The effects of resuscitation with different plasma products on endothelial permeability and organ injury in a rat pneumosepsis model

Daan P van den Brink; Derek J B Kleinveld; Annabel Bongers; Jaël Vos; Joris J T H Roelofs; Nina C Weber; Jaap D van Buul; Nicole P Juffermans

doi:10.1186/s40635-023-00549-9

The effects of resuscitation with different plasma products on endothelial permeability and organ injury in a rat pneumosepsis model

Intensive Care Med Exp. 2023 Sep 20;11(1):62. doi: 10.1186/s40635-023-00549-9.

Authors

Daan P van den Brink^{1

2}, Derek J B Kleinveld^{3

4}, Annabel Bongers³, Jaël Vos³, Joris J T H Roelofs^{5

6}, Nina C Weber³, Jaap D van Buul^{7

8}, Nicole P Juffermans^{3

9}

Affiliations

¹ Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. d.p.vandenbrink@amsterdamumc.nl.
² Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. d.p.vandenbrink@amsterdamumc.nl.
³ Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Intensive Care Medicine, Erasmus MC, Erasmus University of Rotterdam, Rotterdam, The Netherlands.
⁵ Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁶ Cardiovascular Sciences, Amsterdam UMC, Amsterdam, The Netherlands.
⁷ Molecular Cell Biology Lab at Department Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
⁸ Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS) at University of Amsterdam, Amsterdam, The Netherlands.
⁹ Department of Intensive Care Medicine, OLVG Hospital, Amsterdam, The Netherlands.

Abstract

Background: Endothelial injury and permeability are a hallmark of sepsis. Initial resuscitation of septic patients with crystalloids is associated with aggravation of endothelial permeability, which may be related either to low protein content or to volume. We investigated whether initial resuscitation with different types of plasma or albumin decreases endothelial dysfunction and organ injury in a pneumosepsis rat model compared to the same volume of crystalloids.

Study design and methods: Sprague-Dawley rats were intratracheally inoculated with Streptococcus pneumoniae. Twenty-four hours after inoculation, animals were randomized to 2 control groups and 5 intervention groups (n = 11 per group) to receive resuscitation with a fixed volume (8 mL/kg for 1 h) of either Ringer's Lactate, 5% human albumin, fresh frozen plasma derived from syngeneic donor rats (rFFP), human-derived plasma (hFFP) or human-derived solvent detergent plasma (SDP). Controls were non-resuscitated (n = 11) and healthy animals. Animals were sacrificed 5 h after start of resuscitation (T = 5). Pulmonary FITC-dextran leakage as a reflection of endothelial permeability was used as the primary outcome.

Results: Inoculation with S. Pneumoniae resulted in sepsis, increased median lactate levels (1.6-2.8 mM, p < 0.01), pulmonary FITC-dextran leakage (52-134 µg mL^-1, p < 0.05) and lung injury scores (0.7-6.9, p < 0.001) compared to healthy controls. Compared to animals receiving no resuscitation, animals resuscitated with rFFP had reduced pulmonary FITC leakage (134 vs 58 µg/mL, p = 0.011). However, there were no differences in any other markers of organ or endothelial injury. Resuscitation using different human plasma products or 5% albumin showed no differences in any outcome.

Conclusions: Resuscitation with plasma did not reduce endothelial and organ injury when compared to an equal resuscitation volume of crystalloids. Rat-derived FFP may decrease pulmonary leakage induced by shock.

Keywords: Albumin; Endothelial dysfunction; Plasma; Resuscitation; Sepsis; Shock; Transfusion.