Early Goal Directed Therapy

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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

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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”

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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

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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