Abstract
BackgroundFluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival. We have previously demonstrated that resuscitation with normal saline results in increased hepatic leukocyte recruitment in a murine model of sepsis. Given that clinical formulations of albumin are in saline, our objectives were to develop a novel balanced electrolyte solution specifically for sepsis and to determine if supplementing this solution with albumin would improve the inflammatory response in sepsis.MethodsWe developed two novel buffered electrolyte solutions that contain different concentrations of acetate and gluconate, named Seplyte L and Seplyte H, and administered these solutions with or without 5% albumin. Normal saline with or without albumin and Ringer’s lactate served as controls. Sepsis was induced by cecal ligation and puncture (CLP), and the liver microvasculature was imaged in vivo at 6 h after CLP to quantify leukocyte recruitment. Hepatic cytokine expression and plasma cell-free DNA (cfDNA) concentrations were also measured.ResultsSeptic mice receiving either Seplyte fluid showed significant reductions in hepatic post-sinusoidal leukocyte rolling and adhesion compared to normal saline. Hepatic cytokine concentrations varied in response to different concentrations of acetate and gluconate in the novel resuscitation fluids but were unaffected by albumin. All Seplyte fluids significantly increased hepatic TNF-α levels at 6 h compared to control fluids. However, Seplyte H exhibited a similar cytokine profile to the control fluids for all other cytokines, whereas mice given Seplyte L had significantly elevated IL-6, IL-10, KC (CXCL1), and MCP-1 (CCL2). Plasma cfDNA was generally increased during sepsis, but resuscitation fluid composition did not significantly affect cfDNA concentrations.ConclusionsElectrolyte concentrations and buffer constituents of resuscitation fluids can modulate hepatic cytokine production and leukocyte recruitment in septic mice, while the effects of albumin are modest during early sepsis. Therefore, crystalloid fluid choice should be an important consideration for resuscitation in sepsis, and the effects of fluid composition on inflammation in other organ systems should be studied to better understand the physiological impact of this vital sepsis therapy.
Highlights
Fluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival
Electrolyte concentrations and buffer constituents of resuscitation fluids can modulate hepatic cytokine production and leukocyte recruitment in septic mice, while the effects of albumin are modest during early sepsis
Differences between groups were considered to be statistically significant at p < 0.05. Novel resuscitation fluids Both of the novel Seplyte fluids remained stable under a variety of storage conditions over the course of 1 year, except for Seplyte H stored in plastic and exposed to light (Table 2)
Summary
Fluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival. Sepsis is characterized by severe inflammation along with organ dysfunction resulting from a dysregulated host response to infection and requires timely fluid resuscitation to improve patient survival. Fluid resuscitation is a key component of sepsis treatment, the ideal choice of intravenous fluid for early resuscitation of septic patients remains controversial [2, 3] Traditional crystalloid fluids, such as normal saline and Ringer’s lactate, remain as the most commonly used fluids by intensivists to manage sepsis and early septic shock [4, 5]. The Surviving Sepsis Campaign guidelines currently recommend crystalloids as first-line therapy and colloid solutions containing albumin when excessive fluid resuscitation is required [1]. 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
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