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The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm2 (p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm2 (p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm2 (p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters.

BACKGROUND: Handheld vital microscopy allows direct observation of red blood cells within the sublingual microcirculation. Automated analysis allows quantifying microcirculatory tissue perfusion variables - including tissue red blood cell perfusion (tRBCp), a functional variable integrating microcirculatory convection and diffusion capacities.OBJECTIVE: We aimed to describe baseline microcirculatory tissue perfusion in patients presenting for elective noncardiac surgery and test that microcirculatory tissue perfusion is preserved during elective general anaesthesia for noncardiac surgery.DESIGN: Prospective observational study.SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.PATIENTS: 120 elective noncardiac surgery patients (major abdominal, orthopaedic or trauma and minor urologic surgery) and 40 young healthy volunteers.MAIN OUTCOME MEASURES: We measured sublingual microcirculation using incident dark field imaging with automated analysis at baseline before induction of general anaesthesia, under general anaesthesia before surgical incision and every 30 min during surgery. We used incident the dark field imaging technology with a validated automated analysis software.RESULTS: A total of 3687 microcirculation video sequences were analysed. Microcirculatory tissue perfusion variables varied substantially between individuals - but ranges were similar between patients and volunteers. Under general anaesthesia before surgical incision, there were no important changes in tRBCp, functional capillary density and capillary haematocrit compared with preinduction baseline. However, total vessel density was higher and red blood cell velocity and the proportion of perfused vessels were lower under general anaesthesia. There were no important changes in any microcirculatory tissue perfusion variables during surgery.CONCLUSION: In patients presenting for elective noncardiac surgery, baseline microcirculatory tissue perfusion variables vary substantially between individuals - but ranges are similar to those in young healthy volunteers. Microcirculatory tissue perfusion is preserved during general anaesthesia and noncardiac surgery - when macrocirculatory haemodynamics are maintained.

The high complexity of care in the Intensive Care Unit environment has led, in the last decades, to a big effort in term of the improvement of patient's monitoring devices, increase of diagnostic and therapeutic opportunities, and develop-ment of electronic health records. Such advancements have enabled an increasing availability of large amounts of data that were supposed to provide more insight and understanding regarding pathophysiological processes and patient's prognosis providing useful tools able to support physicians in the clinical decision-making process. On the contrary, the interpolation, analysis, and interpretation of a such big amount of data has soon proven to be much more complicated than expected, opening the way for the development of tools based on machine learning (ML) algorithms. However, at the present, most of the AI-based algorithms developed in intensive care do not reach beyond the prototyping and develop-ment environment and are still far from being able to assist physicians at the bedside in the clinical decisions to improve quality and efficiency of care. The present review aimed to provide an overview of the status of ML-based algorithms in intensive care, to explore the concept of digital transformation, and to highlight possible next steps necessary to move towards a routine use of ML-based clinical decision support systems at the bedside. Finally, we described our attempt to apply the pillars of digital transformation in the field of microcirculation monitoring with the creation of the Microcircu-lation Network Research Group (MNRG).

Background: In clinical practice, blood pressure is used as a resuscitation goal on a daily basis, with the aim of maintaining adequate perfusion and oxygen delivery to target organs. Compromised perfusion is often indicated as a key factor in the pathophysiology of anastomotic leakage. This study was aimed at assessing the extent to which the microcirculation of the bowel coheres with blood pressure during abdominal surgery. Methods: We performed a prospective and observational cohort study. In patients undergoing abdominal surgery, the serosal microcirculation of either the small intestine or the colon was visualized using handheld vital microscopy (HVM). From the acquired HVM image sequences, red blood cell velocity (RBCv) and total vessel density (TVD) were calculated using MicroTools and AVA software, respectively. The association between microcirculatory parameters and blood pressure was assessed using Pearson's correlation analysis. We considered a two-sided P-value of 2. Mean arterial pressure (MAP) was 71 ± 12 mm Hg during microcirculatory imaging. MAP was not correlated with RBCv (Pearson's r = −0.049, P = 0.800) or TVD (Pearson's r = 0.310, P = 0.110). Conclusion: In 28 patients undergoing abdominal surgery, we found no association between serosal intestinal microcirculatory parameters and blood pressure.

Most women with epithelial ovarian cancer (EOC) suffer from peritoneal carcinomatosis upon first clinical presentation. Extensive peritoneal carcinomatosis has a poor prognosis and its pathophysiology is not well understood. Although treatment with systemic intravenous chemotherapy is often initially successful, peritoneal recurrences occur regularly. We hypothesized that insufficient or poorly-perfused microvasculature may impair the therapeutic efficacy of systemic intravenous chemotherapy but may also limit expansive and invasive growth characteristic of peritoneal EOC metastases. In 23 patients with advanced EOC or suspicion thereof, we determined the angioarchitecture and perfusion of the microvasculature in peritoneum and in peritoneal metastases using incident dark field (IDF) imaging. Additionally, we performed immunohistochemical analysis and 3-dimensional (3D) whole tumor imaging using light sheet fluorescence microscopy of IDF-imaged tissue sites. In all metastases, microvasculature was present but the angioarchitecture was chaotic and the vessel density and perfusion of vessels was significantly lower than in unaffected peritoneum. Immunohistochemical analysis showed expression of vascular endothelial growth factor and hypoxia inducible factor 1α, and 3D imaging demonstrated vascular continuity between metastases and the vascular network of the peritoneum beneath the elastic lamina of the peritoneum. We conclude that perfusion of the microvasculature within metastases is limited, which may cause hypoxia, affect the behavior of EOC metastases on the peritoneum and limit the response of EOC metastases to systemic treatment. Electronic supplementary material The online version of this article (10.1007/s10585-020-10024-4) contains supplementary material, which is available to authorized users.

