Fluid escapes to the “third space” during anesthesia, a commentary

Abstract

Background The “third fluid space” is a concept that has caused much confusion for more than half a century, dividing anesthesiologists into believers and non‐believers. Aim To challenge the existence of the “third fluid space” based on analysis of crystalloid fluid kinetics. Methods Data on hemodilution patterns from 157 infusion experiments performed in volunteers and from 85 patients undergoing surgery under general anesthesia were studied by population volume kinetic analysis. Elimination of infused crystalloid fluid from the kinetic model could occur either as urine or "third space" accumulation. The latter fluid volume remained in the body, but without equilibrating with the plasma within the 3‐4 h of the experiment. Results The rate constant for "third space" loss of fluid accounted for 20% of the elimination in conscious volunteers and for 75% during general anesthesia and surgery. The two elimination constants showed a reciprocal relationship, resulting in that "third‐space" losses increase when urinary excretion is restricted. The effect on the plasma volume was smaller than indicated by these figures because fluid distributed to the extravascular space continuously redistributed to the plasma. Worked‐out examples show that one‐third of an infused crystalloid volume has been confined to the "third space" after 3 h of surgery. When equilibration with the plasma eventually occurs, which is necessary for excretion of the fluid, is not known. Conclusion During anesthesia and surgery one third of the infused crystalloid fluid is at least temporarily unavailable for excretion, which probably contributes to postoperative weight increase and edema.

Interstitial washdown and vascular albumin refill during fluid infusion: novel kinetic analysis from three clinical trials

“…Unresolved issues remain with regard to the turnover of crystalloid fluid in the human body that may serve to explain such differences. One is the large increase in non-exchangeable volume (e.g., the “third space”) that limits intravascular volume overload during general anesthesia [ 2 ]. Second is the poorly studied mechanism of “interstitial washdown” originally suggested by the eminent physiologist Arthur Guyton to counteract peripheral edema when capillary filtration is increased [ 3 ].…”

Interstitial Washdown and Vascular Albumin Refill During Fluid Infusion: Novel Kinetic Analysis From Three Clinical Trials

“…However, the covariance analysis showed that pronounced interstitial washout is associated with a very high k12, which means that the peripheral accumulation of fluid could have been even greater without the washdown. By contrast, during general anesthesia the main effect of the washdown was an increase of the non-exchangeable ("third space") volume expansion, which is known to occur when urinary excretion is restricted despite adequate body hydration [10].…”

“…The most important difference is that diuretic response to volume loading is strong in volunteers but much weaker (-90%) during general anesthesia [11]. "Non-exchangeable" volume expansion is pronounced during general anesthesia [10], intermediate in diabetic ketoacidosis [9], and very small or even absent in healthy volunteers [5].…”

“…The volume kinetic analysis is likely to closely capture real physiological events [28] but uncertainties exist about the nature of the non-exchangeable volume expansion [10]. This fluid remains in the body but without equilibrating with the plasma within the 3-4 h of the experiment.…”

“…However, fluid may also accumulate in a "third space" which implies elimination from the kinetic system that is not recovered as urine. This flow represented by the rate constant kb was called "nonexchangeable volume expansion" [10].…”