Sepsis Resuscitation: Fluid Choice and Dose

Abstract

Sepsis is a common and life-threatening inflammatory response to severe infection treated with antibiotics and fluid resuscitation. Despite the central role of intravenous fluid in sepsis management, fundamental questions regarding which fluid and in what amount remain unanswered. Recent advances in understanding the physiologic response to fluid administration, and large clinical studies examining resuscitation strategies, fluid balance after resuscitation, colloid versus crystalloid solutions, and high- versus low-chloride crystalloids, inform the current approach to sepsis fluid management and suggest areas for future research.

Keywords: Albumin; Colloids; Crystalloids; Early goal-directed therapy; Fluid resuscitation; Sepsis.

Figure 1. Models of transvascular fluid exchange

In the original Starling model, the gradient of hydrostatic pressure from the capillary (P_c) to the interstitium (P_i) is opposed by the gradient of oncotic pressure from the capillary (π_c) to the interstitium (π_i), with filtration (K_f) and reflection (σ) coefficients. Understanding the web of membrane-bound glycoproteins and proteoglycans on the luminal side of endothelial cells (endothelial glycocalyx layer) suggests the low oncotic pressure under this semipermeable membrane (π_sg) is a more important regulator of transcapillary flow than the interstitial oncotic pressure.

Figure 2. Fluid administration in early goal-directed therapy trials

Volume of IV fluid during the first six hours in each early goal-directed therapy (EGDT) trial. Volume of fluid (black) is mean and standard deviation for all trials except ProMISe, which is median and interquartile range. Mortality (grey X) is through 60 days in ProCESS and 28 days in all other trials. PST is Protocol-based Standard Therapy.

Figure 3. Mortality of sepsis patients in trials of albumin administration

Relative risks of death by 28 days with albumin (n=603) versus saline (n=615) for patients with severe sepsis in the SAFE study, death by 90 days with albumin (n=888) versus crystalloid (n=893) in the ALBIOS study, and death by 28 days with albumin (n=399) versus saline (n=393) in the EARSS study are displayed with accompanying 95% confidence intervals. Adapted from Wiedermann, C. J. & Joannidis, M. Albumin replacement in severe sepsis or septic shock. N. Engl. J. Med. 371, 83 (2014); with permission.