Abstract:The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of saline infusion, specifically on systemic acid-base balance and renal hemodynamics. Studies have shown that electrolyte balance, including effects of saline infusion on serum electrolytes, is often poorly understood among practicing physicians and inappropriate saline prescribing can cause increased morbidity and mortality. Large-volume (>2 L) saline infusion in healthy adults induces hyperchloremia which is associated with metabolic acidosis, hyperkalemia, and negative protein balance. Saline overload (80 ml/kg) in rodents can cause intestinal edema and contractile dysfunction associated with activation of sodium-proton exchanger (NHE) and decrease in myosin light chain phosphorylation. Saline infusion can also adversely affect renal hemodynamics. Microperfusion experiments and real-time imaging studies have demonstrated a reduction in renal perfusion and an expansion in kidney volume, compromising O 2 delivery to the renal parenchyma following saline infusion. Clinically, saline infusion for patients post abdominal and cardiovascular surgery is associated with a greater number of adverse effects including more frequent blood product transfusion and bicarbonate therapy, reduced gastric blood flow, delayed recovery of gut function, impaired cardiac contractility in response to inotropes, prolonged hospital stay, and possibly increased mortality. In critically ill patients, saline infusion, compared to balanced fluid infusions, increases the occurrence of acute kidney injury. In summary, saline is a highly acidic fluid. With the exception of saline infusion for patients with hypochloremic metabolic alkalosis and volume depletion due to vomiting or upper gastrointestinal suction, indiscriminate use, especially for acutely ill patients, may cause unnecessary complications and should be avoided. More education regarding saline-related effects and adequate electrolyte management is needed.