What are the potential complications and management strategies for a patient with pre-existing renal disease undergoing Continuous Renal Replacement Therapy (CRRT) with Continuous Veno-Venous Hemodiafiltration (CVVHDF)?

CRRT CVVHDF Complications and Management

Anticoagulation-Related Complications

Regional citrate anticoagulation is the preferred first-line method for CVVHDF, but requires intensive monitoring to prevent metabolic complications including citrate accumulation, metabolic alkalosis, and ionized calcium disturbances. 1, 2

Citrate-Related Complications

• Citrate accumulation can occur when large amounts of citrate are administered as anticoagulant, particularly in patients with hepatic dysfunction or shock states who cannot metabolize citrate adequately 1
• Metabolic alkalosis develops from citrate metabolism, especially when combined with lactate-buffered replacement fluids 1, 3
• Hyperlactacidemia may result from administration of lactate-containing substitution fluids 1
• Post-filter ionized calcium must be maintained between 0.25-0.4 mmol/L while systemic ionized calcium stays >1.1 mmol/L through calcium chloride infusion 2
• Frequent measurements of post-filter and serum-ionized calcium are mandatory to appropriately titrate citrate and calcium replacement 1
• Monitoring of systemic acid-base balance is essential in patients at high risk for citrate accumulation 1

Heparin-Related Complications

• Heparin-induced thrombocytopenia requires routine platelet monitoring during heparin anticoagulation 1
• Bleeding risk is elevated with systemic heparin, making it inappropriate for high-risk bleeding patients 1
• Regional heparin-protamine anticoagulation cannot be recommended due to protamine accumulation risk in acute renal failure 1

Circuit Clotting

• Filter clotting remains common even with anticoagulation, with circuit life often <24 hours without anticoagulation 1
• Regional citrate anticoagulation extends filter lifetime to 39±11 hours (median 41.5 hours) compared to 38.8±24.8 hours with heparin 2, 4
• Pre-dilution fluid administration improves ultrafiltration rates and reduces filter clotting frequency 5

Vascular Access Complications

Subclavian veins should be avoided for CRRT access in adults due to high risk of thrombosis and late stenosis. 1, 5

• Thrombosis risk varies by access site, with subclavian access carrying the highest risk of long-term stenosis 1
• Infection risk depends on catheter site, insertion technique, and duration of use 1
• Internal jugular and femoral veins are preferred access sites, with site selection based on thrombosis risk, infection risk, ease of placement, and adequacy of function 1
• Single dual-lumen venous catheters are the most commonly used access method 1

Electrolyte and Metabolic Complications

CVVHDF frequently induces hypophosphatemia, hypomagnesemia, and hyponatremia, requiring phosphate-containing replacement solutions and frequent monitoring. 1, 3

Phosphate Depletion

• Hypophosphatemia (serum phosphate <2.5 mg/dL) occurs commonly during prolonged CVVHDF due to continuous phosphate loss in the effluent 3
• Phosphate-containing replacement solutions (HPO4²⁻ 1.0 mmol/L) prevent KRT-related hypophosphatemia while maintaining acid-base balance 3
• Supplementation with sodium glycerophosphate may be required when phosphate losses exceed replacement 3

Other Electrolyte Disturbances

• Hypomagnesemia develops from continuous magnesium loss in dialysate and ultrafiltrate 1
• Hyponatremia can occur with inappropriate dialysate sodium concentrations 1
• Dialysate and substitution fluids should contain physiologic electrolyte concentrations except in patients with extreme imbalances 1, 5

Acid-Base Disturbances

• Metabolic alkalosis results from citrate metabolism and bicarbonate-buffered solutions 1, 3
• Bicarbonate-buffered solutions are preferred over lactate-buffered solutions, particularly in patients with acidosis, hepatic dysfunction, or shock 5, 3
• Lactate-buffered fluids should be avoided in patients with lactic acidosis or liver failure 5

Nutritional Complications

CVVHDF causes significant nutrient losses including 10-15 g amino acids daily plus 5-10 g protein daily, requiring increased nutritional support. 1

Protein and Amino Acid Losses

• Amino acid loss approximates 0.2 g/L filtrate, totaling 10-15 g daily at typical ultrafiltration rates 1
• Protein loss of 5-10 g/day occurs depending on membrane material and therapy type 1
• Increased proteolysis is a metabolic hallmark of acute renal failure, further exacerbated by CRRT 1

Vitamin Depletion

• Water-soluble vitamins are lost in significant amounts during CVVHDF 1
• Plasma concentrations of water-soluble vitamins are reduced, requiring supplementation 1
• Fat-soluble vitamins (E, A) and selenium levels are low with profound depression of the antioxidant system 1

Nutritional Support Requirements

• Malnutrition is present in 42% of acute renal failure patients at admission and independently predicts mortality 1
• Enteral nutrition is preferred over parenteral nutrition and may improve survival in ICU patients with acute renal failure 1
• Gastrointestinal hemorrhage risk is increased in acute renal failure, though enteral nutrition may provide protective effects 1

Medication Dosing Complications

Therapeutic drug monitoring is essential for dialyzable medications during CVVHDF, as drug clearance varies significantly with dialysate flow rates and residual renal function. 6, 7

Antimicrobial Dosing Errors

• Beta-lactam antibiotics require dose adjustments, with piperacillin/tazobactam half-lives significantly shortened during CVVHDF compared to CVVH alone 6
• Drug clearance increases proportionally with dialysate flow rates (typically 1-2 L/hour), with higher flow rates increasing elimination 1, 6, 7
• Hydrophilic antimicrobials (beta-lactams, aminoglycosides, glycopeptides) undergo clinically relevant CRRT clearance requiring dosage increases 7
• Lipophilic compounds (fluoroquinolones, oxazolidinones) generally require no dosage modification 7

Monitoring Requirements

• Therapeutic drug monitoring should occur 24-48 hours after therapy initiation, after dose changes, and with significant clinical status changes 8
• Residual kidney function significantly impacts drug clearance and should be considered when dosing medications, especially with CrCl >50 mL/min 6, 8
• Hypoalbuminemia increases clearance of protein-bound drugs during CRRT 8, 7

Hemodynamic Complications

Hemodynamic instability can occur from rapid fluid shifts, requiring careful fluid balance management and dialysate warming. 5

• Dialysate warming helps maintain hemodynamic stability during therapy 5
• Volume overload must be avoided, especially in patients with acute lung injury 5
• Integrated fluid balance systems provide precise control but require proper equipment rather than adapted IV pumps 5
• Adapted IV infusion pumps for CRRT carry significant risk of fluid balance errors and should be avoided when dedicated CRRT devices are available 5

Quality and Safety Monitoring Pitfalls

Delivered CVVHDF dose frequently falls short of prescribed dose, requiring continuous assessment of actual effluent volume to avoid underdosing. 6

• Target effluent volume is 20-25 mL/kg/h for adequate solute clearance in acute kidney injury 6
• Filter performance should be monitored through transmembrane pressure, urea sieving coefficient, urea equilibration ratio, and filtration fraction 5
• Safety monitoring frequency and methods lack consensus but are recommended during all anticoagulation strategies 1
• Personnel performing CRRT must demonstrate competency, though no specific qualifications are mandated beyond this requirement 1