Renal protection in sepsis: Is hypertonic sodium (lactate) the solution?

Abstract

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Hypertonic sodium solutions are useful for minimizing secondary brain injury from cerebral edema but also attractive for “small-volume” resuscitation in severe hypovolemia and shock because they rapidly mobilize endogenous water from the intracellular reservoir, thereby reducing endothelial cell volume and restoring microcirculation. In an exhaustive study in endotoxic pigs, Duburcq et al. [1] showed that early fluid resuscitation with hypertonic sodium lactate (HSL) attenuated disseminated intravascular coagulation-associated renal microvascular thrombosis and improved renal function. HSL performed significantly better than 0.9% NaCl [normal saline (NS)] and hypertonic sodium bicarbonate (HSB). Two striking findings emanate from this study. First, resuscitation fluids substantially interfere with pathophysiological events that occur during sepsis. Fluids indeed have a direct and intimate contact with damaged and activated endothelium and may be involved in the early intricate endothelial-mediated inflammatory and coagulation processes that determine the course of sepsis (e.g., the intrinsic beneficial effect of 20% albumin infusion on skin endothelial function in septic shock patients [2]). The mechanism of action, however, remains hypothetical, clearly differs between fluids, and probably is multifactorial. Second, hypertonic solutions are not created equal. This is illustrated by the observation that HSB, despite equal amounts of sodium and similar alkalizing, osmotic, and anti-inflammatory effects as HSL, had no better effect on acute kidney injury (AKI) than NS. The study of Duburcq et al. suggests a poor protective renal effect of NS in early sepsis. In recent years, NS has been increasingly stigmatized as an undesirable and even detrimental resuscitation fluid. However, this kidneyunfriendly profile of NS is not reflected in clinical scenarios. Yunos et al. [3] linked NS administration to the development of hyperchloremic metabolic acidosis and AKI. However, lactated/balanced crystalloids and 20% albumin were substituted for 4% albumin, gelatin, and NS according to an unblinded before–after protocol. Which of these changes contributed to the improved renal outcome and whether unidentified confounders may have influenced the incidence of AKI is unknown. Infusion with 0.9% NS versus Plasma-Lyte® in healthy volunteers produced hyperchloremia and significant reductions in mean renal artery flow velocity and renal cortical tissue perfusion in the NS group. However, relevant AKI was not evidenced as shown by similar concentrations of an AKI biomarker in both infusion groups [4]. A meta-analysis assessing highversus low-chloride infusion in 6253 perioperative and critically ill patients found a significant but weak association between high-chloride-containing fluids and a higher incidence of AKI. Excluding the 2 most-weighted studies from this analysis, however, rendered the AKI endpoint non-statistically significant [5]. A subsequent cluster crossover randomized clinical trial did not demonstrate differences in AKI in intensive care (IC) patients who received either NS or Plasma-Lyte® [6]. The recent SALT cluster-randomized, multiple-crossover trial comparing the administration of similar volumes of NS and balanced crystalloids in 974 IC patients showed no difference in a composite “major kidney-related adverse events” endpoint including death, dialysis, and persistent renal dysfunction [7]. Importantly, none of the above studies could demonstrate an increased mortality rate in NS-treated patients. Open Access