Roberta Domizi

Alteration of the sublingual microvascular glycocalyx in critically ill patients

Glycocalyx degradation may contribute to microvascular dysfunction and tissue hypoperfusion during systemic inflammation and sepsis. In this observational study we evaluated the alteration of the sublingual microvascular glycocalyx in 16 healthy volunteers and 50 critically ill patients. Sidestream Dark Field images of the sublingual microcirculation were automatically analyzed by dedicated software. The Perfused Boundary Region (PBR) was calculated as the dimensions of the permeable part of the glycocalyx allowing the penetration of circulating red blood cells, providing an index of glycocalyx damage. The PBR was increased in ICU patients compared to healthy controls (2.7 [2.59-2.88] vs. 2.46 [2.37-2.59]μm, p<0.0001) and tended to be higher in the 32 septic patients compared to non-septics (2.77 [2.62-2.93] vs. 2.67 [2.55-2.75]μm, p=0.05), suggesting more severe glycocalyx alterations. A PBR of 2.76 showed the best discriminative ability towards the presence of sepsis (sensitivity: 50%, specificity: 83%; area under the receiver operating characteristic curve: 0.67, 95% CI 0.52-0.82, p=0.05). A weak positive correlation was found between PBR and heart rate (r=0.3, p=0.03). In 17 septic patients, a correlation was found between PBR and number of rolling leukocytes in post-capillary venules (RL/venule) (r=0.55, p=0.02), confirming that glycocalyx shedding enhances leukocyte-endothelium interaction.

From macrohemodynamic to the microcirculation

ICU patients need a prompt normalization of macrohemodynamic parameters. Unfortunately, this optimization sometimes does not protect patients from organ failure development. Prevention or treatment of organ failure needs another target to be pursued: the microcirculatory restoration. Microcirculation is the ensemble of vessels of maximum 100 μm in diameter. Nowadays the Sidestream Dark Field (SDF) imaging technique allows its bedside investigation and a recent round-table conference established the criteria for its evaluation. First, microcirculatory derangements have been studied in sepsis: they are mainly characterized by a reduction of vessel density, an alteration of flow, and a heterogeneous distribution of perfusion. Endothelial malfunction and glycocalyx rupture were proved to be the main reasons for the observed microthrombi, capillary leakage, leukocyte rolling, and rouleaux phenomenon, even if further studies are necessary for a better explanation. Therapeutic approaches targeting microcirculation are under investigation. Microcirculatory alterations have been recently demonstrated in other diseases such as hypovolemia and cardiac failure but this issue still needs to be explored. The aim of this paper is to gather the already known information, focus the readers attention on the importance of microvascular physiopathology in critical illness, and prompt him to actively participate to achieve a more comprehensive understanding of the issue.

Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

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

Thermodilution vs pressure recording analytical method in hemodynamic stabilized patients

PURPOSE Many mini-invasive devices to monitor cardiac output (CO) have been introduced and, among them, the pressure recording analytical method (PRAM). The aim of this study was to assess the agreement of PRAM with the intermittent transpulmonary thermodilution and continuous pulmonary thermodilution in measuring CO in hemodynamically stabilized patients. MATERIALS AND METHODS This is a prospective clinical study in a mixed medical-surgical intensive care unit (ICU) and in a postcardiac surgical ICU. Forty-eight patients were enrolled: 32 patients to the medical-surgical ICU monitored with PiCCO (Pulsion Medical System AG, Munich, Germany) and 16 were cardiac patients monitored with Vigilance (Edwards Lifesciences, Irvine, CA). RESULTS A total of 112 measurements were made. Ninety-six comparisons of paired CO measurements were made in patients hospitalized in medical-surgical ICU; 16, in cardiac surgical patients. The mean Vigilance-CO was 4.49 ± 0.99 L/min (range, 2.80-5.90 L/min), and the mean PRAM-CO was 4.27 ± 0.88 L/min (range, 2.85-6.19 L/min). The correlation coefficient between Vigilance-CO and PRAM-CO was 0.83 (95% confidence interval, 0.57-0.94; P < .001). The bias was 0.22 ± 0.55 L/min with limits of agreement between 0.87 and 1.30 L/min. The percentage error was 25%. Mean TP-CO was 6.78 ± 2.04 L/min (range, 4.12-11.27 L/min), and the mean PRAM-CO was 6.11 ± 2.18 L/min (range, 2.82-10.90 L/min). The correlation coefficient between PiCCO-CO and PRAM-CO was 0.91 (95% confidence interval, 0.83-0.96; P < .0001). The bias was 0.67 ± 0.89 L/min with limits of agreement -1.07 and 2.41 L/min. The coefficient of variation for PiCCO was 4% ± 2%, and the coefficient of variation for PRAM was 10% ± 8%. The percentage error was 28%. CONCLUSIONS The PRAM system showed good agreement with pulmonary artery catheter and PiCCO in hemodynamically stabilized patients.