Ascorbic acid is an essential cofactor of catecholamine synthesis that increases capillary bed density and improves microcirculation perfusion. We hypothesized early ascorbic acid administration in cardiothoracic surgery would preserve the microcirculatory integrity and minimize postoperative vasoplegia.

This was a single-arm pilot feasibility study of adults undergoing septal myectomy combined with valve intervention or alone using cardiopulmonary bypass. Intravenous ascorbic acid 1,500 mg was administered before and immediately following cardiopulmonary bypass and every 6 h after for 12 doses. Three historical controls were identified and matched to each trial participant on age, gender, body mass index, preoperative ejection fraction, surgery performed, and time on cardiopulmonary bypass. The feasibility endpoint was a composite of successful and timely 1) ascorbic acid administration, 2) laboratory assessment, and 3) microcirculation measurements across the perioperative phases of care. Clinical endpoints included vasoplegia incidence, acute kidney injury, and lengths of stay compared to controls.

Fifteen patients were enrolled and compared to 45 historically matched controls. Participants' median baseline plasma ascorbic acid concentration was 0.5 (0.3, 0.9) mg/dL. Four (27%) patients had suboptimal concentrations. Eleven participants (75%) did not meet the feasibility composite endpoint due to the inability of microcirculation measurement. Incidence of vasoplegia and acute kidney injury, vasopressor duration, and lengths of stay were similar between participants and historical controls. No drug-related adverse events were noted.

Timely microcirculation measurements were challenging in the complex cardiothoracic surgery environment. Compared to historical controls, no meaningful differences in clinical endpoints were noted with ascorbic acid treatment. The utility of ascorbic acid on post-cardiopulmonary bypass vasoplegia remains unclear.

ClinicalTrials.gov (NCT03744702, registered on November 14, 2018).

The effect of perioperative hyperoxia on microcirculation after cardiac surgery remains inconclusive. We evaluated the relationship between intraoperative fractional inspired oxygen and microcirculation after off-pump coronary artery bypass grafting (OPCAB).

Exploratory secondary analysis of a multicenter cluster-randomized trial.

Three teaching hospitals.

Adult patients who underwent OPCAB.

Seven postoperative microcirculatory parameters, including De Backer scores and the proportion of perfused vessels via sublingual microscopy (from all and small vessels), and thenar muscle tissue oxygenation, occlusion slope, and recovery slope via the vascular occlusion test, were compared between patients receiving 30% and 80% oxygen intraoperatively. Generalized estimating equations were used to account for intracluster correlation.

The analysis included 52 and 51 patients from the 30% and 80% oxygen groups, respectively, for sublingual microscopy and 59 and 53 patients for the vascular occlusion test. Although all microcirculatory parameters were similar between groups, the 80% oxygen group had higher De Backer scores for all vessels (mean, 9.8 ± 2.9 mm-1 vs. 8.7 ± 2.0 mm-1; p = 0.011) and small vessels (4.0 ± 1.8 mm-1 vs. 3.4 ± 1.1 mm-1; p = 0.024) than the 30% oxygen group at the end of surgery. The 80% oxygen group also exhibited greater thenar muscle tissue oxygenation immediately before vascular occlusion (78.4% ± 10.5 vs. 74.0% ± 9.3; p = 0.031) and a higher recovery score (4.1%·s-1 ± 1.7 vs. 3.2%·s-1 ± 1.4; p = 0.001).

Patients receiving 80% oxygen during OPCAB had significantly better postoperative microcirculatory profiles than those receiving 30% oxygen. These findings highlight the potential for optimizing perioperative oxygenation to improve or mitigate microcirculatory impairment, thereby reducing postoperative complications.

Excess fluid in the interstitium can adversely affect the microcirculation. We studied how gradual dilution of the blood plasma by crystalloid fluid influences microcirculatory variables and capillary filtration in 20 patients undergoing surgery.

Video recordings of the sublingual mucosal were made on four occasions during the surgery and compared with quasi-measurements of the capillary filtration rate using retrospective volume kinetic data collected over 5-10-minute periods during 262 infusion experiments with crystalloid fluid.

The number of crossings (vessel density) increased up to plasma dilution of 15-20 % whereafter it decreased. The proportion of the vessels that were perfused (PPV) decreased and reached a nadir of -15 % at a dilution of 20-30 %. Changes in the number of crossings and the PPV correlated (r = 0.62, P < 0.001) but the curve was displaced so that crossings showed no change when PPV had decreased by approximately 10 %. However, the PPV of vessels with a thickness of ≤25 μm increased or remained constant in the dilution range of up to 20 %. The volume kinetic analysis showed that the capillary filtration was greater than expected from proportionality with the volume expansion up to a plasma dilution of 15 %, the greatest difference (+89 %) being for plasma dilution up to 5 %.

