50 Years of Sepsis

The past 50 years have been marked by increased understanding of the underpinnings of sepsis, its myriad manifestations, and optimal approaches to therapy.

Below, follow a timeline of sepsis research and treatment. Learn what your role is today in the effort to reduce and treat sepsis in adult and pediatric patients.



  • The pulmonary artery catheter was introduced for bedside measurement of cardiac output and intracardiac pressures, allowing characterization of the hemodynamic profile of septic shock.
  • The link between gram-negative bacteremia, endotoxemia, and manifestations of sepsis was established with the limulus lysate assay.



The deleterious clinical impact of infected central IV catheters in the ICU was recognized.



Animal models of sepsis emerged.



Indirect calorimetry and nitrogen balance were popularized for studying the metabolic response to sepsis.



An exotoxin from Staphylococcus aureus was identified as a cause of toxic shock syndrome and linked to tampon use.



Profound but reversible myocardial depression was reported in patients with septic shock.



  • Critical illness polyneuropathy was recognized, with sepsis as a major risk factor.
  • High-dose methylprednisolone failed to reduce mortality in patients with sepsis and septic shock.



The term “sepsis syndrome” was coined to represent infection-induced organ dysfunction.



Antimediator therapies showed promise in sepsis animal models, and a study of antiendotoxin therapy found an association with improved outcomes.



  • A consensus conference published the first definitions of sepsis.
  • Nitric oxide was named the molecule of the year as its role in the pathophysiology of sepsis continued to be elucidated.



The Sequential Organ Failure Assessment (SOFA) score and the Multiple Organ Dysfunction Score (MODS) emerged as inventories to quantify the severity of organ dysfunction in sepsis.



Large clinical trials of innovative sepsis therapies were unsuccessful.



  • Recombinant human activated protein C (rhAPC) was reported to decrease mortality in severe sepsis.
  • A single-center study demonstrated that early goal-directed therapy (EGDT) improved outcomes in sepsis-induced tissue hypoperfusion.



  • The Society of Critical Care Medicine (SCCM), the European Society of Intensive Care Medicine, and the International Sepsis Forum launched the Surviving Sepsis Campaign (SSC). The 2002 Barcelona Declaration set forth a plan to inform the public and government agencies, develop guidelines, and reduce mortality in sepsis.
  • Replacement therapy with hydrocortisone and fludrocortisone was found to reduce mortality and duration of vasopressor administration in patients with septic shock and relative adrenal insufficiency.



  • The first SSC guidelines for management of severe sepsis and septic shock were published. SSC leadership committed to updates every four years.
  • The first SSC sepsis bundles for the early detection and management of severe sepsis were introduced.



Each hour of delay in administering appropriate antibiotics to patients with septic shock was associated with increased mortality.



A second randomized trial of stress-dose corticosteroids in patients with less severe septic shock failed to validate a mortality reduction associated with replacement therapy.



A follow-up trial of rhAPC administration in patients with septic shock failed to reduce mortality at either 28 or 90 days.



Two large randomized trials of EGDT versus usual care in early septic shock showed no difference in outcomes.



An analysis of over 17,500 patients enrolled in the SSC international performance improvement program demonstrated an association between sepsis bundle compliance and mortality.



A third consensus conference published revised definitions of sepsis and septic shock and recommended eliminating the term “severe sepsis.”



A World Health Organization resolution recognized sepsis as a global health priority.



  • Two large multicenter randomized clinical trials supported the benefit of stress-dose steroids in patients with septic shock who persistently required moderate- to high-dose vasopressors.
  • SCCM commissioned an international task force to formalize and publish a definition of childhood sepsis.



The SSC released the first international sepsis guidelines for children.



  • The COVID-19 pandemic became the highest priority for ICU care. The SSC released guidelines for the care of critically ill patients with COVID-19.
  • The latest SSC guidelines for adult patients were released, with an increased emphasis on improving the care of sepsis patients after ICU discharge.