Vasopressor therapy for septic shock after adequate fluid resuscitation in the emergency department: a systematic review and meta-analysis

Background: Septic shock is a critical emergency, and vasopressor timing after initial fluid resuscitation is under debate. Data from emergency department, prehospital, and intensive care studies benefit from earlier norepinephrine initiation. Methods: We performed a systematic review and meta-analysis of studies evaluating vasopressor therapy, norepinephrine in septic shock after fluid resuscitation, with focus on timing of initiation. Nine studies were included in the qualitative analysis, while studies with extractable event counts were entered into the mortality meta-analysis. Pooled risk ratios (RRs) were calculated for short-term and 28-day mortality. Results: Earlier vasopressor initiation was associated with better hemodynamic and clinical outcomes in the included studies, including faster shock control, lower fluid exposure, and less organ failure progression. In the pooled short-term mortality analysis of four studies, early vasopressor initiation was associated with lower mortality (RR 0.72, 95% CI 0.56–0.92; I²=0%). In the stricter 28-day mortality analysis of three studies, early initiation also favored survival (RR 0.66, 95% CI 0.51–0.86; I²=0%). Conclusion: Early norepinephrine initiation improved short-term outcomes in septic shock. More high-quality emergency department studies are needed to define the best timing threshold and confirm the effect on mortality.