Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies

Background: several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value. Objective: this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI. Methods: a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used. Results: there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled p = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I-2 = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled p = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I-2 = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI. Conclusions: a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored

Old Drugs May Be Good Friends but Always Under Prerequisites

[No abstract available

Measurement of mean systemic filling pressure after severe hemorrhagic shock in swine anesthetized with propofol-based total intravenous anesthesia: Implications for vasopressor-free resuscitation

Background: Mean systemic filling pressure (Pmsf) is a quantitative measurement of a patient's volume status and represents the tone of the venous reservoir. The aim of this study was to estimate Pmsf after severe hemorrhagic shock and cardiac arrest in swine anesthetized with propofol-based total intravenous anesthesia, as well as to evaluate Pmsf's association with vasopressor-free resuscitation. Methods: Ten healthy Landrace/Large-White piglets aged 10-12 weeks with average weight 201 kg were used in this study. The protocol was divided into four distinct phases: stabilization, hemorrhagic, cardiac arrest, and resuscitation phases. We measured Pmsf at 5-7.5 seconds after the onset of cardiac arrest and then every 10 seconds until 1 minute postcardiac arrest. During resuscitation, lactated Ringers was infused at a rate that aimed for a mean right atrial pressure of 4 mm Hg. No vasopressors were used. Results: The mean volume of blood removed was 86020 ml (blood loss, ~61%) and the bleeding time was 43.22 minutes while all animals developed pulseless electrical activity. Mean Pmsf was 4.091.22 mm Hg, and no significant differences in Pmsf were found until 1 minute postcardiac arrest (4.200.22 mm Hg at 5-7.5 seconds and 3.720.23 mm Hg at 55- 57.5 seconds; P=0.102). All animals achieved return of spontaneous circulation (ROSC), with mean time to ROSC being 6.11.7 minutes and mean administered volume being 39420 ml. Conclusions: For the first time, Pmsf was estimated after severe hemorrhagic shock. In this study, Pmsf remained stable during the first minute post-Arrest. All animals achieved ROSC with goal-directed fluid resuscitation and no vasopressors. © 2020 Korean Society of Critical Care Medicine. All right reserved

Assessment of Dynamic Changes in Stressed Volume and Venous Return during Hyperdynamic Septic Shock

The present work investigated the dynamic changes in stressed volume (Vs) and other determinants of venous return using a porcine model of hyperdynamic septic shock. Septicemia was induced in 10 anesthetized swine, and fluid challenges were started after the diagnosis of sep-sis‐induced arterial hypotension and/or tissue hypoperfusion. Norepinephrine infusion targeting a mean arterial pressure (MAP) of 65 mmHg was started after three consecutive fluid challenges. After septic shock was confirmed, norepinephrine infusion was discontinued, and the animals were left untreated until cardiac arrest occurred. Baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of septic shock. Mean circulatory filling pressure (Pmcf) analogue (Pmca), right atrial pressure, resistance to venous return, and efficiency of the heart decreased with time (p < 0.001 for all). Fluid challenges did not improve hemodynamics, but noradrenaline increased Vs from 107 mL to 257 mL (140%) and MAP from 45 mmHg to 66 mmHg (47%). Baseline Pmca and post‐cardiac arrest Pmcf did not differ significantly (14.3 ± 1.23 mmHg vs. 14.75 ± 1.5 mmHg, p = 0.24), but the difference between pre‐arrest Pmca and post‐cardiac arrest Pmcf was sta-tistically significant (9.5 ± 0.57 mmHg vs. 14.75 ± 1.5 mmHg, p < 0.001). In conclusion, the baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of hyperdynamic septic shock. Significant changes were also observed in other determinants of venous return. A new physiological intravascular volume existing at zero transmural distending pressure was identified, termed as the rest volume (Vr). © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Assessment of Dynamic Changes in Stressed Volume and Venous Return during Hyperdynamic Septic Shock