Background: It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases. Optimal management of these discordant cases requires further study. Aim: The aim of the study was to determine the prognostic value of combined FFR and CFR measurements to predict the 24-month rate of major adverse cardiac events. Secondary end points include repeatability of FFR and CFR, angina burden, and the percentage of successful FFR/CFR measurements which will not be excluded by the core laboratory. Methods: This prospective, nonblinded, nonrandomized, and multicenter study enrolled 455 subjects from 12 sites in Europe and Japan. Patients underwent physiologic lesion assessment using the 0.014” Philips Volcano ComboWire XT that provides simultaneous pressure and Doppler velocity sensors. Intermediate coronary lesions received only medical treatment unless both FFR (≤0.8) and CFR ( 0.80 and CFR ≥ 2.0. Enrollment has been completed, and final follow-up will occur in November 2019.

Background: Sonographic assessment of optical nerve sheath diameter (ONSD) has the potential for non-invasive monitoring of intracranial pressure (ICP). Hyperventilation (HV) -induced hypocapnia is used in the management of patients with traumatic brain injury (TBI) to reduce ICP. This study investigates, whether sonography is a reliable tool to detect dynamic changes in ONSD. Methods: This prospective single center trial included patients with TBI and neuromonitoring within 36 h after injury. Data collection and ONSD measurements were performed at baseline and during moderate HV for 50 min. Patients not suffering from TBI were recruited as control group. Results: Ten patients with TBI (70% males, mean age 35 ± 14 years) with a median of first GCS of 5.9 and ten control patients (40% males, mean age 45 ± 16 years) without presumed intracranial hypertension were included. During HV, ICP decreased significantly (p < .0001) in the TBI group. An ONSD response was found for HV (p = .05). Conclusion: We observed a dynamic decrease of ONSD during moderate HV. This suggests a potential use of serial ONSD measurements when applying HV in cases of suspected intracranial hypertension.

Rhabdomyolysis, if severe, can lead to acute kidney injury (AKI). Myoglobin is an iron and oxygen-binding protein that is freely filtered by the glomerulus. Precipitation of myoglobin in the nephrons’ distal parts is responsible for tubular damage with AKI as a consequence. Extracorporeal clearance of myoglobin is conventionally attempted by the use of continuous renal replacement therapy (CRRT) with high cut-off dialysis membranes to limit the extent of the damage. We describe a case of a 56-year-old man with traumatic crush injury and a persistent source of muscle ischaemia unresponsive to high dose CRRT with EMiC-2 filter. Due to therapy failure, he was subsequently treated with the addition of a haemoadsorber (CytoSorb®) to the circuit. This reduced myoglobin and creatine kinase levels successfully despite ongoing tissue ischaemia. However, CytoSorb® was not enough to maintain microcirculatory perfusion, resulting in the eventual demise of the patient due to severity of the injury. Our report indicates that myoglobin was efficiently removed with CytoSorb® following exchange with the conventional high cut-off filter in continuous venovenous haemodialysis in severe traumatic rhabdomyolysis.

The impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on pediatric intensive care units (PICUs) is difficult to quantify. We conducted an observational study in all eight Swiss PICUs between 02/24/2020 and 06/15/2020 to characterize the logistical and medical aspects of the pandemic and their impact on the management of the Swiss PICUs. The nine patients admitted to Swiss PICUs during the study period suffering from pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and constituting 14% (9/63) of all SARS-CoV-2 positive hospitalized patients in Swiss children's hospitals caused a higher workload [total Nine Equivalents of nursing Manpower use Score (NEMS) points, p = 0.0008] and were classified to higher workload categories (p < 0.0001) than regular PICU patients (n = 4,881) admitted in 2019. The comparison of the characteristics of the eight Swiss PICUs shows that they were confronted by different organizational issues arising from temporary regulations put in place by the federal council. These general regulations had different consequences for the eight individual PICUs due to the differences between the PICUs. In addition, the temporal relationship of these different regulations influenced the available PICU resources, dependent on the characteristics of the individual PICUs. As pandemic continues, reflecting and learning from experience is essential to reduce workload, optimize bed occupancy and manage resources in each individual PICU. In a small country as Switzerland, with a relatively decentralized health care local differences between PICUs are considerable and should be taken into account when making policy decisions.

BackgroundIt remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic.MethodsProspective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic.ResultsFour thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years,p p p p 2/FiO2at admission was lower (132 [123–141] mmHg vs 101 [91–113] mmHg,p p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4–7]% vs 20 [14–29],p p p p p ConclusionCharacteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU stay and ventilation-days in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients., Author summary COVID-19 caused by SARS-CoV-2 induces immune-paralysis characterized by misdirected host responses and altered levels of inflammatory mediators. Additionally, bacterial superinfections can further exacerbate the disease. Here, we report an in-depth functional characterization of the effector response and phenotypic properties of neutrophils and monocytes derived from critically ill COVID-19 patients towards bacterial superinfection. We show that elevated levels of specific cytokine clusters, positively correlate with the development of bacterial superinfections in these patients. Neutrophils and monocytes of critically ill COVID-19 patients showed impaired bactericidal capacity, which was mediated by elevated inflammatory mediators in the plasma. The observed impaired bactericidal capacity in critically ill COVID-19 patients was due to reduced classical effector functions of neutrophils and monocytes. Interestingly, lower levels of overall inflammatory mediators as well as reduction in length of ICU stay and ventilation-days in critically ill COVID-19 patients treated with dexamethasone was observed. These data suggest that the exhaustion and paralysis of the cellular innate immunity against bacterial challenge in critically ill COVID-19 patients is driven by a misdirected host-response, characterized by a hyperinflammatory environment including dysregulated cytokine levels. These results further emphasize the utility and importance of dampening these inflammatory mediators via broad anti-inflammatory therapy in COVID-19 patients, which improves the antibacterial effector functions of neutrophils and monocytes.

