IntroductionMicrovascular 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.MethodsIn 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.ResultsNo 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).ConclusionsThis 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 registrationClinicalTrials.gov, NCT01584999

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BackgroundFree hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.MethodsThis is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.ResultsSimilar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).ConclusionsOld RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.Trial RegistrationClinicalTrials.gov NCT01584999

Background: Extracorporeal blood purification therapies have been proposed as a strategy to remove inflammatory mediators during sepsis, thus improving outcome. Objectives: We aimed to evaluate changes in cytokines, haemodynamics and microcirculation during blood purification with Cytosorb adsorber in septic patients. Methods: Prospective observational study on critically ill adult patients with sepsis/septic shock underwent renal replacement therapy (RRT) for acute renal failure and haemoadsorption with Cytosorb as adjunctive therapy for 24 h. Measurements were taken at baseline, after 6 and 24 h: haemodynamic parameters, arterial and central venous blood gases, plasma levels of tumour necrosis factor alpha, interleukin (IL) 1-beta, IL-6, IL-8 and IL-10. The sublingual microcirculation was assessed with sidestream dark field videomicroscopy to evaluate the perfused vessel density (PVD) and microvascular flow quality. Tissue oxygenation and microvascular reactivity were assessed with thenar near infrared spectroscopy (NIRS) with a vascular occlusion test. Results: Nine patients; plasma levels of IL-8 decreased at 24 h (p < 0.05 versus 6 h); no significant variation was found for other cytokines. Haemodynamic remained stable throughout the observation. Microvascular perfusion improved over time, with an increase in PVDs at 6 and 24 h (from 13.9 [13.3–16.4] to 15.7 [15–17.3] and 17 [14.8–18.6] mm/mm2 respectively, p = 0.003) and total vessel densities at 24 h (14.9 [13.9–16.9] vs. 17.9 [15.3–20], p = 0.0015). No significant variation was detected in NIRS-derived parameters. The Sequential Organ Failure Assessment score decreased from 12 ± 3 to 10 ± 1 at 24 h (p = 0.039). Conclusions: In septic patients undergoing RRT, haemoadsorption with Cytosorb seems to determine a decreasing in plasma levels of IL-8, although levels of other cytokines did not vary significantly, and an improvement of microcirculation despite no significant variation in macro-haemodynamics.

BackgroundUntil now, the prognostic value of microcirculatory alterations in critically ill patients has been mainly evaluated in highly selected subgroups. Aim of this study is to monitor the microcirculation daily in mixed group of Intensive Care Unit (ICU)-patients and to establish the association between (the evolution of) microcirculatory alterations and outcome.MethodsThis is a prospective longitudinal observational single-centre study in adult patients admitted to a 12-bed ICU in an Italian teaching hospital. Sublingual microcirculation was evaluated daily, from admission to discharge/death, using Sidestream Dark Field imaging. Videos were analysed offline to assess flow and density variables. Laboratory and clinical data were recorded simultaneously. A priori, a Microvascular Flow Index (MFI) < 2.6 was defined as abnormal. A binary logistic regression analysis was performed to evaluate the association between microcirculatory variables and outcomes; a Kaplan–Meier survival curve was built. Outcomes were ICU and 90-day mortality.ResultsA total of 97 patients were included. An abnormal MFI was present on day 1 in 20.6%, and in 55.7% of cases during ICU admission. Patients with a baseline MFI < 2.6 had higher ICU, in-hospital and 90-day mortality (45 vs. 15.6%, p = 0.012; 55 vs. 28.6%, p = 0.035; 55 vs. 26%, p = 0.017, respectively). An independent association between baseline MFI < 2.6 and outcome was confirmed in a binary logistic analysis (odds ratio 4.594 [1.340–15.754], p = 0.015). A heart rate (HR) ≥ 90 bpm was an adjunctive predictor of mortality. However, a model with stepwise inclusion of mean arterial pressure < 65 mmHg, HR ≥ 90 bpm, lactate > 2 mmol/L and MFI < 2.6 did not detect significant differences in ICU mortality. In case an abnormal MFI was present on day 1, ICU mortality was significantly higher in comparison with patients with an abnormal MFI after day 1 (38 vs. 6%, p = 0.001), indicating a time-dependent significant difference in prognostic value.ConclusionsIn a general ICU population, an abnormal microcirculation at baseline is an independent predictor for mortality. In this setting, additional routine daily microcirculatory monitoring did not reveal extra prognostic information. Further research is needed to integrate microcirculatory monitoring in a set of commonly available hemodynamic variables.Trial registration NCT 02649088, www.clinicaltrials.gov. Date of registration: 23 December 2015, retrospectively registeredElectronic supplementary materialThe online version of this article (10.1186/s13613-018-0411-9) contains supplementary material, which is available to authorized users.

