The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials

Wan-Jie Gu, Fei Wang, Jan Bakker, Lu Tang, Jing-Chen Liu

IntroductionThe Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial show no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality from sepsis.MethodsWe searched the PubMed, EMBASE, CENTRAL, and reference lists of articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.ResultsIn total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effect model (relative risk (RR) 0.83, 95% confidence interval (CI) 0.71 to 0.96, P =0.01, I2¿=¿56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that mortality benefit was seen only in the subgroup of early GDT within the first six hours (seven trials; RR 0.77, 95% CI 0.67 to 0.89, P =0.0004, I2¿=¿40%) but not in the subgroup with a late or unclear timing of GDT (six trials; RR 0.92, 95% CI 0.69 to 1.24, P =0.59, I2¿=¿56%). GDT was significantly associated with the use of dobutamine (five trials; RR 2.71, 95% CI 1.20 to 6.10, P =0.02).ConclusionsThe current meta-analysis suggests that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, due to the variable quality of the studies, strong and definitive recommendations can not be made.