Continuous Renal Replacement Therapy (CRRT): Principles, Dosing & Evidence
Definition & Indications
CRRT = Renal replacement therapy applied continuously (24 hours/day) in ICU setting
Key feature: Slow, continuous removal of solutes & fluid (vs. intermittent HD’s rapid cycling)
Indications: - Acute kidney injury in critically ill (hemodynamic instability) - Fluid overload (pulmonary edema, HF, sepsis) - Severe hyperkalemia (unresponsive to medical management) - Uremia (if intermittent dialysis inadequate or unstable) - Severe acidosis/alkalosis (buffer adjustment via CRRT dialysate) - Toxin removal (theophylline, aspirin, phenobarbital — slower than HD but continuous) - Thermal management (hypothermia or hyperthermic correction via dialysate temperature)
CRRT for AKI: - Better tolerated in unstable patients (gradual fluid/electrolyte changes) - No mortality advantage vs. intermittent HD in randomized trials (ATN/RENAL trials) - Choice driven by hemodynamic stability, not efficacy
CRRT Modalities: How They Differ
CVVH: Continuous Venovenous Hemofiltration
Mechanism: Convection (solvent drag) - Blood passes through filter - Hydrostatic pressure forces fluid + solutes across semipermeable membrane (ultrafiltration) - Ultrafiltrate removed directly - “Replacement fluid” infused either pre- or post-filter to maintain blood volume
Solute removal: - Good small solute clearance (urea, creatinine, electrolytes via convection) - Excellent large solute clearance (β2-microglobulin, middle molecules)
Fluid removal: - Precise: Accurate UF controlled by pump
CVVHD: Continuous Venovenous Hemodialysis
Mechanism: Diffusion (concentration gradient) - Blood on one side of filter; dialysate on other - Solutes move by concentration gradient (like regular hemodialysis but slower) - Minimal ultrafiltration (no replacement fluid)
Solute removal: - Good for small solutes (diffusion-dependent) - Slower for large molecules (convection absent)
Advantage: Less fluid replacement needed (cheaper)
CVVHDF: Continuous Venovenous Hemodiafiltration
Mechanism: Convection + Diffusion (BEST of both) - Combines hemofiltration (convection) + hemodialysis (diffusion) - Ultrafiltrate removed + dialysate run in counter-current - Highest total solute clearance
Advantages: - Best small + large molecule removal - Most “efficient” in clearing uremia
Disadvantage: Highest fluid replacement cost; requires highest vascular access flow
Vascular Access for CRRT
Central Venous Catheter (CVL) Requirements
Catheter type: - Dual-lumen or triple-lumen non-tunneled CVL - Preferably 20 cm length; flow needs adequate lumen diameter - Preferred sites: IJ (right) > subclavian (avoid left) > femoral (last resort; infection risk)
Flow requirements: - Minimal: 80–100 mL/min - Typical: 150–300 mL/min - Better clearance: 300–400 mL/min
Complications
- Infection: Bacteremia, catheter-related bloodstream infection (CRBSI)
- Risk ↑ with femoral access, prolonged duration
- Prevention: Sterile technique, minimize line days, remove when no longer needed
- Stenosis/thrombosis: Catheter partially occludes
- Hemolysis: Catheter malposition or obstruction
- Central vein stenosis: Long-term catheter use (rare in acute setting)
CRRT Dosing: How Much is Enough?
Dose Definition
Effluent flow rate = replacement fluid + dialysate + net ultrafiltration
Expressed as: mL/kg/hour (normalized to body weight)
Landmark Trials: ATN & RENAL
ATN Trial (2008): - Compared standard dose (35 mL/kg/h) vs high dose (45–50 mL/kg/h) - Result: No difference in mortality (60% both groups) - Conclusion: Standard dose adequate
RENAL Trial (2009): - Compared standard dose (20–25 mL/kg/h) vs high dose (35–45 mL/kg/h) - Result: No mortality benefit for high dose (56% mortality both groups) - Conclusion: Lower standard dose (20–25 mL/kg/h) sufficient; reduces filter replacement costs
Current Recommendations (KDIGO 2012)
| Setting | Dose | Modality |
|---|---|---|
| AKI without sepsis | 20–25 mL/kg/h | Any CRRT modality |
| AKI + sepsis | 35 mL/kg/h recommended | CVVHDF preferred |
| Refractory hyperkalemia | Higher dose (>35 mL/kg/h) | CVVHD or CVVHDF |
| Refractory hypoxemia | Variable; depends on goal | Any modality |
Practical dosing: Start at 20–25 mL/kg/h; increase to 30–35 mL/kg/h if sepsis, inadequate UF, or persistent hyperkalemia. No benefit beyond 35–40 mL/kg/h in standard AKI.
