Effects of robotic-assisted early mobilization versus conventional mobilization in intensive care unit patients: prospective interventional cohort study with retrospective control group analysis.

BACKGROUND: Approximately one in three survivors of critical illness suffers from intensive-care-unit-acquired weakness, which increases mortality and impairs quality of life. By counteracting immobilization, a known risk factor, active mobilization may mitigate its negative effects on patients. In this single-center trial, the effect of robotic-assisted early mobilization in the intensive care unit (ICU) on patients' outcomes was investigated. METHODS: We enrolled 16 adults scheduled for lung transplantation to receive 20 min of robotic-assisted mobilization and verticalization twice daily during their first week in the ICU (intervention group: IG). A control group (CG) of 13 conventionally mobilized patients after lung transplantation was recruited retrospectively. Outcome measures included the duration of mechanical ventilation, length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months. RESULTS: During the first week in the ICU, the intervention group received a median of 6 (interquartile range 3-8) robotic-assisted sessions of early mobilization and verticalization. There were no statistically significant differences in the duration of mechanical ventilation (IG: median 126 vs. CG: 78 h), length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months between the IG and CG. CONCLUSION: In this study, robotic-assisted mobilization was successfully implemented in the ICU setting. No significant differences in patients' outcomes were observed between conventional and robotic-assisted mobilization. However, randomized and larger studies are necessary to validate the adequacy of robotic mobilization in other cohorts. TRIAL REGISTRATION: This single-center interventional trial was registered in clinicaltrials.gov as NCT05071248 on 27/08/2021.

Lung Ultrasound as a Promising Diagnostic Tool for Primary Graft Dysfunction after Lung Transplantation.

PURPOSE: The aim of the study was to evaluate whether the quantification of B-lines via lung ultrasound after lung transplantation is feasible and correlates with the diagnosis of primary graft dysfunction. METHODS: Following lung transplantation, patients underwent daily lung ultrasound on postoperative days 1-3. B-lines were quantified by an ultrasound score based on the number of single and confluent B-lines per intercostal space, using a four-region protocol. The ultrasound score was correlated with the diagnosis of primary graft dysfunction. Furthermore, correlation analyses and receiver operating characteristics analyses taking into account ultrasound score, chest radiographs, and PaO2/FiO2 ratio were performed. RESULTS: A total of 32 patients (91 ultrasound measurements) were included, whereby 10 were diagnosed with primary graft dysfunction. The median B-line score was 5 [IQR: 4, 8]. There was a significant correlation between B-line score and the diagnosis of primary graft dysfunction (r = 0.59, p < 0.001). A significant correlation could also be seen between chest X-rays and primary graft dysfunction (r = 0.34, p = 0.008), but the B-line score showed superiority over chest X-rays with respect to diagnosing primary graft dysfunction in the receiver operating characteristics curves with an area under the curve value of 0.921 versus 0.708. There was a significant negative correlation between B-line score and PaO2/FiO2 ratio (r = -0.41, p < 0.001), but not between chest X-rays and PaO2/FiO2 ratio (r = -0.14, p = 0.279). CONCLUSION: The appearance of B-lines correlated well with primary graft dysfunction and outperformed chest radiographs.

Barriers and facilitators in the implementation of mobilization robots in hospitals from the perspective of clinical experts and developers.

BACKGROUND: Early mobilization can help reduce severe side effects such as muscle atrophy that occur during hospitalization. However, due to time and staff shortages in intensive and critical care as well as safety risks for patients, it is often difficult to adhere to the recommended therapy time of twenty minutes twice a day. New robotic technologies might be one approach to achieve early mobilization effectively for patients and also relieve users from physical effort. Nevertheless, currently there is a lack of knowledge regarding the factors that are important for integrating of these technologies into complex treatment settings like intensive care units or rehabilitation units. METHODS: European experts from science, technical development and end-users of robotic systems (n = 13) were interviewed using a semi-structured interview guideline to identify barriers and facilitating factors for the integration of robotic systems into daily clinical practice. They were asked about structural, personnel and environmental factors that had an impact on integration and how they had solved challenges. A latent content analysis was performed regarding the COREQ criteria. RESULTS: We found relevant factors regarding the development, introduction, and routine of the robotic system. In this context, costs, process adjustments, a lack of exemptions, and a lack of support from the manufacturers/developers were identified as challenges. Easy handling, joint decision making between the end-users and the decision makers in the hospital, an accurate process design and the joint development of the robotic system of end-users and technical experts were found to be facilitating factors. CONCLUSION: The integration and preparation for the integration of robotic assistance systems into the inpatient setting is a complex intervention that involves many parties. This study provides evidence for hospitals or manufacturers to simplify the planning of integrations for permanent use. TRIAL REGISTRATION: DRKS-ID: DRKS00023848; registered 10/12/2020.

