Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis

Annelie Barrueta Tenhunen; Jaap van der Heijden; Paul Skorup; Marco Maccarana; Anders Larsson; Anders Larsson; Gaetano Perchiazzi; Jyrki Tenhunen

doi:10.1186/s40635-023-00548-w

Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis

Intensive Care Med Exp. 2023 Sep 21;11(1):63. doi: 10.1186/s40635-023-00548-w.

Authors

Annelie Barrueta Tenhunen¹, Jaap van der Heijden², Paul Skorup³, Marco Maccarana⁴, Anders Larsson⁵, Anders Larsson⁶, Gaetano Perchiazzi^{2

6}, Jyrki Tenhunen²

Affiliations

¹ Department of Surgical Sciences, Division of Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden. annelie.barrueta@surgsci.uu.se.
² Department of Surgical Sciences, Division of Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
³ Department of Medical Sciences, Division of Infectious Diseases, Uppsala University, Uppsala, Sweden.
⁴ Department of Medical Biochemistry and Microbiology, The Biomedical Center, University of Uppsala, Uppsala, Sweden.
⁵ Department of Medical Sciences, Division of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
⁶ Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Abstract

Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.

Keywords: Animal model; Colloid; Fluid therapy; Glycocalyx; Inflammation.