The present work investigated the dynamic changes in stressed volume (Vs) and other determinants of venous return using a porcine model of hyperdynamic septic shock. Septicemia was induced in 10 anesthetized swine, and fluid challenges were started after the diagnosis of sep-sis‐induced arterial hypotension and/or tissue hypoperfusion. Norepinephrine infusion targeting a mean arterial pressure (MAP) of 65 mmHg was started after three consecutive fluid challenges. After septic shock was confirmed, norepinephrine infusion was discontinued, and the animals were left untreated until cardiac arrest occurred. Baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of septic shock. Mean circulatory filling pressure (Pmcf) analogue (Pmca), right atrial pressure, resistance to venous return, and efficiency of the heart decreased with time (p &lt; 0.001 for all). Fluid challenges did not improve hemodynamics, but noradrenaline increased Vs from 107 mL to 257 mL (140%) and MAP from 45 mmHg to 66 mmHg (47%). Baseline Pmca and post‐cardiac arrest Pmcf did not differ significantly (14.3 ± 1.23 mmHg vs. 14.75 ± 1.5 mmHg, p = 0.24), but the difference between pre‐arrest Pmca and post‐cardiac arrest Pmcf was sta-tistically significant (9.5 ± 0.57 mmHg vs. 14.75 ± 1.5 mmHg, p &lt; 0.001). In conclusion, the baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of hyperdynamic septic shock. Significant changes were also observed in other determinants of venous return. A new physiological intravascular volume existing at zero transmural distending pressure was identified, termed as the rest volume (Vr). © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Sublingual microcirculatory alterations during the immediate and early postoperative period: A systematic review and meta-analysis

BACKGROUND: The incidence of postoperative microcirculatory flow alterations and their effect on outcome have not been studied extensively. OBJECTIVE: This systematic review and meta-analysis were designed to investigate the presence of sublingual microcirculatory flow alterations during the immediate and early postoperative period and their correlation with complications and survival. METHODS: A systematic search of PubMed, Scopus, Embase, PubMed Central, and Google Scholar was conducted for relevant articles from January 2000 to March 2021. Eligibility criteria were randomized controlled and non-randomized trials. Case reports, case series, review papers, animal studies and non-English literature were excluded. The primary outcome was the assessment of sublingual microcirculatory alterations during the immediate and early postoperative period in adult patients undergoing surgery. Risk of bias was assessed with the Ottawa-Newcastle scale. Standard meta-analysis methods (random-effects models) were used to assess the difference in microcirculation variables. RESULTS: Thirteen studies were included. No statistically significant difference was found between preoperative and postoperative total vessel density (p=0.084; Standardized Mean Difference (SMD): -0.029; 95%CI: -0.31 to 0.26; I2=22.55%). Perfused vessel density significantly decreased postoperatively (p=0.035; SMD: 0.344; 95%CI: 0.02 to 0.66; I2=65.66%), while perfused boundary region significantly increased postoperatively (p=0.031; SMD: -0.415; 95%CI: -0.79 to -0.03; I2=37.21%). Microvascular flow index significantly decreased postoperatively (p=0.028; SMD: 0.587; 95%CI: 0.06 to 1.11; I2=86.09%), while no statistically significant difference was found between preoperative and postoperative proportion of perfused vessels (p=0.089; SMD: 0.53; 95%CI: -0.08 to 1.14; I2=70.71%). The results of the non-cardiac surgery post-hoc analysis were comparable except that no statistically significant difference in perfused vessel density was found (p=0.69; SMD: 0.07; 95%CI: -0.26 to 0.39; I2=0%). LIMITATIONS: The included studies investigate heterogeneous groups of surgical patients. There were no randomized controlled trials. CONCLUSIONS: Significant sublingual microcirculatory flow alterations are present during the immediate and early postoperative period. Further research is required to estimate the correlation of sublingual microcirculatory flow impairment with complications and survival. © 2022 - IOS Press. All rights reserved

Sublingual microcirculatory alterations during the immediate and early postoperative period: A systematic review and meta-analysis

