Early-goal directed therapy in sepsis – a flawed concept?

Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine 2001; 345: 1368-1377.

RHH Journal Club. June 13th, 2013. Dr Wei Yang Low

Full-text article (if available)

Does early goal-directed therapy before admission to the intensive care unit effectively reduce the incidence of multiorgan dysfunction, mortality, and the use of health care resources among patients with severe sepsis or septic shock?

Study design

  • A single-centre, partially blinded, randomised controlled trial
  • HenryFordHospital, Detroit, USA



  • 263 patients with severe sepsis or septic shock
  • Single-centre (850-bed tertiary hospital)
  • From March 1997-March 2000


  • Block randomization to EGDT or standard therapy(control)
  • EDGT- 500ml crystalloid every 30 min to aim CVP 8-12mmHg. MAP aimed at 65-90mmHg with vasopressors/vasodilators. If ScvO2 <70%, red cells given to aim haematocrit >30.  If SvcO2 still <70%, start dobutamine.
  • Standard therapy- treated at clinician’s discretion according to a protocol for haemodynamic support (aim CVP 8-12mmHg, MAP >/=65mmHg, urine output >/=0.5ml/kg/hour
  • All patients had arterial and CVC inserted in emergency department

Primary outcome

  • In-hospital mortality
  • Power calculation- Assuming a rate of refusal or exclusion of 10 percent, a two-sided type I error rate of 5 percent, and a power of 80 percent, a sample size of 260 patients was required to permit the detection of a 15 percent reduction in in-hospital mortality

Secondary outcomes

  • resuscitation end points (Heart rate, CVP, MAP, ScvO2, Lactate, BE, Arterial pH)
  • organ-dysfunction scores (APACHE II, SAPS II, MODS )
  • coagulation-related variables (Hct, PT, APTT, Fibrinogen, FDP, D-dimer, platelet count)
  • administered treatments (Total fluids, red cell transfusion, vasopressor, inotrope (dobutamine), mechanical ventilation, PA catheterization)
  • consumption of health care resources (duration of vasopressor therapy, mechanical ventilation, length of hospital stay)


  • Were patients randomized? YES
  • Was randomisation concealed? YES
  • Were patients analysed in the groups to which they were randomised? YES (Intention-to-treat)
  • Were groups similar? YES
  • Were patients, clinicians, and outcome assessors aware of group allocation? Study investigators involved in clinical care not blinded to group allocation
  • Was follow up complete? YES


Primary outcome

  • In-hospital mortality rates were significantly higher in the standard-therapy group than in the early-therapy group

 Secondary outcomes

  • APACHE II, SAPS II, MODS scores were significantly higher in standard therapy group (p<0.001) at 7-72 hours
  • Higher PT, FDP and D-dimer concentrations in standard therapy groups (P=0.001, P<0.001, P=0.006 respectively)
  • During the initial six hours, the EGDT group:
  • Received significantly more fluid(P<0.001)
  • A greater percentage received red-cell transfusion (P<0.001) and inotropic support (P<0.001)
  • No significant difference in consumption in healthcare resources

Take home message/application of this research:

 Early goal directed therapy in the treatment of severe sepsis and septic shock reduces mortality at 60 days, although the same cannot be concluded in the longer term

Pressure to discharge patients from emergency department to inpatient wards/critical care (in the UK) may mean sub-optimal implementation of EGDT

From previous clinical experience, not all patients with severe sepsis/septic shock will have had CVC/Arterial lines inserted in ED

Problems with single-centred trial, bias in the sense that investigators were not blinded to the allocations and were involved in the care of patients


2 thoughts on “Early-goal directed therapy in sepsis – a flawed concept?

  1. Pingback: STH Breakfast Club: ARDS | STH Journal Club

  2. Pingback: STH Breakfast Club: Sepsis | STH Journal Club

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