Arterial Blood Ca²⁺ Levels, Cardiac and Respiratory Function

Abstract

In 1944, Allen and his colleagues [1] reported on the tolerance for citrated blood and blood plasma in humans and dogs, and assumed: “The toxic effects of citrate… to be attributable primarily to the immobilization of calcium ion.” These investigators found the lethal dose of citrate in the dog to be 0.30 g/kg (1.02mmol/kg) body weight administered in 15 min or less. However, they concluded that such toxicity was unlikely to occur in human patients with the rates at which citrated blood (containing 5.0 g/1,17.00 mmol/1 citrate) was then being administered in surgical practice, i. e., 1500–2500 ml over 2–6 h. However, in the late 1940s and in the early 1950s, there was renewed interest in this question since new procedures, such as exchange transfusion and surgical treatment of bleeding esophogeal varices, came to be employed. These and other procedures required transfusions of larger volumes (2000–8000 ml) of blood, often in 15 min or less [3]. Bunker and his colleagues [3,4] studied the hemodynamic and cardiovascular effects of citrated blood in human patients receiving such massive transfusions, and investigated the effect of citrate administration in dogs, in order to learn the relationship between citrate levels, plasma ionized calcium, and cardiac function in vivo. They measured total calcium, total protein, and other variables, in blood samples with bench instruments, and estimated plasma ionized calcium using the nomogram of McLean and Hastings [10]. Bunker and his group concluded that significant cardiovascular disturbances could occur under these conditions. Today, each unit (550 ml) of citrate-preserved blood contains 1.08 mmol citrate, or 0.015 mmol per liter total blood volume for a 70 kg patient for each unit of blood transfused [12]. In some surgical procedures, 5 U or more may be transfused [8, 9], resulting in a significant dose of citrate.