Table 2

The source of bias in terms of patient population and methodology of included trials

Rivers et alProCESS, ARISE and ProMISe
Illness severity heterogeneity*
 Fluid challenge before enrolment20 to 30 mL/kg1000 mL
 Blood lactate levels at baseline, mmol/L6.94.2–5.1
 APACHE II score at baseline20.415.8–20.7
 ScvO2, at baseline, %49.2NR
 ScvO2, 0–6 h, %6675.9†
 Mechanical ventilation 0–6 h, %53.819.0–22.4
 28-day mortality49.2%15.9–24.5%
Methodological differences
 CVC, %‡10050.9–61.9
 Corticosteroid useNone8–37%
 Antibiotics treatmentAfter enrolmentBefore enrolment
 Treatment in control groupWell-definedVague
 BlindingDouble blindedUnblinded to the ICU clinicians
 Time of conduction1997–20002008–2014 (EGDT recommendation in SSC Guidelines and the sepsis six)
  • *The data in control groups.

  • †The data in the EGDT group in ARISE.

  • ‡The central venous catheterisation in control group: standard therapy in Rivers et al and usual care in the trio of trials.

  • CVC, central venous catheterisation; EGDT, early goal-directed therapy; NR, not reported; ScvO2, central venous oxygen saturation; SSC, Surviving Sepsis Campaign.