Analysis of the microcirculation is currently performed offline, is time consuming and operator dependent. The aim of this study was to assess the ability and efficiency of the automatic analysis software CytoCamTools 1.7.12 (CC) to measure microvascular parameters in comparison with Automated Vascular Analysis (AVA) software 3.2. 22 patients admitted to the cardiothoracic intensive care unit following cardiac surgery were prospectively enrolled. Sublingual microcirculatory videos were analysed using AVA and CC software. The total vessel density (TVD) for small vessels, perfused vessel density (PVD) and proportion of perfused vessels (PPV) were calculated. Blood flow was assessed using the microvascular flow index (MFI) for AVA software and the averaged perfused speed indicator (APSI) for the CC software. The duration of the analysis was also recorded. Eighty-four videos from 22 patients were analysed. The bias between TVD-CC and TVD-AVA was 2.20 mm/mm (95 % CI 1.37-3.03) with limits of agreement (LOA) of -4.39 (95 % CI -5.66 to -3.16) and 8.79 (95 % CI 7.50-10.01) mm/mm. The percentage error (PE) for TVD was ±32.2 %. TVD was positively correlated between CC and AVA (r = 0.74, p < 0.001). The bias between PVD-CC and PVD-AVA was 6.54 mm/mm (95 % CI 5.60-7.48) with LOA of -4.25 (95 % CI -8.48 to -0.02) and 17.34 (95 % CI 13.11-21.57) mm/mm. The PE for PVD was ±61.2 %. PVD was positively correlated between CC and AVA (r = 0.66, p < 0.001). The median PPV-AVA was significantly higher than the median PPV-CC [97.39 % (95.25, 100 %) vs. 81.65 % (61.97, 88.99), p < 0.0001]. MFI categories cannot estimate or predict APSI values (p = 0.45). The time required for the analysis was shorter with CC than with AVA system [2'42″ (2'12″, 3'31″) vs. 16'12″ (13'38″, 17'57″), p < 0.001]. TVD is comparable between the two softwares, although faster with CC software. The values for PVD and PPV are not interchangeable given the different approach to assess microcirculatory flow.

BackgroundImpaired 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).MethodsProspective 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 (StO2) target) was applied daily until discharge from the ICU or death. A group of healthy volunteers were evaluated in a single session. During occlusion, StO2 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 StO2) were calculated, reflecting microvascular reactivity. Outcomes were ICU and 90-day mortality.ResultsPatients (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 StO2 (7.9 (4.3, 12.6) versus 14.5 (11.2, 21.3), p = 0.001). Upslope and AUC StO2 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 StO2 ≤ 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)).ConclusionsIn critically ill patients, NIRS with a VOT enables identification of alterations in tissue oxygen extraction capacity and microvascular reactivity that can predict mortality.Trial registrationNCT02649088, www.clinicaltrials.gov, date of registration 23rd December 2015, retrospectively registered.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1500-5) contains supplementary material, which is available to authorized users.

BACKGROUND: Despite several clinical index tests that are currently applied for airway assessment, unpredicted difficult laryngoscopy may still represent a serious problem in anesthesia practice. The aim of this systematic review and meta-analysis was to evaluate whether preoperative airway ultrasound can predict difficult direct laryngoscopy in adult patients undergoing elective surgery under general anesthesia. METHODS: We searched the Medline, Scopus, and Web of Science databases from their inception to December 2020. The population of interest included adults who required tracheal intubation for elective surgery under general anesthesia without clear anatomical abnormalities suggesting difficult laryngoscopy. A bivariate model has been used to assess the accuracy of each ultrasound index test to predict difficult direct laryngoscopy. RESULTS: Fifteen studies have been considered for quantitative analysis of summary receiver operating characteristic (SROC). The sensitivity for distance from skin to epiglottis (DSE), distance from skin to hyoid bone (DSHB), and distance from skin to vocal cords (DSVC) was 0.82 (0.74–0.87), 0.71 (0.58–0.82), and 0.75 (0.62–0.84), respectively. The specificity for DSE, DSHB, and DSVC was 0.79 (0.70–0.87), 0.71 (0.57–0.82), and 0.72 (0.45–0.89), respectively. The area under the curve (AUC) for DSE, DSHB, DSVC, and ratio between the depth of the pre-epiglottic space and the distance from the epiglottis to the vocal cords (Pre-E/E-VC) was 0.87 (0.84–0.90), 0.77 (0.73–0.81), 0.78 (0.74–0.81), and 0.71 (0.67–0.75), respectively. Patients with difficult direct laryngoscopy have higher DSE, DSVC, and DSHB values than patients with easy laryngoscopy, with a mean difference of 0.38 cm (95% confidence interval [CI], 0.17–0.58 cm; P = .0004), 0.18 cm (95% CI, 0.01–0.35 cm; P = .04), and 0.23 cm (95% CI, 0.08–0.39 cm; P = .004), respectively. CONCLUSIONS: Our study demonstrates that airway ultrasound index tests are significantly different between patients with easy versus difficult direct laryngoscopy, and the DSE is the most studied index test in literature to predict difficult direct laryngoscopy. However, it is not currently possible to reach a definitive conclusion. Further studies are needed with better standardization of ultrasound assessment to limit all possible sources of heterogeneity.