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Cited by 249Sepsis Diagnosis and TreatmentTrauma, Hemostasis, Coagulopathy, ResuscitationHemodynamic Monitoring and Therapy

Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: Improved short-term survival and acid-base balance with Hextend compared with saline

Kellum, John A.·2002·Critical Care Medicine
DOI 10.1097/00003246-200202000-00006
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Abstract

OBJECTIVE: To compare resuscitation with 0.9% saline with Hextend, a synthetic colloid in a balanced electrolyte solution, in terms of acid-base status and survival time in an experimental model of septic shock in the rat. DESIGN: Randomized, open-label, controlled experiment. SETTING: University research laboratory. SUBJECTS: Sixty adult, male Sprague-Dawley rats. INTERVENTION: Animals were studied for 12 hrs after intravenous infusion of Escherichia coli endotoxin (20 mg/kg). Animals were volume resuscitated to maintain a mean arterial pressure >60 mm Hg using either 0.9% saline (n = 25), Hextend (n = 25), or lactated Ringer's (n = 10). MEASUREMENTS: Arterial blood gases and electrolytes were measured before and after resuscitation (0, 180, 360, and 540 mins after endotoxin infusion). Survival time was measured, up to 12 hrs. RESULTS: Mean survival time among animals treated with saline or Ringer's was 45% less compared with Hextend-treated animals: 391 +/- 151 mins and 362 +/- 94 mins vs. 567 +/- 140 mins, respectively, p <.0001. Overall survival (at 12 hrs) was 0% with saline or Ringer's vs. 20% with Hextend, p =.05. After resuscitation with saline, arterial standard base excess and plasma apparent strong ion difference were both significantly lower (-19.3 +/- 5.2 vs. -12.1 +/- 5.7, p <.001, and 23.0 +/- 6.2 vs. 30.3 +/- 2.9, p <.0001, respectively) and plasma Cl(-) was significantly higher (123 +/- 7 vs. 115 +/- 3 mmol/L, p <.0001) compared with Hextend. Resuscitation with Ringer's solution resulted in a standard base excess, and Cl(-) between that of saline and Hextend (-15.4 +/- 3.1, and 117 +/- 3, respectively). CONCLUSION: Compared with 0.9% saline, volume resuscitation with Hextend was associated with less metabolic acidosis and longer survival in this experimental animal model of septic shock.

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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 [327]

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Authors
Kellum, J. A.
Affiliations
University of Pittsburgh Medical Center (US)
Corresponding author
Kellum, John A.
ORCID
Kellum, John A.
Venue
Critical Care Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2002-02
Volume
30
Issue
2
Pages
300-305
ISSN
0090-3493 (ISSN-L)
DOI
10.1097/00003246-200202000-00006
OpenAlex
W2091601305
Cited by
249
References
28
Citations by year
2026: 6 · 2025: 4 · 2024: 4 · 2023: 13 · 2022: 9 · 2021: 11 · 2020: 2 · 2019: 4 · 2018: 18 · 2017: 6 · 2016: 5 · 2015: 11 · 2014: 12 · 2013: 8 · 2012: 6
FWCI
10.05
Type
journal article
Language
en
Open access
closed
Locations
  • Critical Care Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Center, University of Pittsburgh
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
Keywords
fluid resuscitation, hyperchloremic metabolic acidosis, septic shock, Hextend, synthetic colloids, 0.9% saline, lactated Ringer's solution, endotoxin, acid-base balance, strong ion difference, base excess, plasma chloride, short-term survival, rats, electrolyte balance
MeSH terms
Acid-Base Equilibrium, Acidosis, Analysis of Variance, Animals, Fluid Therapy, Hydroxyethyl Starch Derivatives, Male, Plasma Substitutes, Random Allocation, Shock, Septic, Sodium Chloride, Survival Analysis, Rats, Sprague-Dawley, Rats

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