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  • The Surviving Sepsis Campaign’s 1-hour bundle includes measuring lactate, obtaining blood cultures, administering broad-spectrum antibiotics, administering crystalloid for hypotension (MAP <65) or lactate ≥4 mmol/L, and administering vasopressors if patient was hypotensive during or after fluid resuscitation.

  • Prompt pathogen elimination through source control and antimicrobial therapy is an essential aspect of management.

  • Appropriate fluid resuscitation increases microvascular circulation, improves organ function, and augments cardiac output.

  • Norepinephrine is the guideline-favored first-line vasopressor, with either vasopressin or epinephrine as a second-line.

  • Many emerging novel therapies in sepsis address direct pathogen removal and inflammatory response attenuation.


Expedited appropriate antimicrobial administration, source control, and resuscitation are crucial to decrease morbidity and mortality from sepsis and septic shock. Ultimately, management relies on four fundamental concepts: pathogen elimination, inflammation attenuation, immune modulation, and end-organ support. Strategies to accomplish these goals continue to evolve with improvements in pathogen identification, markers of resuscitation, therapeutic interventions, and protocolization and standardization of sepsis care.


The 1991 Society of Critical Care Medicine (SCCM) and American College of Chest Physicians (ACCP) meeting established the conceptual framework for the definition of sepsis, which they classified as “a systemic inflammatory response to an infectious process.”1 With the advent of this widely recognized definition, standardized approaches to sepsis care emerged. Studies from the 1990s largely focused on hemodynamic goals and resuscitation targets once patients were in the ICU, subsequent to their initial illness presentation. For example, a 1995 trial by the SvO2 Collaborative Group targeted different hemodynamic goals among critically ill patients, such as a normal cardiac index, supranormal cardiac index, or a normal SvO2, but no evidence of differences in morbidity or mortality resulted from this multicenter 762 patient trial.2 In the landmark 2001 early goal-directed therapy in the treatment of severe sepsis and septic shock, 263 patients were randomized to either early goal-directed therapy (EGDT) versus standard therapy. The intervention group received continuous ScvO2 monitoring and EGDT by targeting CVP 8 to 12 cmH2O, MAP ≥65, urine output ≥0.5mL/kg/h, and ScvO270%. The intervention group had a lower in-hospital, 28-day, and 60-day mortality compared with the standard of care group.3 Despite several limitations to Rivers’ study, its profound impact on protocolizing care and shifting the focus of sepsis management to early in the course of illness led to further standardization of early emergency department (ED) sepsis care, as illustrated by its adoption into the 2003 Surviving Sepsis Campaign guidelines.4

Between 2014 and 2015, three trials (ie, ProCESS, PROMISE, and ARISE) (Table 66-1) demonstrated that specific elements of EGDT did not improve septic patient outcomes compared with standard of care. The ProCESS trial randomized 1341 patients in 31 US EDs to either protocol-based EGDT (2001 EGDT protocol), protocol-based standard ...

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