Early Recognition: The Rate-Limiting Step to Quality Care for Severe Sepsis Patients in the Emergency Department

Timely and Appropriate Antibiotics

In a landmark study published by Kumar and colleagues in 2006, the relationship between timing of antibiotics and mortality was established [49]. In 2731 adult septic shock patients, mortality increased 7.6% for every hour delay in effective antimicrobial administration. A striking finding, given that the study population was limited to patients cared for in the ICU, was the fact that only 50% of patients received appropriate antibiotics within 6 hours of onset of shock and nearly one-quarter of patients did not receive antibiotics until the 15th hour. As a direct result, in-hospital mortality was observed to be 58% in this study.

Over the ensuing decade, a series of studies have demonstrated a narrowing of the quality gap in this regard, and the result has coincided with a significant improvement in survival. In 2010, Gaieski and colleagues demonstrated a significant improvement in the prompt administration of antibiotic delivery in patients presenting to an ED with severe sepsis, with the median time from shock onset (sustained hypotension or lactate ≥ 4 mmol/L) to antibiotics down to 42 minutes [50]. Importantly, consistent with the Kumar study, time to appropriate antibiotics, rather than simply initial antibiotics, remained associated with in-hospital mortality independent of initiating early goal-directed therapy. In 2011, Puskarich and colleagues revealed that time to antibiotics continued to improve and, as a result, the investigators did not identify a relationship between time from triage to antibiotics and in-hospital mortality [51]. However, when antibiotics were delayed until after shock recognition, consistent with the study by Kumar and colleagues, survival decreased. Until recently, this important observation was challenging to operationalize clinically as little was known about how to facilitate risk-stratification of those at risk to develop shock. However, Capp and colleagues recently found that deterioration to septic shock 48 hours after ED presentation occurs in approximately one out of eight patients and identified gender (female), transient hypotension, and/or hyperlactatemia upon presentation as risk factors associated with such a deterioration [52].

As an essential element of sepsis care bundles, a focus on timely use of antibiotics in patients with suspected infection, has the potential to increase the use of antibiotics in the ED in patients determined subsequently to not be infected. To combat this acknowledged downstream effect, reconsideration of the utility of empiric antibiotics 48 to 72 hours after admission is required. This step can be accomplished through the use of a sepsis care pathway and/or a formal antibiotic stewardship program.

Quantitative Resuscitation

Rivers and colleagues, in a landmark 2001 trial, examined the effectiveness of a protocolized resuscitation strategy in the most proximal phase of severe sepsis and septic shock [53]. A distinguishing characteristic between the usual care arm and the intervention in this ED-based study, in addition to whether mixed central venous oxygen saturation was measured as a resuscitation end-point, was the inclusion of an ED provider at the bedside to attend to clinical management. The intervention, aimed at achieving physiologic targets, resulted in significantly more fluid resuscitation (3.5 L vs. 5.0 L within the first 6 hours) and a significant decrease in in-hospital mortality compared to the usual care arm (46.5 vs. 30.5%). The study revolutionized the culture and practice of sepsis care, in part by shining a light on the importance of timely resuscitation at the most proximal point of contact between the patient and the healthcare system. It also highlighted the importance of integrating serum lactate measurement into the early screening and risk stratification processes for sepsis care delivery.