Combination of Pharmacokinetic and Pathogen Susceptibility Information To Optimize Meropenem Treatment of Gram-Negative Infections in Critically Ill Patients.

Meropenem is one of the most frequently used antibiotics to treat life-threatening infections in critically ill patients. This study aimed to develop a meropenem dosing algorithm for the treatment of Gram-negative infections based on intensive care unit (ICU)-specific resistance data. Antimicrobial susceptibility testing of Gram-negative bacteria obtained from critically ill patients was carried out from 2016 to 2020 at a tertiary care hospital. Based on the observed MIC distribution, stochastic simulations (n = 1,000) of an evaluated pharmacokinetic meropenem model, and a defined pharmacokinetic/pharmacodynamic target (100%T>4×MIC while minimum concentrations were <44.5 mg/L), dosing recommendations for patients with varying renal function were derived. Pathogen-specific MIC distributions were used to calculate the cumulative fraction of response (CFR), and the overall MIC distribution was used to calculate the local pathogen-independent mean fraction of response (LPIFR) for the investigated dosing regimens. A CFR/LPIFR of >90% was considered adequate. The observed MIC distribution significantly differed from the EUCAST database. Based on the 6,520 MIC values included, a three-level dosing algorithm was developed. If the pathogen causing the infection is unknown (level 1), known (level 2), known to be neither Pseudomonas aeruginosa nor Acinetobacter baumannii, or classified as susceptible (level 3), a continuous infusion of 1.5 g daily reached sufficient target attainment independent of renal function. In all other cases, dosing needs to be adjusted based on renal function. ICU-specific susceptibility data should be assessed regularly and integrated into dosing decisions. The presented workflow may serve as a blueprint for other antimicrobial settings.

[Noninvasive respiratory support and invasive ventilation in COVID­19 : Where do we stand today?] / Nichtinvasive respiratorische Unterstützung und invasive Beatmung bei COVID­19 : Wo stehen wir heute?

The controversy surrounding ventilation in coronavirus disease 2019 (COVID-19) continues. Early in the pandemic it was postulated that the high intensive care unit (ICU) mortality may have been due to too early intubation. As the pandemic progressed recommendations changed and the use of noninvasive respiratory support (NIRS) increased; however, this did not result in a clear reduction in ICU mortality. Furthermore, large studies on optimal ventilation in COVID-19 are lacking. This review article summarizes the pathophysiological basis, the current state of the science and the impact of different treatment modalities on the outcome. Potential factors that could undermine the benefits of noninvasive respiratory support are discussed. The authors attempt to provide guidance in answering the difficult question of when is the right time to intubate?

Target Site Pharmacokinetics of Meropenem: Measurement in Human Explanted Lung Tissue by Bronchoalveolar Lavage, Microdialysis, and Homogenized Lung Tissue.

Pneumonia is one of the most common infections in intensive care patients, and it is often treated with beta-lactam antibiotics. Even if therapeutic drug monitoring in blood is available, it is unclear whether sufficient concentrations are reached at the target site: the lung. The present study was initiated to fill this knowledge gap. Various compartments from 10 patients' explanted lungs were subjected to laboratory analysis. Meropenem was quantified in serum, bronchoalveolar lavage (BAL) fluid, microdialysate, and homogenized lung tissue with isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS). BAL fluid represents diluted epithelial lining fluid (ELF), and microdialysate represents interstitial fluid (IF). Differences between target site and blood concentrations were investigated. The median meropenem concentration in blood, ELF, IF, and tissue were 26.8, 18.0, 12.1, and 9.1 mg/liter, respectively. A total of 37.5% of the target site ELF and IF meropenem concentrations were below the clinical EUCAST breakpoint of 8 mg/liter. The median ELF/serum quotient was 61.8% (interquartile range [IQR], 24.8% to 87.6%), the median IF/serum quotient was 35.4% (IQR, 23.8% to 54.3%), and the median tissue/serum quotient was 34.2% (IQR, 28.3% to 38.2%). We observed a substantial interindividual variability between the blood and the compartments (ELF and IF), whereas the intraindividual variability was relatively low. Target site measurement in different lung compartments was feasible and successfully applied in a clinical setting. A relevant amount of 37.5% of the target site concentrations were below the clinical EUCAST breakpoint, indicating subtherapeutic dosing in high-risk patients receiving perioperative antibiotic prophylaxis in lung transplantation. (This study has been registered at ClinicalTrials.gov under identifier NCT03970265.).

