Balancing Chloride and Glucose in Critical Illness: A 10 Year Study on Diluent Strategies and ICU Outcomes

<b>Background</b>: High-chloride solutions such as 0.9% saline are widely used for medication dilution in intensive care units (ICUs) and are an underrecognized source of hyperchloremia and acid-base disturbances. Excess chloride reduces the strong ion difference (SID), contributing to hyperchloremic metabolic acidosis and worse clinical outcomes. This study evaluated the impact of replacing isotonic saline with 5% dextrose as a diluent on ICU outcomes in mechanically ventilated patients. <b>Methods</b>: In this retrospective cohort study, 4347 adult ICU patients requiring ≥12 h of mechanical ventilation were analyzed across two periods with different diluent strategies (2015-2018: saline-based; 2019-2025: chloride-sparing, dextrose-based). Demographics, comorbidities, illness severity (APACHE II, SOFA), fluid exposure, SID, and laboratory values over the first 48 h were compared. Predictors of mortality were identified using multivariate logistic regression. <b>Results</b>: Mortality decreased from 44.6% to 39.2% after adoption of chloride-sparing diluents (absolute reduction 5.4%, <i>p</i> = 0.003), despite similar renal function across periods. The later cohort demonstrated significantly higher SID (median 39 vs. 38 mmol/L; <i>p</i> < 0.001), lower chloride levels, and more favorable acid-base profiles. In 2015-2018, chloride showed a strong association with mortality (~12-13% increased odds per mmol/L), while in 2019-2025 the association persisted but was attenuated (~2% per mmol/L). SID emerged as a significant marker of improved acid-base balance after the diluent transition. pH remained the most powerful predictor of mortality in both periods. Mean glucose levels increased by ~30-40 mg/dL after switching to dextrose diluents, although insulin requirements did not change. <b>Conclusions</b>: Transitioning from chloride-rich to chloride-sparing diluents was associated with reduced ICU mortality and improved acid-base balance, without changes in renal function. However, modestly increased glucose levels highlight the need for strict glycemic monitoring. These findings support chloride-sparing strategies with robust glycemic monitoring in critical care.