Blood and Plasma Treatments: The Rationale of High-Volume Hemofiltration

Abstract

Since the early 1990s, experts in the field have thought that a reduction in cytokines in the blood compartment could, in theory, reduce mortality, but this is perhaps too naive as the pharmacodynamics and pharmacokinetics of cytokines throughout the body are not well known and are probably much more complicated than previously thought. This ha now led to three leading theories and concepts. Ronco and Bellomo conceived the peak concentration hypothesis in which clinicians concentrate their efforts to remove mediators and cytokines from the blood compartment at the proinflammatory phase of sepsis. By reducing the amount of free cytokines, it is hoped that the level of remote organ (associated) damages can be dramatically decreased and, as a consequence, the overall death rate. In this regard, it is still not known what will happen at the interstitial and tissue level with regard to mediators and cytokines which are obviously the most important part in terms of consequences at the tissue level. In this setting, techniques that can more rapidly and substantially remove great amounts of cytokines or mediators are privileged. Among these, there is high-volume and very high-volume hemofiltration and a number of hybrid therapies encompassing high-permeability hemofiltration, super high-flux hemofiltration, hemo-adsorption or coupled filtration and adsorption and other types of adsorption using physical or chemical forces rather than driving forces as used normally in hemofiltration-derived techniques. The second concept is called the threshold immunomodulation hypothesis, also called the Honoré concept. In this concept the view of the system is much more dynamic. In experiments when removal is occurring on the blood compartment side, the level on the interstitial side and the tissue side is also changing and, because not only mediators but also pro-mediators are being removed, some pathways have really stopped when enough pro-mediators have been removed by this technique. At this point, the cascade is blocked and this point is called the threshold point. At this level, the cascade is lost and no further harm can be done to the tissue of the organism. Obviously, it is difficult to know when this point has been reached once high-volume hemofiltration is applied. But what is known, is that hemodynamics and survival can be improved in some patients as shown by various studies using high-volume hemofiltration without any significant drop in mediators inside the blood compartment itself. This effect is obtained without a dramatic fall Honoré/Joannes-Boyau/Gressens 388 in the plasma cytokine level because the cytokine or mediator levels should fall at the tissue level and not specifically at the blood compartment level. Nevertheless, the exact mechanism by which high-volume hemofiltration increases the flow of mediators and cytokines between the interstitial compartment and the blood compartment (and back to the blood side) is not known. Before the end of 2005, it was found that this missing step is perhaps well explained by t...

Application of bedside continuous blood purification in patients with multiple organ dysfunction syndromes

“…Since then, various other regimens for continuous renal replacement therapy, for example, continuous blood purification (CBP), have been developed. [9,10] CBP is mainly used to remove inflammatory mediators contributing to the occurrence of MODS. [11][12][13][14][15][16] In our study, we found that after CBP treatment, water content, electrolytes and acid-base balance disorders were corrected in the MODS patients, azotemia was prevented, and internal environment was maintained.…”

High-volume Hemofiltration in the Intensive Care Unit

“…41,42 This theory is interesting because it affects cytokines at the tissue level, which is where cytokines are harmful, and it also explains why numerous studies assessing blood purification techniques found an improvement of outcomes with no modification of cytokine blood concentrations as cytokines from the tissues replace those removed from the blood. 43,44 Di Carlo and Alexander also proposed the "mediator delivery hypothesis," in which HVHF is responsible for an increase of the lymphatic flow by 20-to 40-fold because of the high amounts of crystalloid fluids used for replacement with this technique. [45][46][47][48] This leads to a significant drag and displacement of inflammatory mediators to the blood compartment, making them available for removal.…”

High-Volume Hemofiltration in Sepsis and SIRS: Current Concepts and Future Prospects

“…However, in clinical practice when applying high-volume hemofiltration, determining this point is fraught with difficulty as there might be significant changes at interstitial and tissue level, while no changes in the blood compartment can be determined. A number of studies using hemofiltration, although observational only, have demonstrated improved hemodynamics and survival in some patients without a significant drop of mediators inside the blood compartment itself [11][12][13] . It may therefore be concluded that the substantial biological effects of HVHF are obtained without any dramatic fall in plasma cytokine level because cytokine or mediator levels fall at tissue level where they do harm.…”