Stewart’s theory and acid–base changes induced by crystalloid infusion in humans: a randomized physiological trial

Dell'Anna, AM; Grieco, DL; Dominedò, C; Cicetti, M; Cisterna, I; Festa, R; Lamacchia, R; Giannì, G; Filetici, N; Michi, T; Rossi, C; Alcaro, FD; Mele, A; Rocchi, A; Del Prete, D; Meluzio, MC; Tamburrelli, FC; Rossi, M; Antonelli, M

doi:10.1186/s13613-025-01473-9

Hemodynamics, fluids & transfusion

Stewart’s theory and acid–base changes induced by crystalloid infusion in humans: a randomized physiological trial

Ann Intensive CarePublished 22 Apr 2025Randomised controlled trial

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Authors' conclusion

Consistent 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.

Study context

Population: Patients undergoing surgery with minimal blood losses; 10 ml/kg after intubation and 20 ml/kg after 2 h
Participants: 45 patients

Comparison: Normal saline vs lactated Ringer's vs Crystalsol infusion
Salinen = 15
Ringer'sn = 15
Crystalsoln = 15
Primary endpoint: Plasma pH
Follow-up: 1 h after the second fluid bolus

Methodological detailsphysiological trial, three-arm

Physiological trial
Three-arm

Primary result

As reported in the abstract

pH · 1 h after the second bolus

Saline

7.34

median · IQR 7.32–7.36

Ringer's

7.40

median · IQR 7.35–7.43

Crystalsol

7.42

median · IQR 7.38–7.44

Saline vs Ringer's: P < 0.01 · Saline vs Crystalsol: P < 0.01

Secondary outcomes

Chloride received

Salinemedian 449 mEqIQR 383–495

Ringer'smedian 358 mEqIQR 297–419

Crystalsolmedian 318 mEqIQR 240–366

Overall urinary chloride excretion

Salinemedian 36 mEqIQR 28–64

Ringer'smedian 42 mEqIQR 29–68

Crystalsolmedian 44 mEqIQR 27–56

Median

Outcome	Saline	Ringer's	Crystalsol
Hemodilution after first bolus	9% (IQR 6–15)	7% (IQR 4–9)	8% (IQR 5–12)
Hemodilution after second bolus	13% (IQR 5–17)	12% (IQR 9–15)	15% (IQR 10–20)

Hemodilution after first bolus: not different between groups, p = 0.39
Hemodilution after second bolus: not different between groups, p = 0.19
Chloride received: p = 0.001
Overall urinary chloride excretion: not different between groups, p = 0.60

Urinary chloride concentration and diuresis · end of experiments

Urinary chloride concentration higher with saline vs Ringer's and Crystalsol: P = 0.01
Diuresis lower with saline vs Ringer's and Crystalsol: P = 0.04

Reference

Authors: Dell'Anna AM, Grieco DL, Dominedò C, Cicetti M, Cisterna I, Festa R, et al.
All 19 authors
Dell'Anna AM, Grieco DL, Dominedò C, Cicetti M, Cisterna I, Festa R, Lamacchia R, Giannì G, Filetici N, Michi T, Rossi C, Alcaro FD, Mele A, Rocchi A, Del Prete D, Meluzio MC, Tamburrelli FC, Rossi M, Antonelli M
Journal: Annals of Intensive Care
Published: 22 Apr 2025
DOI: 10.1186/s13613-025-01473-9
PubMed: 40263186
Registration: NCT03507062

Topic: Hemodynamics, fluids & transfusion

Intervention details

Saline: normal saline (chloride 154 mEq/L, strong ion difference 0 mEq/L)
Ringer's: lactated Ringer's (chloride 112 mEq/L, strong ion difference 29 mEq/L)
Crystalsol: Crystalsol (chloride 98 mEq/L, strong ion difference 50 mEq/L)

Key notes

Plasma chloride increased significantly over time with saline but not with Ringer's or Crystalsol

Original publication

Stewart’s theory and acid–base changes induced by crystalloid infusion in humans: a randomized physiological trial. Ann Intensive Care. Published 22 April 2025. doi:10.1186/s13613-025-01473-9

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