Plasma dilution of up to 15 % increased the vessel density, and the capillary filtration increased by more than suggested by the volume expansion. Dilution >15 % had a negative influence on these variables.

Capillary refill time (CRT) and skin blood flow (SBF) have been reported to be strong predictors of mortality in critically ill patients. However, the relationship between both parameters remains unclear.

We conducted a prospective observational study in a tertiary teaching hospital. All patients older than 18 years admitted in the intensive care unit (ICU) with circulatory failure and a measurable CRT were included. We assessed index SBF by laser doppler flowmetry and CRT on the fingertip, at T0 (Within the first 48 h from admission) and T1 (4 to 6 h later). Correlation was computed using Spearman or Pearson's formula.

During a 2-month period, 50 patients were included, 54% were admitted for sepsis. At baseline median CRT was 2.0 [1.1-3.9] seconds and median SBF was 46 [20-184] PU. At baseline SBF strongly correlated with CRT (R2 = 0.89; p < 0.0001, curvilinear relationship), this correlation was maintained whether patients were septic or not (R2 = 0.94; p = 0.0013; R2 = 0.87; p < 0.0001, respectively), and whether they received norepinephrine or not (R2 = 0.97; p = 0.0035; R2 = 0.92; p < 0.0001, respectively). Between T0 and T1, changes in SBF also significantly correlated with changes in CRT (R2 = 0.34; p < 0.0001). SBF was related to tissue perfusion parameters such as arterial lactate level (p = 0.02), whilst no correlation was found with cardiac output. In addition, only survivors significantly improved their SBF between T0 and T1. SBF was a powerful predictor of day-28 mortality as the AUROC at T0 was 85% [95% IC [76-91]] and at T1 90% [95% IC [78-100]].

We have shown that index CRT and SBF were correlated, providing evidence that CRT is a reliable marker of microvascular blood flow. Trial registration Comité de protection des personnes Ouest II N° 2023-A02046-39.

Trial registration: Clinicaltrials.gov NCT02270281. Registered October 16, 2014.

Vascular endothelial cells form a single layer of flat cells that line the inner surface of blood vessels, extending from large vessels to the microvasculature of various organs. These cells are crucial metabolic and endocrine components of the body, playing vital roles in maintaining circulatory stability, regulating vascular tone, and preventing coagulation and thrombosis. Endothelial cell injury is regarded as a pivotal initiating factor in the pathogenesis of various diseases, triggered by multiple factors, including infection, inflammation, and hemodynamic changes, which significantly compromise vascular integrity and function. This review examines the causes, underlying molecular mechanisms, and potential therapeutic approaches for endothelial cell injury, focusing specifically on endothelial damage in cardiac ischemia/reperfusion (I/R) injury, sepsis, and diabetes. It delves into the intricate signaling pathways involved in endothelial cell injury, emphasizing the roles of oxidative stress, mitochondrial dysfunction, inflammatory mediators, and barrier damage. Current treatment strategies-ranging from pharmacological interventions to regenerative approaches and lifestyle modifications-face ongoing challenges and limitations. Overall, this review highlights the importance of understanding endothelial cell injury within the context of various diseases and the necessity for innovative therapeutic methods to improve patient outcomes.

Near-infrared spectroscopy (NIRS) enables a non-invasive measurement of tissue oxygen saturation (StO2) in regions illuminated by near-infrared lights. Vascular occlusion test (VOT) serves as a model to artificially induce forearm ischemia-reperfusion. The combination of StO2 monitoring and VOT allows for dynamic evaluation of the balance between oxygen delivery and consumption in tissue, as well as the functional reserve of microcirculation. However, the implications of these measurements for patient outcomes remain inadequately understood. This study aimed to investigate the association between StO2-VOT measurements and the occurrence of postoperative acute kidney injury (AKI), in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Between March 2020 and March 2021, 100 adult patients who scheduled to undergo cardiac surgery with mild hypothermic CPB were enrolled to this prospective observational study. StO2 was continuously monitored at the right forearm and ipsilateral VOT procedure was performed before initiation of CPB, at the time before weaning from CPB, and at the end of surgery. Preoperative and intraoperative factors, along with StO2-VOT parameters, were evaluated for their independent association with the occurrence of AKI following cardiac surgery. StO2-VOT parameters were also compared between patients with hyperlactatemia (peak blood lactate ≥ 4 mmol/L) and those without hyperlactatemia.

