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

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.

Fig. 1

Experimental timeline. Induction of peritonitis, followed by intervention (2-h infusion) and a total of 6 h of observation period after peritonitis induction (end of protocol)

Fig. 2

Kaplan–Meier curve depicting cardiovascular stability (no need for vasopressors) in the two groups throughout the experiment. Blue line represents intervention group and green line, control group

Fig. 3

Mean arterial pressure (MAP) (A), Modified Shock Index (MSI = HR/MAP) (B) and Diastolic Blood Pressure (C) in the two groups throughout the experiment from baseline and hourly after induction of peritonitis. White is intervention group and green is control group. No difference between groups (mixed model)

Fig. 4

Stroke volume variation (SVV) (A), cardiac output (CO) (B) and lactate (C) in the two groups throughout the experiment from baseline and hourly after induction of peritonitis. White is intervention group and green is control group. No difference between groups in SVV during the experiment, CO was higher in the intervention group than in the control group during the infusion and lactate increased more in the intervention group as compared to the control group (mixed model)