Comparison of non-invasive strategies to drive fluid resuscitation in sepsis or septic shock: a meta-analysis of RCTs

Early fluid resuscitation reduces mortality in patients with sepsis or septic shock, but excessive fluid administration may prolong hospitalization and increase complications. Several non-invasive strategies have been proposed to guide fluid resuscitation, yet their comparative efficacy remains uncertain. We systematically searched PubMed and EMBASE through June 2025 to identify randomized controlled trials evaluating non-invasive strategies to guide fluid resuscitation in adult patients with sepsis or septic shock. Pairwise and network meta-analyses were conducted to assess short-term mortality. Length of stay (LOS) in intensive care unit (ICU) was also analyzed. 20 RCTs (2.435 patients) were included. In pairwise meta-analyses, lactate clearance-guided resuscitation was associated with reduced short-term mortality compared to ScvO₂ (RR 0.81, 95% CI 0.65–1.00; I2 = 0%). No significant difference in mortality was observed between capillary refill time versus lactate clearance (RR 0.82; 95% CI 0.65–1.04; I2 = 0%), passive leg-raising plus stroke volume versus usual care (RR 0.91, 95% CI 0.67–1.23; I2 = 14%), echocardiography versus usual care (RR 0.72, 95% CI 0.32–1.61; I2 = 70%), and inferior vena cava collapsibility versus usual care (RR 0.75, 95% CI 0.52–1.09; I2 = 19%). In network meta-analysis, none of the assessed strategies to guide fluid resuscitation reduced mortality compared to usual care. Heterogeneity was moderate. Non-invasive dynamic parameters—lactate clearance, along with capillary refill time and inferior vena cava collapsibility assessment—are promising, bedside-available tools for guiding fluid resuscitation in patients with sepsis or septic shock. Their broader use in clinical practice may be warranted, pending confirmation from high-quality studies.