In our patient population (n = 87), 13.79% (12/87) patients developed AKI after surgery. Multivariable analysis revealed that CPB time and post-CPB desaturation speed (D-speed) were independently associated with AKI. Post-CPB D-speed had an area under receiver operating characteristic (ROC) curve of 0.79 (95% CI, 0.66-0.93) with a cutoff value of 0.08%·min- 1 in predicting AKI. Patients with hyperlactatemia had longer pre-CPB T1 and higher D-speed during CPB. However, ROC analysis indicated that T1 and D-speed exhibited limited predictive capacity for hyperlactatemia. Patients with AKI exhibited an increased risk of prolonged ICU stays, postoperative stroke, reoperation, and in-hospital mortality.

NIRS monitoring combined with VOT shows promise in predicting postoperative AKI in patients undergoing cardiac surgery with mild hypothermic CPB.

ChiCTR1900021436 with registered date 21/02/2019.

Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients.

In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time point, sublingual microcirculation images were obtained using the incident dark field video microscope.

Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25-118) vs 86 (34-129) U/L, p = 0.035) and alanine aminotransferase (50 (26-160) vs 68 (35-172) U/L, p = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group.

Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol.

Background: Impaired systemic tissue oxygenation and microvascular perfusion are associated with adverse outcomes in patients with acute respiratory distress syndrome (ARDS). Tissue oxygenation and microvascular reactivity, assessed by using near-infrared spectroscopy (NIRS), are correlated with disease severity in critically ill populations. This study aimed to detect alterations in these factors and their ability to predict outcomes in patients with ARDS. Methods: We performed NIRS measurements on the first (Day 1) and third (Day 3) days after ARDS diagnosis in 29 patients. We recorded the baseline forearm muscle oxygen saturation (StO2) and calculated the deoxygenation slope (Deoxy) and reoxygenation (Reoxy) slope. We divided the subjects into 28-day survival and non-survival subgroups to compare microcirculatory and oxygenation status differences. Results: The Day 1 StO2 values were significantly higher for the survival subgroup (60.1 ± 13.5%) than the non-survival subgroup (47.2 ± 6.9%) (p = 0.025). The ROC curve showed that Day 1 StO2 was a significant predictor of 28-day mortality (p = 0.025). There was no significant difference between the Deoxy and Reoxy slopes of the two groups (p > 0.05). The ROC of the Day 1 Reoxy slope for survival prediction (AUC0.74) was not statistically significant (p = 0.074). Conclusions: Our study showed poor survival outcomes in patients who had lower skeletal muscle StO2 values in early-stage ARDS. NIRS measurements may provide prognostic value for the survival outcomes in patients with this syndrome.

Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI -0.49 to -0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).

The aim of this study is to investigate the predictive value of indicators associated with microcirculation, capillary refill time (CRT), perfusion index (PI), and mottling score, on the prognosis of patients with septic shock.

A retrospective clinical study was conducted encompassing 78 patients diagnosed with septic shock and admitted to the Department of Critical Care Medicine at our hospital from January 2019 to January 2022. The study collated the clinical data of these patients, focusing on macrocirculatory hemodynamic parameters and microcirculatory indices. The parameters of interest were recorded at 0, 6, 24, and 48 h post-admission, including heart rate, mean arterial pressure (MAP), venous-to-arterial carbon dioxide partial pressure difference, superior vena cava oxygen saturation, lactic acid (LAC), CRT, PI, and mottling score. The enrolled patients were stratified into two cohorts based on the 28-day mortality rate: a survival group and a mortality group. A non-parametric statistical test was employed to compare the CRT, PI, and mottling score between the two groups. Furthermore, the predictive value of these microcirculatory indicators for mortality in septic shock patients was assessed using receiver operating characteristic (ROC) curve analysis. This methodology allowed for the evaluation of the prognostic accuracy of CRT, PI, and mottling score as indicators for mortality in the context of septic shock.

