We don't know shit about IV Fluids

I teach IV fluids to every third year medical student and resident that crosses the threshold at St John Hospital. It's what I do. It's a conventional lecture focusing on the expected fluid distribution following various flavors of IV fluids.

The dogma of IV fluids is that dextrose solutions, crystalloids and plasma expanders distribute across the body compartments in unique ways.

Dextrose solutions distribute like total body water, with two thirds disappearing into the intracellular compartment and the remaining third distributing one part to the plasma compartment and three parts to the interstitial compartment. So approximately 80 milliliters of a liter of D5W remains in the plasma compartment.

Isotonic saline is trapped in the extracellular compartment and one quarter of it expands the plasma compartment. So one quarter of a liter of isotonic saline remains in the plasma compartment.

Plasma expanders are locked to the plasma compartment so one liter of albumin expands the plasma compartment by one liter.

from the label of 4% albumin, the co-star of the SAFE trial 

So in summary:

• one liter of dextrose expands the plasma compartment by 80 mL
• one liter of 0.9% saline expands the plasma compartment by 250 mL
• one liter of 4% albumin expands the plasma compartment by 1,000 mL

These fluids have radically different effects on the plasma compartment so when used for volume resuscitation in critically ill patients we should expect different outcomes. We have empiric data on this. Initially, in the late 90's we were in meta-analysis hell with some saying albumin was poison and others saying there was no difference between the two. Thankfully the Aussies rescued us with a large, well done RCT:

and it showed...nothing:

This blows my mind. 

How can a substance that is four times as efficient as another, at least by the metric we think are critical, have no influence on outcome? 

Shouldn't radically different efficiencies at expanding the plasma compartment have some signal, either good or bad? 

The fact that it made no difference at all makes me think that differentiating them based on their ability to expand the plasma compartment is misguided.

Additionally we didn't even see the 4:1 ratio in efficiency that is expected. Albumin dosing should have been one fourth of saline dosing, but in the study it was only about 70% of saline:

 

The SAFE trial is impossible for me to integrate into the conventional model of how IV fluids work. Is it time to abandon the model?