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Effects of Fluid Resuscitation With 0.9% Saline Versus a Balanced Electrolyte Solution on Acute Kidney Injury in a Rat Model of Sepsis*

Zhou, Feihu MD, PhD1,2; Peng, Zhi-Yong MD, PhD1,3; Bishop, Jeffery V. BS1; Cove, Matthew E. MD1,4; Singbartl, Kai MD1,5; Kellum, John A. MD, MCCM1,3

doi: 10.1097/CCM.0000000000000145
Online Laboratory Investigations

Objective: To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis.

Design: Controlled laboratory experiment.

Setting: University laboratory.

Subjects: Sixty adult, male Sprague-Dawley rats.

Interventions: We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals.

Measurements and Main Results: Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury.

Conclusion: Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short-term survival when compared with 0.9% saline in this experimental animal model of sepsis.

1The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

2Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, China.

3The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

4Department of Cardiac Surgery, National University of Heart Center, Singapore.

5Department of Anesthesiology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA.

* See also p. 1009.

Drs. Zhou and Peng contributed equally to this article.

Dr. Peng received support for article research from the National Institutes of Health (NIH) (R01DK070910). Dr. Cove received support for article research from the NIH (T32HL007820). Dr. Singbartl consulted for Baxter and received support for article research from the NIH. His institution received grant support from the NIH and Baxter. Dr. Kellum consulted for Baxter and received support for article research from the NIH (R01DK070910). His institution received grant support from the NIH and Baxter (various grants to University of Pittsburgh). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart Lung and Blood Institute, or the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: kellumja@ccm.upmc.edu

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins