Veno-Venous (VV) Accesses

CRRT requires veno-venous access: dual-lumen catheter in femoral, internal jugular, or subclavian vein; blood withdrawn continuously, processed through filter/hemofilter, then returned to venous circulation.

Why veno-venous (not arterio-venous)? [3] - Avoids need for arterial puncture (risk of pseudoaneurysm, steal, infection) - Pump drives circulation (arterio-venous relied on arterial-venous pressure gradient; slower, less reliable)

CVVH (Continuous Veno-Venous Hemofiltration)

Mechanism: Ultrafiltration-driven removal; relies on convection; membrane has large pores; solute removal by sieving (solutes move with filtered fluid).

Fluid flows: - Blood flow: 150-250 mL/min - Ultrafiltrate removal: 20-25 mL/min (prescribed rate) → 1-1.5 L/hour - Replacement fluid: Infused post-filter (post-dilution; dilutes filtrate already removed) or pre-filter (pre-dilution; less efficient but may improve membrane life) [3]

Solute clearance mechanism: - Convection: Solutes move WITH fluid across membrane - Sieving coefficient: Varies by solute (small solutes approximately 1.0, large proteins <0.1) - Relative strength: Good for small/medium molecules (Na, K, urea, creatinine); less effective for large molecules [3]

Disadvantages of CVVH alone: - Middle-molecule and larger solute removal may be inadequate (phosphate, beta-2 microglobulin) - Requires high ultrafiltration rates (1-2 L/hour) to achieve adequate small-solute clearance

Use: Combined with other modalities; rarely used as monotherapy [1]

CVVHD (Continuous Veno-Venous Hemodialysis)

Mechanism: Diffusion-driven removal; membrane has small pores; solute removal by concentration gradient (similar to intermittent HD).

Fluid flows: - Blood flow: 150-250 mL/min - Dialysate flow: 16-33 mL/min (1-2 L/hour) — countercurrent to blood - Ultrafiltrate: Minimal (patient-driven fluid removal only, not pump-driven)

Solute clearance mechanism: - Diffusion: Solutes move DOWN concentration gradient (high in blood, low in dialysate) - Clearance independent of ultrafiltration rate: Driven by dialysate flow and dwell time - Relative strength: Excellent for small solutes (urea, creatinine, K); dependent on dialysate concentration

Disadvantages: - Less effective for fluid removal in anuric patients (must rely on patient ultrafiltration need) - Patients with minimal urine output may be inadequately treated

Use: Combined with ultrafiltration component for better fluid removal [1]

CVVHDF (Continuous Veno-Venous Hemodiafiltration)

Mechanism: Combined convection + diffusion; uses both ultrafiltration (convective removal) and diffusion (via dialysate).

Fluid flows: - Blood flow: 150-250 mL/min - Ultrafiltration: 20-25 mL/min (patient/pump-driven) - Dialysate flow: 8-33 mL/min (1-2 L/hour) - Replacement fluid: Post-filter (after hemofilter)

Solute clearance: - Convection (from UF) + Diffusion (from dialysate) - Best of both worlds: Efficient small-solute removal via diffusion + convection; good fluid removal - Clearance: Typically 25-35 mL/kg/hour (higher than CVVH or CVVHD alone)

Advantages: - Superior solute removal for broad molecular weight spectrum - Excellent fluid removal capability - Most physiologic mimicry of native kidney function

Disadvantages: - Most complex; requires pump, dialysate delivery, UF pump control - Highest cost; requires skilled personnel

Use: Preferred modality in most ICUs [1][2]

Prescribed vs. Delivered Dose

Critical distinction: Prescribed dose ≠ delivered dose due to: - Circuit downtime (procedures: imaging, bedside ultrasound, placement of other lines) - Circuit thrombosis → filter clotting - Fluid bag changes, line troubles - Dialysate/replacement fluid changes

Typical delivered dose: 70-90% of prescribed dose (account for ~15-20% downtime) [1].