Dose Calculation Example
Patient: 80 kg male, standard AKI
Dose = 25 mL/kg/h × 80 kg = 2,000 mL/h = 2 L/h total effluent
If using CVVHDF: - CVVH replacement: 1,000 mL/h - Dialysate: 1,000 mL/h - Net UF: 0 mL/h (can adjust based on fluid status)
Anticoagulation in CRRT
Why Anticoagulation?
Problem: Blood + artificial filter + slow flow → thrombosis → filter clotting - Filter life: Without anticoagulation, ~6–12 hours - Filter life: With anticoagulation, ~24–48 hours
Options
| Agent | Mechanism | Pros | Cons |
|---|---|---|---|
| Heparin (unfractionated) | Thrombin inhibition | Cheap, reversible, monitored | Systemically anticoagulated (bleeding risk) |
| Citrate (regional) | Local chelation of Ca → inhibits coagulation | No systemic anticoagulation; safer in bleeding; lower thrombosis | Complex; requires Ca reinfusion; hypernatremia risk |
| Epoprostenol | PGI2 analogue | No systemic anticoagulation | Expensive, flash pulmonary edema risk (vasodilation) |
| Nafamostat mesilate | Factor Xa inhibitor | Regional anticoagulation | Limited availability (Japan); expensive |
| No anticoagulation | Tolerate filter clotting | Avoids bleeding risk | Frequent filter changes; expensive |
Citrate (Preferred in Most ICUs)
Mechanism: - Citrate chelates Ca in filter circuit - Coagulation cascade inhibited (Ca needed for thrombin) - Citrate metabolized in liver → HCO3 regenerated - Systemic ionized Ca reinfused post-filter
Advantages: - Regional anticoagulation (only filter exposure to anticoagulant) - Safe in bleeding patients - ↓ Systemic anticoagulation-related bleeding - Filter longevity 48 hours typical
Complications: - Citrate accumulation: If liver failure; citrate not metabolized → ionized Ca ↓, metabolic alkalosis - Hypernatremia: High Na in citrate solution - Hypomagnesemia: Mg lost with filtrate; need reinfusion
Monitoring: Check ionized Ca (post-filter), electrolytes daily
Filter Selection & Management
Types of Filters
| Membrane Type | Pore Size | Clearance Profile | Cost |
|---|---|---|---|
| Low-flux polysulfone | Small pores | Small molecules; minimal middle molecules | $ |
| High-flux polysulfone/PEPA | Large pores | Excellent small + large molecule | ||* * Hemodiafiltration − optimized(CVVHDF) * *|Variable|Bestoverall(diffusion + convection)|$ |
Choice: High-flux filter > low-flux for sepsis, AKI (better cytokine/mediator removal)
Filter Clotting Prevention
- Adequate anticoagulation (citrate preferred)
- Adequate vascular access flow (>150 mL/min minimum)
- Avoid catheter kinks (position check)
- Regular flushing (NS 100 mL q1h or continuous)
- Avoid hypotension (maintain MAP >65 mmHg)
- Monitor TMP (transmembrane pressure)
- If TMP ↑ rapidly → filter clotting imminent
CRRT Settings & Monitoring
Typical ICU Setup
Hemofilter machine (e.g., Prismaflex, Multifiltrate): - Blood pump: 100–400 mL/min - Replacement fluid pump: 0–1,000 mL/h - Dialysate pump (if CVVHD): 0–1,000 mL/h - Effluent pump (waste removal): automated based on UF goal - Alarms: TMP, line pressure, clotting risk, temperature
Daily Monitoring Parameters
| Parameter | Frequency | Target |
|---|---|---|
| BMP (Cr, K, Na, HCO3) | Daily | Normal range |
| Ionized Ca (if citrate) | Daily | 0.9–1.1 mmol/L (post-filter) |
| Mg, PO4 | Daily–Q2 days | Replete if low |
