# 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)

Key Point

**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**

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## 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

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## 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)

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## 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      |

Clinical Pearl

**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)

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## 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

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## 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**

1.  **Adequate anticoagulation** (citrate preferred)
2.  **Adequate vascular access flow** (\>150 mL/min minimum)
3.  **Avoid catheter kinks** (position check)
4.  **Regular flushing** (NS 100 mL q1h or continuous)
5.  **Avoid hypotension** (maintain MAP \>65 mmHg)
6.  **Monitor TMP** (transmembrane pressure)
    - If TMP ↑ rapidly → filter clotting imminent

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## 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 |

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## 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

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## 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

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## Related Resources

- Comprehensive CRRT Pathophysiology & Management
- AKI Staging & Classification
- RRT Modality Selection

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## Self-Test Questions

1.  **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)
2.  **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)
3.  **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)

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*Version 1.0 \| PA/Medical student level \| Evidence-based 2026-02-28*

**References:** [ATN trial: Intensity of renal support in critically ill patients with AKI (2008)](https://pubmed.ncbi.nlm.nih.gov/18492867/); [RENAL trial: Intensity of continuous renal-replacement therapy (2009)](https://pubmed.ncbi.nlm.nih.gov/19846848/); [KDIGO 2012 AKI guideline](https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-AKI-Guideline-English.pdf).


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