Acute Continuous Renal Replacement Therapy (Developments in Nephrology)

37th Vicenza Course on AKI &CRRT
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Mean SD age was Mean BMI was Mean delivered CRRT dose was ICU mortality rate was However, almost two-thirds of survivors recovered kidney function sufficiently enough to be independent of RRT. Bortolo Hospital, Vicenza - Italy. CAVH soon became a reliable alternative to hemo- or peritoneal dialysis in critically ill patients.

1 Introduction

Acute Continuous Renal Replacement Therapy (Developments in Nephrology): Medicine & Health Science Books @ Acute renal replacement therapy (RRT) provides supportive Continuous renal replacement therapy (CRRT), in particular, . The Early Versus Late Initiation of Renal Replacement Therapy In Critically Ill Patients With Acute Kidney 12 hours of the development of KDIGO stage 3 AKI or upon an absolute.

The alliance with industry led to development of new specialized equipment with improved accuracy and performance in delivering continuous renal replacement therapies CRRTs. Machines and filters have progressively undergone a series of technological steps, reaching a high level of sophistication. The evolution of technology has continued, leading to the development and clinical application of new membranes, new techniques and new treatment modalities.

With the progress of technology, the entire field of critical care nephrology moved forward, expanding the areas of application of extracorporeal therapies to cardiac, liver and pulmonary support. A great deal of research made extracorporeal therapies an interesting option for the treatment of sepsis and intoxication and the additional use of sorbents was explored. With the progress in understanding the pathophysiology of acute kidney injury AKI , new guidelines were developed, driving indications, modalities of prescription, monitoring techniques and quality assurance programs.

Information technology and precision medicine have recently contributed to further evolution of CRRT, with the possibility of collecting data in large databases and evaluating policies and practice patterns. This is likely to ultimately result in improved patient care.

CRRTs are 40 years old today, but they are still young and full of potential for further evolution. Acute renal failure was mostly treated with peritoneal dialysis or haemodialysis, but in critically ill patients, these modalities were often contraindicated or precluded due to severe cardiovascular instability.

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In the year following the first description of CAVH, a significant evolution of acute renal replacement therapy ARRT and related technology occurred, leading to the modern techniques of continuous renal replacement therapy CRRT. In this process of evolution, the centre of Vicenza has always been leading the edge and it has significantly contributed to the birth of a new speciality called Critical Care Nephrology.

It may be incomplete or partial, but certainly every single minute of this history has been personally lived with passion and dedication. The introduction of CAVH made it possible to perform renal replacement therapy even in ICUs not fully equipped or trained for hemodialysis. Our first patient was treated in Vicenza with the original Amicon 20 diafilter in In the late s we extended the use of the technique used in adults to neonates with the use of specific Minifilters Fig.

We developed specific filters with reduced flow resistance, suitable for operating in arterio-venous mode that are today preserved in our Vicen- za Dialysis Museum. In spite of several advantages, CAVH soon demonstrated limitations in efficiency and frequent complications due the need for arterial cannulation. This spurred new research for alternative techniques.

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A remarkable increase in treatment efficiency and urea removal was achieved with the addition of diffusion. In the case of excessive ultrafiltration, fluid losses were partially or completely replaced, allowing accurate fluid balance control. The problem of arterial cannulation was still the main drawback of the technique.

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Manual control of ultrafiltration was initially achieved by positioning the filtrate bag at different heights, thus modifying the negative suction pressure generated by the filtrate column. Delivery of replacement fluid was initially regulated manually and later new systems were designed to provide automatic fluid balance 6.

The systems operated by gravity, using scales and electronic clamps, although peristaltic pumps soon replaced these simple mechanisms with more advanced equipment. Because arterial-venous techniques were associated with significant complications related to arterial cannulation and low blood flow in the extracorporeal circulation, continuous veno-venous hemofiltration CVVH or hemodialysis CVVHD hemodiafiltration CVVHDF took over thanks to the availability of double lumen venous catheters and machines with a peristaltic blood pump 7 — This resulted in better control of hyper-catabolic states and other severe pathophysiological derangements.

Initially veno-venous circuits took advantage of already existing technology, often creating a combination of devices blood pump, UF pump, reinfusion pump, anticoagulation, etc. Adoptive technology allowed significant advances to be made, but it soon proved inadequate when a clear need for integrated and safer devices became evident in clinical practice. In Vicenza we started the process of integration of blood and dialysate filtrate pumps in a single machine and pushed the industry of the field toward new research to create dedicated devices for CRRT With this effort, companies mostly involved in chronic hemodialysis began to collect components from chronic machines and to integrate them into machines for CRRT 11 , Using this approach, several companies made new equipment: B.

