ArticleAnnals of intensive care2025
Stewart's theory and acid-base changes induced by crystalloid infusion in humans: a randomized physiological trial.
Article in Annals of intensive care, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03507062 (Effect of Crystalloids With Different SID on Hemodilution, Plasmatic Acid Base Equilibrium and Urinary Electrolytes in Patients During General Anesthesia), which is not on this map. Cited by 7 papers.
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The trial behind it
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Effect of Crystalloids With Different SID on Hemodilution, Plasmatic Acid Base Equilibrium and Urinary Electrolytes in Patients During General Anesthesia
Who cites it
7 citing papers in PubMed.
- Effect of Ringer's Lactate versus normal saline irrigation on postoperative morbidity after surgical removal of mandibular impacted third molars: a randomized split-mouth clinical trial.BMC oral health · 2026Trial
- Comparison of two different bicarbonate replacement fluids during CVVH with RCA: a prospective, randomized, controlled trial.Intensive care medicine · 2025Trial
- Balanced crystalloids versus normal saline for initial fluid resuscitation in diabetic ketoacidosis: a systematic review and meta-analysis of randomized controlled trials.Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2026Review
- Reply to: Effective buffers in intravenous solutions: reconciling the acid-base effects of organic anions.Critical care (London, England) · 2026Article
- The Physiology, Pathophysiology, and Clinical Implications of Fluid Resuscitation in Critically Ill Patients.Cureus · 2026Review
- Plasma Bicarbonate as a Determinant of Fluid-Induced Acid-Base Changes in Postoperative Critically Ill Patients: A Retrospective Analysis.Journal of clinical medicine · 2026Article
- Buffers in intravenous solutions: is the source of bicarbonate a source of confusion?Critical care (London, England) · 2025Review
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Authors and funding
19 authors.
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Abstract
backgroundStewart's acid-base theory states that, under isocapnic conditions, crystalloid infusion affects plasma pH due to changes in strong ion difference and total weak acid concentration: a comprehensive study also assessing renal response and hemodilution effects has not been conducted in humans. We aimed to evaluate Stewart's approach during crystalloid infusion in humans.
methodsIn this randomized trial, patients undergoing surgery with minimal blood losses were randomized to receive to normal saline (chloride content 154 mEq/L, strong ion difference 0 mEq/L), lactated Ringer's (chloride content 112 mEq/L, strong ion difference 29 mEq/L) or Crystalsol (chloride content 98 mEq/L, strong ion difference 50 mEq/L): patients received 10 ml/kg immediately after intubation, and 20 ml/kg after 2 h. Plasma/urinary acid-base and electrolytes were measured before study start and then at prespecified timepoints. The primary endpoint was pH one hour after the second fluid bolus: secondary outcomes included urinary/plasmatic electrolyte concentrations and strong ion difference during the study.
resultsForty-five patients were enrolled (15 in each group). The extent of hemodilution achieved with the first (median [Interquartile range]: saline 9% [6-15], Ringer's 7% [4-9], Crystalsol 8% [5-12]) and the second fluid bolus (saline 13% [5-17], Ringer's 12% [9-15], Crystalsol 15% [10-20]) was not different between groups (p = 0.39 and p = 0.19, respectively). Patients in saline group received more chloride (449 mEq [383-495]) vs. Ringer's (358 mEq [297-419]) and Crystalsol groups (318 mEq [240-366]) (p = 0.001). One hour after the second bolus, pH was lower in saline group (7.34 [7.32-7.36]) vs. Ringer's (7.40 [7.35-7.43) and Crystalsol groups (7.42 [7.38-7.44]) (both p < 0.01), since plasma chloride increased significantly over time in saline group but not in Ringer's and Crystalsol groups. Overall chloride urinary excretion was not different between study groups (saline 36 mEq [28-64], Ringer's 42 mEq [29-68], Crystalsol 44 mEq [27-56], p = 0.60) but, at the end of experiments, urinary chloride concentration was higher and diuresis was lower in saline group vs. Ringer's and Crystalsol groups (p = 0.01, p = 0.04, respectively).
conclusionsConsistent with Stewart's approach, crystalloid solutions with high chloride content lower pH due to reduced strong ion difference, progressive hemodilutional acidosis and limited renal response to chloride load.
trial registrationRegistered on clinicaltrials.gov (NCT03507062) on April, 24th 2018.
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