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

Background: 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. Methods: 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. Results: Mortality decreased from 44.6% to 39.2% after adoption of chloride-sparing diluents (absolute reduction 5.4%, p = 0.003), despite similar renal function across periods. The later cohort demonstrated significantly higher SID (median 39 vs. 38 mmol/L; p < 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. Conclusions: 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.