Effect of ringers acetate in different doses on plasma volume in rat models of hypovolemia

Even though crystalloids are the first choice for fluid resuscitation in hemodynamically unstable patients, their potency as plasma volume expanders in hypovolemia of different etiologies is largely unknown. The objective of the study was to investigate dose-response curves of a crystalloid in hypovolemia induced by either sepsis or hemorrhagic shock.

Rats were randomized to resuscitation with Ringers acetate at a dose 10, 30, 50, 75, or 100 ml/kg at 4 h after induction of sepsis by cecal ligation and puncture (CLP) or 2.5 h after a 30 ml/kg hemorrhage. Plasma volume (¹²⁵I-albumin) was the primary outcome. Plasma volume decreased by about 11.8 (IQR 9.9-14.5) ml/kg relative baseline after CLP and increased dose-dependently by at most 5.8 (IQR 3.3-7.0) ml/kg in the 100 ml/kg group at 15 min after resuscitation. In the hemorrhage group, the plasma volume increased by at most 13.8 (IQR 7.1-15.0) ml/kg in 100 ml/kg group. Blood volumes at baseline, calculated using hematocrit and plasma volumes, were 72.4 (IQR 68.2-79.5) ml/kg in sepsis group and 71.1 (IQR 69.1-74.7) ml/kg in hemorrhage group. At 15 min after resuscitation with a dose of 100 ml/kg blood volumes increased to 54.8 (IQR 52.5-57.7) ml/kg and ; 49.6 (IQR 45.3-56.4) ml/kg, in the sepsis and hemorrhage groups, respectively. Plasma volume expansion as the percentage of dose at 15 min was 5.9 (IQR 2.5-8.8)% and 14.5 (IQR 12.1-20.0)% in the sepsis and hemorrhage groups, respectively. At 60 min, average plasma volume as the percentage of dose had decreased to 2.9 (IQR ([-2.9] - 8.3)% (P = 0.006) in the sepsis group whereas no change was detected in the hemorrhage group. A dose-dependent decrease in the plasma oncotic pressure, which was more marked in sepsis, was detected at 60 min after resuscitation.

We conclude that the efficacy of Ringers acetate as a plasma volume expander is context dependent and that plasma volume expansion is lower than previously realized across a wide range of doses. Ringers acetate decreases plasma oncotic pressure in sepsis, in part, by mechanisms other than dilution.