A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators

Purpose: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Methods: Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. Results: From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 [495/2134] versus control: 22.4 [582/2601]; pooled OR 1.01 [95 CI 0.88?1.16], P = 0.9, with heterogeneity [I2 = 57 ; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95 CI 0.86?1.15), P = 0.93] with no heterogeneity (I2 = 0.0 ; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95 CI 1.10?1.41]; P <0.001) and ICU admission [OR 2.19 (95 CI 1.82?2.65); P <0.001]. Including six non-ED randomised trials increased heterogeneity (I2 = 71 ; P <0.001) but did not change overall results [pooled OR 0.94 (95 CI 0.82 to 1.07); P = 0.33]. Conclusion: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.