BACKGROUND: The incidence of postoperative microcirculatory flow alterations and their effect on outcome have not been studied extensively. OBJECTIVE: This systematic review and meta-analysis were designed to investigate the presence of sublingual microcirculatory flow alterations during the immediate and early postoperative period and their correlation with complications and survival. METHODS: A systematic search of PubMed, Scopus, Embase, PubMed Central, and Google Scholar was conducted for relevant articles from January 2000 to March 2021. Eligibility criteria were randomized controlled and non-randomized trials. Case reports, case series, review papers, animal studies and non-English literature were excluded. The primary outcome was the assessment of sublingual microcirculatory alterations during the immediate and early postoperative period in adult patients undergoing surgery. Risk of bias was assessed with the Ottawa-Newcastle scale. Standard meta-analysis methods (random-effects models) were used to assess the difference in microcirculation variables. RESULTS: Thirteen studies were included. No statistically significant difference was found between preoperative and postoperative total vessel density (p = 0.084; Standardized Mean Difference (SMD): -0.029; 95%CI: -0.31 to 0.26; I2 = 22.55%). Perfused vessel density significantly decreased postoperatively (p = 0.035; SMD: 0.344; 95%CI: 0.02 to 0.66; I2 = 65.66%), while perfused boundary region significantly increased postoperatively (p = 0.031; SMD: -0.415; 95%CI: -0.79 to -0.03; I2 = 37.21%). Microvascular flow index significantly decreased postoperatively (p = 0.028; SMD: 0.587; 95%CI: 0.06 to 1.11; I2 = 86.09%), while no statistically significant difference was found between preoperative and postoperative proportion of perfused vessels (p = 0.089; SMD: 0.53; 95%CI: -0.08 to 1.14; I2 = 70.71%). The results of the non-cardiac surgery post-hoc analysis were comparable except that no statistically significant difference in perfused vessel density was found (p = 0.69; SMD: 0.07; 95%CI: -0.26 to 0.39; I2 = 0%). LIMITATIONS: The included studies investigate heterogeneous groups of surgical patients. There were no randomized controlled trials. CONCLUSIONS: Significant sublingual microcirculatory flow alterations are present during the immediate and early postoperative period. Further research is required to estimate the correlation of sublingual microcirculatory flow impairment with complications and survival

A Critical Appraisal of the Effects of Anesthetics on Immune-system Modulation in Critically Ill Patients With COVID-19

Purpose: The aim of the present article was to briefly summarize current knowledge about the immunomodulatory effects of general anesthetics and the possible clinical effects of this immunomodulation in patients with COVID-19. Methods: The PubMed, Scopus, and Google Scholar databases were comprehensively searched for relevant studies. Findings: The novel coronavirus causes a wide spectrum of clinical manifestations, with a large absolute number of patients experiencing severe pneumonia and rapid progression to acute respiratory distress syndrome and multiple organ failure. In these patients, the equilibrium of the inflammatory response is a major determinant of survival. The impact of anesthetics on immune-system modulation may vary and includes both pro-inflammatory and anti-inflammatory effects. Implications: Inhibition of the development of severe inflammation and/or the enhancement of inflammation resolution by anesthetics may limit organ damage and improve outcomes in patients with COVID-19. © 2021 Elsevier Inc

Elevated preoperative suPAR is a strong and independent risk marker for postoperative complications in patients undergoing major noncardiac surgery (SPARSE)

Background: Patients undergoing major surgery are often at risk of developing postoperative complications. We investigated whether a preoperative marker of chronic inflammation, soluble urokinase plasminogen activator receptor, can aid in identifying patients at high risk for postoperative complications, morbidity, and mortality. Methods: In this prospective observational study (ClinicalTrials.gov identifier: NCT03851965), EDTA blood was collected from consecutive adult White patients scheduled for major noncardiac surgery with expected duration ≥2 hours under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists physical status I to IV. Plasma soluble urokinase plasminogen activator receptor levels were determined using the suPARnostic quick triage lateral flow assay. The primary endpoint was postoperative complications defined as presence of any complication and/or admission to intensive care unit and/or mortality within the first 90 postoperative days. Results: Preoperative soluble urokinase plasminogen activator receptor had an odds ratio of 1.50 (95% confidence interval: 1.24–1.82) for every ng/mL increase. When including age, sex, American Society of Anesthesiologists score, C-reactive protein, and grouped soluble urokinase plasminogen activator receptor in multivariate analysis, patients with soluble urokinase plasminogen activator receptor between 5.5 and 10 ng/mL had an odds ratio of 11.2 (confidence interval: 3.1–40.8) and patients with soluble urokinase plasminogen activator receptor >10 ng/mL had an odds ratio of 19.9 (95% confidence interval: 4.3–92.9) compared to patients with soluble urokinase plasminogen activator receptor ≤5.5 ng/mL, respectively. Receiver operating characteristic analysis of soluble urokinase plasminogen activator receptor showed an area under the curve of 0.82 (confidence interval: 0.72–0.91). Receiver operating characteristic analysis combining age, sex, C-reactive protein levels, and American Society of Anesthesiologists score and had an area under the curve of 0.71 (95% confidence interval: 0.61–0.82). Adding soluble urokinase plasminogen activator receptor to this model increased the area under the curve to 0.83 (95% confidence interval: 0.74–0.92) (P = .033). Conclusion: Preoperative soluble urokinase plasminogen activator receptor provided strong and independent predictive value on postoperative complications in White patients undergoing major noncardiac surgery. © 2021 Elsevier Inc