0.9% saline is neither normal nor physiological

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 O2 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.

Keywords: 0.9% saline; Acidosis; Balanced fluids; Hyperchloremia; Hyperkalemia; Renal hemodynamics.

Fig. 1

Strong ion difference (SID) in normal circulation (a) and after 0.9% saline infusion (b) (a) Based on the Stewart model, the difference between cations and anions in normal serum should be approximately 40 mmol/L (pH=7.4). SID decreases when negatively charged anions disproportionately increase compared to positively charged cations, resulting in a pH decline and acidosis. SID increases when anions disproportionately decrease, compared to cations causing pH elevation, metabolic alkalosis. (b) In normal serum, the predominant cation is Na (140 mmol/L) and predominant anions is Cl (100 mmol/L). The SID is approximately 40 mmol/L when pH is 7.4. 0.9% saline infusion causes elevations in both Na and Cl, but Cl increases in a larger magnitude, resulting in a net SID reduction and acidosis

Fig. 2

A disproportionate increase in Cl and hyperchloremic acidosis caused by 0.9% saline infusion The Cl filters into renal tubules. Through macular densa cells, the Cl signal is transmitted to afferent arterioles causing vasoconstriction, resulting in glomerular filtration rate (GFR) reduction and reduction in urine output. Regional ischemia due to saline-associated kidney volume expansion could further stimulate renin secretion from juxtaglomerular cells, leading to activation of the intra-renal renin angiotensin system (RAS). RAS activation would further enhance the proximal tubular Na absorption and afferent arteriolar vasoconstriction via tubuloglomerular feedback (TGF) activation