV incidence is highly recommended.
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http://dx.doi.org/10.1007/s00101-021-01045-zDOI Listing
October 2021

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS-a randomized, placebo-controlled, double-blind trial.

Trials 2021 Sep 20;22(1):643. Epub 2021 Sep 20.

Department of Anesthesiology, University Hospital of Ludwig-Maximilians-University (LMU), Munich, Germany.

Background: Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.

Methods: This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days.

Discussion: The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.

Trial Registration: This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47 .
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http://dx.doi.org/10.1186/s13063-021-05588-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450703PMC
September 2021

Impaired psychological well-being of healthcare workers in a German department of anesthesiology is independent of immediate SARS-CoV-2 exposure - a longitudinal observational study.

Ger Med Sci 2021 1;19:Doc11. Epub 2021 Sep 1.

Department of Anesthesiology, Würzburg University Hospital, Würzburg, Germany.

The study aimed to assess the mental well-being of healthcare professionals at a German department of anesthesiology and critical care with a specialized ICU for treatment of COVID-19 patients during the first two peaks of the 2020 pandemic, and identifying risk and protective factors. A single-center longitudinal, online-based survey was conducted in healthcare workers from a department of anesthesiology and critical care in Bavaria, the most affected federal state in Germany at the time of assessment. Validated scores for depression, anxiety, somatic disorders, burnout, resilience, and self-management were used and complemented by questions about perceived COVID-19-related stressors. In parallel, patient characteristics in the ICU were collected. 24 and 23 critically ill COVID-19 patients were treated during both observation periods in April/May and November/December 2020, respectively. 87.5% and 78.2% of patients had moderate to severe acute respiratory distress syndrome. From March 6, 2020 onwards, the hospital had switched to a command and control-based hospital incident command system (HICS) and increased work forces. Point prevalence of depression-like symptoms (13.6% and 12.8%) and burnout (21.6% and 17.4%) in the department's healthcare professionals was high. Exposure to SARS-CoV-2 did not increase psychological burden. Consequences of the lockdown were rated as highly distressing by a majority of all ICU personnel. High self-reported trait resilience was protective against signs of depression, generalized anxiety, and burnout. During the pandemic, healthcare professionals have been suffering from increased psychological distress compared to reference data for both the general population and ICU personnel. General effects of the lockdown appear more relevant than actual COVID-19 patient contact. High trait resilience has a protective effect, yet vulnerable individuals may require specific support. Prevention against potential after effects of the lockdown, and in particular measures allowing to avoid another lockdown, appear warranted.
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http://dx.doi.org/10.3205/000298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422798PMC
September 2021

Importance of the Assessment Time Window for Intravenous Tranexamic Acid and Thromboembolic Events-Reply.

JAMA Surg 2021 Sep 1. Epub 2021 Sep 1.

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

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http://dx.doi.org/10.1001/jamasurg.2021.4141DOI Listing
September 2021

Physician's Subjective Increase in Awareness towards Perioperative Anaemia, Patient's Blood Resource, and Transfusion after the Implementation of Patient Blood Management: A Nationwide Multicentre Survey.

Acta Haematol 2021 Aug 31:1-8. Epub 2021 Aug 31.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Introduction: Patient blood management (PBM) is a clinical and multidisciplinary, 3-pillar concept. The aim of this study was to detect the subjective increase in physician's awareness towards perioperative anaemia, patient's blood resource, and transfusion after the implementation of PBM in German hospitals.

Material And Methods: A survey among 56 hospitals from the German PBM Network group was conducted from October 27 to December 19, 2020. An electronic questionnaire with 28 questions was sent to the local PBM coordinator for the distribution at the hospital level. For assessment of the physician's subjective increase in awareness, numeric rating scales (0 [no increase] - 10 [maximum increase]) were used.

Results: In total, 404 clinicians from 56 hospitals completed the survey. The mean (±standard deviation) time of an existing PBM program was 4.8 (±2.2) years. The physician's subjective increase in awareness towards anaemia (8.2 [±2.0]), patient's blood resource (7.6 [±2.5]), and transfusion (8.1 [±1.9]) was the highest in physicians from hospitals with ≥21 implemented PBM measures. In addition, a subjective increase in awareness towards anaemia (6.6 [±3.3]), patient's blood resource (7.0 [±3.3]), and transfusion (6.6 [±3.4]) was the highest in physicians with daily PBM contact.

