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Background: Impaired microcirculatory perfusion and tissue oxygenation during critical illness are associated with adverse outcome. The aim of this study was to detect alterations in tissue oxygenation or microvascular reactivity and their ability to predict outcome in critically ill patients using thenar near-infrared spectroscopy (NIRS) with a vascular occlusion test (VOT)., Methods: Prospective observational study in critically ill adults admitted to a 12-bed intensive care unit (ICU) of a University Hospital. NIRS with a VOT (using a 40 % tissue oxygen saturation (StO 2 ) target) was applied daily until discharge from the ICU or death. A group of healthy volunteers were evaluated in a single session. During occlusion, StO 2 downslope was measured separately for the first (downslope 1) and last part (downslope 2) of the desaturation curve. The difference between downslope 2 and 1 was calculated (delta-downslope). The upslope and area of the hyperaemic phase (receive operating characteristic (ROC) area under the curve (AUC) of StO 2 ) were calculated, reflecting microvascular reactivity. Outcomes were ICU and 90-day mortality., Results: Patients (n = 89) had altered downslopes and upslopes compared to healthy volunteers (n = 27). Mean delta-downslope was higher in ICU non-survivors (2.8 (0.4, 3.8) %/minute versus 0.4 (-0.8, 1.8) in survivors, p = 0.004) and discriminated 90-day mortality (ROC AUC 0.72 (95 % confidence interval 0.59, 0.84)). ICU non-survivors had lower mean upslope (141 (75, 193) %/minute versus 185 (143, 217) in survivors, p = 0.016) and AUC StO 2 (7.9 (4.3, 12.6) versus 14.5 (11.2, 21.3), p = 0.001). Upslope and AUC StO 2 on admission were significant although weak predictors of 90-day mortality (ROC AUC = 0.68 (0.54, 0.82) and 0.70 (0.58, 0.82), respectively). AUC StO 2  ≤ 6.65 (1st quartile) on admission was independently associated with higher 90-day mortality (hazard ratio 7.964 (95 % CI 2.211, 28.686)). The lowest upslope in the ICU was independently associated with survival after ICU discharge (odds ratio 0.970 (95 % CI 0.945, 0.996))., Conclusions: In critically ill patients, NIRS with a VOT enables identification of alterations in tissue oxygen extraction capacity and microvascular reactivity that can predict mortality., Trial Registration: NCT02649088, www.clinicaltrials.gov , date of registration 23rd December 2015, retrospectively registered.

Introduction: Microvascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2) delivery but rarely improves tissue O2 uptake in patients with sepsis. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused RBCs on microcirculation in patients with sepsis., Methods: In a prospective randomized trial, 20 patients with sepsis were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2 saturation (StO2) and tissue hemoglobin index (THI) were determined with near-infrared spectroscopy, and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage, and glycocalyx compounds (syndecan-1, hyaluronan, and heparan sulfate) were measured in the serum., Results: No differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When within-group changes were examined, microcirculatory improvement was observed only in patients who received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01), and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2 upslope increased in both groups. StO2 and StO2 downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03)., Conclusions: This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in patients with sepsis, although it suggests a more favorable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings., Trial Registration: ClinicalTrials.gov, NCT01584999.