| Citrate level (if accumulation suspected) | As needed | <20 mmol/L |
| TMP (transmembrane pressure) | Continuous | <300 mmHg; ↑ = clotting |
| Fluid balance | Hourly | Prescribed UF |
| CBC (Hgb, platelets) | Q1–2 days | Track for bleeding/transfusion |
| Fibrinogen, PTT | If citrate | Monitor citrate metabolism |
Special CRRT Scenarios
CRRT in Sepsis
Rationale: Continuous removal may clear inflammatory mediators (TNF-α, IL-6)
Evidence: Landmark trials (PRISM, CCM 2020) show no mortality benefit of high-dose CRRT vs standard - Some evidence: Early CRRT (within 6h) may improve outcomes (inconsistent) - Recommendation: Standard dose 25–30 mL/kg/h; high-flux filter preferred
CRRT for Toxin Removal
Best modality: CVVHDF (convection + diffusion)
Examples: - Phenobarbital: Long half-life; CRRT helpful for clearance - Aspirin (salicylate): Intermittent HD actually better (high dose clearance) - Theophylline: CRRT adequate; low urgency - Methanol/ethylene glycol: Intermittent HD preferred (faster removal)
CRRT Weaning & Discontinuation
Indicators to stop CRRT: 1. GFR recovery: Cr plateau or ↓; patient producing adequate urine 2. Hemodynamic stability: Can tolerate intermittent RRT 3. Electrolyte stability: No longer need continuous correction
Weaning protocol: 1. Reduce effluent flow (from 25 mL/kg/h → 20 → 15 → 10 mL/kg/h) 2. Reduce frequency (discontinue intermittently; e.g., 20h/day → 12h → 6h → off) 3. Trial off CRRT: If stable 24 hours, can discontinue
Complications Specific to CRRT
Electrolyte Imbalances
- Hypokalemia: ↑ K removal; common; monitor daily; may need K reinfusion
- Hypomagnesemia: Mg lost with ultrafiltrate; need repletion
- Hypernatremia: Excess Na in replacement/dialysate; manage fluid carefully
- Hypocalcemia: Citrate chelation; monitor; reinfuse ionized Ca as needed
Hypothermia
Mechanism: Large fluid volumes at room temperature → core temp ↓
Management: Warm replacement/dialysate to 37°C; insulate tubing
Malnutrition
Problem: Continuous UF removes glucose, amino acids - Patients often require propofol (sedation; lipid calories), high-dose dextrose - Overall: Protein-catabolic state in sepsis; nutrition support critical
Strategy: Early enteral nutrition; if unable, TPN with high amino acids + dextrose
Self-Test Questions
- 80 kg male in septic shock, AKI Stage 3, K 6.2, pH 7.22
- CRRT modality: CVVHDF (best for sepsis + refractory hyperkalemia)
- Dose: 30–35 mL/kg/h (ATN/RENAL trials show no benefit >35, but sepsis may warrant higher end)
- Anticoagulation: Citrate (regional; safer if bleeding risk from sepsis coagulopathy)
- CRRT filter clotting at 8 hours despite heparin
- Causes: Low vascular access flow? Hypotension? Catheter malposition?
- Troubleshoot: Check TMP, line pressures, blood flow rate, BP
- Switch anticoagulation: Try citrate (longer filter life expected)
- Mg 1.4 (low), K 3.2 (low), Ca post-filter 0.8 (low)
- Abnormalities: Typical CRRT losses
- Management: Mg reinfusion (1–2 g/day), K reinfusion if continuing RRT, Ca reinfusion post-filter
- Avoid: Over-replacement (rebound hyperkalemia when RRT stops)
Version 1.0 | PA/Medical student level | Evidence-based 2026-02-28
References: ATN Trial (NEJM 2008), RENAL Trial (NEJM 2009). KDIGO 2012 CRRT Dosing & Modality Guidelines. Ronco C, Bellomo R. Continuous Renal Replacement Therapy. Crit Care Clin. 2021.