Third Space: Fantasy indeed !

Dr S.N.Bhagirath,

The Dilemma..!

3rd Space

Then where is all the fluid

administered going to..?

3rd Space

Then why is it so difficult to quantify it..?

Over – estimated fluid deficit due to preoperative fasting

Lamke LO Nilsson GE & Reithner HL1977Over – estimated fluid deficit due to Insensible losses

Virgilio RW, Rice CL, Smith DE Proof of overcorrection – weight gain upto 10Kgs

Dawidson IJ, Willms CD, Sandor ZF et alProof of overcorrection – weight gain upto 10Kgs

1979

1991

Jacob M, Chappell D, Conzen2008

Third Space

?

Traditional Concepts

Preoperatively fasted patient – hypovolemic After fasting –

ECV slightly decreases

Intravascular volume remains within normal range

Insensible loss – dramatic loss

Basal Evaporative loss – 0.5mL/Kg/hr

1 mL/kg/hr during large abdominal surgeries

Fluid shift into third space – needs substitution

Overload is not a problem – Kidneys can manage..!

???

!!!

Intraoperative fluid dynamics

Overcorrection leading to weight gain..!

Peak of fluid shifting at 5 hrs after trauma and persists up to 72 hrs

depending on location and duration of surgery.

Lowell et al. found 40% of patient admitted to SICU had an

excessive increase in body water of more than 10% of preoperative

weight.

Hypervolemic loading with crystalloids:

Physiologically distribute within the ECV.

4/5 will leave the vasculature.

Hypervolemic loading with colloids:

60% do not remain in the vasculature

due to volume effect.

Fluid Shift

What does this

overloading imply..?

Endothelial GlycocalyxHealthy vascular endothelium coated by endothelial glycocalyx – a layer of membrane-bound proteoglycans and glycoproteins.

Fluid shift into the interstitial space can be

divided into two types:

Type 1 – physiologic shift.

-- Colloid-free fluid and electrolytes.

Type 2 – pathologic shift. -- Protein-rich fluids. -- Functionally altered vascular barrier.

Endothelial Glycocalyx

Endothelial Glycocalyx

Type 2 shift, result of 2 intraoperative factors.

Surgical: Endothelial damage due to mechanical stress, endotoxin exposure, ischemia-reperfusion injury and SIRS.

Iatrogenic: Acute hypervolemia!

Effects of overloading (even with colloids)

Damaged Endothelial Glycocalyx manifests as

• Delayed wound healing

• Tissue edema

• Pulmonary edema

• Anastomotic leakage

Exercise caution in overloading (even if it is not crystalloids..)

Is it accumulating in the third space…..?

• Described as non-anatomical..?!!!

• Except for one study, and even that with sulphur and bromide tracers, no other tracer study has shown the third space to exist

• Are tracers really reliable..?

What are the considerations weighing against them..?

So, Where is all this overcorrection

accumulating..?

If so, where is this third space….?

• The selection of a suitable tracer which distributed exclusively in the third space

• How long one ought to wait till the tracer has distributed exclusively in the third space before it begins redistributing elsewhere?

• How does one validate the method adopted to quantify this third space?

• The requirement of a steady state condition necessary for a tracer to function optimally rules out states of hemodynamic shock or even surgical stress which defeats the purpose wholly.

• Settings of hypotension or hypovolemia prolong equilibration of the tracer causing more of it to remain in the plasma rather than the third space.

• Sequestration of the above preferred tracers inside the erythrocytes, plasma components and subsequent accumulation in liver and kidney further alienates its efficacy.

Something to do with fluid shift mechanics….perhaps….

There exists a gradient across the vessel and the interstitium, with the intravascular compartment having a high hydrostatic pressure as opposed to a low hydrostatic pressure in the Interstitium.

This calls for a substantial inwardly acting colloidal osmotic pressure intravascularly to counter the hydrostatic pressure gradient. In this setting, if one were to transfuse iso-oncotic colloids, they would not change the intravascular colloid osmotic pressure.

On the contrary, if one were to transfuse crystalloids, since they would not exert any colloid osmotic pressure, there is no inwardly acting force to keep them trapped within the vascular compartment. i.e. crystalloids readily cross the vascular barrier into the interstitium as opposed to their colloidal counterparts.

Administration of crystalloids in a normovolemic patient does not therefore increase the intravascular volume.

Consequently, preloading a patient prior to anaesthesia with crystalloids ill serves the purpose of preventing intraoperative hypotension secondary to anaesthesia15, 16.

In summary, in a normovolemic patient – infused colloid tends to remain intravascularly and infused crystalloid tends to cross over into the interstitium

How long does this dictum hold good…? After a certain limit, once infusion of colloids leads to a relative state of hypervolemia, strangely enough, the colloidal fluid hitherto trapped intravascularly begins to cross over into the interstitium.

Volume depletion secondary to normal preoperative fasting is insignificant

Volume depletion secondary to fasting is significant only if a bowel wash has been administered, dehydrated patients and hypovolaemic patients.

Preloading with crystalloids before administration of anesthesia as routine practice is best reconsidered.

Generous fluid replacement intraoperatively does more harm than good to the patient.

Volume replacement based on only urinary output is best avoided.Use colloids judiciously.

Protection or restoration of this endothelial glycocalyx might be an

important therapeutic goal.

prevent perioperative fluid shifting - judicious use of crystalloids

and colloids as necessary

avoid third space shifting. (if you still believe it exists)

In Summary

To believe or not to believe in third space, that is the question…!?

?

Bruegger D, Jacob M, Rehm M et al. Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea pig hearts. American Journal of Physiology. Heart and Circulatory Physiology 2005; 289:H1993–H1999.

Jacob M, Chappell D, Conzen P et al. Blood volume is normal after preoperative overnight fasting. Acta Anaesthesiologica Scandinavica 2008; 52: 522–529

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