Frigato, in Mirandola. Medica built an integrated version of the Equapump and Equaline, while in Germany, Fresenius Medical Care commercializsed the DM08 with 1 blood pump and 2 pumps for dialysate or fluid balance 13 — Bellco utilized the blood module of the Multimat chronic machine to create the Multimat B Acute version, and Gambro adjusted a special version of the AK 10 module for continuous dialysis. All these machines derived from the technology generated for chronic hemodialysis, but they represented the seeds for the upcoming generation of specific CRRT equipment 16 , With the progress in understanding the pathophysiology of AKI and its clinical implications, the targets for renal replacement therapy became clearer 18 — Special requirements for easier institution of CRRT and easier monitoring of treatment had led to the development of the first generation of CRRT integrated machines with several pumps and different technique capabilities.

Started in , in Vicenza we concluded the first randomized trial on treatment dose in the year Subsequent studies have demonstrated that lower doses can be equally safe and successful in treating the critically ill patient 27 — 33 , although effective delivery often differs significantly from the prescription 34 — The new machines developed by industry with the possibility of moving toward more sophisticated techniques such as coupled plasma filtration-adsorption CPFA and high-volume hemofiltration HVHF fulfilled these new performance requirements — Improved usability and user-friendly interfaces with systematic instructions made CRRT machines popular and widely used in every ICU The original observation that higher doses of treatment could be beneficial in patients with sepsis introduced the rationale for HVHF and CPFA with the intent to remove chemical mediators 42 — Since a cytokine network that is synergistic, redundant, autocatalytic and self-augmenting characterizes sepsis and systemic inflammatory response syndrome, it is unlikely to achieve the control of such a nonlinear system by simple blockade or elimination of some specific mediators.

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 changes in every study and the population treated is not homogeneous. Further research is needed in this field, 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 the documented benefits of 1 specific technology for the general population. Adequate technological support becomes mandatory to fulfil all these expectations and new machines have been upgraded with specific circuits to support organs other than the kidney.

The possibility of supporting or partially replacing the function of organs such as the liver, the lung and the heart with modified extracorporeal circuits, make multiple organ support therapy MOST a reality in the critical care setting. CRRT machines become platforms for multiple organ support via extracorporeal therapies carried out with specific biomaterials and devices 45 , Hemoperfusion has been available for detoxification purposes since the second part of the last century. Zeolites and charcoal were the most common sorbents, although soon a new generation of more hemocompatible materials became available.

In recent years, cartridges with polymixin-B-coated polystyrenic fibres designed for the adsorption of endotoxin have been used for the treatment of sepsis. This therapy seems particularly beneficial in patients with post-surgery abdominal septic shock 47 , New sorbents, derived from the original experience carried out by our group in the early years of the new century, are today appearing as a new option for the treatment of sepsis 49 —. The latest generation of machines available on the market today, which represent the evolution of the past 4 decades of research and development is shown in Figure 3.

Specific machines have now been designed to permit safe and reliable performance of the therapy. These new devices are equipped with a user-friendly interface that allows for easy performance and monitoring. The apparent complexity of the circuit is made simple by a self-loading circuit or a cartridge that includes the filter and the blood and dialysate lines. Priming is performed automatically by the machine and pre- or post-dilution reinfusion of substitution fluid before or after the filter can easily be performed by changing the position of the reinfusion line.

These new machines permit all CRRT techniques to be performed by programming the flows and the total amounts of fluid to be exchanged or circulated as a counter-current dialysate throughout the session. This was a starting point to generate a harmonized terminology and to advance in a standardized environment for the generation of useful pragmatic trials. Today we have several examples of new machines that include software and terminology coherent with the recommended nomenclature. The consensus group also focused on the identification of patients requiring CRRT and the correct timing of application, technological needs and expected advances, pointing out the desirable characteristics of new equipment, membranes and the importance of integration of information technology into the process of patient care and decision-making 58 — The ADQI group has recently recommended the use of modern information technology IT tools to improve practice and patient care. Such tools can be used for data acquisition and storage but also for treatment monitoring Manual, authorized or automatic feedback technology is available today in chronic dialysis machines and has been advocated for CRRT machines as well.

Integration of patient and machine signals through IT tools and connectivity with electronic health record EMR and data collection systems will be required to allow pragmatic trials and make big data registries available for analysis. Machine connectivity can be provided via different tools. Machine and patient chip-cards can be used to extract data from single treatments from the front-end terminal CRRT machine.

Cable or wireless connectivity may permit the download of technical and clinical parameters from single or multiple machines and to analyse single treatment data as well as trends or statistics in multiple treatments. Cloud-based connectivity could help clinicians to generate virtual registries and analyse the performance of single treatments or centres in absolute terms, or relative to other units.

