# CRRT Principles and Management ## Overview Continuous renal replacement therapy (CRRT) represents a gentler, continuous approach to renal replacement in hemodynamically unstable critically ill patients. Unlike intermittent hemodialysis (IHD), CRRT provides gradual, sustained removal of water and solutes over 24 hours, reducing hypotension and permitting higher net fluid removal in patients with sepsis, cardiogenic shock, and multi-organ failure. Understanding CRRT modalities, dosing, and complications is essential for intensive care nephrology practice and board examination \[1\]\[2\]. High-Yield Board Point CRRT indications: **hemodynamic instability, cerebral edema, hyperammonemia (acute liver failure), sepsis-induced AKI**. Standard dose: **20-25 mL/kg/h delivered dose** (prescribed dose higher to account for circuit loss). **Anticoagulation:** Regional citrate preferred over systemic heparin (avoids bleeding in coagulopathic patients). **Modalities:** CVVH (convection), CVVHD (diffusion), CVVHDF (combined convection + diffusion). Transition to IHD when hemodynamically stable or if CRRT-specific complications (bleeding, thrombosis) develop \[1\]\[2\]. ## CRRT Modalities: Mechanisms and Indications ### 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CRRT requires **veno-venous access**: dual-lumen catheter in femoral, internal jugular, or subclavian vein; blood withdrawn continuously, processed through filter/hemofilter, then returned to venous circulation.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 \[1\]\[2\] ## CRRT Dosing ### 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 Key Point Higher CRRT dose does NOT improve mortality or renal recovery. Standard 20-25 mL/kg/hour is recommended. Focus on **achieving this dose consistently** (minimizing circuit downtime) rather than escalating above standard dose \[1\]\[2\]. ## Anticoagulation Strategies CRRT circuits are highly thrombogenic (blood contact with synthetic membrane, slow flow in large lines). Anticoagulation is essential to prevent circuit clotting and maintain filter life. ### 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 - Metabolized citrate can cause alkali excess; impaired citrate metabolism can instead cause citrate accumulation and acidosis - **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 RCA monitoring: obtain baseline systemic ionized and total calcium, sodium, magnesium, phosphate, and acid–base measurements. Recheck soon after initiation or any citrate/calcium/flow change and at the validated protocol interval; once-daily testing is not an adequate universal start-up schedule. Post-filter ionized calcium assesses circuit anticoagulation; systemic ionized calcium guides patient calcium replacement. Evaluate rising total-to-ionized calcium ratio, acidosis, and escalating calcium requirements for possible citrate accumulation. Regional citrate anticoagulation requires a validated protocol specific to the citrate concentration, CRRT platform, solutions, and blood/effluent flows. Citrate dose, post-filter ionized calcium, and systemic calcium replacement are different quantities and must not be interchanged. Adjust citrate and calcium through the local protocol with systemic/post-filter ionized calcium, total calcium, acid–base, sodium, and magnesium surveillance. ### 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 \[1\] ## Electrolyte and Acid-Base Management ### Replacement Fluid Composition **Standard composition** (varies by product; example): | **Electrolyte** | **mEq/L** | **Purpose** | |----|----|----| | **Sodium (Na+)** | 140 | Prevent hyponatremia; matches plasma | | **Potassium (K+)** | 0-4 | Prevent hyperkalemia; can adjust (low K+ formulation available) | | **Calcium (Ca2+)** | 2.5-3.5 | Prevent hypocalcemia | | **Magnesium (Mg2+)** | 1.0-1.5 | Prevent hypomagnesemia | | **Chloride (Cl-)** | 110-120 | Prevent hyperchloremic acidosis | | **Bicarbonate (HCO3-)** | 25-35 | Buffering; prevent acidosis | | **Phosphate (PO4)** | 0 | Usually absent; monitor; may need supplementation | | **Glucose (Glu)** | 100-200 | Varies; standard formulations have minimal glucose | ### 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 \[1\]. ## Drug Dosing During CRRT ### 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 \[1\] ## Nutrition and Metabolic Support ### 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 \[1\]. ## Transition from CRRT to Intermittent Dialysis ### 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 \[1\]\[2\] ## CRRT Complications | **Complication** | **Mechanism** | **Management** | |----|----|----| | **Circuit thrombosis** | Coagulation activation; slow flow; inadequate anticoagulation | Inadequate anticoagulation (heparin check); filter replacement; increase heparin/citrate | | **Bleeding** | Systemic anticoagulation (heparin); coagulopathy underlying | Reduce anticoagulation if possible; transfuse if Hgb \<7; consider RCA if bleeding severe | | **Catheter complications** | Infection, thrombosis, stenosis, malposition | Sterile technique; monitor; replace if infected | | **Hypernatremia** | Sodium in citrate or dialysate solutions; fluid removal net sodium loss | Monitor serum Na; adjust replacement fluid composition; free water supplementation if needed | | **Hypocalcemia (RCA)** | Inadequate post-filter calcium infusion; citrate chelation | Increase calcium infusion rate; monitor ionized calcium | | **Metabolic alkalosis** | Excess citrate metabolism; HCO3- in replacement fluid | Reduce citrate; use low-HCO3- fluids; avoid hypokalemia (K+ wasting) | | **Hyperkalemia (if K+ \>4 in fluid)** | Excessive K+ replacement | Use K-free replacement fluid; monitor K+; may need dialysate K+ adjustment | | **Hypothermia** | Infusion of cold replacement fluid | Use inline warmer for replacement fluid | | **Hemodynamic instability** | Excessive fluid removal; sepsis worsening | Reduce UF rate; improve sepsis management; vasopressor support | ## References 1. Palevsky PM, Zhang JH, O’Connor TZ, et al. Intensity of renal support in critically ill patients with acute kidney injury. *N Engl J Med.* 2008;359(1):7-20. [PMID: 18492867](https://pubmed.ncbi.nlm.nih.gov/18492867/) 2. RENAL Replacement Therapy Study Investigators; Bellomo R, Cass A, Cole L, et al. Intensity of continuous renal-replacement therapy in critically ill patients. *N Engl J Med.* 2009;361(17):1627-38. [PMID: 19846848](https://pubmed.ncbi.nlm.nih.gov/19846848/) 3. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. *Nephron Clin Pract.* 2012;120(4):c179-84. [PMID: 22890468](https://pubmed.ncbi.nlm.nih.gov/22890468/) 4. Gattas DJ, Rajbhandari D, Bradford C, et al. A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults. *Crit Care Med.* 2015;43(8):1622-9. [PMID: 25853591](https://pubmed.ncbi.nlm.nih.gov/25853591/) ## Related Resources - AKI Staging and Classification - Acute Tubular Necrosis - Dialysis Initiation and Modality Selection - Peritoneal Dialysis Principles - Dialysis and RRT Hub ## Educational Resources - Student Guide: Dialysis Student Guide — PA/medical student educational guide - Student Guide: Dialysis Hub — PA/medical student educational guide - Student Handout: Crrt — PA/medical student educational guide --- [Website version](https://urinenephrology.org/mastery/dialysis-advanced/crrt-principles.html) · Markdown synchronized October 3, 2026.