Introduction: Low-flow veno-venous extracorporeal CO2 removal (ECCO2R) is an adjunctive therapy to support lung protective ventilation or maintain spontaneous breathing in hypercapnic respiratory failure. Low-flow ECCO2R is less invasive compared to higher flow systems, while potentially compromising efficiency and membrane lifetime. To counteract this shortcoming, a high-longevity system has recently been developed. Our hypotheses were that the novel membrane system provides runtimes up to 120 h, and CO2 removal remains constant throughout membrane system lifetime. Methods: Seventy patients with pH ≤ 7.25 and/or PaCO2 ≥9 kPa exceeding lung protective ventilation limits, or experiencing respiratory exhaustion during spontaneous breathing, were treated with the high-longevity ProLUNG system or in a control group using the original gas exchanger. Treatment parameters, gas exchanger runtime, and sweep-gas VCO2 were recorded across 9,806 treatment-hours and retrospectively analyzed. Results: 25/33 and 23/37 patients were mechanically ventilated as opposed to awake spontaneously breathing in both groups. The high-longevity system increased gas exchanger runtime from 29 ± 16 to 48 ± 36 h in ventilated and from 22 ± 14 to 31 ± 31 h in awake patients (p < 0.0001), with longer runtime in the former (p < 0.01). VCO2 remained constant at 86 ± 34 mL/min (p = 0.11). Overall, PaCO2 decreased from 9.1 ± 2.0 to 7.9 ± 1.9 kPa within 1 h (p < 0.001). Tidal volume could be maintained at 5.4 ± 1.8 versus 5.7 ± 2.2 mL/kg at 120 h (p = 0.60), and peak airway pressure could be reduced from 31.1 ± 5.1 to 27.5 ± 6.8 mbar (p < 0.01). Conclusion: Using a high-longevity gas exchanger system, membrane lifetime in low-flow ECCO2R could be extended in comparison to previous systems but remained below 120 h, especially in spontaneously breathing patients. Extracorporeal VCO2 remained constant throughout gas exchanger system runtime and was consistent with removal of approximately 50% of expected CO2 production, enabling lung protective ventilation despite hypercapnic respiratory failure.

Background The modifications to the standard intensive care unit (ICU) organization that had to be urgently implemented worldwide to overcome the surge of ICU admissions due to patients with a severe coronavirus disease 2019 (COVID-19) have resulted in increased workload and patients-to-nurse ratio. The aim of this study was to investigate whether level of critical care staffing could be associated with an increased risk of ICU mortality (primary endpoint), length of stay, mechanical ventilation and the evolution of disease (secondary study endpoints) in critically ill patients with COVID-19. Methods Retrospective multicenter analysis of the international Risk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry that prospectively enrolls patients developing critical illness due to COVID-19 in several countries worldwide. The analysis was limited to the period between March 1st, 2020 and May 31st, 2020, to ICUs in Switzerland that have collected additional data on nurse and physician staffing. Hierarchical regression models were used to investigate crude and adjusted effects of critical care staffing ratio on study endpoints. We adjusted for diseases severity and weekly caseload. Results Among the 38 Swiss participating ICUs, 17 recorded critical care staffing information. The study population included 437 patients and 2342 daily assessments of patient-to-nurse/physician ratio. Median of daily patient-to-nurse ratio started at 1.0 ([IQR] 0.5–1.5; calendar week 9) and peaked at 2.4 (IQR 0.4-2.0; calendar week 16), while the median of daily patient-to-physician ratio started at 4.0 (IQR 2.1-5.0; calendar week 9) and peaked at 6.8 (IQR 6.3–7.3; calendar week 19). Neither the patient-to-nurse ratio [adjusted Odds Ratio (OR) 1.28, 95% confidence interval (CI) 0.85–1.94; doubling of ratio] nor the patient-to-physician ratio [adjusted OR 1.08, 95% CI 0.87–1.32; doubling of ratio] was associated with ICU mortality. We found no association of critical care staffing on the investigated secondary study endpoints in adjusted models. COnclusion The Swiss health care system successfully overcame the first wave of the COVID-19 pandemic with regards to the unprecedented demand for ICU treatments. The reduced availability of critical care staffing resources per critically ill patient in Swiss ICUs did not translate in an overall increased risk of mortality.

Background : Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods : We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results : The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model {0.86 vs. 0.69, P

Purpose: Monitoring the sublingual and oral microcirculation (SM-OM) using hand-held vital microscopes (HVMs) has provided valuable insight into the (patho)physiology of diseases. However, the microvascular anatomy in a healthy population has not been adequately described yet. Methods: Incident dark field-based HVM imaging was used to visualize the SM-OM. First, the SM was divided into four different fields; Field-a (between incisors-lingua), Field-b (between the canine-first premolar-lingua), Field-c (between the first-second premolar-lingua), Field-d (between the second molar-wisdom teeth-lingua). Second, we investigated the buccal area, lower and upper lip. Total/functional vessel density (TVD/FCD), focus depth (FD), small vessel mean diameters (SVMDs), and capillary tortuosity score (CTS) were compared between the areas. Results: Fifteen volunteers with a mean age of 29 ± 6 years were enrolled. No statistical difference was found between the sublingual fields in terms of TVD (p = 0.30), FCD (p = 0.38), and FD (p = 0.09). SVMD was similar in Field-a, Field-b, and Field-c (p = 0.20–0.30), and larger in Field-d (p < 0.01, p = 0.015). The CTS of the buccal area was higher than in the lips. Conclusion: The sublingual area has a homogenous distribution in TVD, FCD, FD, and SVMD. This study can be a description of the normal microvascular anatomy for future researches regarding microcirculatory assessment.

The continued digitalization of medicine has led to an increased availability of longitudinal patient data that allows the investigation of novel and known diseases in unprecedented detail. However, to accurately describe any underlying pathophysiology and allow inter-patient comparisons, individual patient trajectories have to be synchronized based on temporal markers. In this pilot study, we use longitudinal data from critically ill ICU COVID-19 patients to compare the commonly used alignment markers “onset of symptoms,” “hospital admission,” and “ICU admission” with a novel objective method based on the peak value of the inflammatory marker C-reactive protein (CRP). By applying our CRP-based method to align the progression of neutrophils and lymphocytes, we were able to define a pathophysiological window that improved mortality risk stratification in our COVID-19 patient cohort. Our data highlights that proper synchronization of longitudinal patient data is crucial for accurate interpatient comparisons and the definition of relevant subgroups. The use of objective temporal disease markers will facilitate both translational research efforts and multicenter trials.

