2. CRRT Indications

Quick Recap

Renal System, Protocol 2/7.

1. Indications for Renal Replacement Therapy

Conventional indications: metabolic acidosis refractory to medical management, hyperkalemia refractory to medical treatment, volume overload refractory to diuretics, severe uremic symptoms (encephalopathy, pericarditis, coagulopathy) refractory to medical management. Additional indication: certain intoxications (ethylene glycol, methanol, lithium, salicylates) where the substance or toxic metabolite is dialyzable.

Practical oliguria algorithm before committing to RRT: rule out mechanical obstruction (blocked catheter, urinary retention — check bladder by exam/ultrasound) -> assess volume status clinically/by ultrasound -> if hypovolemic/euvolemic, trial fluid bolus (usually responds within ~2h if truly volume-responsive) -> if fluid-overloaded/cardiac failure, trial furosemide (bolus, then consider continuous infusion if hemodynamically stable) -> if still oliguric/anuric with fluid overload despite these steps, AVOID further diuretics and proceed to RRT rather than escalating diuretic doses indefinitely in a truly diuretic-refractory patient.

RRT is initiated when conservative medical management has FAILED to control the fluid, electrolyte, and metabolic complications of AKI — it is a rescue therapy for failed medical management, not a default early intervention.

2. Modality Comparison

Critical outcome data: CRRT has NOT shown improved survival over IHD in critically ill patients, nor a difference in time to renal recovery or ICU/hospital length of stay in randomized trials — modality selection is driven by hemodynamic tolerance and logistics, NOT by a proven survival advantage of one approach over another. PIRRT/SLED has shown similar safety/efficacy to both CRRT and IHD in randomized studies, and its convenience/cost profile has driven increasing adoption.

3. CRRT Sub-Modalities

• SCUF (slow continuous ultrafiltration): fluid removal ONLY, no significant solute clearance
• CVVH (continuous venovenous hemofiltration): solute clearance by CONVECTION, requires replacement fluid; predominantly volume + additional solute removal
• CVVHD (continuous venovenous hemodialysis): solute clearance by DIFFUSION, requires dialysate fluid; clears mainly small molecules (urea) with controlled fluid removal
• CVVHDF (continuous venovenous hemodiafiltration): combines BOTH convection and diffusion (both replacement fluid AND dialysate) — highly efficient solute AND volume removal

4. Dialysis Dose

No conclusively determined "ideal" dose in critically ill patients — ICU patients' actual urea clearances run ~25% LOWER than predicted from stable CKD dialysis patients, complicating direct extrapolation of chronic dialysis dosing targets.

IHD: landmark ATN study (large multicenter RCT) found NO mortality or renal recovery benefit with more frequent dialysis (6x/week vs 3x/week). Recommendation: IHD 3x/week, targeting urea reduction ratio >70% or Kt/V 1.2-1.4 per treatment.

CRRT: early small RCTs suggested a survival benefit with high-intensity dialysis, but the largest trials (ATN study: 35 vs 20 mL/kg/h effluent; RENAL study: 40 vs 25 mL/kg/h effluent) showed NO survival advantage with higher-intensity dialysis at day 60, and higher intensity did NOT improve renal recovery or reduce nonrenal organ failure. Subsequent meta-analyses confirmed this.

Recommended CVVHDF dosing: 20 mL/kg/h flow, divided equally between replacement and dialysate flow rates, with a MINIMUM of 20 hours/day on therapy.

If actual delivered therapy time is <18-20h/24h (due to diagnostic testing, procedures, circuit clotting, etc.), increase the prescribed dose by 15-20% to ensure the ACTUAL delivered dose still approximates 20 mL/kg/h — an important practical correction factor, since prescribed dose and delivered dose diverge whenever downtime occurs.

Use higher flow rates specifically for patients needing higher clearance for severe acidosis or hyperkalemia — dose can and should be individualized upward for these specific indications rather than applying a single flat rate to everyone.

5. Anticoagulation

Heparin is the preferred/most common anticoagulant at many institutions for CRRT circuit patency.

Heparin-induced thrombocytopenia: use a direct thrombin inhibitor — argatroban or bivalirudin.

