Sepsis Series, part I
Sepsis: A Little History
Sepsis, a term originally used by Hippocrates around 400 BC, was derived form the Greek sepein, meaning, “make rotten,” and has been an ever-evolving medical concept. Originally viewed as an illness introduced by toxic air, advances in medicine have most recently allowed us to understand sepsis as a maladaptive systemic host response to infection that progresses along a spectrum of severity.
The last fifteen years have brought about sweeping changes in the way sepsis is viewed and managed.
First, there was the Rivers Early Goal Directed Therapy (EGDT) trial.
This trial placed emphasis on prompt identification of sepsis, aggressive fluid resuscitation, and early antibiotics with source control.
However, it also mandated use invasive hemodynamic monitoring and liberal administration of vasopressors, inotropes, and blood products for patients with persistent hypotension following fluid challenge or evidence of hypoprofusion based on a lactate >4 mmol/L1.
Not long after EGDT, the Surviving Sepsis Campaign (SSC) was developed to bring awareness to the subject and call for drastic reduction in sepsis mortality through implementation of EGDT.
Subsequent revisions have incorporated ever-evolving evidence on the topic and currently include recommendations on topics from choice of fluid for resuscitation (crystalloids) to the preferred vasopressor (NE 1st line, Epi 2nd line) to the role of steroids in sepsis (add IV hydrocortisone if fluids and pressors are unable to maintain adequate BP)2.
The changes developed and endorsed by EGDT and SSC led to significant reductions in sepsis related mortality, but controversy developed over various aspects of EGDT, particularly the required monitoring techniques and the risk imposed to certain patients by some elements of the protocol.
The concerns prompted development of a series of trials, PRoCESS, ARISE, and ProMIse, that aimed to compare EGDT vs usual care.
The trials all reached the same conclusion for the primary outcome of mortality, there was no difference between EGDT and usual care3,4,5.
These studies together support the argument that many of the advancements in early and aggressive sepsis management emphasized by the Rivers trial have become ingrained into current “usual care,” with increased emphasis on identification of sepsis, early fluids, and appropriate antibiotics with invasive monitoring and vasopressor support added based on the clinical picture.
1) Rivers et al. Early Goal Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. The New England Journal of Medicine. 2001. 345(19):1368-1377.
2) Dellinger et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Medicine 2013; 39 (2):165-228.
3) PRoCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. N Engl J Med 2014; 370:1683-1693.
4) ARISE Investigators. Goal-Directed Resuscitation for Patients with Early Septic Shock. N Engl J Med 2014; 371:1496-1506.
5) Mouncey at al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med 2015; 372:1301-1311.