Effect of Ringer’s acetate in different doses on plasma volume in rat models of hypovolemia

Abstract

BackgroundEven 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.ResultsRats 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.ConclusionsWe 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.

Survey of non-resuscitation fluids administered during septic shock: a multicenter prospective observational study

“…Third, the assumption that reductions in volume of non-resuscitation fluid would not be offset by increased administration of resuscitation fluids could be questioned, since crystalloid maintenance fluids will also distribute in the intravascular space. However, intravascular retention of crystalloids over time is most likely very low and is reported to be < 10% in inflammatory conditions meaning that this source of error is reasonably small [18, 19]. Lastly, the physicians caring for the included patients may have aimed for a positive cumulative fluid balance when prescribing non-resuscitation fluids in patients with a perceived preexisting fluid deficit.…”

Protocolised reduction of non-resuscitation fluids versus usual care in patients with septic shock (REDUSE): a protocol for a multicentre feasibility trial

“…It could be argued that the expected reduction in administration of non-resuscitation fluids could lead to haemodynamic instability which could result in increased administration of resuscitation fluids, which in turn could offset the expected reduction in the total administered intravenous fluids. We believe that this is unlikely because glucose solutions are poor plasma volume expanders and because intravascular retention of crystalloids over time is most likely low, reported to be <10% in inflammatory conditions 31–33. Should we be wrong in our assumption that our intervention will not influence haemodynamic stability, we believe that that non-protocolised administration of resuscitation fluid is an important safety mechanism by which clinically apparent hypovolemia caused by our intervention will trigger administration of resuscitation fluids.…”

Beyond the fluid bolus

“…It is increasingly recognized that the duration and magnitude of the plasma volume expansion after the redistribution phase following a fluid bolus is context dependent. This means that in a hypovolemic patient with intact homeostatic mechanisms, such as following a hemorrhage or dehydration, compensatory mechanism will add to the plasma volume expansion obtained by the fluid bolus resulting in a large and sustained increase in plasma volume (5)(6)(7). During these conditions, plasma volume may increase by 20-25% of the infused volume after the initial distribution.…”