Purpose: This study aims to compare protocol adherence, neurological outcome and adverse effects associated with a controlled hypothermia versus a controlled normothermia protocol in patients successfully resuscitated after cardiac arrest. Methods: In this retrospective single-center study in a university intensive care unit in Switzerland, post-cardiac arrest patients were compared before and after a protocol change from targeted temperature management at 33 °C (TTM-33) to 36 °C (TTM-36) using an intravascular cooling device. Protocol adherence was assessed as the primary outcome. Secondary outcomes were in-hospital mortality, neurological outcome and adverse effects. Results: 373 patients after cardiac arrest were screened, of whom a total of 133 patients were included. Protocol adherence was lower in the TTM-33 group (47% vs 87% of patients, p < 0.01). In-hospital mortality (59% vs 45%, p = 0.15) and neurological outcome (modified Rankin Score < 4 in 33% vs 39% and CPC-Score < 3 in 33% vs 39% of patients, p = 0.60 and 0.97) were similar. Overall incidence of adverse effects was comparable, with bradycardic arrhythmias occurring more frequently in the TTM-33 group. Conclusion: Protocol adherence was higher in the TTM-36 group. In-hospital mortality and neurological outcome were similar, while bradycardic arrhythmias were encountered more often in TTM-33.

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

Objective: The aim of this study was to apply an innovative methodology to incident dark-field (IDF) imaging in coronary artery bypass grafting (CABG) patients for the identification and quantification of rolling leukocytes along the sublingual microcirculatory endothelium. Methods: This study was a post hoc analysis of a prospective study that evaluated the perioperative course of the sublingual microcirculation in CABG patients. Video images were captured using IDF imaging following the induction of anesthesia (T0) and cardiopulmonary bypass (CPB) (T1) in 10 patients. Rolling leukocytes were identified and quantified using frame averaging, which is a technique that was developed for correctly identifying leukocytes. Results: The number of rolling leukocytes increased significantly from T0 (7.5 [6.4–9.1] leukocytes/capillary-postcapillary venule/4 s) to T1 (14.8 [13.2–15.5] leukocytes/capillary-postcapillary venule/4 s) (p < 0.0001). A significant increase in systemic leukocyte count was also detected from 7.4 ± 0.9 × 109/L (preoperative) to 12.4 ± 4.4 × 109/L (postoperative) (p < 0.01). Conclusion: The ability to directly visualize leukocyte-endothelium interaction using IDF imaging facilitates the diagnosis of a systemic inflammatory response after CPB via the identification of rolling leukocytes. Integration of the frame averaging algorithm into the software of handheld vital microscopes may enable the use of microcirculatory leukocyte count as a real-time parameter at the bedside.

ObjectivesHepatobiliary scintigraphy using technetium-99m mebrofenin has been validated as a quantitative liver function test. Preoperative portal vein embolization (PVE) is performed in patients to increase future remnant liver function and volume. Changes in hepatic microcirculation after PVE remain largely unknown and may influence the uptake of mebrofenin. The aim was to evaluate microcirculatory changes after PVE to examine differences in perfusion that might influence the uptake of mebrofenin, and consequently, assessment of function.Patients and methodsPatients undergoing liver resection with or without preoperative PVE were included. Future remnant liver volume and function were measured before and after PVE. Hepatic microcirculation was measured in the embolized and the nonembolized lobes during resection. Microcirculatory flow index, perfused vessel density, sinusoidal diameter and red blood cell velocity were assessed.ResultsA total of 16 patients, eight with preoperative PVE and eight control patients without PVE, were included. After PVE, both function and volume of the nonembolized lobe were significantly increased, and the functional increase exceeded the increase in volume. Perfused vessel density and sinusoidal diameter were significantly higher in the nonembolized liver lobe (P

Objective: This study investigates whether noninvasive focal depth (FD) measurements correlate with vaginal wall epithelial thickness (ET). If FD accurately reflects ET of the vaginal wall, this would allow noninvasive longitudinal assessment of (newly developed) treatment modalities aiming to increase ET, without the need for invasive biopsies. Methods: Fourteen women, median age 62 years (inter quartile ranges: 57-65), undergoing vaginal prolapse surgery because of anterior and/or posterior compartment pelvic organ prolapse were included. We used the CytoCam, a handheld video microscope based on incident dark field imaging, and performed FD measurements of the vaginal wall before surgery. Histology was performed on tissue that was removed during the surgical procedure, and ET was measured in stained sections. We compared ET with FD interindividually, and determined the expected linear correlation and agreement between the two measurements. Results: Seventeen ET measurements (mean 125 mu m +/- 38.7, range 48-181 mu m) were compared with 17 FD measurements (mean 128 mu m +/- 34.3, range 68-182 mu m). The lineair correlation between the two measurements was strong (r = 0.902, P < 0.01). Bland-Altman analysis demonstrated a mean difference of 13.5 mu m when comparing ET to FD. Conclusions: The results demonstrate good agreement between ET and FD measurements. We consider the mean difference demonstrated with Bland-Altman analysis acceptable for these measurements. This suggests that FD accurately reflects ET, which further supports the use of FD to measure ET of the vaginal wall. For a complete assessment of the vaginal wall, FD measurements are preferably combined with the assessment of vaginal angioarchitecture.

