Johannes T, Mik EG, Nohé B, Unertl KE, Ince C. Acute decrease in renal microvascular PO 2 during acute normovolemic hemodilution. Am J Physiol Renal Physiol 292: F796 -F803, 2007. First published October 31, 2006 doi:10.1152/ajprenal.00206.2006.-Large differences in the tolerance of organ systems to conditions of decreased O2 delivery such as hemodilution exist. The kidney receives ϳ25% of the cardiac output and O2 delivery is in excess of the oxygen demand under normal circumstances. In a rat model of acute normovolemic hemodilution (ANH), we studied the effect of reduced hematocrit on renal regional and microvascular oxygenation. Experiments were performed in 12 anesthetized male Wistar rats. Six animals underwent four steps of ANH (hematocrit 25, 15, 10, and Ͻ10%). Six animals served as time-matched controls. Systemic and renal hemodynamic and oxygenation parameters were monitored. Renal cortical (c) and outer medullary (m) microvascular PO 2 (PO2) and the renal venous PO 2 (PrvO2) were continuously measured by oxygen-dependent quenching of phosphorescence. Despite a significant increase in renal blood flow in the first two steps of ANH, cPO 2 and mPO2 dropped immediately. From the first step onward oxygen consumption (V O2ren) became dependent on oxygen delivery (DO 2ren). With a progressive decrease in hematocrit, a significant correlation between PO 2 and V O2ren could be observed, as well as a PO2 gap between PO2 and P rvO2. Furthermore, there was a high correlation between V O2ren and RBF over a wide range of flows. In conclusion, the oxygen supply to the renal tissue is becoming critical already in an early stage of ANH due to the combination of increased V O2ren, decreased DO2ren, and intrarenal O 2 shunt. This has clinical relevance as recent publications reporting that hemodilution during surgery forms a risk factor for postoperative renal dysfunction.

Background Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration “ClinicalTrials” (clinicaltrials.gov) under NCT04455451.

Local anesthetic dose and structure dependently inhibit inflammatory and immunologic parameters of granulocyte functions. Ropivacaine shows low interference with granulocyte immunologic and inflammatory functions.

IntroductionThis study was carried out to determine whether interactions of cell activation, shear stress and platelets at sites of endothelial injury explain the paradoxical maldistribution of activated leukocytes during sepsis away from local sites of infection towards disseminated leukocyte accumulation at remote sites.MethodsHuman umbilical venous endothelial cells (HUVEC) and polymorphonuclear neutrophils (PMN) were activated with lipopolysaccharide at 100 and 10 ng/ml to achieve adhesion molecule patterns as have been reported from the hyper- and hypo-inflammatory stage of sepsis. To examine effects of leukocyte activation on leukocyte-endothelial interactions, activated HUVEC were perfused with activated and non-activated neutrophils in a parallel plate flow chamber. Adhesion molecule expression and function were assessed by flow cytometry and blocking antibodies. In a subset of experiments the sub-endothelial matrix was exposed and covered with platelets to account for the effects of endothelial injury. To investigate interactions of these effects with flow, all experiments were done at various shear stress levels (3 to 0.25 dyne/cm2). Leukocyte-endothelial interactions were analyzed by videomicroscopy and analysis of covariance.ResultsActivation of neutrophils rendered adhesion increasingly dependent on shear stress reduction. At normal shear stress, shedding of L-selectin decreased adhesion by 56%. Increased rolling fractions of activated PMN at low shear stress revealed impaired integrin affinity despite numerical up-regulation of CD11b. On sub-maximally activated, intact HUVEC shear stress became the prevailing determinant of adhesion. Presence of a platelet-covered injury with high surface density of P-selectin was the strongest variable for adhesion. When compared to maximally activated HUVEC, platelets increased neutrophil adhesion by 2.7-fold. At sub-maximal activation a 10-fold increase was observed (P < 0.05 for all).ConclusionsL-selectin shedding and integrin dysfunction render leukocyte adhesion increasingly susceptible to shear stress and alternative adhesion receptors. In combination, these effects inhibit recruitment to normally perfused sites with intact endothelium and favor maldistribution towards sites with compromised perfusion or endothelial injury.

This study shows that synthetic colloids inhibit neutrophil adhesion by a neutrophil-dependent mechanism rather than interfering with endothelial cell activation. This suggests that inhibition of leukocyte sequestration by volume support is a common and transient phenomenon depending on the colloid concentration in plasma.