A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.
Angus DC., Barnato AE., Bell D., Bellomo R., Chong C-R., Coats TJ., Davies A., Delaney A., Harrison DA., Holdgate A., Howe B., Huang DT., Iwashyna T., Kellum JA., Peake SL., Pike F., Reade MC., Rowan KM., Singer M., Webb SAR., Weissfeld LA., Yealy DM., Young JD.
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 [I(2) = 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 (I(2) = 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 (I(2) = 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.