Digestive enzymes of fungal origin as a relevant cause of false positive Aspergillus antigen testing in intensive care unit patients.

BACKGROUND: Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. METHODS: Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1-Nortase-therapy, group 2-no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and ß-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. RESULTS: Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and ß-1,3-D-glucan. CONCLUSIONS: Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.

An invasive infection caused by the thermophilic mold Talaromyces thermophilus.

BACKGROUND: Increasing incidence of invasive infections caused by rare fungi was observed over the recent years. CASE: Here, we describe the first reported case of an infection caused by the thermophilic mold Talaromyces thermophilus. Cultivation and, hence, identification of this fastidious organism is challenging since standard incubation conditions are not sufficient. Retrospective analysis of patient samples and in vitro experiments demonstrated that testing for fungal antigens, i.e., the cell wall components galactomannan and ß-1,3-D-glucan, is a promising tool.

Left and right ventricular dysfunction in patients with COVID-19-associated myocardial injury.

PURPOSE: SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury. METHODS: We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography. RESULTS: A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037). CONCLUSION: In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up. TRIAL REGISTRATION: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Comparing posaconazole and itraconazole for antifungal prophylaxis in critically ill lung transplant recipients: Efficacy and plasma concentrations.

BACKGROUND: Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal-induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis. METHODS: Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7 days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500 µg/L for itraconazole and ≥700 µg/L for posaconazole. RESULTS: Two hundred seventy-five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P < .01) more often in subtherapeutic concentrations than tablets (68% vs 10%). Patients treated with posaconazole showed less positive fungal records resulting in a transition from prophylaxis to therapy than patients treated with itraconazole (10% vs 33%, P-value: .029). The detection of a fungal pathogen was not associated with the measured plasma concentrations or the achievement of the target concentrations. CONCLUSION: Our findings suggest that posaconazole should be used instead of itraconazole for systemic prophylaxis in critically ill lung transplant recipients.

Blood purification with a cytokine adsorber for the elimination of myoglobin in critically ill patients with severe rhabdomyolysis.

BACKGROUND: Rhabdomyolysis is frequently occurring in critically ill patients, resulting in a high risk of acute kidney injury (AKI) and potentially permanent kidney damage due to increased myoglobin levels. The extracorporeal elimination of myoglobin might be an approach to prevent AKI, but its molecular weight of 17 kDa complicates an elimination with conventional dialysis membranes. Question of interest is, if myoglobin can be successfully eliminated with the cytokine adsorber Cytosorb® (CS) integrated in a high-flux dialysis system. METHODS: Patients were included between 10/2014 and 05/2020 in the study population if they had an anuric renal failure with the need of renal replacement therapy, if CS therapy was longer than 90 min and if myoglobin level was > 5.000 ng/ml before treatment. The measurement times of the laboratory values were: d-1 = 24-36 h before CS, d0 = shortly before starting CS and d1 = 12-24 h after starting CS treatment. Statistical analysis were performed with Spearman's correlation coefficient, Wilcoxon test with associated samples and linear regression analysis. RESULTS: Forty-three patients were included in the evaluation (median age: 56 years, 77% male patients, 32.6% ECMO therapy, median SAPS II: 80 points and in-hospital mortality: 67%). There was a significant equilateral correlation between creatine kinase (CK) and myoglobin at all measurement points. Furthermore, there was a significant reduction of myoglobin (p = 0.03, 95% confidence interval (CI): - 9030, - 908 ng/ml) during CS treatment, with a median relative reduction of 29%. A higher median reduction of 38% was seen in patients without ongoing rhabdomyolysis (CK decreased during CS treatment, n = 21). In contrast, myoglobin levels did not relevantly change in patients with increasing CK and therefore ongoing rhabdomyolysis (n = 22, median relative reduction 4%). Moreover, there was no significant difference in myoglobin elimination in patients with and without ECMO therapy. CONCLUSION: Blood purification with Cytosorb® during high-flux dialysis led to a significant reduction of myoglobin in patients with severe rhabdomyolysis. The effect might be obscured by sustained rhabdomyolysis, which was seen in patients with rising CK during treatment. Prospective clinical trials would be useful in investigating its benefits in avoiding permanent kidney damage.

