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Cited by 235Sepsis Diagnosis and TreatmentRenal function and acid-base balanceAcute Kidney Injury Research

Hyperchloremic Acidosis Increases Circulating Inflammatory Molecules in Experimental Sepsis

Kellum, John A., Song, Mingchen, Almasri, Eyad·2006·Chest
DOI 10.1378/chest.130.4.962
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Abstract

Rationale Hyperchloremic acidosis is common in the critically ill and is often iatrogenic. We have previously shown that hyperchloremic acidosis increases nuclear factor-kappaB 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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  • Normal saline may cause hyperchloremic metabolic acidosis, renal vasoconstriction, increased cytokine secretion, and concern for acute kidney injury.

    “potential adverse effects that include hyperchloremic metabolic acidosis, renal vasoconstriction, increased cytokine secretion and concern about acute kidney injury (AKI) have led to increased interest in chloride-restrictive solutions, known as balanced or buffered solutions [326–330].”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [328]

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Authors
Kellum, J. A., Song, M., & Almasri, E.
Affiliations
University of Pittsburgh (US)
Corresponding author
Kellum, John A.
ORCID
Venue
Chest
Publisher
Elsevier BV
Published
2006-10
Volume
130
Issue
4
Pages
962-967
ISSN
0012-3692 (ISSN-L)
DOI
10.1378/chest.130.4.962
OpenAlex
W2122715588
Cited by
235
References
36
Citations by year
2026: 10 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 14 · 2021: 15 · 2020: 13 · 2019: 15 · 2018: 24 · 2017: 15 · 2016: 17 · 2015: 11 · 2014: 17 · 2013: 9 · 2012: 10
FWCI
4.39
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • CHEST Journal (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
hyperchloremic metabolic acidosis, sepsis, TNF-α, interleukin-6, IL-10, cecal ligation and puncture, hydrochloric acid infusion, standard base excess, cytokines, critically ill patients
MeSH terms
Acid-Base Equilibrium, Acidosis, Animals, Blood Pressure, Chlorides, Enzyme-Linked Immunosorbent Assay, Fluid Therapy, Hydrochloric Acid, Male, Shock, Septic, Tumor Necrosis Factor-alpha, Interleukin-6, Interleukin-10, Rats, Sprague-Dawley, Inflammation Mediators, Rats

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