The 'third space'--fact or fiction?

For decades, the 'third space' was looked upon as an actively consuming compartment. Therefore, perioperative fluid regimens were traditionally based on a generous replacement of this assumed primary loss, in addition to deficits due to insensible perspiration and fasting. The practical consequence was an extremely positive fluid balance in order to maintain blood volume during major surgery. Whereas the insensible perspiration and the preoperative deficits are in fact often negligible, and the third space appears to be only a fictional construct, the excess fluid most likely accumulates interstitially. Such shifting is related to a destruction of the endothelial glycocalyx, a key structure of the vascular barrier, by traumatic inflammation and iatrogenic hypervolaemia. This explains why patients undergoing major surgical interventions benefit significantly from an infusion regimen which does not substitute but avoids 'third-space shifting'. In summary, eradicating this notion from our minds could be a further key to achieving perioperative fluid optimisation.