Early Antibiotics and Fluids Are More Important than Strict Protocol Adherence in the Treatment of Sepsis

March 18, 2014

Early Antibiotics and Fluids Are More Important than Strict Protocol Adherence in the Treatment of Sepsis

  1. Ali S. Raja, MD, MBA, MPH, FACEP

Mortality was similar among patients in septic shock who were randomized to early goal-directed therapy, less invasive but protocolized standard care, or provider-directed usual care.

  1. Ali S. Raja, MD, MBA, MPH, FACEP

A landmark 2001 study demonstrated that early and aggressive treatment of patients with sepsis improved their outcomes (NEJM JW Infect Dis Dec 21 2001). However, the early goal-directed therapy (EGDT) bundle used in that study required invasive central venous pressure and central venous oxygen saturation monitoring, in addition to other treatments. To determine which aspects of EGDT are truly necessary, investigators in the NIH-funded ProCESS study randomized patients with septic shock at 31 U.S. emergency departments to one of three groups: EGDT, a less invasive 6-hour protocol involving peripheral access and slightly different hemodynamic goals, or provider-directed usual care.

The primary endpoint of 60-day mortality did not differ significantly among the three groups (21% for EGDT, 18% for protocol-based care, and 19% for usual care). Cumulative 90-day and 1-year mortalities also were similar among groups. Patients in the EGDT and protocol-based groups received more intravenous fluids and vasopressors than the usual-care group, however, 97% to 98% of patients in all three groups received antibiotics within 6 hours.


This result suggests that frequent monitoring of central venous pressure and central venous oxygen saturation does not improve care of patients with septic shock. The lesson for clinical practice is that the interventions of the 2001 Rivers study were important, but the diagnostic testing probably was not. Patients with septic shock require close attention by a vigilant physician and should be given as much isotonic crystalloid as they can tolerate, fast. Attention to early antibiotics, source-of-infection control, lung-protective ventilation, and patient safety are more likely to make a difference than invasive monitoring.

Dr. Raja practices in the same hospital as one of the study investigators but was not involved in the study.

Editor Disclosures at Time of Publication

  • Disclosures for Ali S. Raja, MD, MBA, MPH, FACEP at time of publication Consultant / Advisory board Diagnotion, LLC Speaker's bureau Airway Management Education Center Grant / research support NHLBI; Brigham and Women’s Hospital Eleanor and Miles Shore Award; Harvard Medical School Milton Foundation; DHHS/CMS; NIBIB Editorial boards Western Journal of Emergency Medicine Leadership positions in professional societies Society for Academic Emergency Medicine; Brigham and Women’s Physician Organization


Reader Comments (5)

dr dipak bhuktar Physician, Critical Care Medicine, india

agressive ,vigilent approach with use of bedside 2D echo , songraphy shall help a lot in defining short term goals .i think source control , early antibiotics ,fluid resuscitation play vital role in treatment strategy . goal shall be - 'PROTECT LUNGS ,PRESERVE KIDNEYS ' at any cost...

Fadhil Zwer Physician, Critical Care Medicine, retired intensivist

I believe that is very important to start fluid to repair hemodynmic state of patient and given an antibiotic at starting point of management of septic shock and thereafter going to other aspects of managements as a life saving maneuvers.

Matt Reavill Other, Other, ReavillMED
Competing Interests: I'm the inventor of a device to measures CVP and ScvO2.

If ED physicians think that this is the golden ticket to get them out of doing the central lines (they weren't doing anyway), they're wrong.

Waiting to aggressively treat Severe Sepsis until only after it's been determined to be Septic Shock is doing too little too late.

Air bags that deploy after the car crash have no effect on collission survivability either.

KURT KACZANDER Physician, Emergency Medicine

Agreed that you should be aggressive early; however you don't have to have a central line to do it. Pouring in fluid through an IO, or good 18 ga peripheral lines works just as well.
I'll gladly put in a central line.. just sometimes you don't have time ( multiple traumas..etc )..
We should put one in if we have time.. and it always should be treated aggressively if you suspect it.

carlos hecker Physician, Preventive Medicine, Community clinic

It would be very interesting to read the postings of physicians in different specialties (or subspecialties ). In spite of the many publications about the nearly inevitable complications of central venous monitoring not much has changed.

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