Conclusion: Results suggest that physician's awareness towards perioperative anaemia, patient's blood resource, and transfusion has increased, depending on the hospital's number of implemented PBM measures and physician's PBM contact in everyday clinical practice.
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http://dx.doi.org/10.1159/000517607DOI Listing
August 2021

Voice alerting as a medical alarm modality for next-generation patient monitoring: a randomised international multicentre trial.

Br J Anaesth 2021 Nov 26;127(5):769-777. Epub 2021 Aug 26.

Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Background: Acoustic alarms in medical devices are vital for patient safety. State-of-the-art patient monitoring alarms are indistinguishable and contribute to alarm fatigue. There are two promising new sound modalities for vital sign alarms. Auditory icons convey alarms as brief metaphorical sounds, and voice alerts transmit information using a clear-spoken language. We compared how reliably healthcare professionals identified alarms using these two modalities.

Methods: This investigator-initiated computer-based multicentre simulation study included 28 anaesthesia providers who were asked to identify vital sign alarms in randomised order, once with voice alerts and once with auditory icons. We further assessed time to decision, diagnostic confidence, and perceived helpfulness. We analysed the results using mixed models, adjusted for possible confounders.

Results: We assessed 14 alarms for each modality, resulting in 392 comparisons across all participants. Compared with auditory icons, healthcare providers had 58 times higher odds of correctly identifying alarms using voice alerts (odds ratio 58.0; 95% confidence interval [CI]: 25.1-133.6; P<0.001), made their decisions about 14 s faster (coefficient -13.9; 95% CI: -15.8 to -12.1 s; P<0.001), perceived higher diagnostic confidence (100% [392 of 392] vs 43% [169 of 392; P<0.001]), and rated voice alerts as more helpful (odds ratio 138.2; 95% CI: 64.9-294.1; P<0.001). The participants were able to identify significantly higher proportions of alarms with voice alerts (98.5%; P<0.001) and auditory icons (54.1%; P<0.001) compared with state-of-the-art alarms (17.9%).

Conclusions: Voice alerts were superior to auditory icons, and both were superior to current state-of-the-art auditory alarms. These findings demonstrate the potential that voice alerts hold for patient monitoring.
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http://dx.doi.org/10.1016/j.bja.2021.07.015DOI Listing
November 2021

Independent Risk Factors for RBC Transfusion in Children Undergoing Surgery. Analysis of 14,248 Cases at a German University Hospital.

Children (Basel) 2021 Jul 25;8(8). Epub 2021 Jul 25.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt, Germany.

Background: paediatric patients are vulnerable to blood loss and even a small loss of blood can be associated with severe shock. In emergency situations, a red blood cell (RBC) transfusion may become unavoidable, although it is associated with various risks. The aim of this trial was to identify independent risk factors for perioperative RBC transfusion in children undergoing surgery.

Methods: to identify independent risk factors for perioperative RBC transfusion in children undergoing surgery and to access RBC transfusion rates and in-hospital outcomes (e.g., length of stay, mortality, and typical postoperative complication rates), a monocentric, retrospective, and observational study was conducted. Descriptive, univariate, and multivariate analyses were performed.

Results: between 1 January 2010 and 31 December 2019, data from = 14,248 cases were identified at the centre. Analysis revealed an RBC transfusion rate of 10.1% ( = 1439) in the entire cohort. The independent predictors of RBC transfusion were the presence of preoperative anaemia ( < 0.001; OR = 15.10 with preoperative anaemia and OR = 2.40 without preoperative anaemia), younger age ( < 0.001; ORs between 0.14 and 0.28 for children older than 0 years), female gender ( = 0.036; OR = 1.19 compared to male gender), certain types of surgery (e.g., neuro surgery ( < 0.001; OR = 10.14), vascular surgery ( < 0.001; OR = 9.93), cardiac surgery ( < 0.001; OR = 4.79), gynaecology ( = 0.014; OR = 3.64), visceral surgery ( < 0.001; OR = 2.48), and the presence of postoperative complications (e.g., sepsis ( < 0.001; OR = 10.16), respiratory dysfunction ( < 0.001; OR = 7.56), cardiovascular dysfunction ( < 0.001; OR = 4.68), neurological dysfunction ( = 0.029; OR = 1.77), and renal dysfunction ( < 0.001; OR = 16.17)).