Background Perioperative arterial blood pressure management is a physiologically complex challenge influenced by multiple factors. Methods A multidisciplinary, international working subgroup of the Third Perioperative Quality Initiative (POQI) consensus meeting reviewed the (patho)physiology and measurement of arterial pressure as applied to perioperative medicine. We addressed predefined questions by undertaking a modified Delphi analysis, in which primary clinical research and review articles were identified using MEDLINE. Strength of recommendations, where applicable, were graded by National Institute for Health and Care Excellence (NICE) guidelines. Results Multiple physiological factors contribute to the perioperative physiological importance of arterial pressure: (i) arterial pressure is the input pressure to organ blood flow, but is not the sole determinant of perfusion pressure; (ii) blood flow is often independent of changes in perfusion pressure because of autoregulatory changes in vascular resistance; (iii) microvascular dysfunction uncouples microvascular blood flow from arterial pressure (haemodynamic incoherence). From a practical clinical perspective, we identified that: (i) ambulatory measurement is the optimal method to establish baseline arterial pressure; (ii) automated and invasive arterial pressure measurements have inherent physiological and technical limitations; (iii) individualised arterial pressure targets may change over time, especially in the perioperative period. There remains a need for research in non-invasive, continuous arterial pressure measurements, macro- and micro-circulatory control, regional perfusion pressure measurement, and the development of sensitive, specific, and continuous measures of cellular function to evaluate blood pressure management in a physiologically coherent manner. Conclusion The multivariable, complex physiology contributing to dynamic changes in perioperative arterial pressure may be underappreciated clinically. The frequently unrecognised dissociation between arterial pressure, organ blood flow, and microvascular and cellular function requires further research to develop a more refined, contextualised clinical approach to this routine perioperative measurement.

BACKGROUND: An observational cohort study was conducted to identify potential sublingual microcirculation parameters as a target for goal-directed fluid therapy. METHODS: Patients that were scheduled for an open elective pancreatico-biliary surgery in Erasmus Medical Center were included. All patients underwent sublingual microcirculatory measurement at three time points: one day before surgery (T0), within the first 24 hours after surgery (T1) and on the fourth day after surgery (T2). The following parameters were obtained: microvascular flow index (MFI (AU)), Total vessels density (TVD (mm/mm2/)), Perfused vessels density (PVD (mm/mm2)), and proportion of perfused vessels (PPV (%)). RESULTS: Sixteen patients were included in the final analysis. The differences between the time points T1 and T0 in patients without clinical significant complication and in patients with these complications gave a significant difference for PVD small vessels (PVDs) (delta PVDs mean -0.1 vs -8.2, p=0.01) and PPV small vessels (PPVs) (delta PPVs median 7.0 % vs -15.5 %, p=0.01). CONCLUSION: The most significant microcirculatory parameter for a perioperative complicated course is the change of PVD and PPV. In the first 24 hours after surgery, if these parameters decrease there is a high chance of a complicated perioperative course.

Background: The microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized and the non-embolized lobes after right PVE. Methods: Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3–6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv). Results: 16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 μm (p < 0.040)). RBCv, PPV and the MFI were not significantly different. Conclusion: The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.

Background Drift is a well-known issue affecting intracoronary pressure measurements. A small pressure offset at the end of the procedure is generally considered acceptable, while repeat assessment is advised for drift exceeding ±2 mmHg. This practice implies that drift assessed after wire pullback equals that at the time of stenosis appraisal, but this assumption has not been systematically investigated. Our aim was to compare intra-and post-procedural pressure sensor drift and assess benefits of correction for intra-procedural drift and its effect on diagnostic classification. Methods In 70 patients we compared intra- and post-procedural pressure drift for 120 hemodynamic tracings obtained at baseline and throughout the hyperemic response to intracoronary adenosine. Intra-procedural drift was derived from the intercept of the stenosis pressure gradient-velocity relationship. Diagnostic reclassification after correction for intra-procedural drift was assessed for the mean distal-to-aortic pressure ratio at baseline (Pd/Pa) and hyperemia (fractional flow reserve, FFR), and corresponding stenosis resistances. Results Post- and intra-procedural drift exceeding the tolerated threshold was observed in 73% and 64% of the hemodynamic tracings, respectively. Discordance in terms of acceptable drift level was present for 42% of the tracings, with avoidable repeat physiological assessment in 25% and unacceptable intra-procedural drift unrecognized at final drift check in 17% of the tracings. Correction for intra-procedural drift caused higher reclassification rates for baseline than hyperemic functional indices. Conclusions Post-procedural pressure drift frequently does not match drift during physiological assessment. Tracing-specific correction for intra-procedural drift can potentially lower the risk of inadvertent diagnostic misclassification and prevent unnecessary repeats.

Motivation of the project is the analysis of systematic errors in contrast-enhanced cardiac perfusion imaging by CFD simulations of contrast agent transport in the arterial epicardial vasculature. This requires the realistic modeling of volume blood flow (VBF) in the coronary arteries to provide a physiologically relevant computational framework for the transport simulations. For this purpose, 3D-models of the left and right coronary trees are extracted from high-resolution cardiovascular cryomicrotome imaging data and meshed with computational grids. A dedicated model integrating characteristics of coronary blood flow is used to generate boundary conditions (BCs). Subsequently, VBF is analyzed in left and right ventricular myocardial regions (\(\mathrm{VBF}_\mathrm{m}\)) and in dependence of the vessel sizes (\(\mathrm{VBF}_\mathrm{v}\)). Regarding the distribution of \(\mathrm{VBF}_\mathrm{m}\) in the myocardial segments, good agreement with literature values is found. Partial compliance of the findings of the \(\mathrm{VBF}_\mathrm{v}\)-analysis with results from other groups is promising, however, indicates room for improvement.

Background: Clinical evaluation of the effects of fluid therapy remains cumbersome and strategies are based on the assumption that normalization of macrohemodynamic variables will result in parallel improvement in organ perfusion. Recently, we and others suggested the use of direct in-vivo observation of the microcirculation to evaluate the effects of fluid therapy. Methods: A single-centre observational study, using in-vivo microscopy to assess total vessel density (TVD) in two subsets of ICU patients. Results: After fluid resuscitation TVD showed no difference between sepsis patients (N = 47) and cardiac surgery patients (N = 52): 18.4[16.8–20.8] vs 18.7[16.8–20.9] mm/mm2, p = 0.59. In cardiac surgery patients there was a significant correlation between the amount of fluids administered and TVD, with an optimum in the third quartile. However, such correlation was absent in septic patients. Conclusions: TVD after fluid administration is not different between 2 subtypes of intensive care patients. However, only in septic patients we observed a lack of coherence between the amount of fluids administered and TVD. Further research is needed to determine if TVD may serve as potential endpoint for fluid administration.

