Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock: A pilot randomized, controlled trial☆
Introduction
Early resuscitation of patients with septic shock reduces death from sepsis [1]. The initial treatment strategy is complex and first requires the rapid identification of these patients. It follows with a package of care that includes early institution of broad-spectrum antibiotics and optimization of oxygen delivery with the administration of intravenous fluids, vasopressors, inodilators, and red blood cells to support blood pressure and optimize cardiac output [1].
Recent evidence suggests that the type of resuscitation fluid administered in this setting may impact clinical outcomes. The debate regarding crystalloid vs colloid fluid is now several decades old. It has reemerged because recent randomized trials and systematic reviews of the literature suggest that the most commonly used colloid fluid, hydroxyethyl starch, may cause harm through increasing the risk of acute kidney injury, the requirement for renal replacement therapy, and possibly death [2], [3], [4], [5]. In contrast, a subgroup analysis of patients with severe sepsis from the Saline versus Albumin for Fluid Evaluation [6] trial and a meta-analysis comparing albumin for fluid resuscitation with other fluids in patients with sepsis [7] suggest that the odds of death may be significantly reduced when albumin is used for fluid resuscitation.
With the hypothesis that early identification and resuscitation of patients with septic shock may have the greatest impact on reducing mortality, our investigative team is planning a large pragmatic international randomized, stratified controlled trial comparing the effectiveness of 5% albumin to 0.9% sodium chloride for resuscitation on 90-day mortality (Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock [PRECISE] randomized, controlled trial). To inform the design of this trial, we conducted a multicenter Canadian pilot study to examine the feasibility of conducting a large resuscitation trial in this setting. In this report, we summarize the study design, the feasibility, and lessons learned during the conduct of the PRECISE pilot trial.
Section snippets
Study design
We conducted a concealed, double-blind, randomized, controlled trial in 6 academic emergency departments (EDs) and intensive care units (ICUs) across Canada. Patients were stratified according to presentation in the ED or ICU for logistic reasons; the fluid boxes were made up ahead of time according to randomization lists so that they were immediately available for use in each department. Approval to conduct this trial was obtained from the research ethics boards at each participating site.
Screening and enrollment of participants
Participating sites screened 133 patients. A total of 51 eligible patients were recruited with staggered start dates between April 2009 and December 2009.
Reasons for exclusions
Eighty-three patients were excluded from the trial. One patient who was very unstable after enrollment was immediately withdrawn by the treating physician because the treating nurse was unable to open the vent on the intravenous tubing that allowed the free flow of study fluid. This patient received no study fluid before being withdrawn from
Discussion
Recruitment into our PRECISE pilot trial met our prespecified feasibility criteria to determine feasibility of conducting a phase III trial of sufficient size to assess the effect of treatment on 90-day mortality. Although recruitment rates into this pilot trial do not guarantee successful recruitment in the large trial, the collaborations formed and lessons learned have helped in the design of the larger trial and will aid in its timely completion. Moreover, the protocol was simple; protocol
Acknowledgments
The authors thank Jodi Peters for her help formatting this manuscript, Elham Sabri for her help with the statistical analyses, and the Canadian Critical Care Trials Group for their support and guidance of the PRECISE pilot trial and for their critical review of this manuscript. The authors also thank all of the PRECISE research coordinators, research pharmacists, and Blood Bank staff for their help with the PRECISE trial operations and with the preparation of study fluid.
Dr McIntyre holds a
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Conflicts of Interest: Dr McIntyre received joint funding from the Canadian Institute of Health Research and CSL Behring to hold 2 PRECISE planning meetings. Dr Finfer received partial funding for the SAFE trial and travel funding for industry sponsored and academic meetings from CSL Behring.