Conservative Fluid Management After Sepsis Resuscitation: A Pilot Randomized Trial

Abstract

Rationale: The feasibility and clinical outcomes of conservative fluid management after sepsis resuscitation remain unknown.

Objectives: To evaluate the effect of a conservative fluid management protocol on fluid balance and intensive care unit (ICU)-free days among patients with sepsis.

Methods: In a single-center phase II/III randomized trial, we enrolled adults with suspected infection, ≥2 systemic inflammatory response syndrome criteria, and either shock (mean arterial pressure <60 mm Hg or vasopressors) or respiratory insufficiency (mechanical ventilation or oxygen saturation <97% and fraction of inspired oxygen ≥0.3). Patients were randomized 1:1 to usual care or a conservative fluid management protocol. The protocol restricted intravenous fluid administration during shock to treatment of oliguria or increasing vasopressor requirement. In the absence of shock, loop diuretic infusion targeted equal fluid input and output each study day. The primary outcomes were mean daily fluid balance (phase II) and ICU-free days (phase III).

Results: At the completion of phase II (n = 30), the difference in mean daily fluid balance between groups (-398 mL) was less than the prespecified threshold (-500 mL) and the trial was stopped. Patients in the conservative fluid management (n = 15) and usual care (n = 15) groups experienced similar cumulative fluid input (8450 mL vs 7049 mL; P = .90) of which only 14% was intravenous crystalloid or colloid. Loop diuretic infusion occurred more frequently in the conservative fluid management group (40% vs 0%; P = .02), and cumulative fluid output was 10 645 mL in the conservative fluid management group compared to 6286 mL in the usual care group (P = .39). Hemodynamic, respiratory, and renal function did not differ between the groups.

Conclusions: In this phase II trial, a conservative fluid management protocol did not decrease mean daily fluid balance by more than 500 mL among patients with sepsis.

Registration: Clinicaltrials.gov; NCT02159079.

Keywords: acute kidney injury; intravenous fluid; sepsis.

Conflict of interest statement

CONFLICTS OF INTEREST

All authors completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declared no potential conflicts of interest with the current work. W.H.S. reported serving on advisory boards for Venaxis, Inc., Ferring Pharmaceuticals, and Cempra Pharmaceuticals, and as a consultant for Abbott Point-of-Care. T.W.R. reported serving on an advisory board for Avisa Pharma, LLC and as the Director of Medical Affairs for Cumberland Pharmaceuticals, Inc.

Figures

Figure 1.. Flow of participants through the trial.

Of 192 patients screened, 30 met inclusion criteria without meeting exclusion criteria and were enrolled, randomized, followed, and analyzed. Two potentially eligible patients were excluded by study investigators, one receiving scheduled fluid boluses prior to amphotericin administration and one with septic shock in the context of severe mitral stenosis. SIRS = systemic inflammatory response syndrome, cardiopulmonary dysfunction criteria = shock (mean arterial pressure

Figure 2.. Fluid management by study group.

Cumulative fluid input (upper left panel), fluid output (upper right panel), and fluid balance (lower left panel) among patients in the conservative fluid management group (dotted line) and usual care group (solid line). The lower right panel displays the mean difference between groups in fluid balance on each study day. The diamond (mean) and bars (standard deviation) display the primary outcome of the difference between groups in mean daily fluid balance over the course of the trial. The numbers of patients in the conservative fluid management and usual care groups, respectively, were: 15 and 15 (day of enrollment), 14 and 14 (day 1), 10 and 9 (day 2), 7 and 8 (day 3), 5 and 3 (day 4), 4 and 3 (day 5), 2 and 1 (day 6), and 2 and 1 (day 7). The increase in cumulative fluid input in the conservative fluid management group on study days 7 and 8 resulted from a single patient who received 5,850 mL of oral free water over 48 hours for a sodium of 150 mmol/L.

Figure 3.. Cumulative Fluid Balance for Each Individual Patient.

For patients in the conservative fluid management group (left) and usual care group (right), the cumulative fluid balance is displayed for each study day. Data are censored at the time of death or transfer out of the intensive care unit.