The vasoactive drug dose, PI, LAC, mottling score, and CRT upon admission in the survival group were significantly better than those in the mortality group at hour 6 of treatment, hour 24 of treatment, and hour 48 of treatment (P < 0.05). The predictive value of the three microcirculatory indicators at various time points was highest for the Perfusion Index (PI) at 48 h of treatment, the mottling score at 24 h of treatment, and the Capillary Refill Time (CRT) upon admission. The Area Under the Curve (AUC) for PI at 48 h of treatment was 0.941 (0.885-0.996), with a sensitivity of 90.9 % and a specificity of 94.1 %. For the mottling score at 24 h of treatment, the AUC was 0.889 (0.805-0.972), with a sensitivity of 82.4 % and a specificity of 88.6 %. The AUC for CRT upon admission was 0.872 (0.788-0.956), with a sensitivity of 91.2 % and a specificity of 77.3 %. Among the three indicators: PI, mottling score, and CRT, PI at hour 48 of treatment had the highest predictive value for the prognosis of patients with septic shock.

Microcirculatory indicators have specific predictive value for the prognosis of patients with septic shock.

This review discusses the pivotal role of microcirculation in maintaining tissue oxygenation and waste removal and highlights its significance in various pathological conditions. It delves into the cellular mechanisms underlying hemodynamic coherence, elucidating the roles of the endothelium, glycocalyx, and erythrocytes in sustaining microcirculatory integrity. Furthermore, the review gives comprehensive information about microcirculatory changes observed in cardiac surgery, sepsis, shock, and COVID-19 disease. Through comprehensive exploration, the review underscores the intricate relationship between microcirculation, disease states, and clinical outcomes, emphasizing the importance of understanding and monitoring microvascular dynamics in critical care settings.

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (β -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (β -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (β -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (β -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research.

To assess microvascular reactivity during a skin thermal challenge early post-cardiac surgery and its association with outcomes.

Noninvasive physiological study.

Thirty-five-bed department of intensive care.

Patients admitted to the intensive care unit post-cardiac surgery.

Thermal challenge.

A total of 46 patients were included; 14 needed vasoactive or ventilatory support for at least 48 hours (slow recovery), and 32 had a more rapid recovery. Skin blood flow (SBF) was measured on the anterior proximal forearm using skin laser Doppler. A thermal challenge was performed by abruptly increasing local skin temperature from 37°C to 43°C while monitoring SBF. The ratio between SBFs at 43°C and 37°C was calculated to measure microvascular reactivity. SBF at 37°C was not significantly different in patients with a slow recovery and those with a rapid recovery, but SBF after 9 minutes at 43°C was lower (48.5 [17.3-69.0] v 85.1 [45.2-125.7], p < 0.01), resulting in a lower SBF ratio (2.8 [1.5-4.7] v 4.8 [3.7-7.8], p < 0.01). Patients with lower SBF ratios were more likely to have dysfunction of at least one organ (assessed using the sequential organ dysfunction score) 48 hours post-cardiac surgery than those with higher ratios: 88% versus 40% versus 27% (p < 0.01), respectively, for the lowest, middle, and highest tertiles of SBF ratio. In multivariable analysis, a lower SBF ratio was an independent risk factor for slow recovery.

Early alterations in microvascular reactivity, evaluated by a skin thermal challenge, are correlated with organ dysfunction. These observations may help in the development of new, simple, noninvasive monitoring systems in postoperative patients.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in case of potentially reversible cardiac failure and restores systemic hemodynamics. However, whether this is followed by improvement of microcirculatory perfusion is unknown. Moreover, critically ill patients have possible pre-existing microcirculatory perfusion disturbances. Therefore, this review provides an overview of alterations in sublingual microcirculatory perfusion in critically ill adult patients receiving VA-ECMO support. Pubmed, Embase (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched according to PRISMA guidelines. Studies reporting sublingual microcirculatory perfusion measurements in adult patients supported by VA-ECMO were included. Outcome parameters included small vessel density (SVD), perfused vessel density (PVD), perfused small vessel density (PSVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and the heterogeneity index (HI). The protocol was registered at PROSPERO (CRD42021243930). The search identified 1215 studies of which 11 were included. Cardiogenic shock was the most common indication for VA-ECMO (n=8). Three studies report increased PSVD, PPV, and MFI 24 hours after initiation of ECMO compared to pre-ECMO. Nonetheless, microcirculatory perfusion stabilized thereafter. Four out of four studies showed higher PSVD and PPV in survivors compared to non-survivors. Over time, survivors showed recovery of microcirculatory perfusion within hours of initiation of ECMO, whereas this was absent in non-survivors. Notwithstanding the limited sample, VA-ECMO seems to improve microcirculatory perfusion shortly after initiation of ECMO, especially in survivors. Further research in larger cohorts is needed to clarify the longitudinal effects of ECMO on microcirculatory perfusion.

