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The following is a summary of “Stewart’s theory and acid–base changes induced by crystalloid infusion in humans: a randomized physiological trial,” published in the April 2025 issue of Annals of Intensive Care by Dell’Anna et al. 

Researchers conducted a retrospective study to evaluate Stewart’s acid-base theory during crystalloid infusion in humans, focusing on the effects on plasma pH, renal response, and hemodilution.  

They randomized patients undergoing surgery with minimal blood loss to receive normal saline (NS) (chloride (Cl) content 154 mEq/L, strong ion difference (SID) 0 mEq/L), Lactated Ringer’s (LR) (Cl content 112 mEq/L, SID 29 mEq/L), or Crystalsol (CR) (Cl content 98 mEq/L, SID 50 mEq/L). Each group received 10 ml/kg immediately after intubation and 20 ml/kg after 2 hours. Plasma and urinary acid-base and electrolyte levels were measured before the study and at specified time points. The primary endpoint was pH 1 hour after the second bolus, with secondary outcomes including urinary/plasmatic electrolyte concentrations and SID.  

The results showed that 45 individuals were enrolled (15 in each group). The extent of hemodilution after the first fluid bolus was similar across groups (saline 9% [6–15], Ringer’s 7% [4–9], CR 8% [5–12]; P= 0.39), as was the second bolus (saline 13% [5–17], Ringer’s 12% [9–15], CR 15% [10–20]; P= 0.19). Patients in the saline group received more Cl (449 mEq [383–495]) compared to the Ringer’s (358 mEq [297–419]) and CR groups (318 mEq [240–366]) (P= 0.001), 1 hour after the second bolus, pH was significantly lower in the saline group (7.34 [7.32–7.36]) compared to Ringer’s (7.40 [7.35–7.43]) and CR (7.42 [7.38–7.44]) groups (both P< 0.01), as plasma Cl increased over time in the saline group, but not in the other groups. Urinary Cl excretion did not differ across groups (saline 36 mEq [28–64], Ringer’s 42 mEq [29–68], CR 44 mEq [27–56], P= 0.60). However, the saline group showed higher urinary Cl concentration and lower diuresis compared to Ringer’s and CR groups (P= 0.01, P= 0.04, respectively).  

Investigators concluded that, consistent with Stewart’s approach, crystalloid solutions with high Cl content lowered pH through a reduced SID, progressive hemodilutional acidosis, and a limited renal response to the Cl load. 

Source: annalsofintensivecare.springeropen.com/articles/10.1186/s13613-025-01473-9