KDIGO/ATN Trial Evidence on Dose

The ATN Trial (2008): Randomized 1,124 critically ill AKI patients to: - More intense CRRT: 35 mL/kg/hour - Less intense CRRT: 20 mL/kg/hour

Results: No difference in mortality, ICU LOS, or renal recovery between 20 vs. 35 mL/kg/hour [2].

RENAL Trial (Australia/New Zealand): Confirmed no benefit to high-dose (40 mL/kg/hour) vs. standard-dose (25 mL/kg/hour) CRRT [2].

Current KDIGO Recommendations

Standard CRRT dose: 20-25 mL/kg/hour delivered dose [1][2]

• Body weight calculation: Use actual dry body weight (if obesity, may adjust)
• Achieved via: CVVHDF with UF + dialysate, or high-volume CVVH
• Frequency: Continuously (24 hours); equivalent to ~120-150 mL/kg/week
• No benefit to doses >25 mL/kg/hour

Regional Citrate Anticoagulation (RCA) — PREFERRED

Mechanism: - Citrate infusion pre-filter: Binds calcium → chelates ionized Ca → blocks coagulation cascade in circuit - Calcium reinfusion post-filter: Restores serum calcium to normal (systemic coagulation normal; circuit anticoagulated) - Calcium removal in ultrafiltrate: Modest (some calcium in replacement fluid)

Advantages: - Most effective: Longest filter lifespan (7-10 days; vs. heparin 1-3 days) - Safest: No systemic anticoagulation; reduced bleeding risk (critical in coagulopathic/post-op patients) - No heparin-induced thrombocytopenia (HIT) risk - Reduced thrombotic complications in high-bleeding-risk patients

Disadvantages: - Complex; requires meticulous monitoring - Citrate-induced metabolic alkalosis (if citrate not fully metabolized) - Hypocalcemia risk if post-filter calcium infusion inadequate; conversely, hypercalcemia if excessive calcium replacement - Hypernatremia (sodium in citrate solutions) - Hypophosphatemia (phosphate rapidly removed; may need supplementation) - Hepatic impairment: Citrate metabolism impaired → citrate accumulation, calcium chelation

Monitoring (RCA): - Baseline: Baseline Ca, phosphate, Na, Mg, acid-base, albumin - Daily: Ionized calcium (pre-filter >2.0 mEq/L, post-filter 1.1-1.3 mEq/L), acid-base, electrolytes, albumin, PT/INR - Citrate level: If citrate accumulates (can measure plasma citrate; rarely needed clinically) - Calcium balance: Track calcium in/out; adjust post-filter calcium infusion

Circuit citrate protocol: - Citrate infusion rate: ~160-180 mEq/liter blood flow (or ~3 mL citrate/100 mL blood) - Post-filter calcium: ~3 mEq/liter of dialysate/replacement fluid - Regional anticoagulation achieved; systemic citrate/calcium balanced [1]

Systemic Anticoagulation (if RCA contraindicated)

Unfractionated Heparin (UFH): - Bolus: 50-100 units/kg pre-filter - Infusion: 10-20 units/kg/hour maintenance - Monitoring: aPTT (goal 45-60s, regional target) - Disadvantages: HIT risk (approximately 3-5%) [4], increased bleeding risk, shorter filter life [4]

Low-molecular-weight heparin (LMWH): - Less used in CRRT (less reversible than UFH); enoxaparin if necessary - Monitoring: Anti-Xa levels

Direct thrombin inhibitors: - Argatroban: If HIT; used in select ICUs [1]

Anticoagulation-Free CRRT

Rationale: Some patients are coagulopathic (DIC, liver failure, post-op bleeding); anticoagulation contraindicated.

