Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1288-3) contains supplementary material, which is available to authorized users.

Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.

Study objective: We identify factors associated with delayed emergency department (ED) antibiotics and determine feasibility of a 1-hour-from-triage antibiotic requirement in sepsis.Methods: We studied all ED adult septic patients in accordance with Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures in 2 consecutive 12-month intervals. During the second interval, a quality improvement intervention was conducted: a sepsis screening protocol plus case-specific feedback to clinicians. Data were abstracted retrospectively through electronic query and chart review. Primary outcomes were antibiotic delay greater than 3 hours from documented onset of hypoperfusion (per Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures) and antibiotic delay greater than 1 hour from triage (per 2018 Surviving Sepsis Campaign recommendations).Results: We identified 297 and 357 septic patients before and during the quality improvement intervention, respectively. Before and during quality improvement intervention, antibiotic delay in accordance with Centers for Medicare & Medicaid Services measures occurred in 30% and 21% of cases (-9% [95% confidence interval -16% to -2%]); and in accordance with 2018 Surviving Sepsis Campaign recommendations, 85% and 71% (-14% [95% confidence interval -20% to -8%]). Four factors were independently associated with both definitions of antibiotic delay: vague (ie, nonexplicitly infectious) presenting symptoms, triage location to nonacute areas, care before the quality improvement intervention, and lower Sequential [Sepsis-related] Organ Failure Assessment scores. Most patients did not receive antibiotics within 1 hour of triage, with the exception of a small subset postquality improvement intervention who presented with explicit infectious symptoms and triage hypotension. Conclusion:The quality improvement intervention significantly reduced antibiotic delays, yet most septic patients did not receive antibiotics within 1 hour of triage. Compliance with the 2018 Surviving Sepsis Campaign would require a wholesale alteration in the management of ED patients with either vague symptoms or absence of triage hypotension.