# 8.1: Infusion of Isomolar Fluids

## Consider the Distribution & Excretion of 1,000 mls of various fluids.

As an exercise in applied fluid physiology is to compare the distribution and excretion of a rapid intravenous infusion of 1000 mls of various fluids. This serves to emphasise some of the factors involved in the selection of an appropriate fluid. In this exercise we will tend to ignore cardiovascular changes such as increased venous capacitance.

Certain simplifing assumptions are made in clinical practice about the sizes of the various fluid compartments to facilitate the mental arithmetic without loss of any clinically relevant precision. The water of dense connective tissue & bone is significant in volume (15% of total body water) but as a kinetically slow compartment. It is not important in consideration of short term fluid distribution. Transcellular fluids are small in volume and usually slow so they too are excluded from this clinical analysis.

This leaves three big compartments:

• Intracellular fluid (55% of TBW, 23 liters)
• Interstitial fluid (20% of TBW, 8.4 liters)

• Intravascular fluid (Plasma 7.5% of TBW, 3.2 liters and Red cell volume 1.8 liters).

The IVF is the blood volume with 5 liters in total. The red cell volume is part of the ICF but also is part of the blood volume. The ratio of ICF to ECF is 23:11.6 (about 2:1). The ratio of ISF to plasma volume is 8.4:3.2 and this will be treated as about 3:1. This discussion only considers those parts of the total body water that are rapidly equilibrating. These are the only components that need to be considered in acute fluid changes.

### Assumptions used for this Simple Analysis

• TBW is one-third ECF & two-thirds ICF
• ECF is one-quarter plasma & three-quarters ISF
• The threshold of the volume receptors is 7-10% change in blood volume
• The osmoreceptors are sensitive to a 1-2% change in osmolality.
• Plasma osmolality is normal prior to the transfusion (ie 287-290 mOsm/kg)

Now, consider the rapid IV administration of 1,000 mls of the following fluids: Dextrose 5%, normal saline and plasma protein solution. The type of questions to be considered are:

How are these different fluids distributed in the body?

How are tonicity and intravascular volume affected?

What are the mechanisms the body uses to excrete these fluids?

Which is excreted the most rapidly?

## Dextrose 5%

Dextrose 5% is a Maintenance Fluid. (Dextrose is d-glucose). It is isosmotic as administered and does not cause haemolysis. The glucose is rapidly taken up by cells. The net effect is of administering pure water, so it is distributed throughout the total body water. Each compartment receives fluid in proportion to its contribution to the TBW (ie 2/3rd to ICF and 1/3rd to ECF; the ECF fluid is distributed one quarte to plasma & three quarters to ISF).

The distribution of 1,000 mls of dextrose 5% is:

• ICF 670mls
• ECF 330mls (with ISF 250mls and plasma 80mls).

(The figures are rounded slightly)

Intravascular volume increases from 5000 to 5080 mls. This volume increase of less then 2% which will not be sensed by the volume receptors (as it is below the 7-10% threshold).

The osmolality of plasma (3,200 mls) will decrease by: [ $$287- \frac {287 \times 3.20} {3.28}$$ ] which is about 7 mOsmoles/l or a 2.5% decrease. This is enough to be detected by the osmoreceptors. ADH release will be decreased and renal water excretion will rise. A delay will occur because the changes have to be detected centrally and then ADH levels need 3 half-lives to fall to a new steady state.

## Normal Saline

Normal saline is an ECF Replacement Fluid. Its [Na+] is similar to that of the extracellular fluid and this effectively limits its distribution to the ECF (distributing between the ISF & the plasma in proportion to their volume ie 3:1).

The ISF will increase in volume by 750 mls. The plasma volume will increase by 250 mls. This is why blood loss of 1,000 mls requires about 3 to 4 times the volume of IV replacement fluid to restore normal intravascular volume.

Plasma osmolality and tonicity will be unchanged because normal saline is isosmotic. The osmoreceptors do not contribute anything to the excretion of normal saline. Blood volume increases to 5250 mls; an increase of 5%. This is below the sensitivity of the volume receptors. It seems that the body has no clear way of excreting this excess fluid as neither osmoreceptors nor volume receptors are stimulated! However, experiments have shown that replacement fluids are excreted the most rapidly of all these groups!

How does this happen? An additional mechanism is relevant here. Normal saline contains no protein so the oncotic pressure in the blood is slightly lowered following the saline infusion. This has 2 effects:

• Movement of fluid into the ISF is favoured (Starling's Hypothesis)
• Glomerulo-tubular imbalance occurs: the lowered oncotic pressure immediately leads to an increase in GFR and a smaller reabsorption of water in the proximal tubule. Urine flow increases. This is a strictly local effect without any hormonal intermediary. The urine flow increases immediately. Fluid then moves back into the intravascular compartment and the urine flow continues until all the transfused fluid is excreted.

## Plasma Protein Solution

Plasma protein solution is a colloid and is distributed only to the intravascular fluid. The tonicity is unaltered. The blood volume increases from 5,000 mls to 6,000 mls; an increase of 20%. This is above the 7 to 10% threshold for the volume receptors. The result is a fall in ADH levels and the excretion of the excess water commences.

This water loss tends to increase the plasma oncotic pressure and water moves from the ISF to the IVF. Vascular reflexes are important also in causing venous pooling and a decrease in the effective circulating volume. These mechanisms tend to slow the excretion of the water load. The albumin is partly slowly redistributed to the ISF and metabolised. These changes are slow so the effect of plasma protein infusion on blood volume is both more pronounced and more prolonged.

The pressure-volume control mechanisms important in long term regulation of blood volume are slow in onset but become relevant here as the blood volume change is more significant and more prolonged and occurs without change in osmolality (or initially in plasma oncotic pressure either).

## Overview

Dextrose 5% is essentially treated by the body as pure water and a significant percent moves intracellularly. It is a useful fluid to replenish intracellular fluid but does so at the expense of tonicity. It is inappropriate for intravascular volume replacement. It is excreted because ADH levels decline in response to the drop in plasma osmolality.

Normal saline is a replacement fluid (meaning ECF replacement) because it adds only to the ECF volume. Only about a third remains intravascularly. To replace intravascular volume will require transfusion with about 3 times the volume of blood lost. It is cheap and readily available. It is excreted because the small drop in plasma oncotic pressure causes glomerulotubular imbalance. ADH is not affected.

Plasma protein solutions (eg 5% human albumin) are excellent for replacing intravascular volume. ISF and ICF will not be replenished. Albumin is slow to be excreted and the transfused volume is excreted much slower than with replacement solutions. Plasma protein solutions are expensive and supply is limited. The fluid is initially excreted because of a fall in ADH level falling stimulation of the volume receptors.