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This may result in important feedback to clinicians, to either strictly control outliers, or to change policies and procedures in the event of repeatedly unsatisfactory results. Data collected and stored in EMRs may be rapidly evaluated and managed by ad hoc designed electronic sniffers that can alert clinicians about dangerous trends or unwanted effects of CRRT.

Solutions to the problem may be listed as suggestions or even automatically fed back into devices such as pumps and CRRT machines. There are several areas of investigation where evolution in new therapeutic options and new devices is likely to occur. Different biomaterials and surface modifications have been introduced on semipermeable membranes to increase biocompatibility, to reduce thrombogenicity and the tendency toward fouling, and finally to modify sieving and adsorption properties.

Vitamin E-coated membranes represent an example in which alpha-tocopherol has been covalently bound to a polysulfone membrane to reduce oxidant stress These and other new membranes should be further investigated to elucidate the potential for improving the inflammatory pattern in sepsis. Software integration should become a tool for new equipment to perform safer and more efficient CRRT treatments. The integration of bioimpedance and on-line haematocrit measurements may result in important effects on hemodynamic stability and treatment delivery The integration of blood temperature monitoring may have the potential to control thermal energy balance and the patient's temperature.

A significant heat loss can in fact occur when the extracorporeal circuit is exposed to room temperature Automated circuit pressure control with flow adjustment feedback could provide the best possible blood flow in presence of a malfunctioning catheter or could provide early warning of access malfunction, preventing inadequate treatment delivery.

On-line chemical sensors for acid-base and electrolytes may provide the basis for continuous control via biochemical feedback on dialysate and replacement fluid composition.

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There is a great deal of interest in applying nanotechnology, microfluidics and other emerging sciences to the field of renal replacement. In Vicenza we tested the first wearable system for ultrafiltration For the original wearable belt, we mostly used components off the shelf, but we recently made new developments by creating a new design and applying newly conceived, dedicated technology 67 — Wearable devices are mostly conceived for ambulatory care and out-of-hospital patients.

Nevertheless, it seems that miniaturized systems may become useful even in the acute patient, allowing mobility, low-priming-volume extracorporeal circuits and better care at the bedside. This new paradigm of beneficial effect in increasing RRT dose was further addressed by two large studies: One showed better outcomes for patients treated by daily haemodialysis rather than three times a week Schiffl et al.

However, two points remain unanswered. Vesconi et al. Secondly, the debate about the dose remains open for septic patients as some small prospective or randomised studies have shown a beneficial effect of high dose haemofiltration Honore et al.

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When to commence RRT is also a major question. This was hampered in the past by a lack of a clear and consensual definition of acute kidney injury to enable stratification of the degree of renal impairment and to homogenise patients for study purpose and to help to define the best moment to start RRT. These classifications alert aware clinicians about the presence of AKI and to allow early intervention. Some studies or meta-analysis published in the last few years have possibly fuelled interest for commencing RRT early but large RCT's to define the best moment to start are awaited Shiao et al.

One RCT regarding timing to start haemofiltration was negative Bouman et al. Anticoagulation remains a field of continuous development and research, in particular since the description of citrate anticoagulation and new dedicated machines.

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Despite the fact that unfractionated heparin UFH remains the most commonly use anticoagulant around the world for RRT, citrate and other alternatives begin to assume more importance. The most recent important study was provided by Oudemans van Straaten and coll where they compared citrate anticoagulation to low molecular weight heparin LMWH but only in the surgical subgroup Oudemans-van Straaten et al. Although no difference was found in terms of efficacy, they found an unexplained improved outcome for patients treated with citrate.

Thought must also be given to antithrombin levels when using UFH during RRT as it is a mandatory clotting co-factor and sometime forgotten although its activity level is often reduced, particularly in septic ICU patients and need to be supplemented Lafargue et al. The last point is the one concerning the replacement fluids, where new products on the shelf are becoming closer to the plasma composition, in particular with phosphorus implementation directly in the fluid bag Broman et al.

In conclusion, more and more developments are occurring in the field of RRT. Large RCTs on various key subjects are warranted to try to improve our knowledge and save more lives as patients suffering from AKI in ICU continue to have an unacceptably high mortality rate.

In the meantime, the odyssey in the RRT universe will continue for the intensivists, enabling them to expand our knowledge in this exciting field. Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a metaanalysis. Crit Care Med ; Recent trials in critical care nephrology.

Role of Acute Dialysis (CRRT, SLED, Intermittent hemodialysis, other) - Renal and Urology News

Contrib Nephrol ; Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med ; Phosphate-containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy. Acta Anaesthesiol Scand ;