Introduction: Intestinal blood flow is often named as a key factor in the pathophysiology of anastomotic leakage. The distribution between mucosal and serosal microperfusion during surgery remains to be elucidated. Objective: The aim of this study was to assess if the mucosal microcirculation of the intestine is more vulnerable to a surgical hit than the serosal microcirculation during surgery. Methods: In an observational cohort study (n = 9 patients), the microcirculation of the bowel serosa and mucosa was visualized with incident dark-field imaging during surgery. At the planned anastomosis, the following microcirculatory parameters were determined: microvascular flow index (MFI), percentage of perfused vessels (PPV), perfused vessel density (PVD), and total vessel density (TVD). Data are presented as median (interquartile range [IQR]). Results: Perfusion parameters and vessel density were significantly higher for the mucosa than the serosal microcirculation at the planned site for anastomosis or stoma. Mucosal MFI was 3.00 (IQR 3.00–3.00) compared to a serosal MFI of 2.75 (IQR 2.21–2.94), p = 0.03. The PPV was 99% (IQR 98–100) versus 92% (IQR 66–94), p = 0.01. The TVD was 16.77 mm/mm2 (IQR 13.04–18.01) versus 10.42 mm/mm2 (IQR 9.36–11.81), p = 0.01, and the PVD was 15.44 mm/mm2 (IQR 13.04–17.78) versus 9.02 mm/mm2 (IQR 6.43–9.43), p = 0.01. Conclusions: The mucosal microcirculation was preserved, while lower perfusion of the serosa was found at the planned anastomosis or stoma during surgery. Further research is needed to link our observations to the clinically relevant endpoint of anastomotic leakage.

This study aimed to determine the response of systemic circulation, pulmonary microcirculation, and alveoli to high positive end-expiratory pressure (PEEP) in a canine model. This study was conducted in nine mixed-breed dogs on mechanical ventilation under anesthesia. The PEEP was initially set at 5 cmH2O (PEEP5), the PEEP was then increased to 25 cmH2O (PEEP25), and then saline was used for fluid loading. Data were obtained at the following time points: PEEP5; PEEP25 prefluid loading; and PEEP25 postfluid loading. The images of subpleural lung microcirculation were assessed by sidestream dark-field microscopy, and the hemodynamic data were collected from pulse contour waveform-derived measurements. Compared with PEEP5, the lung microvascular flow index (MFI, 2.3 ± 0.8 versus 0.9 ± 0.8, P = 0.001), lung perfused vessel density (PVD, 4.2 ± 2 versus 1.5 ± 1.8, P = 0.004), lung proportion of perfused vessel (PPV, 93 ± 14 versus 40 ± 4, P = 0.003), cardiac output (2.5 ± 0.6 versus 1.4 ± 0.5, P = 0.001), and mean blood pressure (116 ± 24 versus 91 ± 31, P = 0.012) were significantly lower at PEEP25 prefluid loading. After fluid loading, there were no significant differences in cardiac output or mean arterial pressure between the PEEP5 and PEEP25 postfluid loading levels. However, the lung microcirculatory MFI, PVD, and PPV at PEEP25 postfluid loading remain lower than at PEEP5. A significant increase in septal thickness was found at PEEP25 postfluid loading relative to septal thickness at PEEP25 prefluid loading (25.98 ± 5.31 versus 40.76 ± 7.9, P = 0.001). Under high PEEP, systemic circulation was restored after fluid loading, but lung microcirculation was not. Moreover, the septal thickness of alveoli significantly increased after fluid loading. NEW & NOTEWORTHY An excessively high positive end-expiratory pressure (PEEP) can impair the systemic circulation and alveolar microcirculation. In the high-PEEP condition, fluid loading restored the systemic circulation but did not affect the impaired lung microcirculation. The septal thickness of the alveoli significantly increased after fluid loading in the high-PEEP condition.

BACKGROUND: Diaphragmatic respiratory effort during mechanical ventilation is an important determinant of patient outcome, but direct measurement of diaphragmatic contractility requires specialized instrumentation and technical expertise. We sought to determine whether routinely collected clinical variables can predict diaphragmatic contractility and stratify the risk of diaphragm atrophy. METHODS: We conducted a secondary analysis of a prospective cohort study on diaphragm ultrasound in mechanically ventilated subjects. Clinical variables, such as breathing frequency, ventilator settings, and blood gases, were recorded longitudinally. Machine learning techniques were used to identify variables predicting diaphragm contractility and stratifying the risk of diaphragm atrophy (> 10% decrease in thickness from baseline). Performance of the variables was evaluated in mixed-effects logistic regression and random-effects tree models using the area under the receiver operating characteristic curve. RESULTS: Measurements were available for 761 study days in 191 subjects, of whom 73 (38%) developed diaphragm atrophy. No routinely collected clinical variable, alone or in combination, could accurately predict either diaphragm contractility or the development of diaphragm atrophy (model area under the receiver operating characteristic curve 0.63–0.75). The risk of diaphragm atrophy was not significantly different according to the presence or absence of patient-triggered breaths (38.3% vs 38.6%; odds ratio 1.01, 95% CI 0.05–2.03). Diaphragm thickening fraction < 15% during either of the first 2 d of the study was associated with a higher risk of atrophy (44.6% vs 26.1%; odds ratio 2.28, 95% CI 1.05–4.95). CONCLUSIONS: Diaphragmatic contractility and the risk of diaphragm atrophy could not be reliably determined from routinely collected clinical variables and ventilator settings. A single measurement of diaphragm thickening fraction measured within 48 h of initiating mechanical ventilation can be used to stratify the risk of diaphragm atrophy during mechanical ventilation.