Conclusion: preoperative anaemia, younger age, female gender, certain types of surgery, and postoperative complications are independent predictors for RBC transfusion in children undergoing surgery. Future prospective studies are urgently required to identify, in detail, the potential risk factors and impact of RBC transfusion in children.
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http://dx.doi.org/10.3390/children8080634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394932PMC
July 2021

Patient Blood Management in der Chirurgie.

Zentralbl Chir 2021 Aug 24;146(4):367-370. Epub 2021 Aug 24.

Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland.

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http://dx.doi.org/10.1055/a-1209-6009DOI Listing
August 2021

Evidence on the efficacy of ivermectin for COVID-19: another story of apples and oranges.

BMJ Evid Based Med 2021 Aug 20. Epub 2021 Aug 20.

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wurzburg, Wurzburg, Bayern, Germany

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http://dx.doi.org/10.1136/bmjebm-2021-111791DOI Listing
August 2021

Machine learning identifies ICU outcome predictors in a multicenter COVID-19 cohort.

Crit Care 2021 Aug 17;25(1):295. Epub 2021 Aug 17.

Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany.

Background: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes.

Methods: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported.

Results: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy.

Conclusions: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.
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http://dx.doi.org/10.1186/s13054-021-03720-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370055PMC
August 2021

Intraoperative management of combined general anesthesia and thoracic epidural analgesia: A survey among German anesthetists.

Acta Anaesthesiol Scand 2021 Nov 5;65(10):1490-1496. Epub 2021 Sep 5.

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

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.
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http://dx.doi.org/10.1111/aas.13971DOI Listing
November 2021

Ivermectin for preventing and treating COVID-19.

Cochrane Database Syst Rev 2021 07 28;7:CD015017. Epub 2021 Jul 28.

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

Background: Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting.

Objectives: To assess the efficacy and safety of ivermectin compared to no treatment, standard of care, placebo, or any other proven intervention for people with COVID-19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS-CoV-2 (postexposure prophylaxis).

Search Methods: We searched the Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, identifying completed and ongoing studies without language restrictions to 26 May 2021.

Selection Criteria: We included randomized controlled trials (RCTs) comparing ivermectin to no treatment, standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity, treated in inpatient or outpatient settings, and for prevention of SARS-CoV-2 infection. Co-interventions had to be the same in both study arms.  We excluded studies comparing ivermectin to other pharmacological interventions with unproven efficacy.

Data Collection And Analysis: We assessed RCTs for bias, using the Cochrane risk of bias 2 tool. The primary analysis excluded studies with high risk of bias. We used GRADE to rate the certainty of evidence for the following outcomes 1. to treat inpatients with moderate-to-severe COVID-19: mortality, clinical worsening or improvement, adverse events, quality of life, duration of hospitalization, and viral clearance; 2. to treat outpatients with mild COVID-19: mortality, clinical worsening or improvement, admission to hospital, adverse events, quality of life, and viral clearance; (3) to prevent SARS-CoV-2 infection: SARS-CoV-2 infection, development of COVID-19 symptoms, adverse events, mortality, admission to hospital, and quality of life.

