The effects of limited infusion rate of fluid in the early resuscitation of sepsis on syndecan-1 shedding: a randomized controlled trial (life3s trial)

Abstract

Background: Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. Methods: A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/hr) or limited rate (10 ml/kg/hr) of fluid for the first 30 ml/kg fluid resuscitation. The primary outcome was the change in plasma syndecan-1 levels over six hours. Secondary outcomes included adverse events, organ failure and 90-day mortality. Results: We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in six hours in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35 – 52 ml/kg) vs. 53 ml/kg (IQR 46-64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first six hours. There were no significantly different changes in syndecan-1 levels at six hours between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66 – 1.02; p = 0.07). There were no significant differences in adverse events or organ failure outcomes or 90-day mortality between the two groups. Conclusions: In sepsis resuscitation, the administration of resuscitative fluid with the limited-rate strategy did not significantly mitigate the glycocalyx damages compared to the standard-rate approach.