Fluid Management in Sepsis

Abstract

Among critically ill adults, sepsis remains both common and lethal. In addition to antibiotics and source control, fluid resuscitation is a fundamental sepsis therapy. The physiology of fluid resuscitation for sepsis, however, is complex. A landmark trial found early goal-directed sepsis resuscitation reduced mortality, but 3 recent multicenter trials did not confirm this benefit. Multiple trials in resource-limited settings have found increased mortality with early fluid bolus administration in sepsis, and the optimal approach to early sepsis resuscitation across settings remains unknown. After initial resuscitation, excessive fluid administration may contribute to edema and organ dysfunction. Using dynamic variables such as passive leg raise testing can predict a patient's hemodynamic response to fluid administration better than static variables such as central venous pressure. Whether using measures of "fluid responsiveness" to guide fluid administration improves patient outcomes, however, remains unknown. New evidence suggests improved patient outcomes with the use of balanced crystalloids compared to saline in sepsis. Albumin may be beneficial in septic shock, but other colloids such as starches, dextrans, and gelatins appear to increase the risk of death and acute kidney injury. For the clinician caring for patients with sepsis today, the initial administration of 20 mL/kg of intravenous balanced crystalloid, followed by consideration of the risks and benefits of subsequent fluid administration represents a reasonable approach. Additional research is urgently needed to define the optimal dose, rate, and composition of intravenous fluid during the management of patients with sepsis and septic shock.

Keywords: fluid therapy; intensive care unit; sepsis; shock.

Figure 1.. Relationship between intracardiac pressure and stroke volume according to the Frank Starling Curve

The same increase in preload (ΔP) can either cause a significant increase in stroke volume (ΔSV) (a), or no significant increase in stroke volume (b, c) depending on the initial preload (starting point on the curve) (b) or the shape of the curve, such as a flattened curve from decreased contractility (c). Unfortunately, this simple view fails to capture all the ways in which intravenous fluid may affect stroke volume. P, preload; SV, stroke volume.

Figure 2.. Fluid administration in EGDT trials

Volume of intravenous fluid during the first 6 hours in each EGDT trial, including pre-enrollment fluid. Volume is presented as mean and standard deviation for all trials except ProMISe and SSSP-2, which are median and interquartile range. Mortality (gray X) is through 60 days in ProCESS and 28 days in all other trials. PST, protocol-based standard therapy or sepsis protocol therapy.

Figure 3.. Odds of death with use of balanced crystalloids vs saline for ICU patients with sepsis

SPLIT, SALT, and SMART are three randomized trials comparing the use of balanced crystalloids versus saline in the ICU. Odds ratios of in-hospital mortality are shown for SPLIT, odds ratios of 30-day in-hospital mortality are shown for SALT and SMART.

Figure 4.. Odds of death with albumin use in septic shock

Odds ratios for 90-day mortality are displayed for albumin compared to crystalloid for patients with septic shock. Subgroup analysis of patients with septic shock from the SAFE and ALBIOS trials suggests a possible mortality benefit with albumin use. In the SAFE study, patients in the albumin group were given 4% albumin rather than crystalloid. In the ALBIOS study, patients in the albumin group were given 20% albumin in addition to crystalloid to maintain a serum level of 30 g/L.