What is Continuous Kidney Replacement Therapy (CKRT) with high-dose Continuous Veno-Venous Hemodialysis (CVVHD)?

Continuous Kidney Replacement Therapy (CKRT) with High-Dose CVVHD

High-dose CVVHD is a specialized form of continuous kidney replacement therapy that uses elevated dialysate flow rates relative to blood flow (Qd/Qb >1.5) to achieve rapid clearance of toxins, particularly in cases of severe hyperammonemia.

Definition and Technical Parameters

High-dose CVVHD (Continuous Veno-Venous Hemodialysis) is characterized by:

• Blood flow rate (Qb) of 30-50 ml/min 1
• Dialysate flow rate to blood flow rate ratio (Qd/Qb) >1.5 1, 2
• Dialysate flow rate (Qd) >1,000 ml/h to maximize clearance potential 1
• Clearance rates of up to 8,000 ml/1.73 m²/h in some cases 1

Clinical Applications

High-dose CVVHD is primarily indicated for:

1. Severe hyperammonemia management:

   • First-line treatment for hyperammonemia when feasible 1
   • Particularly effective for blood ammonia levels >1,000 μmol/l (1,703 μg/dl) 1
   • Provides greater ammonia clearance than CVVH (Continuous Veno-Venous Hemofiltration) 1

2. Specific clinical scenarios requiring initiation:

   • Rapidly deteriorating neurological status with ammonia >150 μmol/l 1, 2
   • Coma or cerebral edema with ammonia >150 μmol/l 1, 2
   • Moderate/severe encephalopathy 1, 2
   • Persistently high ammonia levels >400 μmol/l refractory to non-kidney replacement therapy 1, 2
   • Rapid rise in ammonia levels to >300 μmol/l within hours 1, 2

Advantages Over Other Modalities

• Compared to intermittent hemodialysis (HD):

  • Better hemodynamic stability 1
  • Lower risk of rebound hyperammonemia 1
  • Avoids rapid osmotic shifts that could worsen cerebral edema 1
  • Can be completed in a single dialysis run without equipment changes 1

• Compared to standard CKRT:

  • Faster clearance of toxins 1
  • More efficient for severe hyperammonemia 1

Technical Considerations

• Not all CKRT machines can achieve optimal Qd values:

  • Asahi Sigma Plasauto: allows Qd up to 6 l/h 1
  • Prismaflex and Fresenius (pediatric circuits): limit Qd to 1 l/h 1

• Warming the dialysate helps maintain hemodynamic stability 1

• Step-down to standard CKRT can follow when ammonia levels are <200 μmol/l on at least two consecutive hourly measurements 1

Potential Challenges

• Vascular access limitations 1
• Heparinization complications 1
• Electrolyte alterations (particularly hypophosphatemia) 3
• Membrane/circuit clotting 1

Hybrid Approaches

For patients with very high ammonia levels or hemodynamic instability:

• Combination with ECMO (Extracorporeal Membrane Oxygenation) may be beneficial:

  • Increases patient's blood volume 1
  • Enables use of larger cannula 1
  • Improves hemodynamic control 1
  • Particularly useful in small neonates with poor vascular access 1

• Sequential therapy with HD followed by CKRT:

  • HD first for rapid reduction of very high levels 1
  • Followed by CKRT to prevent rebound 1

Monitoring During Treatment

• Hourly ammonia level measurements until stabilization 1, 2
• Electrolyte monitoring, particularly calcium, phosphate, and sodium 4, 3
• Acid-base balance assessment 4, 3
• Hemodynamic parameters 1

High-dose CVVHD represents an important advancement in the management of severe hyperammonemia, offering improved clearance while maintaining hemodynamic stability compared to conventional modalities.