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

Abele Donati, Elisa Damiani, Michele Luchetti, Roberta Domizi, Claudia Scorcella, Andrea Carsetti, Vincenzo Gabbanelli, Paola Carletti, Rosella Bencivenga, Hans Vink, Erica Adrario, Michael Piagnerelli, Armando Gabrielli, Paolo Pelaia, Can Ince, Abele Donati, Elisa Damiani, Michele Luchetti, Roberta Domizi, Claudia Scorcella, Andrea Carsetti, Vincenzo Gabbanelli, Paola Carletti, Rosella Bencivenga, Hans Vink, Erica Adrario, Michael Piagnerelli, Armando Gabrielli, Paolo Pelaia, Can Ince

Abstract

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.

Figures

Figure 1
Figure 1
Individual changes in microcirculatory parameters after blood transfusion in non-leukodepleted and leukodepleted groups. (A) Microcirculatory flow index (in small vessels). (B) Total small vessel density. (C) Perfused small vessel density. (D) Proportion of perfused small vessels. (E) De Backer score. (F) Blood flow velocity. *P <0.05, Wilcoxon matched-pairs signed-rank test; #P <0.05, Mann-Whitney U test.
Figure 2
Figure 2
Individual changes in near-infrared spectroscopy (NIRS)-derived variables after blood transfusion in non-leukodepleted and leukodepleted groups. (A) Tissue oxygen saturation (StO2) baseline. (B) StO2 downslope (ischemic phase during the vascular occlusion test). (C) StO2 upslope (reperfusion phase during the vascular ocllusion test). *P <0.05, Wilcoxon matched-pairs signed-rank test.
Figure 3
Figure 3
Effects of the transfusion of non-leukodepleted and leukodepleted red blood cells (RBCs) on the endothelial glycocalyx. (A) Perfused boundary region. (B) Syndecan-1. (C) Heparan sulfate. (D) Hyaluronan. *P <0.05, Wilcoxon matched-pairs signed-rank test; #P <0.05, Mann-Whitney U test.
Figure 4
Figure 4
Correlation between perfused boundary region (PBR) and serum heparan sulfate (HS). (A) Correlation between all PBR values and serum HS values. (B) Correlation between changes in PBR and serum HS after blood transfusion.

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