Dialytrauma

Dialytrauma refers to the set of possible and non-desired complications associated with the use of renal-replacement therapies (RRT).[1]

Origin

The Dialytrauma Concept was introduced into medical literature in 2008 by a Spanish group of intensivists.[2] The idea was born as a consequence of the publication of the first major trial (known as the ATN Study[3]) looking at the intensity of renal support in critically ill patients with acute kidney injury (AKI). In this multicenter, randomized, controlled trial, renal support was delivered using different RRT modalities: intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemodiafiltration. The main result of this study (including 1,124 patients) was that a fixed “intensive” dose (35 mL/Kg/h) delivered with different RRT modalities, produced the same clinical outcomes than a “less-intensive” dose (20 mL/Kg/h). The authors’ conclusion was that critically ill patients with AKI requiring RRT should be treated with this “less-intensive” dose, given that it will achieve the same results as the “intensive” one. Nevertheless, the rate of complications and adverse events detected was higher in the “intensive” dose arm of this study. As such, the aforementioned Spanish group of intensivists, wrote a letter to the Editor of the same Journal[2] postulating the idea that all those complications (grouped under the term “Dialytrauma”) could have been responsible for the results of the ATN Study. In the same letter to the Editor, and according to what had been previously published by Dr. Schiffl,[4] they hypothesized that a dynamic adjustment of the dose of RRT, would be more physiological due to the dynamic nature of AKI in critical illness. This therapeutic schedule, named “Dynamic Approach”, would reduce the incidence of dialytrauma and, probably, would achieve better clinical outcomes.

However, given the lack of level 1 clinical trials on this “Theory of Dynamic Approach”, the authors of the ATN Study branded this idea as being “speculative”.[5] Despite this, a year later Dr. Palevsky (ATN Study’s first author) wrote an Editorial comment[6] on the RENAL Study[7] (the second major trial looking at the intensity of renal support) concluding that the:

Failure to demonstrate improved outcomes with more intensive renal-replacement therapy in critically ill patients […] does not imply that the intensity of renal-replacement therapy does not matter. [...] Furthermore, it should not be forgotten that patient care needs to be individualized – more intensive therapy may be required for the treatment of hyperkalemia, metabolic acidosis, or extreme hypercatabolism – and that the true adequacy of renal-replacement therapy is defined by more than just the clearance of small solutes.
— Palevsky PM,«Renal Support in Acute Kidney Injury — How Much Is Enough?» (2009)N Engl J Med 361(17):1699-1701.

In this way, finally, he seemed to support the Theory of Dynamic Approach, that is: we need to tailor the RRT dose to the clinical scenario of the individual patient.

From then on, both the Dialytrauma Concept and the Theory of Dynamic Approach have been referenced in several publications by impact groups in the field of RRT.[8][9][10]

The dialytrauma concept

The potential complications associated with the use of RRT are numerous.[11] But among them all, non-desired mass transference is probably one of the most relevant from a clinical point of view. Due to the non-specific pattern of molecule elimination achieved with RRT (either using diffusion or convection) and with most of blood purification extracorporeal therapies (such as plasmapheresis, CPFA, etc.), they can produce significant clearance of “valuable substances”. This will mean micronutrient depletion, hypophosphatemia, hypokalemia, subtherapeutic doses of antibiotics, etc. The loss of these molecules without appropriate replacement could engender useless, or even harmful a therapy (such as RRT) intended to improve the outcomes of critically ill patients with AKI. But the dialytrauma concept is wider and also encompasses the problems associated with vascular access (mechanical and infectious), dialysis-associated hypotension, hematological complications (blood losses derived from circuit clotting, bleeding associated with the anticoagulation needed to run a RRT, thrombocytopenia, etc.), non-desired heat loss, and increased costs among others.[1]

The theory of dynamic approach

Critical illness is highly dynamic. As such, critically ill patients needing RRT, depending on the clinical severity (AKI alone, or AKI associated with other organs dysfunction), could require a higher depurative dose of renal support[4]. As a matter of fact, the treatment of a patient with a toxic hyperkalemia, or a severe lactic acidosis due to a metformin intoxication, will need a different (and higher) depurative dose than a patient whose main problem derived from AKI is just anuria. However the two main trials that have studied the intensity of renal support in critically ill patients with AKI[3], [7], allocated them to a higher or lower dose without taking into account the clinical status of each patient. Only in the ATN Study[3] was the modality of RRT changed (from intermittent to extended or continuous) depending on the hemodynamic status of the patient, (patients in shock were managed with extended or continuous modalities), supporting the general idea that intermittent dialysis is not well tolerated by patients with unstable hemodynamic status. Not surprisingly both studies concluded that clinical outcomes were the same whether using a higher or lower intensity of renal support. However, as already mentioned before, they also found a higher incidence of complications (hypothermia, hypokalemia, hypophosphatemia, etc.) in the patients randomized to receive a higher dose. Taking together the results of both studies, it determined that the incidence of both under and overtreatment must have been the same in all groups of patients (whether randomized to receive a higher or lower fixed intensity of renal support, they would have received an improper dose at any time – i.e. if with severe hyperkalemia and allocated to a lower dose, initially undertreated, or if with a normal potassium and assigned to receive a higher dose, overtreated). Trying to conceal this problem, the Theory of Dynamic Approach postulates that we have to adapt the intensity of renal support according to the patient’s clinical situation, transforming in this way a fixed-dose-RRT schedule into a goal-directed-RRT, one to avoid Dialytrauma.[1]

References

  1. ↑ Maynar Moliner J, Honore PM, Sánchez-Izquierdo Riera JA, Herrera Gutiérrez M, Spapen HD. Handling continuous renal replacement therapy-related adverse effects in intensive care unit patients: the dialytrauma concept. Blood Purif. 2012;34(2):177-185.
  2. ↑ Maynar-Moliner J, Sánchez-Izquierdo-Riera JA, Herrera-Gutierrez M: Renal support in critically ill patients with acute kidney injury. N Engl J Med 2008(18); 359: 1960–1961.
  3. ↑ Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudury D et al for the VA/NIH Acute Renal Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359(1):7-20.
  4. ↑ Schiffl H Daily haemodialysis in acute renal failure. Old wine in a new bottle? Minerva Urol Nefrol. 2004 Sep;56(3):265-277.
  5. ↑ Palevsky PM, et al. Renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359(18):1961-1962.
  6. ↑ Palevsky PM. Renal Support in Acute Kidney Injury — How Much Is Enough? N Engl J Med 2009; 361(17):1699-1701.
  7. ↑ RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S: Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009, 361:1627-1638.
  8. ↑ Helmut Schiffl. The dark side of high-intensity renal replacement therapy of acute kidney injury in critically ill patients. Int Urol Nephrol (2010) 42: 435–440.
  9. ↑ Vesconi S, Cruz D, Fumagalli R, Kindgen-Milles D, Monti G, Marinho A, Mariano F, Formica M, Marchesi M, Rene R, Livigni S, Ronco C Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury. Crit Care 2009; 13:R57.
  10. ↑ Bouchard J, Macedo E, Mehta RL. Dosing of Renal Replacement Therapy in Acute Kidney Injury: lessons learned from clinical trials. Am J Kidney Dis 2010; 55: 570-579.
  11. ↑ Finkel KW, Podoll AS. Complications of Continuous Renal Replacement Therapy. Semin Dial 2009 22 (2): 155-159.


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