RESUMO
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/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician's discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. 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 6 h 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 6 h. There were no significantly different changes in syndecan-1 levels at 6 h 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, organ failure outcomes, or mortality between the two groups. CONCLUSIONS: In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. TRIAL REGISTRATION: Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064.
RESUMO
BACKGROUND: Degradation of the endothelial glycocalyx is recognized as a major part of the pathophysiology of sepsis. Previous clinical studies, mostly conducted in intensive care settings, showed associations between glycocalyx shedding and clinical outcomes. We aimed to explore the association of plasma syndecan-1, a marker of glycocalyx degradation, with the subsequent fluid requirements and clinical outcomes of emergency department patients with sepsis. METHODS: This was a post hoc analysis of a randomized trial of fluid resuscitation in the emergency department. The study was conducted in the emergency department of an urban 1500-bed tertiary care center. The data of 95 adults who were diagnosed with sepsis-induced hypoperfusion and had undergone baseline syndecan-1 measurement were included. The syndecan-1 levels at baseline (T0) and hour 6 (T6) were studied to characterize their association with clinical outcomes, including subsequent fluid administration, organ failure outcomes and mortality. RESULTS: The median syndecan-1 levels at T0 and T6 were 207 (IQR 135-438) and 207 (IQR 128-490) ng/ml, respectively. Syndecan-1 levels at T0 were correlated with baseline sequential organ failure assessment (SOFA) score (ρ = 0.35, p < 0.001). Syndecan-1 levels at both T0 and T6 were correlated with subsequent fluid administration over 24 and 72 h and associated with the diagnosis of septic shock, the maximum dose of vasopressors and the need for renal replacement therapy (p < 0.05). Higher syndecan-1 levels at T6 were associated with higher 90-day mortality (p = 0.03). CONCLUSIONS: In the emergency department, syndecan-1 levels were associated with fluid requirements, sepsis severity, organ dysfunction, and mortality.