Main Results: We found 14 studies with 1678 participants investigating ivermectin compared to no treatment, placebo, or standard of care. No study compared ivermectin to an intervention with proven efficacy. There were nine studies treating participants with moderate COVID-19 in inpatient settings and four treating mild COVID-19 cases in outpatient settings. One study investigated ivermectin for prevention of SARS-CoV-2 infection. Eight studies had an open-label design, six were double-blind and placebo-controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias.  Ivermectin doses and treatment duration varied among included studies.  We identified 31 ongoing and 18 studies awaiting classification until publication of results or clarification of inconsistencies. Ivermectin compared to placebo or standard of care for inpatient COVID-19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 2 studies, 185 participants; very low-certainty evidence) and clinical worsening up to day 28 assessed as need for invasive mechanical ventilation (IMV) (RR 0.55, 95% CI 0.11 to 2.59; 2 studies, 185 participants; very low-certainty evidence) or need for supplemental oxygen (0 participants required supplemental oxygen; 1 study, 45 participants; very low-certainty evidence), adverse events within 28 days (RR 1.21, 95% CI 0.50 to 2.97; 1 study, 152 participants; very low-certainty evidence), and viral clearance at day seven (RR 1.82, 95% CI 0.51 to 6.48; 2 studies, 159 participants; very low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on clinical improvement up to 28 days (RR 1.03, 95% CI 0.78 to 1.35; 1 study; 73 participants; low-certainty evidence) and duration of hospitalization (mean difference (MD) -0.10 days, 95% CI -2.43 to 2.23; 1 study; 45 participants; low-certainty evidence). No study reported quality of life up to 28 days. Ivermectin compared to placebo or standard of care for outpatient COVID-19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality up to 28 days (RR 0.33, 95% CI 0.01 to 8.05; 2 studies, 422 participants; very low-certainty evidence) and clinical worsening up to 14 days assessed as need for IMV (RR 2.97, 95% CI 0.12 to 72.47; 1 study, 398 participants; very low-certainty evidence) or non-IMV or high flow oxygen requirement (0 participants required non-IMV or high flow; 1 study, 398 participants; very low-certainty evidence). We are uncertain whether ivermectin compared to placebo reduces or increases viral clearance at seven days (RR 3.00, 95% CI 0.13 to 67.06; 1 study, 24 participants; low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on the number of participants with symptoms resolved up to 14 days (RR 1.04, 95% CI 0.89 to 1.21; 1 study, 398 participants; low-certainty evidence) and adverse events within 28 days (RR 0.95, 95% CI 0.86 to 1.05; 2 studies, 422 participants; low-certainty evidence). None of the studies reporting duration of symptoms were eligible for primary analysis. No study reported hospital admission or quality of life up to 14 days. Ivermectin compared to no treatment for prevention of SARS-CoV-2 infection We found one study. Mortality up to 28 days was the only outcome eligible for primary analysis. We are uncertain whether ivermectin reduces or increases mortality compared to no treatment (0 participants died; 1 study, 304 participants; very low-certainty evidence). The study reported results for development of COVID-19 symptoms and adverse events up to 14 days that were included in a secondary analysis due to high risk of bias. No study reported SARS-CoV-2 infection, hospital admission, and quality of life up to 14 days.

Authors' Conclusions: Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.
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http://dx.doi.org/10.1002/14651858.CD015017.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406455PMC
July 2021

Corona Health-A Study- and Sensor-Based Mobile App Platform Exploring Aspects of the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 07 10;18(14). Epub 2021 Jul 10.

Department of Clinical Psychology and Psychotherapy, Ulm University, 89081 Ulm, Germany.

Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.
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http://dx.doi.org/10.3390/ijerph18147395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303497PMC
July 2021

Clinical Outcome and Risk Factors of Red Blood Cell Transfusion in Patients Undergoing Elective Primary Meningioma Resection.

Cancers (Basel) 2021 Jul 18;13(14). Epub 2021 Jul 18.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany.

