Objective: Fluid responsiveness is proposed as a physiology-based method to titrate fluid therapy based on preload dependence. The objectives of this study were to determine if a fluid responsiveness protocol would decrease progression of organ dysfunction, and a fluid responsiveness protocol would facilitate a more aggressive resuscitation.
Methods: Prospective, 10-center, randomized interventional trial.
Inclusion criteria: suspected sepsis and lactate 2.0 to 4.0 mmol/L. Exclusion criteria (abbreviated): systolic blood pressure more than 90 mmHg, and contraindication to aggressive fluid resuscitation.
Intervention: fluid responsiveness protocol using Non-Invasive Cardiac Output Monitor (NICOM) to assess for fluid responsiveness (>10% increase in stroke volume in response to 5 mL/kg fluid bolus) with balance of a liter given in responsive patients.
Control: standard clinical care.
Outcomes: primary-change in Sepsis-related Organ Failure Assessment (SOFA) score at least 1 over 72 h; secondary-fluids administered. Trial was initially powered at 600 patients, but stopped early due to a change in sponsor's funding priorities.
Results: Sixty-four patients were enrolled with 32 in the treatment arm. There were no significant differences between arms in age, comorbidities, baseline vital signs, or SOFA scores (P > 0.05 for all). Comparing treatment versus Standard of Care-there was no difference in proportion of increase in SOFA score of at least 1 point (30% vs. 33%) (note bene underpowered, P = 1.0) or mean preprotocol fluids 1,050 mL (95% confidence interval [CI]: 786-1,314) vs. 1,031 mL (95% CI: 741-1,325) (P = 0.93); however, treatment patients received more fluids during the protocol (2,633 mL [95% CI: 2,264-3,001] vs. 1,002 mL [95% CI: 707-1,298]) (P < 0.001).
Conclusions: In this study of a "preshock" population, there was no change in progression of organ dysfunction with a fluid responsiveness protocol. A noninvasive fluid responsiveness protocol did facilitate delivery of an increased volume of fluid. Additional properly powered and enrolled outcomes studies are needed.