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...
From the recent past, hemofiltration, particularly high-volume hemofiltration, has rapidly evolved from a somewhat experimental treatment to a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine-resistant hypodynamic septic shock. Nonetheless, this approach lacks prospective randomized studies (PRTs) evaluating the critical role of early hemofiltration in sepsis. An important milestone, which could be called the 'big bang' in terms of hemofiltration, was the publication of a PRT in patients with acute renal failure (ARF). Before this study, nobody believed that hemofiltration could change the survival rate in intensive care. Since that big bang, many physicians consider that hemofiltration at a certain dose can change the survival rate in intensive care. We now must try to define what the exact dose in septic ARF should be. As suggested by many studies this dose might well be higher than 35 ml/kg/h in the septic ARF group. The issue of the dosage of continuous high-volume hemofiltration must be tested in future randomized studies. Since the Vicenza study has shown that 35 ml/kg/h is the best dose in terms of survival when dealing with nonseptic ARF in the intensive care unit (ICU), several studies from different groups have shown that a higher dose might be correlated with better survival in septic ARF. This has also been shown in some way by the Vicenza group but not with a statistically significant value. New PRTs have just started in Europe such as the IVOIRE (hIgh VOlume in Intensive Care) study. The RENAL study is another large study looking more basically at dose in nonseptic ARF in Australasia. The ATN study in the USA is also testing the importance of dose in the treatment for ARF. Nevertheless, 'early goal-directed hemofiltration therapy' has to be studied in our critically ill patients. Regarding this issue, fewer studies, mainly retrospective, exist; but again the IVOIRE study will address this issue by studying septic patients with acute renal injury according to the RIFLE classification. This chapter will focus on the early application and adequate dose of continuous high-volume hemofiltration in septic shock in order to improve not only the hemodynamics but also survival in this very severely ill cohort of patients. This could be called the big bang of hemofiltration as one could have never anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of septic ARF patients in the ICU. Apart from the use of an early and adequate dose of Honoré/Joannes-Boyau/Gressens 372 hemofiltration in sepsis, a higher dose could also provide a better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this presentation will also review brand-new papers regarding the use of hemofiltration in systemic inflammatory response syndrome and out-of-hospital cardiac arrest.
Implementing continuous renal replacement therapy (CRRT) in a intensive care unit (ICU) is a somewhat difficult issue and quiet different from starting a new ventilation mode or a new hemodynamic device. It may indeed require an on-call medical emergency CRRT team as expertise in this field is really a key issue to success. Education for the nursing team is another key point, especially as ongoing or continuous education is changing very quickly. Uniformity of the type of device used is another crucial part in the organization process with regard to CRRT implementation in the ICU. Involvement of both the ICU and nephrology teams is another key to success especially when different modes and higher exchange rates are used. Also, a nursing group devoted to the ongoing implementation and education of the ICU team is very useful in order to attain the goals that have been set. Already in 1984 acute renal failure was described as one of the remaining and challenging problems in the ICU. Hemodialysis was not always feasible then because of the hemodynamic instability of critically ill patients. Under those circumstances continuous arteriovenous hemofiltration (CAVH) was advocated as an efficient alternative method with less detrimental hemodynamic effects. At the time it was thought that CAVH would be found to be an effective 'artificial kidney' (control of body fluid, electrolyte and acid-base homeostasis and uremia) and this without serious side effects. But already nearly 25 years ago, it was found that continuous anticoagulation was a major problem that could cause life-threatening complications in posttraumatic and surgical patients. At the time, it was thought that running a protamine infusion on the venous line would help to diminish these complications. CRRT has been carried out in our ICU since 1985, first with CAVH and since 1989 with some early forms of continuous veno-venous hemofiltration (CVVH). The unit has used BSM 22, BM 25 and Prisma for nearly 10 years, and Aquarius since the end of 2001. The educational process started at the beginning of 1990 with the implementation of CVVH using BSM 22 and BM 25. Very soon it was realized that a new strategy implementing pulse high-volume hemofiltration (pulse-HVHF) was really needed. Therefore, a nursing group composed of 5-8 nurses who would be taught beforehand was started, and this dedicated group would then teach the rest CRRT Technology and Logistics 355 of the staff nurses. This group exists today and has at least 6-8 meetings/year in which all the problems that must be faced in the implementation of CRRT are dealt with. Here all the steps made by our and other units in this field will be discussed, including an overview of the various protocols implemented and a description of our dedicated nursing group with regard to CRRT.
Early recognition of acute kidney injury (AKI) in the intensive care unit (ICU) remains a critical problem, with a rising incidence and a high mortality rate. As a consequence, the actual lack of an early and effective biomarker results in a significant delay in initiating appropriate therapy. The accurate diagnosis of AKI is especially problematic in critically-ill patients, in whom we know that renal function is in an unsteady state; therefore the validity of creatinine-based baseline assessment measures is reduced. Because the rationale for assessing AKI markers in critically-ill patients is strong at the present time, researchers are stimulated to establish a multidimensional AKI classification system. This system should in essence grade AKI severity. The most widely referenced classification is the RIFLE system. Thus, early recognition of AKI, well before changes in serum creatinine occur, has come under intensive research, because it is evidenced that even small increases in serum creatinine are associated with an increase in patient mortality. The development of a biomarker kit in which several early markers with different characteristics are combined, is essential. Multi-centre, randomized studies indicate a potential for early biomarkers able to diagnose AKI 48 hours before creatinine changes. In conclusion, time has come to leave serum creatinine behind as a marker of renal function in patients with AKI on the ICU. Only then will we be able to offer early goal-directed therapy for the kidney in the ICU setting.
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