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Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: Improved short-term survival and acid-base balance with Hextend compared with saline
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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“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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Metadata
- Authors
- Kellum, J. A.
- Affiliations
- University of Pittsburgh Medical Center (US)
- Corresponding author
- Kellum, John A.
- ORCID
- Kellum, John A.
- Venue
- Critical Care Medicine
- Published
- 2002-02
- Volume
- 30
- Issue
- 2
- Pages
- 300-305
- ISSN
- 0090-3493 (ISSN-L)
- 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 › Critical Care and Intensive Care Medicine › 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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