Thursday, June 3, 2010

Volume, a new target for dialysis and acute renal failure?

One of the major advancements in nephrology in the first decade of the 21ast century was the rejection of Kt/V as a treatment target in dialysis. In a field that is lacking in randomized clinical trials we had three well done randomized clinical trials designed to verify the mounds of observational data. In all three Kt/V as an expression of dose failed.

Chronic hemodialysis: HEMO

  • eKt/V of 1.05 vs 1.45 (or a spKt/V of 1.2 vs 1.6) 

Peritoneal dialysis: ADEMEX

  • Increase in PD dose such that they move from less than 40% at Kt/V of 2.0 to 83% at Kt/V of 2.0

Dialytic support for acute renal failure: VA/NIH ATN trial
  • 3 days a week dialysis versus 6 days a week all at a single-pool Kt/V of 1.2 to 1.4 per session
  • Hemodynamicly unstable patients were randomized to one of two levels of CVVH 20 or 35 ml/kg/hour of total CRT effluent
All three looked at variations on Kt/V tuned to the individual clinical scenario. Varying Kt/V in each of these clinical scanrio made not a whif of difference to the patients.

In the aftermath of such intellectual carnage nephrology is desperately seeking a replacement. My experience with nocturnal dialysis and the amazing work coming out of Canada makes home hemo look like the most appealing option. Getting results comparable to transplant makes it look like an entirely new modality compared to traditional in-center hemo.

One of the aspects that made Kt/V so appealing was how it was a useful in any situation involving dialysis. (The lessons from NCDS study on chronic in-center hemodialysis guided the definition of adequate dialysis for ARF in the ATN trial)

What lessons does home hemo have to teach acute renal failure in the ICU? What lessons does it have for peritoneal dialysis. One could argue that one of the central problems in modern dialysis is fluid management. Too many of my patients are chronically fluid overloaded leading to hypertension and over worked hearts. Home hemo corrects hypertension. Is solving that cardiovascular problem accounting for much of the improved clinical outcomes?

If that is the case, then there is a clear lesson that we can take from home hemo and apply to the ICU. 
Don't let your patients get volume overloaded
We covered this in journal club last thursday: Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy

The study is a retrospective interpretation of registry data on children with acute renal failure receiving continuous renal replacement therapy. Each patient was given a fluid overload score by calculating a percentage overload:
They divided patients into three strata:

  1. <10% overload
  2. 10-20% overload
  3. ≥20% overload
They also used percentage overload as a continuous variable for the primary multivariate analysis.

The primary data is shown in table 2.
It should be immediatly obvious that the patients with more volume overload were sicker, they had signifigantly:
  • longer ICU stay
  • higher mortality
  • more multi-organ dysfunction
  • more likely to be intubated
  • more inotropes
  • more sepsis
  • higher PRISM score
For that reason I am not going to spend time discussing the univariate analysis and go straight to the multivariate analysis:
Worse fluid overload severity remained independently associated with mortality (OR, 1.03; 95% CI, 1.01-1.05). The relationship was satisfactorily linear and the OR suggests a 3% increase in mortality for each 1% increase in degree of fluid overload at CRRT initiation.
That is impressive. If the results hold up and aplies to adults it should scare the crap out of anyone who regularly rounds in the ICU. Think of a typical 80 kg adult who has total input of 2,400 mL (100 mL/hr) and has 1,600 mL of urine output, 67 mL/hour. That is a positive balance of 800 mL or 1% of body weight. If that goes on for 3 days and then the patient becomes oliguric with only 400 mL of urine output for two days (2,000 mL positive per day) before initiating CRT. That patient would be up 6,400 mL or 8% of bodyweight: Those relatively innocuous seeming numbers would represent a 24% increase in mortality compared to someone with matched ins and outs. Yowsa!

This is an observational study and it is important not to accept he results as truth but it is certainly a suggestive lead.
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