When should physiologic derangements in sepsis be corrected?
In 2001, a seminal paper from Rivers et al. demonstrated that timely intervention, called “early goal-directed therapy” (EGDT), for the treatment of severe sepsis and septic shock improved outcomes.
In particular, treatment goals for improving tissue oxygenation, such as central venous pressure (CVP), mean arterial blood pressure (MAP), central venous oxygen saturation (ScvO 2 ), and blood lactate concentration, were achieved as a protocolized bundle within 6 hours after presentation.
These measures were codified as the surviving sepsis care bundles:
- a. To be completed within 3 hours:
- i. Measure lactate level
- ii. Obtain blood cultures prior to administration of antibiotics
- iii. Administer broad-spectrum antibiotics
- iv. Administer 30 mL/kg crystalloid solutions for hypotension or serum lactate ≥4 mmol/L
- b. To be completed within 6 hours:
- i. Add vasopressors (for hypotension refractory to initial fluid resuscitation) to maintain MAP ≥ 65 mm Hg
- ii. In the event of persistent arterial hypotension despite volume resuscitation (shock) or initial serum lactate ≥4 mmol/L:
- 1. Measure CVP with goal of ≥8 mm Hg
- 2. Measure ScvO 2 with a goal of ≥70%
- iii. Re-measure serum lactate if initial serum lactate was elevated (goal is normalization of lactate)
Since the institution of this bundle, the prognosis for patients with sepsis has improved, and one study demonstrated a fall in in-hospital mortality of 59%. However, in 2014, two studies (the PROCESS and ARISE studies) raised uncertainties regarding the efficacy of protocol-based EGDT in contributing to improvements in mortality. In the ARISE study, in critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. In the PROCESS study, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes as well. A third study in 2015 reached a similar conclusion that EGDT did not lead to improvements in outcome but was also associated with increased costs. Importantly, in all three of these studies, the majority of patients met the goals of the 3-hour bundle, highlighting the importance of rapid antibiotic administration and fluid resuscitation, and downgrading the benefits of hemodynamic targets, such as CVP and ScvO 2 .