The impact of secondary bacterial infections (superinfections) in COVID-19 is not well understood. In this prospective, monocentric cohort study we aim to investigate the impact of superinfections in COVID-19 patients with acute respiratory distress syndrome. Patients are assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages and blood cultures. In 45 critically ill patients, we identify 19 patients with superinfections (42.2%). Superinfections are detected on day 10 after intensive care admission. The proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days (VFDs) at 28 days) is substantially lower in patients with superinfection (subhazard ratio 0.37, 95%-CI 0.15-0.90, p=0.028). Patients with pulmonary superinfections have a higher incidence of bacteraemia, virus reactivations, yeast colonization, and required intensive care treatment for a longer time. Superinfections are frequent and associated with reduced VFDs at 28 days despite a high rate of empirical antibiotic therapy., Graphical Abstract, Buehler et al. show that detection of bacterial pulmonary superinfection is associated with a more severe disease course in COVID-19 patients, especially a lower likelihood of being alive and off invasive mechanical ventilation at study day 28 (ventilator-free days at 28 days).

RATIONALE: The COVID-19 pandemic induces considerable strain on intensive care unit resources. OBJECTIVES: We aim to provide early predictions of individual patients' intensive care unit length of stay, which might improve resource allocation and patient care during the on-going pandemic. METHODS: We developed a new semiparametric distributional index model depending on covariates which are available within 24h after intensive care unit admission. The model was trained on a large cohort of acute respiratory distress syndrome patients out of the Minimal Dataset of the Swiss Society of Intensive Care Medicine. Then, we predict individual length of stay of patients in the RISC-19-ICU registry. MEASUREMENTS: The RISC-19-ICU Investigators for Switzerland collected data of 557 critically ill patients with COVID-19. MAIN RESULTS: The model gives probabilistically and marginally calibrated predictions which are more informative than the empirical length of stay distribution of the training data. However, marginal calibration was worse after approximately 20 days in the whole cohort and in different subgroups. Long staying COVID-19 patients have shorter length of stay than regular acute respiratory distress syndrome patients. We found differences in LoS with respect to age categories and gender but not in regions of Switzerland with different stress of intensive care unit resources. CONCLUSION: A new probabilistic model permits calibrated and informative probabilistic prediction of LoS of individual patients with COVID-19. Long staying patients could be discovered early. The model may be the basis to simulate stochastic models for bed occupation in intensive care units under different casemix scenarios.

Supplemental Digital Content is available in the text., OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm–2), functional capillary density (mm × mm–2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (μm × s–1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s–1) and capillary RBC microaggregates (4 s–1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.

BACKGROUND: With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO2 removal (ECCO2R). However, current evidence in these indications is limited. A European ECCO2R Expert Round Table Meeting was convened to further explore the potential for this treatment approach. METHODS: A modified Delphi-based method was used to collate European experts' views to better understand how ECCO2R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus. RESULTS: Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO2R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO2R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO2R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO2 levels. Driving pressure (≥ 14 cmH2O) followed by plateau pressure (Pplat; ≥ 25 cmH2O) was considered the most important criteria for ECCO2R initiation. Key treatment targets for patients with ARDS undergoing ECCO2R included pH (> 7.30), respiratory rate ( 7.30-7.35), respiratory rate (, SCOPUS: ar.j, info:eu-repo/semantics/published

Erythropoietin (EPO) boosts exercise performance through increase in oxygen transport capacity following regular administration of EPO but preclinical study results suggest that single high dose of EPO also may improve exercise capacity. Twenty-nine healthy subjects (14 males/15 females; age: 25 ± 3 years) were included in a randomized, double-blind, placebo-controlled crossover study to assess peak work load and cardiopulmonary variables during submaximal and maximal cycling tests following a single dose of 60.000 IU of recombinant erythropoietin (EPO) or placebo (PLA). Submaximal exercise at 40%/60% of peak work load revealed no main effect of EPO on oxygen uptake (27.9 ± 8.7 ml min–1⋅kg–1/ 37.1 ± 13.2 ml min–1⋅kg–1) versus PLA (25.2 ± 3.7 ml min–1⋅kg–1/ 33.1 ± 5.3 ml min–1⋅kg–1) condition (p = 0.447/p = 0.756). During maximal exercise peak work load (PLA: 3.5 ± 0.6 W⋅kg–1 vs. EPO: 3.5 ± 0.6 W kg–1, p = 0.892) and peak oxygen uptake (PLA: 45.1 ± 10.4 ml⋅min–1 kg–1 vs. EPO: 46.1 ± 14.2 ml⋅min–1 kg–1, p = 0.344) reached comparable values in the two treatment conditions. Other cardiopulmonary variables (ventilation, cardiac output, heart rate) also reached similar levels in the two treatment conditions. An interaction effect was found between treatment condition and sex resulting in higher peak oxygen consumption (p = 0.048) and ventilation (p = 0.044) in EPO-treated males. In conclusion, in a carefully conducted study using placebo-controlled design the present data failed to support the hypothesis that a single high dose of EPO has a measurable impact on work capacity in healthy subjects., Frontiers in Physiology, 11, ISSN:1664-042X

