Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock

Abstract

Background Currently, guidelines recommend initial resuscitation with intravenous (IV) crystalloids during severe sepsis/septic shock. Albumin is suggested as an alternative. However, fluid mixtures are often used in practice, and it is unclear whether the specific mixture of IV fluids used impacts outcomes. The objective of this study is to test the hypothesis that the specific mixture of IV fluids used during initial resuscitation, in severe sepsis, is associated with important in-hospital outcomes. Methods Retrospective cohort study includes patients with severe sepsis who were resuscitated with at least 2 l of crystalloids and vasopressors by hospital day 2, patients who had not undergone any major surgical procedures, and patients who had a hospital length of stay (LOS) of at least 2 days. Inverse probability weighting, propensity score matching, and hierarchical regression methods were used for risk adjustment. Patients were grouped into four exposure categories: recipients of isotonic saline alone (“Sal” exclusively), saline in combination with balanced crystalloids (“Sal + Bal”), saline in combination with colloids (“Sal + Col”), or saline in combination with balanced crystalloids and colloids (“Sal + Bal + Col”). In-hospital mortality was the primary outcome, and hospital LOS and costs per day (among survivors) were secondary outcomes. Results In risk-adjusted Inverse Probability Weighting analyses including 60,734 adults admitted to 360 intensive care units across the United States between January 2006 and December 2010, in-hospital mortality was intermediate in the Sal group (20.2%), lower in the Sal + Bal group (17.7%, P < 0.001), higher in the Sal + Col group (24.2%, P < 0.001), and similar in the Sal + Bal + Col group (19.2%, P = 0.401). In pairwise propensity score–matched comparisons, the administration of balanced crystalloids by hospital day 2 was consistently associated with lower mortality, whether colloids were used (relative risk, 0.84; 95% CI, 0.76 to 0.92) or not (relative risk, 0.79; 95% CI, 0.70 to 0.89). The association between colloid use and in-hospital mortality was inconsistent, and survival was not uniformly affected, whereas LOS and costs per day were uniformly increased. Results were robust in sensitivity analyses. Conclusions During the initial resuscitation of adults with severe sepsis/septic shock, the types of IV fluids used may impact in-hospital mortality. When compared with the administration of isotonic saline exclusively during resuscitation, the coadministration of balanced crystalloids is associated with lower in-hospital mortality and no difference in LOS or costs per day. When colloids are coadministered, LOS and costs per day are increased without improved survival. A large randomized controlled trial evaluating crystalloid choice is warranted. Meanwhile, the use of balanced crystalloids seems reasonable. (Anesthesiology 2015; 123:1385-93)

Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: An international cross-sectional study

“…[22] The majority of evidence to support the change in clinical practice to the use of buffered salt solutions is from observational and registry based studies. [11,13,14,23] Recent evidence from a cluster cross-over randomised trial that compared a proprietary buffered salt solution (Plasma-Lyte 148 ® , Baxter Healthcare, Australia) to saline did not find a difference between fluid groups on the primary outcome of risk of acute kidney injury or the secondary outcomes of renal replacement therapy and in-hospital mortality. [24] Of note the majority of patients included in the SPLIT trial were elective surgical admissions to the ICU and the volumes of fluid administered were small, raising the possibility of a type II error.…”

Sepsis associated acute kidney injury

“…Patients receiving albumin had higher central venous pressures over the first three days and a non-significant trend to decreased mortality but no difference in RRT rates across the two groups (18.7% v 18.2%; P=0.98) 120. Subsequent studies of albumin have also found modest improvements in outcomes such as hemodynamic variables but have not shown improvements in AKI or mortality 121122123124. This high quality literature has not shown significant benefit to albumin containing regimens, so their use cannot be recommended over less costly crystalloid solutions.…”

“…One retrospective cohort of 60 734 adults with septic shock found that patients receiving exclusively isotonic saline had higher inpatient mortality than those who were co-administered balanced solutions (20.2% v 17.7%; P<0.001) 124. Two large prospective trials have recently added to this literature 129130.…”

Resuscitation fluid composition affects hepatic inflammation in a murine model of early sepsis

“…The fact that commonly used resuscitation fluids may have serious adverse effects justifies the need to investigate how traditional fluids compare to emerging balanced fluids, electrolyte solutions containing ion and buffer concentrations that closely resemble those of healthy plasma [15–19]. Current evidence suggests that resuscitation with balanced fluids may reduce the risk of mortality in patients with sepsis [11, 20], but the physiological mechanisms involved are unclear.…”