Transfusion of red blood cells (RBC) in patients undergoing major elective cranial surgery is associated with increased morbidity, mortality and prolonged hospital length of stay (LOS). This retrospective single center study aims to identify the clinical outcome of RBC transfusions on skull base and non-skull base meningioma patients including the identification of risk factors for RBC transfusion. Between October 2009 and October 2016, 423 patients underwent primary meningioma resection. Of these, 68 (16.1%) received RBC transfusion and 355 (83.9%) did not receive RBC units. Preoperative anaemia rate was significantly higher in transfused patients (17.7%) compared to patients without RBC transfusion (6.2%; = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher ( < 0.0001) compared to non-transfused patients. After multivariate analyses, risk factors for RBC transfusion were preoperative American Society of Anaesthesiologists (ASA) physical status score ( = 0.0247), tumor size ( = 0.0006), surgical time ( = 0.0018) and intraoperative blood loss ( < 0.0001). Kaplan-Meier curves revealed significant influence on overall survival by preoperative anaemia, RBC transfusion, smoking, cardiovascular disease, preoperative KPS ≤ 60% and age (elderly ≥ 75 years). We concluded that blood loss due to large tumors or localization near large vessels are the main triggers for RBC transfusion in meningioma patients paired with a potential preselection that masks the effect of preoperative anaemia in multivariate analysis. Further studies evaluating the impact of preoperative anaemia management for reduction of RBC transfusion are needed to improve the clinical outcome of meningioma patients.
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http://dx.doi.org/10.3390/cancers13143601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307823PMC
July 2021

[Ethical, Psychosocial and Legal Aspects of the Treatment of Pregnant Patients with Brain Death].

Anasthesiol Intensivmed Notfallmed Schmerzther 2021 Jul 23;56(7-08):536-543. Epub 2021 Jul 23.

The therapy of brain-dead pregnant women is an extreme example not only of the possibilities in current critical care, but also of resulting ethical, social and legal controversies, an area not familiar to most clinicians. Based on the case of a patient with fatal traumatic brain injury, a previously unknown early pregnancy and stated will to donate organs, we will discuss several aspects using published case reports: therapeutic goals, especially palliative care vs. continuation; implications of brain death diagnosis; considerations on legal care; involvement of relatives, especially the child's father; dynamics within the care team; and finally the issue of putative organ donation. This complex case once more depicts that even facing such highly unfavourable framework and seemingly irreconcilable factors, pregnancy can prevail. The researched facts and considerations in this article are intended to give an overview of potential dilemmas and might serve as a starting point in similar situations.
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http://dx.doi.org/10.1055/a-1203-2826DOI Listing
July 2021

[Pregnancy and Irreversible Loss of Brain Functions - Case Report].

Anasthesiol Intensivmed Notfallmed Schmerzther 2021 Jul 23;56(7-08):526-535. Epub 2021 Jul 23.

A 29-year-old woman suffered major traumatic brain injury caused by a car accident. As diagnostic measures had revealed an early pregnancy (9th week), treatment on the intensive care unit was continued for 5 months, after unfavourable cerebral prognosis was followed by an irreversible loss of brain function in the 10th week of pregnancy. After assisted vaginal delivery of a healthy child in the 31th week of pregnancy on the critical care unit, organ procurement took place according to the presumed will of the patient. The article presents the details of the critical care therapy and discusses the supportive medical measures. Those measures served primarily to uphold the pregnancy und support the healthy development and delivery of the fetus and only in second instance the organ preservation aiming on organ donation. Necessary measures included maintenance of vital functions, hemostasis of electrolytes, nutrition, treatment of infection, prevention of adverse effects on the fetus, substitution of hormones and vitamins as well as the preparation of a planned or an unplanned delivery.
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http://dx.doi.org/10.1055/a-1203-3031DOI Listing
July 2021

Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry.

Thromb Haemost 2021 Jul 13. Epub 2021 Jul 13.

Institute of Biostatistics and Mathematical Modelling, Goethe University, Frankfurt, Germany.

Background:  Direct oral anticoagulants (DOACs) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations.

Methods:  A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In samples collected as part of routine care DOAC drug concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Anticoagulant intensity at first presentation and drug half-life ( ), tested in repeat samples, were evaluated.

Results:  A total of 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. Note that 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban-treated patients was 17.3 hours (95% confidence interval [CI]: 15.4-19.7) without significant difference in both groups (major bleeding: 16.7 hours, 95% CI: 14.7-19.3; urgent surgery: 19.7 hours, 95% CI: 15.2-27.9;  = 0.292). In apixaban-treated patients was 25.0 hours (95% CI: 22.9-27.6) with a longer after urgent surgery ( : 30.8 hours; 95% CI: 26.9-36.4) compared with severe bleeding ( : 20.8 hours; 95% CI: 18.8-23.2;  < 0.001).

