Early goal-directed resuscitation of patients with septic shock: current evidence and future directions

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. 56.9^a (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. 18.9^a (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. 18.8^b (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. 29.2^b (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

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