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Original Research: CRITICAL CARE MEDICINE |

Hyperchloremic Acidosis Increases Circulating Inflammatory Molecules in Experimental Sepsis*

John A. Kellum, MD, FCCP; Mingchen Song, MD, PhD; Eyad Almasri, MD
Author and Funding Information

*From the MANTRA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Correspondence to: John A. Kellum, MD, FCCP, University of Pittsburgh, School of Medicine, Department of Critical Care Medicine, 3550 Terrace St, Pittsburgh, PA 15261; e-mail: Kellumja@ccm.upmc.edu



Chest. 2006;130(4):962-967. doi:10.1378/chest.130.4.962
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Rationale: Hyperchloremic acidosis is common in the critically ill and is often iatrogenic. We have previously shown that hyperchloremic acidosis increases nuclear factor-κB DNA binding in lipopolysaccharide-stimulated RAW 264.7 cells. However, evidence that hyperchloremic acidosis leads to increased inflammation in vivo has been limited to nitric oxide.

Objectives: To determine if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase circulating inflammatory mediator levels in an experimental model of severe sepsis in rats.

Methods: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups infusion continued 8 h or until the animal died.

Measurements and main results: We measured arterial blood gases, whole-blood lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared to group 1, animals in groups 2 and 3 exhibited greater increase in all three cytokines, with the greatest increases seen with severe acidosis.

Conclusion: Moderate (SBE, – 5 to – 10) and severe (SBE, – 10 to – 15) acidosis, induced by HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in normotensive septic rats.

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