Skin injuries are a major healthcare problem that are not well understood or prevented in the critically ill, suggesting that underappreciated variables are contributing. This pilot study tested the hypothesis that perfusion-related factors contribute to skin injuries diagnosed as hospital-acquired pressure injuries (HAPIs). A total of 533 adult patients were followed over 2574 critical care days (mean age 62.4, standard deviation (SD) 14.3 years, mean body mass index 30.4 (SD 7.4) kg/m2, 36.4% female). This was a secondary analysis of prospective, non-randomised clinical data from an intensive care unit at a large urban teaching hospital. Factors related to perfusion, specifically two or more infusions of vasopressors/inotropes, temporary mechanical circulatory support (MCS), extracorporeal membrane oxygenation, and durable MCS, were analysed to determine whether they were more strongly associated with HAPIs than immobility due to prolonged mechanical ventilation (>72 h) or operating room time (>6 h). Patients diagnosed with a HAPI had a statistically significant higher risk of being exposed to variables related to perfusion and immobility (P < 0.05 for each variable). Perfusion-related variables, except durable MCS, had a larger effect on skin breakdown (number needed to harm (NNH) 4-10) than immobility-associated variables (NNH 12-17). The finding that perfusion-related variables predicted HAPIs may warrant consideration of alternative diagnoses, such as skin failure due to impaired perfusion as a pathophysiological process that occurs concurrently with multisystem organ failure. Differentiation of skin injuries primarily from circulatory malfunction, rather than external pressure, may guide the development of more effective treatment and prevention protocols. This pilot study suggests that the contribution of perfusion to skin injuries should be explored further.

Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes.Trial registration NCT04169204.

The importance of microvascular imaging in diagnosis and therapeutic targeting of various diseases is increasingly recognized. The new approach emphasizes the need for holistic studies to understand the inter-organ vascular cross-talk. Here, we report on the development of a novel perfusion protocol which consistently delivers a micro-computed tomography contrast agent to micro-vessels of multiple organs in a single experimental animal. We describe the achieved repeatability of the perfusions, as well as the image analysis steps developed individually for each organ type. We also optimize image acquisition by investigating the compromise between shortening of the scanning time and preservation of the highest possible spatial resolution. Taking together, with the multi-organ perfusion, optimized image acquisition, and the conceived image analysis steps, we provide a comprehensive and reliable experimental protocol for studying vascular morphology and pathology in multi-organ diseases.

Multiple organ dysfunction syndrome (MODS) is one of the main causes of death in intensive care units. There is evidence that microcirculation in sepsis and coronary shock is regulated separately from hemodynamics. This study investigates the relationship between heart rate (HR), cardiac output (CO) and microcirculation in patients with MODS.

This is a partial analysis of the "MODIFY study" (Reducing Elevated Heart Rate in Patients With Multiple Organ Dysfunction Syndrome [MODS] by Ivabradine). During the period 05/2010-09/2011, the microcirculation of 46 patients with septic and coronary MODS was measured using the sidestream dark field technique on the day of inclusion and 96 h later. Patients were randomized into a control and ivabradine treatment group.

Overall, there is a relevant improvement in microcirculation over time small perfused vessels, SPV [%] on day 0, d0:56.5 ± 34.2/d4:73.2 ± 22.1 (p = 0.03); perfused vessel density, PVDsmall [1/mm2] d0:7.5 ± 5.0/d4:9.8 ± 3.4 (p = 0.04); proportion of perfused vessels, PPVsmall [%] d0:51.6 ± 31.6/d4:66.7 ± 21.8 (p = 0.04); microcirculatory flow index, MFI d0:1.7 ± 1.0/d4:2.2 ± 0.7 (p = 0.05). Administration of ivabradine shows no effect. In patients with coronary MODS, there is a relevant correlation between microcirculatory parameters and cardiac output (SPV [%]: r = 0.98, p = 0.004). Patients with coronary MODS show better microcirculation values at high heart rates (> 100 bpm), while patients with septic MODS show an opposite relationship.

The results indicate that in critically ill patients, depending on the genesis of the MODS, there are different relationships between HF or CO values, on the one hand, and the parameters of the microcirculation, on the other.

Circulatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.

Sublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.

54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.

Critically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

We evaluated time-varying perinatal risk factors associated with early (≤7 post-natal days) and late (>7 post-natal days) severe acute kidney injury (AKI) occurrence and duration.

A secondary analysis of Preterm Erythropoietin Neuroprotection Trial data. We defined severe AKI (stage 2 or 3) per neonatal modified Kidney Disease: Improving Global Outcomes criteria. Adjusted Cox proportional hazards models were conducted with exposures occurring at least 72 h before severe AKI. Adjusted negative binomial regression models were completed to evaluate risk factors for severe AKI duration.

Of 923 participants, 2% had early severe AKI. In the adjusted model, gestational diabetes (adjusted HR (aHR) 5.4, 95% CI 1.1-25.8), non-steroidal anti-inflammatory drugs (NSAIDs) (aHR 3.2, 95% CI 1.0-9.8), and vancomycin (aHR 13.9, 95% CI 2.3-45.1) were associated with early severe AKI. Late severe AKI occurred in 22% of participants. Early severe AKI (aHR 2.5, 95% CI 1.1-5.4), sepsis (aHR 2.5, 95% CI 1.4-4.4), vasopressors (aHR 2.9, 95% CI 1.8-4.6), and diuretics (aHR 2.6, 95% CI 1.9-3.6) were associated with late severe AKI. Participants who had necrotizing enterocolitis or received NSAIDs had longer severe AKI duration.

We identified major risk factors for severe AKI that can be the focus of future research.

Time-dependent risk factors for severe acute kidney injury (AKI) and its duration are not well defined among infants born <28 weeks' gestation. Over 1 in 5 infants born <28 weeks' gestation experienced severe AKI, and this study identified several major time-dependent perinatal risk factors occurring within 72 h prior to severe AKI. This study can support efforts to develop risk stratification and clinical decision support to help mitigate modifiable risk factors to reduce severe AKI occurrence and duration.

In clinical practice, there is vast knowledge regarding the evaluation of macrocirculatory parameters, such as systemic blood pressure and cardiac output, for the hemodynamic monitoring of patients. However, assessment of the microcirculation has not yet been incorporated into the bedside armamentarium. Hand-held intravital video microscopy enables the direct, noninvasive, evaluation of the sublingual microcirculation at the bedside, offering insights into the status of the systemic microcirculation. It is easily performed and may be employed in several clinical settings, providing immediate results that may help guide patient management. Therefore, the incorporation of hand-held intravital video microscopy into clinical practice may lead to tremendous improvements in the quality of care of critical, unstable patients or offer new data in the evaluation of patients with chronic diseases, especially those with microcirculatory involvement, such as occurs in diabetes.

Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters. Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature - tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured. Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters. In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.

Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients.

This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function.

The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 μm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS).

SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.

The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO2), microvascular flow index (MFI) and plasmatic D-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock.

Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.

Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock.

In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05).

The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage.

The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.

To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.

We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.

Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.

Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.

Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury.

This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function.

Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage.

Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Horses undergoing abdominal exploratory surgery are at risk of hypotension and hypoperfusion. Normal mean arterial pressure is used as a surrogate for adequate tissue perfusion. However, measures of systemic circulation may not be reflective of microcirculation. This study measured the mean arterial pressure, cardiac index, lactate, and four microcirculatory indices in six healthy, anesthetized adult horses undergoing elective laparotomies. The microcirculatory parameters were measured at three different sites along the gastrointestinal tract (oral mucosa, colonic serosa, and rectal mucosa) with dark-field microscopy. All macro- and microcirculatory parameters were obtained when the horses were normotensive, hypotensive, and when normotension returned following treatment with dobutamine. Hypotension was induced with increases in inhaled isoflurane. The horses successfully induced into hypotension did not demonstrate consistent, expected changes in systemic perfusion or microvascular perfusion parameters at any of the three measured gastrointestinal sites. Normotension was successfully restored with the use of dobutamine, while the systemic perfusion and microvascular perfusion parameters remained relatively unchanged. These findings suggest that the use of mean arterial pressure to make clinical decisions regarding perfusion may or may not be accurate.

A relative hypovolemia occurs during septic shock (SS); the early phase is clinically reflected by tachycardia and low blood pressure. In the prehospital setting, simple objective tools to assess hypovolemia severity are needed to optimize triaging.

The aim of this study was to evaluate the relationship between shock index (SI), diastolic SI (DSI), modified SI (MSI), and age SI (ASI) and 28-day mortality of patients with SS initially cared for in a prehospital setting of a mobile intensive care unit (MICU).

