Early Goal Directed Therapy
Rivers E et al. "Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock". The New England Journal of Medicine. 2001; 345:1368-1377 .
Link to Article: https://www.nejm.org/doi/full/10.1056/NEJMoa010307
Clinical Question
In adults with severe sepsis or septic shock, does the use of early goal-directed therapy (EGDT) reduce the mortality?
Type of Trial: RCT
Blinding: no blinding of clinicians, study personnel or patients
Setting: Single hospital in Detroit, Michigan from March 1997-March 2000
PICO
Population:
236 patients with severe sepsis or septic shock defined as:
>/= 2 SIRS features AND either SBP<90 mmHg after 20-30cc/kg IVF over 30 min OR blood LA>4 mmol/L
Excluded: Age<18 years, pregnancy, other acute neurological/cardiac/GI/respiratory pathology, CI to CVL insertion, uncured cancer, immunosupression, limitations defined for active care
Intervention:
EGDT for 6 hours
Remained in ED for 6 hours and protocolized therapy managed by an ED physician, two residents and three nurses
Oxygen +/- intubation and mechanical ventilation
CVL catheterization capable of measuring continuous SCVO2
500 cc fluid boluses until CVP 8-12 mmHg
Vasopressors or vasodilators until MAP 65-90 mmHg
If SCVO2<70%:
Transfused red cells until Hct > 30%
If still SCVO2 <70%
Dobutamine 2.5-20 microgram/kg/min until SCVO2>70%
Dobutamine limited or reduced if MAP<65mmHg or pulse>120/mi
Control:
Usual care for 6 hours without protocol - treatment at discretion of the clinician and patient admitted to ICU as soon as possible after consult + lines inserted
Oxygen +/- intubation and mechanical ventilation
CVL and arterial cathterization
Targets defined without treatment algorithim:
CVP>/= 8-12mmHg
MAP>/= 65 mmHg
UOP>/= 0.5 cc/kg/hr
Outcome:
Primary outcome: in-hospital mortality
Statistically and clinically significant in EGDT intervention group compared to control group (30.5% in intervention vs 46.5% in control, p=0.009)
Secondary outcomes: all favored EGDT
Severity of Sepsis (30.5% in intervention vs 46.5% in control, p=0.009)
28 day and 70 day mortality (30.5% in intervention vs 46.5% in control, p=0.009)
Cause of in-hospital death being CV collapse and MSOF (30.5% in intervention vs 46.5% in control, p=0.009)
Tertiary Data Collection
EGDT group received more fluid over 6 hour period, but there was no difference in total amount of fluid over 72 hours in either group
More red cell transfusions were given in EGDT group
Early inotropic use more prevalent in EGDT group (not statistically different over 72h period)
Vasopressor use more prevalent in usual care group
Intubation/ventilation more prevalent in usual care group
Conclusions
“Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock”
Strengths
Adequate trial design
90% completed study
Weaknesses
Single center study
Non-blinded
Intervention was a bundle of care and individual components not investigated separately
In-hospital mortality outcome had limitations; some patients will go to institutions or home to die
Lead author was a paid consultant for manufacturer of SCVO2 measuring CVL; has registered EGDT and Early goal-directed therapy as trademarks
Take Note
ProCESS, ARISE and ProMISe has changed the game; but prior to these trials, this trial was best evidence for EGDT
Lots of criticism and concerns for EGDT but despite this has become widespread standard of care
Would be nice to test individual elements
Overall, provides a way to treat patients with sepsis; but you must mindfully deviate
Sources:
https://www.thebottomline.org.uk