A recent study reported an 8 percent increased progression to septic shock from severe sepsis for every hour antibiotics were delayed from triage.9 The potential to mitigate disease progression through early intervention is a core emergency medicine principle. However, prior to operationalization, the difference between retrospective sepsis database evaluations and clinical implementation should be considered. Observational and retrospective evaluation of prospectively collected data support early antibiotic administration impact as life-saving in septic shock patients.

However, benefit is less clear in less acutely ill patients. In the New York study, there was an hourly mortality benefit for treatment after diagnosis for septic shock. However, for severe sepsis, the confidence initiated with one, making the association with an hourly mortality benefit less clear.

In a recent randomized, controlled trial of approximately 2,700 patients, antibiotics were administered by EMS prior to emergency department arrival in 1,548. The difference in median time to antibiotics was approximately 96 minutes, resulting in no mortality difference between early EMS-administered antibiotics and usual care where antibiotics were administered after assessment in the ED.10

Attempts to meet a one-hour timeline in undifferentiated patients will result in antibiotics administration to patients who ultimately did not require them. The unanswered question is, would one or two doses of unnecessary antibiotics be harmful? That risk must be quantified and compared to the risk of antibiotics being potentially delayed in those who do need them while determining bacterial infection.

Current data are imperfect. One retrospective evaluation of gram-negative severe sepsis or septic shock found those who previously received antibiotics within 90 days of admission had an increased length of stay, increased mortality, and increased cost.11

At this time, adherence with the CMS measure of antibiotic administration within three hours from diagnosis of severe sepsis and septic shock is reasonable. An optimal goal of initiating antibiotics within one hour of septic shock diagnosis is also reasonable as the majority of data on time to antibiotics and benefit is are septic shock patients.

Fluid Volume and Type

There is currently an ongoing trial to assess restrictive (at least 2 L IV fluid) compared to liberal fluid therapy. Large-volume infusions with normal saline may cause hyperchloremic acidosis. After 2 L, changing to a more balanced solution such as lactated Ringer’s may be beneficial. Data surrounding albumin are conflicting because the meta-analyses performed often combine heterogeneous patient populations. If the patient is in septic shock, especially if cirrhotic, albumin may be of benefit after the first 2 L of crystalloid.12,13

Vasopressors

Norepinephrine is still the drug of choice in septic shock. However, with global myocardial dysfunction or baseline congestive heart failure, an inotrope may be beneficial.

Hydrocortisone, Thiamine, and Vitamin C

A small before-and-after evaluation of 47 patients reported reduced mortality. However, hypoglycemia case reports have been cited with high-dose vitamin C. Due to anti­oxidizing activity, patients with a normal serum glucose may have a point-of-care glucose reading that is falsely elevated. When treated, patients may become hypoglycemic. Although hypothesis generating, administration of high-dose vitamin C requires more extensive evaluation before general application.

Conclusion

Emergency medicine has impacted sepsis research in multiple areas, including but not limited to early sepsis recognition, treatment, pathogenesis, genetics, biomarkers, microcirculation, immunomodulation, quality improvement, and a new area of compassionomics where compassionate care is linked to better outcomes, lower cost, and less clinician burnout.14 A cursory literature search of ([Title]: septicemia OR septicaemia OR sepsis OR severe sepsis OR septic shock) OR ([Title]: pneumonia AND severe) AND ([All fields] Emergency) resulted in 2,036 total articles, broken down as follows:

• 1960–1989: 48 articles
  1990–1999: 116 articles
  2000–present: 1,872 articles

Emergency medicine has an increasing number of researchers with funding and multi-institutional networks investigating science at an amazing pace.