Table 2.
Randomized trials of early goal-directed therapy for patients with septic shock
| Trial | Study setting | Sample size | Baseline characteristics of patients receiving EGDT | EGDT in the first 6 hours | Mortality | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| APACHE II score | Lactate, mmol/l | Source of sepsis | Total fluids, l | Vasopressor therapy, % | Red cell transfusion, % | Inotropic therapy, % | EGDT vs. usual care, % | |||
| Rivers et al. [7] | Single center in USA | 263 | 21.4 ± 6.9 | 7.7 ± 4.7 | 38.5 % lungs, 25.6 % urinary, 35.9 % other | 4.9 ± 2.9 | 27.4 | 64.1 | 13.7 | 44.3 vs. 56.9a (P = 0.03) |
| ProCESS [49] | 31 centers in USA | 1,341 | 20.8 ± 8.1 | 4.8 ± 3.1 | 31.9 % lungs, 22.8 % urinary, 45.3 % other | 2.8 ± 1.9 | 54.9 | 14.4 | 8.0 | 21.0 vs. 18.9a (P = 0.83) |
| ARISE [50] | 51 centers in Australia and New Zealand | 1,591 | 15.4 ± 6.5 | 6.7 ± 3.3 | 36.5 % lungs, 18.7 % urinary, 44.8 % other | 2.5 ± 1.2 | 66.6 | 13.6 | 15.4 | 18.6 vs. 18.8b (P = 0.90) |
| ProMISe [52] | 56 centers in England | 1,251 | 18.7 ± 7.1 | 7.0 ± 3.5 | 36.5 % lungs, 17.3 urinary, 46.2 % other | 2.2 ± 1.4 | 53.3 | 8.8 | 18.1 | 29.5 vs. 29.2b (P = 0.90) |
The Protocolized Care for Early Septic Shock (ProCESS), Australasian Resuscitation in Sepsis Evaluation (ARISE), and Protocolised Management of Sepsis (ProMISe) trials failed to replicate positive findings of the original trial by Rivers and colleagues [7]. The study by Rivers and colleagues was conducted at a single emergency department in a low-income community of Detroit, Michigan. It had a high control group mortality rate, which likely reflects health problems unique to an impoverished patient population as well as delays in treatment. Still, a subgroup analysis in the ARISE trial showed that early goal-directed therapy (EGDT) did not improve mortality in patients with increased disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) score >25, n = 69). Control group mortality rates were markedly lower in the ProCESS, ARISE, and ProMISe trials, which may reflect broad shifts in clinical practice over the last decade toward earlier initiation of antibiotics and vasopressor therapy as well as conservative thresholds for blood transfusion. Indeed, the ARISE trial reported a median time of 70 minutes between initial presentation and administration of antibiotics in the EGDT group versus 67 minutes in usual care
aMortality at 60 days
bMortality at 90 days