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

Abstract

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.

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Conflicts of interest

The authors declare no conflict of interest.

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Corresponding author

Correspondence to S. L. Peake.

Additional information

For the ARISE, ProCESS, ProMISe and PRISM Investigators.

Take-home message: EGDT for patients presenting to the ED with early septic shock does not decrease mortality but does increase ICU resource utilisation.

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Angus, D.C., Barnato, A.E., Bell, D. et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med 41, 1549–1560 (2015). https://doi.org/10.1007/s00134-015-3822-1

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Keywords

  • Early goal-directed therapy or EGDT
  • Resuscitation
  • Septic shock
  • Central venous oxygen saturation
  • Meta-analysis
  • Systematic review
  • Randomised clinical trials