[Characteristics and outcome of 70 ventilated COVID-19 patients : Summary after the first wave at a university center]. / Charakteristika und Outcome von 70 beatmeten COVID-19-Patienten : Bilanz nach der ersten Welle an einem universitären Zentrum.

BACKGROUND: In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE: Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS: Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS: In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62 points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION: The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.

Robot-assisted early mobilization for intensive care unit patients: Feasibility and first-time clinical use.

BACKGROUND: Early mobilization is only carried out to a limited extent in the intensive care unit. To address this issue, the robotic assistance system VEMOTION® was developed to facilitate (early) mobilization measures more easily. This paper describes the first integration of robotic assistance systems in acute clinical intensive care units. OBJECTIVE: Feasibility test of robotic assistance in early mobilization of intensive care patients in routine clinical practice. SETTING: Two intensive care units guided by anesthesiology at a German university hospital. PARTICIPANTS: Patients who underwent elective surgery with postoperative treatment in the intensive care unit and had an estimated ventilation time over 48 h. METHODS: Participants underwent robot-assisted mobilization, scheduled for twenty-minute sessions twice a day, ten times or one week, conducted by nursing staff under actual operational conditions on the units. No randomization or blinding took place. We assessed data regarding feasible cutoff points (in brackets): the possibility of enrollment (x ≥ 50 %), duration (pre- and post-setup (x ≤ 25 min), therapy duration (x = 20 min), and intervention-related parameters (number of mobilizing professionals (x ≤ 2), intensity of training, events that led to adverse events, errors or discontinuation). Mobilizing professionals rated each mobilization regarding their physical stress (x ≤ 3) and feasibility (x ≥ 4) on a 7 Point Likert Scale. An estimated sample size of at least twenty patients was calculated. We analyzed the data descriptively. RESULTS: Within 6 months, we screened thirty-two patients for enrollment. 23 patients were included in the study and 16 underwent mobilization using robotic assistance, 7 dropped out (enrollment eligibility = 69 %). On average, 1.9 nurses were involved per therapy unit. Participants received 5.6 robot-assisted mobilizations in mean. Pre- and post-setup had a mean duration of 18 min, therapy a mean of 21 min. The robot-assisted mobilization was started after a median of 18 h after admission to the intensive care unit. We documented two adverse events (pain), twelve errors in handling, and seven unexpected events that led to interruptions or discontinuation. No serious adverse events occurred. The mobilizing nurses rated their physical stress as low (mean 2.0 ±â€¯1.3) and the intervention as feasible (mean 5.3 ±â€¯1.6). CONCLUSIONS: Robot-assisted mobilization was feasible, but specific safety measures should be implemented to prevent errors. Robotic-assisted mobilization requires process adjustments and consideration of unit staffing levels, as the intervention does not save staff resources or time. REGISTRATION: clinicaltrials.org TRN: NCT05071248; Date: 2021/10/08; URL https://clinicaltrials.gov/ct2/show/NCT05071248. TWEETABLE ABSTRACT: Robot-assisted early mobilization in intensive care patients is feasible and no adverse event occurred.

Effects of the "ICU Support" team meeting concept on patient-centered and staff-centered outcomes: study protocol for a randomized controlled multicenter study.

