Acetated Ringer´s Solution in Experimental Hypovolemia — Volu-Flow  

Hemodynamic Instability Clinical Trial

Official title: A Randomized Study to Investigate Central and Cerebral Hemodynamic Effects and Volume Kinetics of Ringer´s Acetate Compared With no Intravenous Fluids, During Experimental Hypovolemia Compared With Euvolemia, in Healthy Human Volunteers

Status Recruiting

Clinical Trial Summary

Intravenous fluids are often given to increase stroke volume and thereby improve global oxygen delivery. The effect is however often transient, but the effect of a fluid bolus on stroke volume and other hemodynamic variables over time are poorly described. The volume effect of a fluid bolus (effect on blood volume) can be calculated by measuring Haemoglobin. The purpose of this study is to elucidate the hemodynamic effects of a fluid bolus during normovolemia and hypovolemia in healthy volunteers. Study details include:

• Study Duration: 2 visits of approximately 2 h duration each + follow-up visit. Visits 1 and 2 are at least 2 days apart. Number of Participants: A maximum of 15 participants will be enrolled to study intervention such that 12 evaluable participants complete the study

Clinical Trial Description

Administration of intravenous fluids is one of the most commonly performed procedures in anaesthesia, critical care and emergency medicine. Intravenous fluids can be given to achieve specific goals depending on the type of fluid, but often, fluid is given simply to expand the intravascular volume. The volume-expanding effect of intravenous fluids is however time-dependent, and often of limited duration as fluid is distributed out of the intravascular space and eliminated mainly in the kidneys.

The goal of intravascular volume expansion is to improve haemodynamic variables, such as SV, CO and ABP. The reasoning is that volume expansion increases SV mainly mediated by the Frank-Starling mechanism. The degree to which SV increases with volume expansion is termed fluid responsiveness.1 The increase in SV does however in most cases seem to be transient. The reason for the transient nature of the hemodynamic response is not known, but may be related to reduction in intravascular volume expansion as described above or other factors, such as vasodilation.

Calculation of volume expansion:

The volume-expanding effect of intravenous fluids has been studied by measuring concentration of hemoglobin. Under the assumption that hemoglobin is evenly distributed in, and does not leave the intravascular space, intravascular volume can be calculated and kinetic studies of the volume effect (volume kinetics) can be performed.

Hb = intravascular amount of hemoglobin V0 = Intravascular volume at time 0 Vt = Intravascular volume at time t [Hb]0 = Hemoglobin concentration at time 0 [Hb]t = Hemoglobin concentration at time t Eq1: (Hb)o= Hb/Vo. Vo = Hb/(Hb)o Eq 2: (Hb)t= Hb/Vt. Vo = Hb/(Hb)t.

Assuming that the amount of hemoglobin is constant, from Eq 1 ang Eq 2, it follows that:

Eq 3: Vt/V0=(Hb)o/(Hb)t which therefore gives the relative value of intravascular volume at time=t to compared to time=0; Vt_rel.

Kinetic model of outcomes:

Similar to the volume expansion, the relative value of the hemodynamic variables compared to baseline can be calculated, expressed as value at time=t, Vt.

A pharmacokinetic model can then be fitted to the observations. In a two-compartment model, the relative value (e.g. volume) of the observed value at time=t (Vt) can be described as:

Eq 4: V_(t_rel)=D(〖Ae〗^(-αt)+〖Be〗^(-βt))

A one-compartment model can be described as:

Eq 5: V_(t_rel)=D(〖Ae〗^(-αt)) A two-compartment model will typically describe a rapid equilibration with one compartment and a slower elimination. Initially the reduction in Vt is dominated by distribution, and later by the slower elimination. Each of these effects have their own half-lives, given by α and β. For a one-compartment model, the reduction in Vt is best described by a single half-life.

LBNP-model:

LBNP is a model that has been used for several decades. Lower body negative pressure (LBNP) is a model of central hypovolemia where negative pressure is applied to the body from the waist-down. Thereby, blood is displaced from the central compartment of the upper body to the lower extremities and pelvis. The model has been used for more than half a century and is considered useful model for studying hypovolemia in conscious volunteers.

The volume kinetics of intravenous fluids has been shown to be affected by volume status, with a longer lasting volume effect during hypovolaemia.The effects of volume status on the hemodynamic response to intravenous fluids has been less explored.

Aim of the study The aim of the present study is to explore the effects over time of an intravenous fluid bolus. The effects on the volume expanding effects and the hemodynamic effects will be measured. ;

Related Conditions & MeSH terms

• Fluid Loss
• Hemodynamic Instability
• Hypovolemia

• NCT number: NCT05705115
• Study type: Interventional
• Source: Oslo University Hospital
• Status: Recruiting
• Phase: Phase 4
• Start date: March 2, 2024
• Completion date: July 29, 2024