The effects of a limited infusion rate of fluid in the early resuscitation of sepsis on glycocalyx shedding measured by plasma syndecan-1: a randomized controlled 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/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

Ventilator-Associated Pneumonia in Patients with COVID-19: A Systematic Review and Meta-Analysis

“…The full search output is available as Supplementary Material S3 . After the exclusion of duplicates and not relevant records, twenty studies were included in the systematic review and meta-analysis, for a total of 2611 patients with COVID-19 who developed at least one episode of VAP [ 9 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The process of inclusion and exclusion is detailed in the PRISMA flow diagram, provided in Figure 1 .…”

“…The characteristics of the included studies are provided in Table 1 . Eighteen studies had an observational retrospective design (18/20, 90%), of which five were multicenter [ 9 , 17 , 22 , 27 , 32 ] and thirteen were performed in a single center [ 15 , 16 , 19 , 20 , 21 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 ]. Two studies had a prospective observational design (2/20, 10%) and were multicenter.…”

“…Eleven of the included studies reported data on mortality in patients with COVID-19 and VAP [ 9 , 15 , 16 , 20 , 21 , 23 , 24 , 25 , 30 , 31 , 32 ]. The pooled estimated occurrence of mortality (at the longest available follow-up) was 42.7% (95% C.I.…”

“…Seven of the included studies reported data on ICU LOS in patients with COVID-19 and VAP [ 16 , 21 , 23 , 24 , 25 , 31 , 32 ], with an estimated summary mean of 28.58 days (95% C.I. 21.4–35.8; I 2 = 98%; Figure S3, Supplementary Material S2 ).…”

“…2.2–4.7; P = 0.015; I 2 = 67.7%; Figure 4 ). We also performed a sensitivity analysis including studies reporting data on mortality in patients with COVID-19 and VAP in comparison to the same patients’ cohort who did not develop VAP [ 15 , 16 , 20 , 21 , 23 , 25 , 30 , 31 ]. This unadjusted analysis found no significantly different risk of death in COVID-19 patients with VAP versus non VAP (OR 1.16; 95% C.I.…”