BACKGROUND: Providing optimal care for critically ill patients is an extremely important but also highly demanding task, both emotionally and physically. The "ICU Support" team meeting concept aims to support intensive care unit (ICU) teams by promoting interprofessional communication, peer support, and patient safety by providing a structure for daily team meetings. This protocol describes a study to explore the effectiveness of "ICU Support" for patient- and staff-centered outcomes. METHODS: ICU Support will be implemented at nine university hospitals located in Germany, following a two-arm randomized parallel group design with an intervention and a control condition and three data collection periods. In the intervention arm, leading ICU personnel (physicians and nurses) will be trained in ICU Support and implement the ICU Support elements into the daily work routine of their units upon completion of data collection period T0 (baseline). In the control arm, ICU Support will not be implemented until the completion of the data collection period T1 (1 month after study start). Until then, the regular daily schedule of the ICU teams will be maintained. The final data collection period (T2) will take place 4 months after the start of the study. Primary outcomes include the number of intensive care complications per patient during their ICU stay during T1 and the sick-related absence of ICU staff during T1. Secondary outcomes include, among others, the average severity of intensive care complications per patient and employee self-reported data regarding their teamwork and patient safety behaviors. DISCUSSION: The need for healthy and well-trained ICU staff is omnipresent; thus, structured and evidence-based interventions aimed at supporting ICU teams and facilitating patient safety are required. This multicenter study aims to explore the effectiveness of ICU Support for patient- and staff-centered outcomes. The insights derived from this study have the potential to significantly improve ICU patient safety, staff communication, and connectedness and decrease sickness-related expenses and social costs associated with high work demands among ICU staff. TRIAL REGISTRATION: German Clinical Trials Register DRKS00028642 . Registered on 4 April 2022.

Extracorporeal Membrane Oxygenation.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO), also known as extracorporeal life support (ECLS), can both be used to treat patients with acute pulmonary or cardiovascular failure. METHODS: This review is based on publications retrieved by a selective search in PubMed on the topics of cardiogenic shock and acute pulmonary failure, also known as the acute respiratory distress syndrome (ARDS), as well as on ECMO. Attention was given chiefly to randomized, controlled trials and guidelines. RESULTS: Initial findings from prospective, randomized trials of VV-ECMO are now available. Trials of ECLS therapy are now in progress or planned. A meta-analysis of two randomized, controlled trials of VV-ECMO for ARDS revealed more frequent survival 90 days after randomization among patients treated with VV-ECMO, compared to the control groups (36% vs. 48%; RR = 0.75 [95% confidence interval 0.6; 0.94]). For selected patients, after evaluation of the benefit-risk profile, VV-ECMO is a good treatment method for severe pulmonary failure, and ECLS for cardiogenic shock and resuscitation. The goal is to secure the circulation so that native heart function can be stabilized in the patient's further course or a permanent left-heart support system can be implanted, or else to support lung function until recovery. CONCLUSION: ECMO is a valid option in selected patients when conservative treatment has failed.

Trough concentrations of meropenem and piperacillin during slow extended dialysis in critically ill patients with intermittent and continuous infusion: A prospective observational study.

Beta-lactam dosing is challenging in critically ill patients with slow extended daily dialysis (SLEDD). This prospective observational study aimed to investigate meropenem and piperacillin concentrations and half-lives during SLEDD and in SLEDD-free intervals. Critically ill patients with SLEDD-therapy and meropenem or piperacillin therapy were included. Breakpoints of target attainment were defined as 2 and 20.8 mg/L for meropenem and piperacillin, respectively. Daily TDM was performed and therapies were adapted based on the measured concentrations. Elimination rate constants were determined by using nonlinear regression analysis. Seventeen patients were included (48 SLEDD intervals; median SLEDD-duration: 7.25 h). The median antibiotic trough concentrations and half-lives were significantly (p < 0.001) lower during and after the SLEDD-therapy compared to SLEDD-free intervals (median meropenem: 22.3 (IQR: 12.8, 25.6) vs. 28.3 mg/L (IQR: 16.9, 37.4); median piperacillin: 55.8 (IQR: 45.1, 84.9) vs. 130 mg/L (IQR: 91.5, 154.5); relative change: -48.0% each, IQR meropenem: -33.3, -58.5%; IQR piperacillin: -36.3, -52.1%). However, none of the measured trough concentrations were subtherapeutic during SLEDD. SLEDD leads to a reduction in meropenem and piperacillin concentrations of approximately 50% independently of the initial concentration. If the concentration is twice as high as the breakpoint of target attainment before SLEDD-therapy, subtherapeutic levels can be avoided.

Does the cytokine adsorber CytoSorb® reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study.

