Renal Intensity – How High ?

The ANZICS group appear to have done it again; that is taken a single centre trial done in Europe, repeated it in a sensible and pragmatic way but in a much larger, adequately powered multi centre setting and determined an evidence based outcome. It’s something of a shame that again the evidence based outcome doesn’t support the optimism of the initial trial.
This time the therapy in question is the ‘dose’ of RRT (renal replacement therapy). A previous trial by influential group led by Ronco suggested a survival benefit of 35mls/kg/hr effluent flow rate as opposed to 20ml/kg/hr. A major US study (the Veterans/NIH study) showed no difference in mortality but was limited in its application is the UK because of the relatively large proportion of patients who received intermittent heamodialysis, and the slightly complicated rationale for choosing which patients received which therapy. Most UK ICUs would provide only CVVH (or variants) to ICU patients.
Intensity of Renal Replacement Therapy in Critically Ill Patients. 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.   N Engl J Med.   2009 Oct 22;361(17):1627-3.


Trial design : Multicentre RCT in Australia & NZ, 1508 patients enrolled to 2 interventions (40mls/kg/hr or 25mls/kg/hr) across 35 ICUs. Primary outcome was mortality at 90 days, follow up was complete in 97%. The groups appeared to be well matched at baseline. Inclusion criteria were oligouria (<100mls in 6 hours unresponsive to fluid challenge), a K>6.5, pH <7.2, Urea > 25mmol or Creatine >300mmol or clinically significant fluid overload. Patients with CRF on dialysis were excluded. The trial was powered to 90% to detect an 8.5% absolute reduction from a mortality of 60%. There was adequate explanation of statistical methods, but of note actual trial mortality was of the order of 45%. Therefore, the study could be underpowered (although as we shall see this is unlikely). Importantly limitations in therapy were adequately explained and non-significantly different between groups.
The critical question is what therapy the patients actually received rather than the target (higher effluent rates being tricky to achieve due to filter downtime etc). The duration of therapy was similar, at a mean of 6 days. Actual flow rates were 22±17 and 33±12 (p-0.001), so a good separation in therapy was achieved.
Outcomes : Mortality was non-significant (44.7% vs 44.7%!). Likewise secondary endpoints were non-significant. There was an excess of hypophosphatemaia in the intensive group, but in general complication rates were low. Predetermined subgroup analysis of specified groups (septic, renal impairment) was likewise negative.
Should this influence our practise ? Yes it should. Until further evidence to the contrary there is no rationale to use high dose CVVH. However, we ought to note all the trials done have found that the actual delivered dose is less than that prescribed (due to gaps in treatment). Therefore as some, including Ronco, have argued it’s important to aim above the 25mls/kg/hr dose. How high above depends on individual CVVH performance, and this should be regularly audited within units.

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