From April 6, 2016 through December 31, 2021, 530 patients with SS cared for at a prehospital MICU were analyzed retrospectively. Initial SI, MSI, DSI, and ASI values, that is, first measurement after MICU arrival to the scene were calculated. A propensity score analysis with inverse probability of treatment weighting (IPTW) method was used to assess the relationship between SI, DSI, MSI, and ASI and 28-day mortality.

SS resulted mainly from pulmonary, digestive, and urinary infections in 44%, 25%, and 17% of patients. The 28-day overall mortality was 31%. IPTW propensity score analysis indicated a significant relationship between 28-day mortality and SI (adjusted odds ratio [aOR] 1.13; 95% CI 1.01-1.26; p = 0.04), DSI (aOR 1.16; 95% CI 1.06-1.34; p = 0.03), MSI (aOR 1.03; 95% CI 1.01-1.17; p = 0.03), and ASI (aOR 3.62; 95% CI 2.63-5.38; p < 10-6).

SI, DSI, MSI, and ASI were significantly associated with 28-day mortality among patients with SS cared for at a prehospital MICU. Further studies are needed to confirm the usefulness of SI and SI derivates for prehospital SS optimal triaging.

To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock.

Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities.

Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article.

A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis?

Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

Sepsis is a systemic syndrome involving physiological, pathological, and biochemical abnormalities precipitated by infection and is a major global public health problem. Endothelial cells (ECs) dysfunction is a major contributor to sepsis-induced multiple organ failure. This bibliometric analysis aimed to identify and characterize the status, evolution of the field, and new research trends of ECs and sepsis over the past 20 years. For this analysis, the Web of Science Core Collection database was searched to identify relevant publications on ECs in sepsis published between January 1, 2002, and December 31, 2022. Microsoft Excel 2021, VOSviewer software, CiteSpace software, and the online analysis platform of literature metrology (http://bibliometric.com) were used to visualize the trends of publications' countries/regions, institutions, authors, journals, and keywords. In total, 4200 articles were identified and screened, primarily originating from 86 countries/regions and 3489 institutions. The USA was the leading contributor to this research field, providing 1501 articles (35.74 %). Harvard University's scientists were the most prolific, with 129 articles. Overall, 21,944 authors were identified, among whom Bae Jong Sup was the most prolific, contributing 129 publications. Additionally, Levi Marcel was the most frequently co-cited author, appearing 538 times. The journals that published the most articles were SHOCK, CRITICAL CARE MEDICINE, and PLOS ONE, accounting for 10.79 % of the total. The current emerging hotspots are concentrated on "endothelial glycocalyx," "NLRP3 inflammasome," "extracellular vesicle," "biomarkers," and "COVID-19," among others. In conclusion, this study provides a comprehensive overview of the scientific productivity and emerging research trends in the field of ECs in sepsis. The evidence supporting the significant role of ECs in both physiological and pathological responses to sepsis is continuously growing. More in-depth studies of the molecular mechanisms underlying sepsis-induced endothelial dysfunction and EC-targeted therapies are warranted in the future.

The objective of this meta-analysis was to compare the impact of a high-normal and a low-normal mean arterial pressure (MAP) target on outcomes in patients with sepsis or shock. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, two investigators conducted a thorough literature search across online databases, including PubMed, Cochrane Library, Web of Science, and EMBASE, spanning from inception to December 10, 2023. The assessed outcomes encompassed all-cause mortality, the need for renal replacement therapy, and the length of intensive care unit (ICU) stay. A total of four randomized controlled trials (RCTs) were included, involving 3507 participants with individual study participant counts ranging from 118 to 2463. The pooled analysis revealed no statistically significant difference in the risk of all-cause mortality between the two groups (Risk Ratio (RR): 0.94, 95% Confidence Interval (CI): 0.87 to 1.01). Furthermore, there was no disparity in the rates of renal replacement therapy and the duration of ICU stay between the high-normal and low-normal MAP groups. Our findings indicate no significant distinctions in mortality, rates of renal replacement therapy, or ICU stay duration between the two groups. However, future trials with larger sample sizes are warranted to comprehensively understand the nuanced effects of different MAP settings on outcomes in patients with sepsis and shock.

Growth failure due to infection in children is a major health problem throughout the world. It provokes a systemic immune response, with increased interleukin (IL)-6 and reduced IL-10. Lactoferrin (Lf) is a multifunctional iron-binding protein that can be found in whey protein inside formula milk such as oral nutrition supplement (ONS), which is able to upregulate anti-inflammatory cytokines (IL-10) and modulate pro-inflammatory cytokines. We conducted this study to investigate the effect of Lf supplementation in ONS on IL-6 and IL-10 levels in children with failure to thrive and infection.

