What’s New: A Review of the Sepsis Literature

Author: David Bostick, MD, MPH (EM Resident Physician, University of Maryland) // Editor: Alex Koyfman, MD & Justin Bright, MD

There have been a number of new publications reviewing our approach to managing sepsis. Both the ProCESS Trial and ARISE trial published in 2014 editions of the New England Journal question whether invasive procedures and rigid protocols are required to have positive patient outcomes. Other studies included in this power review examine the importance of early antibiotic therapy, effects of different mean arterial pressure parameters, and impact of chloride heavy versus chloride restricted solutions.


A Randomized Trial of Protocol-Based Care for Early Septic Shock (aka “The ProCESS Trial”) The ProCESS Investigators. N Engl J Med 2014; 370: 1683-1693.

This is the first of two studies this year comparing early goal-directed therapy – or more specifically protocol based care – to usual care in patients with sepsis and its effect on mortality within 60 days. This randomized control trial performed in 31 academic hospitals randomized patients into 3 different treatment arms: protocol based early goal-directed therapy (EGDT), protocol based sepsis therapy without placement of central venous catheter, inotropes, or blood transfusion, and usual care which was defined as a bedside physician directing care without extra staff. They found that the 60-day mortality was similar between the three groups. The secondary outcomes examined which included 90-day and 1-year mortality and other markers of significant morbidity were also not significantly different.

Bottom Line: The overall suggestion from the ProCESS Trial is that a protocol driven treatment did not improve outcomes.

Goal-Directed Resuscitation for Patients with Early Septic Shock (aka “The ARISE Trial”) NEJM Oct 1 2014 (ePub); DOI: 10.1056/NEJMoa1404380

Hot off the presses, the ARISE trial compares early goal-directed therapy (EDGT) and standard therapy in a multi-center, unblinded, randomized controlled trial with 1,600 patients. The EDGT group had arterial lines and central venous catheters (CVCs) for ScvO2 and blood pressure monitoring within one hour of randomization. All interventions followed the 2001 Emmanuel Rivers protocol in his landmark paper. The usual care group had interventions such as arterial lines and CVCs placed as needed and treatment was at the discretion of the treating clinician. What they found was similar to the results of the PROCESS trial, in that there was no difference in mortality at 90 days. There was also no difference in many of the secondary outcomes which included hospital and ICU length of stay, duration of vasopressor infusion, or 28 day all-cause mortality. The EDGT group did have higher vasopressor requirements and received more fluid in the first 6 hours.
Bottom line: in septic patients the most important things are early identification, rapid and appropriate antibiotic therapy / source control, and fluid resuscitation.

Antibiotics in Severe Sepsis and Septic Shock

Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock from the First Hour: Results from a Guidelines Based Performance Improvement Program
Ferrer. Care Med 2014; 38:367-374

Early identification and appropriate antibiotic therapy has been shown to improve outcomes of patients with sepsis. This study by Ferrer examined the timing of antibiotics in sepsis and its effect on hospital mortality. Over 1,700 patients from 165 different ICUs across the US, Europe, and South America were examined by this retrospective observation cohort study which found a lower mortality in patients that received antibiotics within the first 2 hours of identification of sepsis. The morbidity and mortality risk increased for every hour that antibiotics were delayed.

Bottom-line: time-to-diagnosis and administration of antibiotics is crucial in patients with severe sepsis and septic shock.

SEPSISPAM: High versus Low Blood-Pressure Target in Patients with Septic Shock Asfar. NEJM. 2014;370 1583-1593.

Mean Arterial Pressure (MAP) goals have been identified as an important parameter in the management of hypotensive septic patients. One question this study wanted to answer was: does a higher MAP goal improve mortality in patients with septic shock? This randomized, open label controlled trial examined a MAP goal of 80-85 vs 65-70 with appropriate fluid resuscitation (no difference in fluid intake between groups); norepinephrine was the first line vasopressor in the vast majority of centers, with epinephrine used in the others. They found that there was no significant difference in the primary outcome of mortality at 28 days. Of the secondary outcomes, there was no significant difference in serious adverse outcomes or 90 day mortality. There was an increased rate of new onset atrial fibrillation and increased risk of renal complications in patients with chronic pre-existing hypertension that were maintained at the lower MAP goals.

Bottom line: the majority of patients with septic shock should have a MAP goal of 65-70 but there should be consideration of higher MAP goals in patients with hypertension to prevent AKI and renal replacement therapy (i.e. dialysis).

Balanced Solutions

Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults. Yunos et al. JAMA. 308.15 (2012): 1566-1572.

The concept of balanced solutions is new to the care of critically ill patients, and something that needs to be considered when managing patients with severe sepsis and septic shock. This article examined the use of chloride-liberal (including normal saline) vs chloride-restrictive (lactated ringer’s, plasmalyte, or albumin) IV fluids in the management of critically ill patients and specifically examined the incidence of acute kidney injury along with secondary outcomes being the need for renal replacement therapy, length of stay in hospital and ICU, and survival. What they found was that patients in the chloride-liberal group had higher creatinine levels, higher incidence of acute kidney injury, and need for renal replacement therapy.

Bottom line: consider using or switching to balanced solutions for resuscitation to avoid renal complications in septic patients.

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