BACKGROUND: Hemadsorption of cytokines is used in critically ill patients with sepsis or septic shock. Concerns have been raised that the cytokine adsorber CytoSorb® unintentionally adsorbs vancomycin. This study aimed to quantify vancomycin elimination by CytoSorb®. METHODS: Critically ill patients with sepsis or septic shock receiving continuous renal replacement therapy and CytoSorb® treatment during a prospective observational study were included in the analysis. Vancomycin pharmacokinetics was characterized using population pharmacokinetic modeling. Adsorption of vancomycin by the CytoSorb® was investigated as linear or saturable process. The final model was used to derive dosing recommendations based on stochastic simulations. RESULTS: 20 CytoSorb® treatments in 7 patients (160 serum samples/24 during CytoSorb®-treatment, all continuous infusion) were included in the study. A classical one-compartment model, including effluent flow rate of the continuous hemodialysis as linear covariate on clearance, best described the measured concentrations (without CytoSorb®). Significant adsorption with a linear decrease during CytoSorb® treatment was identified (p < 0.0001) and revealed a maximum increase in vancomycin clearance of 291% (initially after CytoSorb® installation) and a maximum adsorption capacity of 572 mg. For a representative patient of our cohort a reduction of the area under the curve (AUC) by 93 mg/L*24 h during CytoSorb® treatment was observed. The additional administration of 500 mg vancomycin over 2 h during CytoSorb® attenuated the effect and revealed a negligible reduction of the AUC by 4 mg/L*24 h. CONCLUSION: We recommend the infusion of 500 mg vancomycin over 2 h during CytoSorb® treatment to avoid subtherapeutic concentrations. Trial registration NCT03985605. Registered 14 June 2019, https://clinicaltrials.gov/ct2/show/NCT03985605.

Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study.

RATIONALE: The concentration-time profile of linezolid varies considerably in critically ill patients. Question of interest is, if the site of infection influences linezolid serum concentrations. METHODS: 68 critically ill patients, treated with linezolid, were included. The concentration-time-profile for linezolid was determined using maximum a-posteriori predictions. A trough concentration (Cmin) between 2 and 10 mg/L was defined as the target. A generalized linear model (GLM) was established to evaluate potential covariates. RESULTS: The indications for linezolid therapy were in descending order: peritonitis (38.2%), pneumonia (25.0%), infectious acute respiratory distress syndrome (ARDS) (19.1%), and other non-pulmonary infection (17.7%). 27.2 and 7.9% of Cmin were subtherapeutic and toxic, respectively. In the GLM, ARDS (mean: -2.1 mg/L, CI: -3.0 to -1.2 mg/L) and pneumonia (mean: -2.2 mg/L, CI: -2.8 to -1.6 mg/L) were significant (p < 0.001) determinants of Cmin. Patients with ARDS (mean: 2.3 mg/L, 51.2% subtherapeutic, 0.0% toxic) and pneumonia (mean: 3.5 mg/L, 41.5% subtherapeutic, 7.7% toxic) had significantly (p < 0.001) lower Cmin than those with peritonitis (mean: 5.5 mg/L, 14.4% subtherapeutic, 9.3% toxic) and other non-pulmonary infection (mean: 5.2 mg/L, 3.3% subtherapeutic, 16.5% toxic). CONCLUSION: Linezolid serum concentrations are reduced in patients with pulmonary infections. Future studies should investigate if other linezolid thresholds are needed in those patients due to linezolid pooling in patients´ lung.

REDUCE - Indication catalogue based ordering of chest radiographs in intensive care units.

PURPOSE: To advance a transition towards an indication-based chest radiograph (CXR) ordering in intensive care units (ICUs) without compromising patient safety. MATERIALS AND METHODS: Single-center prospective cohort study with a retrospective reference group including 857 ICU patients. The routine group (n = 415) received CXRs at the discretion of the ICU physician, the restrictive group (n = 442) if specified by an indication catalogue. Documented data include number of CXRs per day and CXR radiation dose as primary outcomes, re-intubation and re-admission rates, hours of mechanical ventilation and ICU length of stay. RESULTS: CXR numbers were reduced in the restrictive group (964 CXRs in 2479 days vs. 1281 CXRs in 2318 days) and median radiation attributed to CXR per patient was significantly lowered in the restrictive group (0.068 vs. 0.076 Gy x cm2, P = 0.003). For patients staying ≥24 h, median number of CXRs per day was significantly reduced in the restrictive group (0.41 (IQR 0.21-0.61) vs. 0.55 (IQR 0.34-0.83), P < 0.001). Survival analysis proved non-inferiority. Secondary outcome parameters were not significantly different between the groups. CXR reduction was significant even for patients in most critical conditions. CONCLUSIONS: A substantial reduction of the number of CXRs on ICUs was feasible and safe using an indication catalogue thereby improving resource management. TRIAL REGISTRATION: DRKS00015621, German Clinical Trials Register.