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The objective of this study is to develop a physicochemical model of the projected change in standard base excess (SBE) consequent to the infused volume of crystalloid solutions in common use. A clinical simulation of modeled acid-base and fluid compartment parameters was conducted in a 70-kg test participant at standard physiologic state: pH = 7.40, partial pressure of carbon dioxide (PCO2)= 40 mm Hg, Henderson-Hasselbalch actual bicarbonate ([HCO3]HH) = 24.5 mEq/L, strong ion difference (SID) = 38.9 mEq/L, albumin = 4.40 g/dL, inorganic phosphate = 1.16 mmol/L, citrate total = 0.135 mmol/L, and SBE = 0.1 mEq/L. Simulations of multiple, sequential crystalloid infusions up to 10 L were conducted of normal saline (SID = 0), lactated Ringer's (SID = 28), plasmalyte 148 (SID = 50), one-half normal saline + 75 mEq/L sodium bicarbonate (NaHCO3; SID = 75), 0.15 mol/L NaHCO3 (SID = 150), and a hypothetical crystalloid solution whose SID = 24.5 mEq/L, respectively. Simulations were based on theoretical completion of steady-state equilibrium and PCO2 was fixed at 40 mm Hg to assess nonrespiratory acid-base effects. A crystalloid SID equivalent to standard state actual bicarbonate (24.5 mEq/L) results in a neutral metabolic acid-base status for infusions up to 10 L. The 5 study solutions exhibited curvilinear relationships between SBE and crystalloid infusion volume in liters. Solutions whose SID was greater than 24.5 mEq/L demonstrated a progressive metabolic alkalosis and less, a progressive metabolic acidosis. In a human model system, the effects of crystalloid infusion on SBE are a function of the crystalloid and plasma SID, volume infused, and nonvolatile plasma weak acid changes. A projection of the impact of a unit volume of various isotonic crystalloid solutions on SBE is presented. The model's validation, applications, and limitations are examined.