Background

Continuous renal replacement therapy (CRRT) is commonly used in the intensive care unit (ICU) setting and can consist of continuous venovenous hemodialysis (CVVHD), continuous venovenous hemofiltration (CVVH), or continuous venovenous hemodiafiltration (CVVHDF). Each of these procedures involves the slow passage of blood, continuously (24 hours a day), through a filter to remove various waste products and/or fluid.

How to Use It

CRRT is often referred to as a gentler form of hemodialysis (HD), as the infusion of the dialysate or replacement fluid is much slower. This is ideal for patients in the ICU who require dialysis but are hemodynamically unstable, on vasopressors, and cannot tolerate large fluid shifts over a short period of time. Generally speaking, a 24-hour session of CRRT is equivalent to a single 3-hour session of HD. Despite this advantage, no randomized trial has shown a mortality benefit for CRRT versus intermittent HD, though these trials excluded the treatment of the sickest patients with HD. Current Kidney Disease: Improving Global Outcomes guidelines recommend initiating CRRT for hemodynamically unstable patients.

How It Is Done

CRRT is initiated via a double lumen catheter inserted into either the jugular or femoral vein, like some catheter placements for HD. See Chapter 34: Hemodialysis Access for more details. Unlike HD, arteriovenous access cannot be used in CRRT, as there is significant risk of damage to the artery during the continuous blood flow. Dialyzers for CRRT fall in the high-flux category. Dialysate and replacement fluid come premixed in 2.5–5 L bags; the most common suppliers are Baxter and Nxstage. One should refer to the package inserts for the exact chemical composition of the fluid. Replacement fluids are generally needed with convection to restore volume and maintain the body’s physiological electrolyte composition. CVVHD refers to a continuous form of renal replacement that utilizes only dialysis solution (no replacement fluid is given), and the primary method of solute removal is diffusion. CVVH is a form of CRRT that utilizes only replacement fluid and relies on convection for solute clearance. A transmembrane gradient between the blood compartment and ultrafiltrate compartment causes water to be filtered across the membrane; as water crosses the membrane, it sweeps along with it (nonprotein-bound) small and large molecules (pore size permitting). CVVHDF is a combination of the two modalities listed above. The clearance of molecules is similar in the aforementioned modalities, and the modality utilized is at the discretion of the individual institution and nephrologist. ^,

Medication Implications

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  Vascular access for CRRT is identical to some types of catheter access for HD. See Chapter 34: Hemodialysis Access for more details.

  
  
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  Filter clotting is one of the most common complications associated with CRRT. This leads to extracorporeal blood loss (roughly 100–150 mL) and a reduction in dialysis efficiency, as a new circuit must be started.

  
  
  
  
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    Anticoagulation can be used to reduce filter clotting; however, as patients in the ICU are critically ill with significant comorbidities, such as gastrointestinal bleeding, coagulopathies, and thrombocytopenia, a risk/benefit discussion must occur with the ICU team prior to initiation. If anticoagulation is contraindicated, keeping blood flow at 200 mL/minute or greater can minimize clotting.

    
    
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    Unfractionated heparin is the most common anticoagulant used in CRRT. Citrate, infused pre-filter, is an additional anticoagulation option, though it does hold some caveats. It works by chelating calcium and thereby inhibiting the coagulation cascade. This can lead to profound hypocalcemia, and therefore frequent monitoring of the ionized calcium concentration is warranted. An infusion of calcium chloride post-filter is generally required to maintain adequate calcium levels. The major contraindication to citrate therapy is liver dysfunction, as these patients are unable to metabolize the citrate into bicarbonate. ^,

  
  
  
  
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  The main advantages of CRRT over HD is that it is better tolerated from a hemodynamic standpoint, is highly effective in volume removal, has less of an effect on intracranial pressure (important in cerebral edema), and results in better control of electrolyte and acid-base disturbances due to steady-state chemistries.

  
  
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  Hypophosphatemia during CRRT is a common complication, as conventional CRRT fluids have no phosphorus. Therefore, frequent monitoring and supplementation with phosphorus is given when necessary. Phoxillum is the only commercially available solution that contains phosphorus; however, it is not available at all institutions.

  
  
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  The ideal dose of CRRT is not known, as there are conflicting studies. One major study showed a 16% reduction in mortality in a prescribed effluent flow of 35–45 mL/kg/hour compared with 20 mL/kg/hour. However, a subsequent study comparing 40 mL/kg/hour with 20 mL/kg/hour failed to show any mortality benefit in the higher dose. ^,

  
  
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  When aiming for a higher flow (and therefore clearance), one should also be cognizant that the higher clearance may lead to inadequate concentrations of important medications such as antibiotics. It is imperative to dose antibiotics to the prescribed effluent dose. This can be particularly difficult in a patient who experiences multiple episodes of clotting, because the prescribed effluent rate and the delivered effluent rate may differ significantly due to time off of the machine.

  
  
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  Medication clearance in CRRT is complex, and due to the variability in techniques, it may be extremely challenging to predict. Molecular weight, extent of protein binding, and the volume of distribution of a medication will all factor into the clearance. In addition, the prescribed prescription of CRRT (i.e., dialysate/effluent rate) will influence the clearance of a medication. Higher flow rates will increase clearances, and higher doses of medications will be required.

  
  
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  An additional factor that is unique in CRRT is the variable residual renal function. Patients on CRRT are critically ill and can have highly fluctuating residual renal function within a given day; it is extremely important to account for this especially when dosing antibiotics.

  
  
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  As there are so many variables for medication dosing in CRRT, it is always best to use a reference such as Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children or The Renal Drug Handbook. ^,