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When does the "third fluid space" open?

Robert G Hahn1

  • 1Karolinska Institutet at Danderyds Hospital (KIDS), Stockholm, 171 77 , Sweden. robert.hahn@ki.se.

Pflugers Archiv : European Journal of Physiology
|December 16, 2025
PubMed
Summary
This summary is machine-generated.

Accumulation of infused crystalloid fluid in the third fluid space (Vt2) depends on interstitial pressure (Pif) and requires over 1.2 L of fluid. Fluid uptake into Vt2 begins around 30-35 minutes post-infusion.

Keywords:
Crystalloid fluid, pharmacokineticsHemodilutionInterstitial fluidWater–electrolyte balance, physiology

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Area of Science:

  • Physiology
  • Pharmacokinetics
  • Fluid Dynamics

Background:

  • The interstitial space has two functional fluid compartments.
  • Understanding fluid shifts is crucial for intravenous therapy.
  • The "third fluid space" (Vt2) represents a slow-exchange compartment.

Purpose of the Study:

  • To investigate the prerequisites for crystalloid fluid accumulation in the third fluid space (Vt2).
  • To determine the volume threshold and timing for Vt2 filling.
  • To assess the influence of interstitial pressure on Vt2 accumulation.

Main Methods:

  • Volume kinetic analysis using log likelihood mathematics on retrospective data from 132 infusions in 85 volunteers.
  • Analysis of blood hemoglobin concentration and urine output.
  • Three substudies manipulating interstitial pressure, fluid volume, and timing.

Main Results:

  • Vt2 filling was dependent on interstitial pressure (Pif), as shown by reduced Vt2 volumes after blood withdrawal.
  • Consideration of Vt2 in kinetic analyses was appropriate for infusions exceeding 1.2 L.
  • Fluid uptake into Vt2 was initiated between 30 and 35 minutes post-infusion, not gradually.

Conclusions:

  • Crystalloid fluid accumulation in Vt2 is contingent upon interstitial pressure.
  • A threshold of >1.2 L of infused crystalloid fluid is necessary for significant Vt2 filling.
  • Vt2 fluid uptake is a time-initiated event occurring after 30 minutes, rather than a continuous process.