Preemptive Resuscitation for Eradication of Septic Shock

Sepsis is a challenging and elusive entity with a high mortality rate. As a syndrome,
clinicians are challenged to distinguish individuals with systemic infection warranting
further interventions from lower severity patients. Sepsis is now recognized as a
time-sensitive emergency, as patients stand the best chance for survival when effective
therapeutic interventions are delivered as early as possible.

Recent data has shown that in-hospital disease progression from sepsis to septic shock is
associated with a higher risk of morbidity and mortality than those with shock on initial
presentation. Yet, even when identified and treated with early aggressive interventions, the
development of septic shock is still associated with a mortality rate of 25-40%.

Although the presence of sustained arterial hypotension or serum lactate elevation (>4.0
mmol/L) are the currently recommended threshold to define the presence of overt shock and the
need for aggressive resuscitation, the investigators have shown that, in patients with
systemic infection, a moderate lactate elevation (2.0-3.9 mmol/L) is a common occurrence and
an important warning sign for the increased risk of disease progression and death. Sepsis
with an elevated lactate between 2.0-3.9, referred to as the "PRE-SHOCK" state, identifies
this population of patients at-risk for poor outcome. Current guidelines for sepsis
management do not recommend any specific resuscitation measures or therapies for this at-risk
population. This study marks the first in a series of investigations addressing the PRE-SHOCK
population to further define the adverse events within this cohort and to investigate novel
interventions to improve outcomes.

The investigators hypothesize that an early quantitative resuscitation strategy using a
protocol-directed IV fluid resuscitation will result in a significant reduction in the
development of worsening organ failure (including shock) and mortality compared to standard
care.

Inclusion Criteria:

- Emergency department patient with suspected or confirmed infection as primary reason
for admission

- Serum venous lactate 2.0 - 3.9 mmol/L

- Hospital admission planned

Exclusion Criteria:

- Age < 18 years

- Pregnancy

- Serum lactate ≥ 4.0 mmol/L

- Any vasopressor or inotrope requirement

- Mechanical ventilation or non-invasive positive pressure ventilation

- Chronic end-stage renal disease requiring hemodialysis

- Pulmonary edema as diagnosed by the primary care team

- Requirement for surgery within the treatment protocol timeframe

- Inability to obtain informed consent from subject or surrogate

- Patient to receive comfort measures only