Objectives: Reliable automated handheld vital microscopy image sequence analysis and the identification of disease states and effects of therapy are prerequisites for the routine use of quantitative sublingual microcirculation measurements at the point-of-care. The present study aimed to clinically validate the recently introduced MicroTools software in a large multicentral database of perioperative and critically ill patients and to use this automatic algorithm to data-mine and identify the sublingual microcirculatory variable changes in response to disease and therapy. Design: Retrospective algorithm-based image analysis and data-mining within a large international database of sublingual capillary microscopy. Algorithm-based analysis was compared with manual analysis for validation. Thereafter, MicroTools was used to identify the functional microcirculatory alterations associated with disease conditions and identify therapeutic options for recruiting functional microcirculatory variables. Setting: Ten perioperative/ICU/volunteer studies in six international teaching hospitals. Patients: The database encompass 267 adult and pediatric patients undergoing surgery, treatment for sepsis, and heart failure in the ICU and healthy volunteers. Interventions: Perioperative and ICU standard of care. Measurements and Main Results: One thousand five hundred twenty-five handheld vital microscopy image sequences containing 149,257 microscopy images were analyzed. 3.89 × 1012 RBC positions were tracked by the algorithm in real time, and offline manual analysis was performed. Good correlation and trending ability were found between manual and automatic total and functional capillary density (r = 0.6–0.8; p < 0.0001). RBC tracking within the database demonstrated changes in functional capillary density and/or RBC velocity in septic shock, heart failure, hypovolemia, obstructive shock, and hemodilution and thus detected the presence of a disease condition. Therapies recruiting the microcirculatory diffusion and convection capacity associated with systemic vasodilation and an increase in cardiac output were separately identified. Conclusions: Algorithm-based analysis of the sublingual microcirculation closely matched manual analysis across a broad spectrum of populations. It successfully identified a methodology to quantify microcirculatory alterations associated with disease and the success of capillary recruitment, improving point-of-care application of microcirculatory-targeted resuscitation procedures.

Background: Wave speed is needed to separate net wave intensity into forward and backward traveling components. However, wave speed in diseased coronary arteries cannot be assessed from hemodynamic measurements obtained distal to a stenosis. Wave speed inherently depends on arterial wall properties which should be similar proximal and distal to a stenosis. Our hypothesis is that proximal wave speed can be used to separate net wave intensity obtained distal to a stenosis.Methods: We assessed coronary wave speed using the sum-of-squares single-point technique (SPc) based on simultaneous intracoronary pressure and flow velocity measurements in human coronary arteries. SPc at resting flow was determined in diseased coronary vessels of 12 patients both proximal and distal to the stenosis. In seven of these vessels, distal measurements were additionally obtained after revascularization by stent placement. SPc was also assessed at two axial locations in 14 reference vessels without a stenosis.Results: (1) No difference in SPc was present between proximal and distal locations in the reference vessels. (2) In diseased vessels with a focal stenosis, SPc at the distal location was paradoxically larger than SPc proximal to the stenosis (28.4 ± 3.7 m/s vs. 18.3 ± 1.8 m/s, p < 0.02), despite the lower distending pressure downstream of the stenosis. The corresponding separated wave energy tended to be underestimated when derived from SPc at the distal compared with the proximal location. (3) After successful revascularization, SPc at the distal location no longer differed from SPc at the proximal location prior to revascularization (21.9 ± 2.0 m/s vs. 20.8 ± 1.9 m/s, p = 0.48). Accordingly, no significant difference in separated wave energy was observed for forward or backward waves.Conclusion: In diseased coronary vessels, SPc assessed from distal hemodynamic signals is erroneously elevated. Our findings suggest that proximal wave speed can be used to separate wave intensity profiles obtained downstream of a stenosis. This approach may extend the application of wave intensity analysis to diseased coronary vessels.

Background Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p

Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave‐free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect ‐Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian‐Dutch‐English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed. CFC classified prerevascularization lesions as normal (14), mildly reduced (40), moderately reduced (31), and severely reduced (48). Lesions with larger impairment of CFC showed greater increase in coronary flow and vice versa (median percent increase in coronary flow by revascularization: 4.2%, 25.9%, 50.1%, and 145.5%, respectively; P 50% increase in coronary flow after percutaneous coronary intervention. Receiver operating characteristic curve analysis demonstrated that only CFC has a superior predictive efficacy to CFR ( P P Conclusions CFC showed significant improvement of identification of lesions that benefit from revascularization compared with CFR with respect to coronary flow increase. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02328820.

Purpose: Bolus‐based dynamic contrast agent (CA) perfusion measurements of the heart are subject to systematic errors due to CA bolus dispersion in the coronary arteries. To better understand these effects on quantification of myocardial blood flow and myocardial perfusion reserve (MPR), an in‐silico model of the coronary arteries down to the pre‐arteriolar vessels has been developed. Methods: In this work, a computational fluid dynamics analysis is performed to investigate these errors on the basis of realistic 3D models of the left and right porcine coronary artery trees, including vessels at the pre‐arteriolar level. Using advanced boundary conditions, simulations of blood flow and CA transport are conducted at rest and under stress. These are evaluated with regard to dispersion (assessed by the width of CA concentration time curves and associated vascular transport functions) and errors of myocardial blood flow and myocardial perfusion reserve quantification. Results: Contrast agent dispersion increases with traveled distance as well as vessel diameter, and decreases with higher flow velocities. Overall, the average myocardial blood flow errors are −28% ± 16% and −8.5% ± 3.3% at rest and stress, respectively, and the average myocardial perfusion reserve error is 26% ± 22%. The calculated values are different in the left and right coronary tree. Conclusion: Contrast agent dispersion is dependent on a complex interplay of several different factors characterizing the cardiovascular bed, including vessel size and integrated vascular length. Quantification errors evoked by the observed CA dispersion show nonnegligible distortion in dynamic CA bolus‐based perfusion measurements. We expect future improvements of quantitative perfusion measurements to make the systematic errors described here more apparent.

The coronavirus disease 2019 (COVID-19) pandemic is overwhelming healthcare systems worldwide. There is no evidence from randomised clinical trials that any potential therapy improves outcome in COVID-19 pneumonia, and therapeutic strategies have been based on a progressively increasing knowledge of the clinical presentation of the disease. Some clinicians have found the clinical features of COVID-19 pneumonia to be similar to high-altitude pulmonary oedema (HAPE) [1], and such theory has been amplified via social media. We question this relationship., COVID-19 pneumonia is a viral infection; high-altitude pulmonary oedema is a non-cardiogenic oedema. Some clinicians have found the clinical features similar. It is important to clarify such misconceptions to prevent erroneous treatment strategies https://bit.ly/2KOBi3F