Stewart's theory and acid-base changes induced by crystalloid infusion in humans: a randomized physiological trial.

Abstract

Background: Stewart'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.

Methods: In 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.

Results: Forty-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).

Conclusions: 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.

Trial registration: Registered on clinicaltrials.gov (NCT03507062) on April, 24th 2018.