Technique: - Frequent filter changes (1-2x/day) due to circuit clotting - Saline flushes every 4 hours to maintain patency - Higher cost (multiple filters) and labor-intensive - Avoid if possible; usually temporary until coagulation corrected [1]

Replacement Fluid Composition

Standard composition (varies by product; example):

Acid-Base Considerations

Hyperchloremic acidosis risk: - High chloride in replacement/dialysate → hyperchloremia → metabolic acidosis - Solution: Use balanced replacement fluids (lower Cl-, higher HCO3-) when possible

Citrate-induced alkalosis: - Citrate metabolism → HCO3- generation - Solution: Monitor pH; adjust citrate infusion rate; use citrate-free patients in liver failure

Metabolic acidosis: - If persistent, increase dialysate HCO3-; ensure adequate citrate metabolism

Phosphate Management

Phosphate rapidly removed in CRRT (no bound fraction; fully filtered).

• Risk: Hypophosphatemia (can cause respiratory failure, rhabdomyolysis if severe)
• Monitoring: Phosphate levels daily; if <2.0 mg/dL, add phosphate to replacement fluid or dialysate
• Supplementation: Available in some formulations; standard products often lack phosphate

Dextrose in Replacement Fluid

Most CRRT replacement fluids have minimal glucose (100-200 mg/dL equivalent). Hyperglycemia common in ICU from stress and glucose administration; usually managed with insulin, not increased glucose in CRRT fluids [1].

Renally Excreted Drugs

CRRT clearance varies by: drug characteristics, CRRT modality (CVVH > CVVHD), flow rates.

General principles: 1. Standard dose drugs unlikely to accumulate during CRRT (e.g., cephalosporins, fluoroquinolones) 2. Drugs requiring adjustment: Vancomycin, aminoglycosides, antivirals (acyclovir, ganciclovir), anticoagulants 3. Recommendation: Check drug-specific dosing; consider TDM (therapeutic drug monitoring) for critical drugs

Examples: - Vancomycin: Empiric dosing in CRRT differs from IHD; target trough 15-20 µg/mL; check levels - Aminoglycosides: Extended-interval dosing more suitable; CRRT continuous clearance changes kinetics - Antivirals: Acyclovir adjusted based on CRRT dose; risk of crystal nephropathy if under-dosed - Anticoagulants (UFH, enoxaparin): Clearance variable; monitor aPTT/anti-Xa as needed

Tools: Renal dosing databases (e.g., KDIGO, Kidney Disease: Improving Global Outcomes); pharmacist consultation recommended [1]

Caloric and Protein Requirements

CRRT patients typically hypercatabolic (sepsis, trauma, severe illness).

• Energy: 25-35 kcal/kg/day
• Protein: 1.5-2.0 g/kg/day (higher than non-critical CKD due to losses in ultrafiltrate and increased metabolism)

Nutrient Losses in CRRT

Ultrafiltrate contains: - Amino acids (5-10 g/day loss) - Water-soluble vitamins (B vitamins, vitamin C) - Trace elements (zinc, selenium, iron) - Glucose (if using glucose-containing dialysate)

Replacement strategy: - High-protein supplementation (enteral preferred over parenteral) - Multivitamin supplementation daily - Trace element supplementation (zinc, selenium especially) [1]

Glucose Management

Tight glycemic control (glucose 80-110) not superior to moderate control (140-180) in ICU; target <180 mg/dL typically. CRRT allows any dextrose concentration in replacement fluid; insulin requirements usually necessary [1].

Timing of Transition

Hemodynamic stability indicators: - Vasopressor requirement decreased/discontinued - Systolic BP consistently >90 mmHg without pressors - Urine output improving (if recovering AKI) - Acidosis/hyperkalemia controlled

Transition protocol: - Start with 2x/week intermittent HD sessions (short/low-efficiency) - Continue CRRT on off-dialysis days initially - Gradually reduce CRRT to PRN and discontinue as IHD adequacy achieved - May take 3-7 days to fully transition [1][2]