We performed a quasi-experimental pre- and post-study in children aged 12-60 months old with failure to thrive due to infectious illness. The subjects received 400 ml of oral nutritional supplements (ONS, 1 ml equivalent to 1 kcal) each day for 90 days, and their parents received dietary advice and medication based on the underlying illness. Blood was drawn to measure IL-6 and IL-10 before and after the intervention.

There were 75 subjects recruited and divided into group-1 and group-2 based on age. The incidence of undernutrition was 37.33%. Lf in ONS intervention improved body weight and body length. Lf also reduced IL-6, although there was not a significant difference before and after the intervention. However, the IL-6 reduction was significantly higher in subjects with undernutrition compared with subjects with weight faltering. Pre-intervention IL-6 levels were higher in children with stunting than in children with normal stature. There was a greater change in IL-6 in children with severe stunting than in children with normal stature or stunting. IL-10 was significantly reduced after the intervention.

In addition to improving body weight and length, Lf supplementation in ONS improved immune response homeostasis by balancing IL-6 and IL-10 levels and by improving the IL-6/IL-10 ratio.ClinicalTrials.gov number ID: NCT05289674, dated May 3 rd 2022.

Sepsis is defined as the dysregulated immune response leading to multi-organ dysfunction and injury. Sepsis-induced acute kidney injury is a significant contributor to morbidity and mortality. Alamandine (ALA) is a novel endogenous peptide of the renin-angiotensin-aldosterone system. It is known for its anti-inflammatory and anti-apoptotic effects, but its functional and vascular effects on sepsis remain unclear. We aimed to investigate the effects of ALA, as a pre- and post-treatment agent, on lipopolysaccharide (LPS)-induced systemic and renal dysfunction and injury in the LPS-induced endotoxemia model in rats via functional, hemodynamic, vascular, molecular, biochemical, and histopathological evaluation. 10 mg/kg intraperitoneal LPS injection caused both hepatic and renal injury, decreased blood flow in several organs, and renal dysfunction at 20 h in Sprague-Dawley rats. Our results showed that ALA treatment ameliorated systemic and renal inflammation, reduced inflammatory cytokines, prevented the enhancement of the mortality rate, reversed vascular dysfunction, corrected decreased blood flows in several organs, and reduced renal and hepatic injury via inhibiting iNOS (inducible nitric oxide synthase) and caspase expressions in the kidney. In addition, expressions of different ALA-related receptors showed alterations in this model, and ALA treatment reversed these alterations. These data suggest that ALA's systemic and renal protective effects are achieved through its anti-inflammatory, anti-pyroptotic, and anti-apoptotic effects on hemodynamic and vascular functions via reduced iNOS expression.

Sepsis begins with vascular endothelial barrier breakdown and causes widespread organ failure. Protease-activated receptor 1 (PAR1) is an important target for modulating vascular endothelial permeability; however, little research has been undertaken in sepsis, and its putative molecular mechanism remains unknown. The vascular endothelial permeability was examined by detecting FITC-dextran flux. F-actin was examined by immunofluorescence (IF). PAR1, ERM phosphorylation, and RhoA/ROCK signaling pathway expression in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) line were examined by IF and Western blot. To develop the sepsis model, cecal ligation and puncture (CLP) were conducted. The PAR1 inhibitor SCH79797 was utilized to inhibit PAR1 expression in vivo. Vascular permeability in main organs weres measured by Evans blue dye extravasation. The pathological changes in main organs were examined by HE staining. The expression of PAR1, ERM phosphorylation, and the RhoA/ROCK signaling pathway was examined using IF, immunohistochemical and WB in CLP mice. In vitro, in response to LPS stimulation of HUVECs, PAR1 mediated the phosphorylation of ERM, promoted F-actin rearrangement, and increased endothelial hyperpermeability, all of which were prevented by inhibiting PAR1 or RhoA. Additionally, inhibiting PAR1 expression reduced RhoA and ROCK expression. In vivo, we showed that inhibiting PAR1 expression will reduce ezrin/radixin/moesin (ERM) phosphorylation to relieve vascular endothelial barrier dysfunction and thereby ameliorate multiorgan dysfunction syndrome (MODS) in CLP-induced septic mice. This study revealed that PAR1-mediated phosphorylation of ERM induced endothelial barrier dysfunction, which in turn led to MODS in sepsis, and that the RhoA/ROCK signaling pathway underlay these effects.

Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock.

This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis.

Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups.

Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.