Conclusion:  Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer .
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http://dx.doi.org/10.1055/a-1549-6556DOI Listing
July 2021

Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS.

Nutrients 2021 Jun 20;13(6). Epub 2021 Jun 20.

Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.

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 ( = 0.027) and selenoprotein P levels (SELENOP; = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time ( = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r = -0.495), PCT (r = -0.413), IL-6 (r = -0.429), IL-1β (r = -0.440) and IL-10 (r = -0.461). Positive associations were found for CD8 T cells (r = 0.636), NK cells (r = 0.772), total IgG (r = 0.493) and PaO/FiO ratios (r = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors ( = 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.
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http://dx.doi.org/10.3390/nu13062113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235175PMC
June 2021

Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study.

Thromb J 2021 Jun 2;19(1):39. Epub 2021 Jun 2.

Department of Anesthesiology and Critical Care, University Hospital Wuerzburg, Oberdürrbacherstr. 6, 97080, Wuerzburg, Germany.

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 PaO/FiO 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..
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http://dx.doi.org/10.1186/s12959-021-00293-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170428PMC
June 2021

Getting hit by the bus around the world - a global perspective on goal directed treatment of massive hemorrhage in trauma.

Curr Opin Anaesthesiol 2021 Aug;34(4):537-543

Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

Purpose Of Review: Major trauma remains one of the leading causes of death worldwide with traumatic brain injury and uncontrolled traumatic bleeding as the main determinants of fatal outcome. Interestingly, the therapeutic approach to trauma-associated bleeding and coagulopathy shows differences between geographic regions, that are reflected in different guidelines and protocols.

Recent Findings: This article summarizes main principles in coagulation diagnostics and compares different strategies for treatment of massive hemorrhage after trauma in different regions of the world. How would a bleeding trauma patient be managed if they got hit by the bus in the United States, United Kingdom, Germany, Switzerland, Austria, Denmark, Australia, or in Japan?

Summary: There are multiple coexistent treatment standards for trauma-induced coagulopathy in different countries and different trauma centers. Most of them initially follow a protocol-based approach and subsequently focus on predefined clinical and laboratory targets.
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http://dx.doi.org/10.1097/ACO.0000000000001025DOI Listing
August 2021

The impact of timing of intravenous iron supplementation on preoperative haemoglobin in patients scheduled for major surgery.

Blood Transfus 2021 May 26. Epub 2021 May 26.

Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Germany.

Background: Anaemia is frequent and an independent risk factor for morbidity and mortality in patients undergoing surgery. Iron deficiency (ID) is the main cause for anaemia and can be corrected by intravenous (IV) iron. The aim of this study was to investigate the timing of preoperative IV iron supplementation on preoperative haemoglobin (Hb) level.

Materials And Methods: Surgical patients were screened for the presence of anaemia and ID from November 2015 to January 2020. In case of ID or iron deficiency anaemia (IDA), patients received IV iron supplementation. The timing of IV iron supplementation on preoperative Hb level was analysed by days and time frames clustered by 5 days before surgery.

Results: In total, 404 patients with IV iron supplementation were analysed. In all patients, IV iron was administered with a median (interquartile range [IQR]) of 3.0 (1.0; 9.0) days before surgery. Preoperative Hb level increased steadily starting from 6 days (0.13 [±1.2] g/dL) until 16 days before surgery (1.75 [±1.1] g/dL). Group comparison revealed a median preoperative Hb change of -0.2 (-0.5; 0.2) g/dL for days 1-5, 0.2 (0.0; 0.7) g/dL for days 6-10, 0.7 (0.2; 1.1) g/dL for days 11-15, 0.7 (0.2; 1.8) g/dL for days 16-20, 0.9 (0.3; 1.7) g/dL for days 21-25, 1.5 (0.4; 2.6) g/dL for days 26-30, and 0.6 (0.0; 1.7) g/dL for >31 days. Three patients received multiple administrations of IV iron which resulted in an increase in Hb of >4 g/dL.

Discussion: Supplementation of IV iron to increase Hb concentration preoperatively may be most effective if administered at least ten days before surgery.
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http://dx.doi.org/10.2450/2021.0058-21DOI Listing
May 2021
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