Dosing Continuous Renal Replacement Therapies (CRRT): What is Enough?

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To better understand continuous renal replacement therapies (CRRT), we must understand the process of solute removal by diffusion and convection.

Diffusion is the process by which “molecules that are present in a solvent and can pass freely across a semipermeable membrane tend to move from the region of higher concentration into the region of lower concentration.”

On the other hand, convection is where “solutes pass across the semipermeable membrane in association with the plasma water” as a result of a transmembrane pressure gradient.

Let’s meet the CRRT players:

  • Continuous Veno-venous Hemofiltration (CVVH)
  • Continuous Veno-Venous Hemodialysis (CVVHD)
  • Continuous Veno-Venous Hemodiafiltration (CVVHDF)
Continuous Renal Replacement Therapy (CRRT) Modalities

These modalities are distinguished by their underlying mechanism of solute removal.

  • CVVH utilizes convection. Replacement fluid is administered to maintain euvolemia and dilute the plasma concentration of solutes not present in the replacement fluid (i.e. urea nitrogen, creatinine).
  • CVVHD utilizes diffusion and convection. Replacement fluid is not used in CVVHD.
  • CVVHDF uses a combination of convection and diffusion. Replacement fluid is also used to maintain euvolemia as in CVVH.

Once deciding on the modality of choice, we must choose a dose. The dose of CRRT is often estimated by the effluent flow rate (mL/kg/hr). It is commonly calculated as the ultrafiltration rate in CVVH, delivered dialysate flow rate in CVVHD, and a combination of both for CVVHDF.

The KDIGO clinical practice guideline for acute kidney injury (AKI) recommends “delivering an effluent volume of 20 to 25 mL/kg/h for CRRT in (AKI).” However, the prescribed dose is not always delivered due to CRRT interruptions due to procedures, clotting, replacement of filters, and tubing changes. Therefore, the guidelines also recommend frequent evaluation and “assessment of the actual delivered dose in order to adjust the prescription.”

There have been several studies examining the dose of CRRT and survival among critically ill patients (Table 1 summarizes these studies, adapted from Prowle, J et al.). Out of those studies, there are 2 large multi-center randomized controlled trials that have assessed the intensity of RRT with mortality: Acute Renal Failure Trial Network (VA/NIH ATN) and the Randomized Evaluation of Normal versus Augmented Level (RENAL).

Randomized Controlled Trials (RCT) Comparing CRRT Dosing. (NS: not significant; S-RCT: single center RCT). 

ATN:
This study included 1124 critically ill patients in the US and compared conventional management with intermittent HD 3-times per week for hemodynamically stable patients or CVVHDF with a prescribed effluent flow rate of 20 ml/kg/hr or sustained low-efficiency dialysis (SLED) 3-times per week for hemodynamically unstable patients to intensive management with intermittent HD 6-times per week for hemodynamically stable patients and high-intensity CVVHDF at 35 ml/kg/hr or SLED 6-times per week for hemodynamically unstable patients.

RENAL:
This study was conducted in 35 centers in Australia and New Zealand. It compared the effects of post-dilution CVVHDF with effluent flow rates of 25 or 40 ml/kg/h on 28 and 90-day mortality rates in 1464 critically ill patients with AKI requiring RRT.

Neither of these trials found improvements in mortality with higher intensity RRT. This conclusion was further supported by the 2016 Cochrane systematic review looking at the effects of different CRRT intensities on “mortality and recovery of kidney function in critically ill AKI patients”. The authors from this review concluded “based on the current low quality of evidence identified, more intensive CRRT did not demonstrate beneficial effects on mortality or recovery of kidney function in critically ill patients with AKI”. However, they did note an increased risk of hypophosphatemia with higher intensity CRRT and that “intensive CRRT reduced the risk of mortality in patients with post-surgical AKI”.  Based on the available evidence, more intensive CRRT was not found to have a favorable impact on mortality or kidney recovery.

So, for now, it seems that effluent flow rates of 20-25mL/kg/hr should be sufficient CRRT dosing in AKI – though careful attention should also be paid to actual delivered as well as clinical parameters that may justify dosing adjustments.

Thank you to Samaya Anumudu, MD for her help with this post.

Post by: Enzo Vásquez MD
Nephrology Fellow, Department of Nephrology, National Institute of Cardiology.

4 comments

  1. fixed. Thank you.

  2. Great article, thank you, very enjoyable.

    Typo of morality instead of mortality towards the end made me chuckle though.

  3. Thank you for the comment. This was an error and is now corrected.

  4. However, they did note an increased risk of hyperphosphatemia with higher intensity CRRT and that “intensive CRRT reduced the risk of mortality in patients with post-surgical AKI”.

    It is increased risk of HYPOPHOSPHATAEMIA, not hyperphosphataemia

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