LITMIR.BIZ

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important advantages over intermittent hemodialysis, such as hemodynamic stability with slow continuous volume and solute control. Specific filters with reduced flow resistance that were adequate to operate in an arteriovenous modality were designed to improve performance. In spite of technological ameliorations in the filter and membrane design, CAVH presented limited ultrafiltration and solute clearance as well as risk derived from arterial cannulation.

      The Addition of Diffusion and the Birth of Hemodiafiltration

A significant advance was made by designing new filters with 2 ports in the dialysate/filtrate compartment that allowed the circulation of dialysate fluid countercurrent to blood and obtained additional diffusive solute clearance. This modified technique was named continuous arteriovenous hemodiafiltration or hemodialysis, respectively [5]. With the arrival of continuous arteriovenous hemodialysis and continuous arteriovenous hemodiafiltration, uremic control became easier in patients irrespective of their weight or catabolic state simply by increasing countercurrent dialysate flow rates to 1.5 or 2 L/h as necessary.

      Ultrafiltration and Fluid Balance Control

Originally, ultrafiltration control was done manually and transmembrane pressure was modified by positioning the ultrafiltrate (UF) collecting bag at different heights in respect to the filter. The replacement solution was delivered using manually regulated clamps. The negative pressure generated by the UF column regulated the final transmembrane pressure. Subsequently, manual systems were, in some cases, substituted by automatic fluid balance systems called Equaline [6]. The systems operated by gravity utilizing 2 load cells for UF and SF measurement, and a smart clamp provided adequate SF flow to achieve the desired fluid balance.

      Introduction of Venovenous Pumped Techniques

      Arteriovenous therapies were simple because they did not require a peristaltic blood pump, but the morbidity associated with arterial cannulation was substantial. For this reason, venovenous techniques utilizing a double-lumen central venous catheter for vascular access were considered preferable and safe. Thus, within a few years, continuous venovenous hemofiltration or continuous venovenous hemodiafiltration replaced CAVH because of its improved performance and safety. The advance was made possible by the use of blood pumps, calibrated ultrafiltration control systems, and double-lumen venous catheters. These treatment methods were widely utilized at the end of the 1980s and showed excellent uremic control utilizing high blood flows (150 mL/min or more) and large membrane surface areas (0.8 m² or more). To facilitate nursing care, ultrafiltration was soon controlled by devices with reasonable precision. Thus, for clinical purposes, ultrafiltration and reinfusion could be fully regulated to achieve the desired therapeutic goals. This era was characterized, however, by the adoption of technology from other fields (e.g., such as chronic hemodialysis), and multiple devices (blood pump, UF pump, reinfusion pump, anticoagulation, etc.) were connected to the patient without a systematic assembly and a coherent combined strategy. Although efficiency was highly improved and treatment performance was superior to any previous technique, this approach led to potential errors and treatment failures due to the inability of different devices to communicate and operate together.

      From Adoptive Technology to Dedicated Equipment

In the late 1980s, specific machines for CRRT were designed and a new era of RRT in the critically ill patient began [7, 8]. The therapy started to get standardized and clear indications began to be defined. Special requirements from easier institution of CRRT and easier monitoring of treatment led to the development of the first generation of CRRT-integrated machines with several pumps and different technique capabilities. The ‘Prisma’ machine was one of the first integrated CRRT machines designed specifically for acute RRT in intensive care. The preassembled circuit and the autopriming feature made CRRT possible in almost every intensive care unit, with improved safety and performance.

      Technological Response to New Demands

After the extracorporeal therapies had become more or less a routine treatment in intensive care, new studies were performed to determine the importance of accurate delivery of therapy and a minimum quantity (dose) of treatment to be provided in CRRT to optimize results and improve outcomes [9]. New requirements in terms of performance and safety were identified, with the result that technology followed the demand for higher efficiency and large exchange volumes in presence of a user-friendly interface. This process led to the development of a new generation of machines with advanced features, higher performance, and an integrated easy-to-use operator interface [10].

      Evolution of CRRT Techniques

Different techniques are available today for the therapy of the critically ill patient with renal and other organ dysfunction. An interesting aspect is the definition of an “adequate” dose of dialysis in AKI and the potential of different therapies for the treatment of sepsis [9–15]. Originally, 35 mL/kg/h was the value identified to maximize survival, whereas higher doses did not seem to give additional benefits in the general population [9]. Subsequent studies have demonstrated that lower doses can be equally safe and successful in treating the critically ill patient, although effective delivery often differs significantly from prescription [11–20]. The second concept introduces the rationale for high-volume hemofiltration in specific patients with acute renal failure and sepsis [21–27]. High-volume hemofiltration or coupled plasma filtration adsorption can be seen as a potent powerful immunomodulatory treatment in sepsis. Since sepsis and systemic inflammatory response syndrome are characterized by a cytokine network that is synergistic, redundant, autocatalytic, and self-augmenting, the control of such a nonlinear system cannot be approached by simple blockade or elimination of some specific mediators. Therefore, nonspecific removal of a broad range of inflammatory mediators by high-volume hemofiltration and coupled plasma filtration adsorption may be beneficial as recently suggested on the basis of the “peak concentration” hypothesis [24–27].

      From Renal Replacement to Multiple Organ Support Therapy

The effect of different modalities of CRRT on length of stay and recovery of renal function in the general population is still under evaluation since the case mix is changing in every study and the population treated is not homogeneous. In this field, further research is needed, although it has become evident that precision CRRT (personalized prescription) should be adopted in order to optimize results in single patients even in the absence of documented benefits of one specific technology for the general population. Adequate technological support becomes mandatory to fulfil all these expectations, and a generation of new machines and devices has been made compatible with the demand for increased efficiency, accuracy, safety, performance, and cost/benefit ratio. At present, almost all CRRT therapies can be delivered in a safe, adequate, and flexible way, thanks to devices being specifically designed for critically ill patients. The development is a point where multiple organ support therapy is envisaged

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