Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta‐Analysis

Abstract

This comprehensive review comparatively evaluates the safety and benefits of parenteral fluids used in resuscitation with a focus on sepsis. It also provides a random effects meta‐analysis of studies comparing restrictive resuscitation and usual care in sepsis with the primary outcome of mortality. In the septic patient, fluid therapy remains a complex interplay between fluid compartments in the body, the integrity of the endothelial barrier, and the inflammatory tone of the patient. Recent data has emerged describing the pharmacokinetics of fluid resuscitation, which can be affected by the above factors, as well as mean arterial pressure, rate of infusion, volume of fluid infusate, nature of the fluid, and drug interactions. Fluid overload in sepsis has been associated with vasodilation, kidney injury, and increased mortality. Restrictive resuscitation after the initial septic insult is an emerging practice. Our search strategy of Medline databases revealed six randomized studies in 706 patients that examined restrictive resuscitation in sepsis. Results of this meta‐analysis demonstrated no differences in mortality with restrictive resuscitation compared with usual care (30.6% versus 37.8%; risk ratio [RR] of 0.83 with 95% confidence interval [CI] of 0.66 to 1.05, respectively) but was limited by the small number of studies and larger quantities of pre‐randomization fluids. Another approach to address fluid overload is active (diuresis) de‐resuscitation strategies, which may shorten the need for mechanical ventilation and intensive care unit (ICU) length of stay. Data suggest that colloids may confer mortality benefit over saline in the most severely ill septic patients. Compared with isotonic saline, balanced resuscitation fluids are associated with a lower incidence of acute kidney injury and mortality. The benefits of balanced resuscitation fluids are most evident when higher volumes of fluids are utilized for sepsis. Clinicians should consider the above pharmacotherapeutic factors when selecting a fluid, its quantity, and rate of infusion.