solution to the return of autologous blood decreased the mortality rate to 40 percent. Shires and colleagues (1960b) extended this work, measuring intraoperative losses in the effective extracellular fluid volume, plasma volume, and red blood cell mass by the use of radioisotopes. Those studies described a 28 percent decrease in extracellular fluid volume that correlated directly with the degree of operative trauma. Shires and colleagues (1961) subsequently extended this work to trauma patients and described similar shock-mediated losses in extracellular fluid volume. Furthermore, resuscitation of hemorrhagic shock with blood or fresh frozen plasma plus blood failed to correct shock-related reductions in extracellular fluid volume, whereas the addition of lactated Ringer's solution to the return of shed blood ablated extracellular fluid volume deficits and improved the survival rate (Middleton et al., 1969; Shires, 1966; Shires et al., 1964).
The phenomenon of fluid redistribution after major trauma involving blood loss was termed ''third spacing'' and described the translocation of intravascular volume into the peritoneum, bowel, burned tissue, or crush injury sites. Subsequent studies showed that hemorrhagic shock promoted a significant loss of fluid from the extracellular space into the cell, exacerbating third-space losses (Middleton et al., 1969). Fluid was then directed to replace lost intravascular as well as extravascular fluid. Considerable controversy arose, however, regarding the formula or the clinical criteria used to determine the adequacy of fluid resuscitation; in addition, questions arose regarding the type of fluid that was most appropriate for volume replacement. Several studies suggested that normal saline and lactated Ringer's solution were equally effective in maintaining intravascular volume after hemorrhage (Cervera and Moss, 1975; Siegel et al., 1973; Wright, 1974), but complications such as hyponatremia or hypernatremia were reported with the use of 5 percent sodium chloride or molar sodium lactate solutions, respectively. Dillon and colleagues (1966) showed that lactated Ringer's solution (given in a volume that was two to three times the shed blood volume) was as efficacious as 6 percent dextran in saline (given in a volume equal to the shed blood volume) and confirmed that a sodium-containing, colloid-lacking solution could be used effectively to treat blood loss.
Questions arose regarding the effects of large-volume expansion on sodium distribution after hemorrhagic shock as well as the need to correct potassium deficits; although hemorrhage was shown to produce a functional sodium deficit, neither the clinical significance nor the magnitudes of the deficit were determined (Dillon et al., 1966). Large-volume resuscitation with salt-containing solutions gained in popularity because this regimen was consistently associated with improved survival in both clinical and experimental studies of hemorrhagic shock, and few side effects of lactated Ringer's solution were demonstrated. Thereafter research compared the hemodynamic responses to resuscitation with whole blood, plasma expanders, fresh frozen plasma, and saline versus lactated Ringer's solution. In this search for an ideal fluid for adequate restoration of intravascular and extravascular volumes, most studies found no differences in mortality rate or pulmonary function if volume expansion was adequate (Lucas et al., 1986, 1978; Moss et al., 1981).