When systemic anticoagulation is contraindicated: regional CITRATE anticoagulation — citrate chelates serum calcium, inhibiting the coagulation cascade WITHIN the circuit; citrate is rapidly metabolized to bicarbonate in the LIVER, so it does NOT cause systemic anticoagulation (a key mechanistic point explaining its safety profile in patients who cannot tolerate systemic heparin).

Citrate requires calcium replacement via a SEPARATE central venous line, with close monitoring of serum IONIZED calcium (not total calcium, which will be affected by the citrate-calcium complex itself).

Citrate-associated metabolic alkalosis is a recognized complication (from ongoing citrate-to-bicarbonate conversion) — manage by switching the replacement fluid from a bicarbonate-based product to normal saline.

Anticoagulation-free option: periodic saline flush (100mL every 30 minutes) of the blood filter can safely maintain circuit patency without any anticoagulant in appropriately selected cases — remember to include the saline flush volume in the ultrafiltration rate calculation to avoid inadvertent volume accumulation.

6. CRRT-Specific Complications

Hypotension can still occur despite CRRT's gentler hemodynamic profile compared to IHD, particularly with high ultrafiltration rates.

Electrolyte derangements from uninterrupted high-flow clearance: dramatic hypophosphatemia, hypokalemia, and hypomagnesemia can develop — monitor electrolytes at least DAILY. Correct hypokalemia by increasing potassium concentration in replacement fluid/dialysate; correct hypophosphatemia/hypomagnesemia by direct supplementation.

Hypothermia is well-recognized, common at high flow rates — significant heat loss from the slow-flowing extracorporeal circuit can drop body temperature 2-5C. Use in-line warmers (dialysate/replacement fluid warmers or venous return tubing warmers) to mitigate — but this creates a diagnostic blind spot for fever detection, since the warming counteracts the temperature signal of an underlying infection; rely on other clinical infection signs rather than routine culture screening, as unpublished data show no advantage to reflexive culturing in this context.

7. Vascular Access Considerations

Thrombus/fibrin sheath formation around/inside catheters can impair blood flow — hub-instilled heparin after dialysis does not reliably prevent this. For catheter malfunction: instill 1-2mg alteplase into each catheter lumen, cap for 2-3 hours, then aspirate before resuming dialysis — NEVER administer alteplase systemically for this indication. If malfunction persists, replace the catheter completely (not over a guidewire).

Avoid subclavian veins for dialysis catheters in CKD patients — high risk of subclavian venous stenosis, which can preclude future arteriovenous fistula/graft placement in that extremity.

Tunneled catheters: no data showing infection-rate or dialysis-adequacy superiority over temporary catheters specifically in ICU AKI patients — reserve for patients with multiple malfunctioning temporary catheters, poor early renal recovery likelihood, or transfer to another facility. Clotted tunneled catheters require interventional radiology consultation for endoluminal brushing.

8. Drug Dosing During CRRT

Pharmacokinetics during CRRT are highly complex, depending on drug molecular size, protein binding, volume of distribution, dialyzer membrane permeability, dialysis dose, and modality (CVVHD vs CVVH vs CVVHDF). Limited data exists specifically for critically ill patients — recommendations should not replace clinical judgment given how much clinical situations vary. Key principle: CRRT clearance is CONTINUOUS, so most drugs need MORE FREQUENT dosing (2-3x daily) than their standard non-renal-failure intervals would suggest — measure drug levels daily when available.

Selected antimicrobial dosing during CRRT (CVVH vs CVVHD/CVVHDF):

PIRRT drug dosing is even LESS predictable than CRRT given machine/center-dependent variability in dialyzer membrane, blood flow, and dialysate flow rates; once-daily meds should be given POST-PIRRT; twice-daily meds: first dose post-PIRRT, second dose 12h later; ideally standardize PIRRT timing to the same time each day; close pharmacist-nephrology-ICU communication is essential.

9. Discontinuation of RRT

Continue RRT until evidence of renal recovery: decreasing creatinine after reaching a steady state (oliguric patients), or increasing urine output (nonoliguric patients).

If uncertain, obtain a 24-hour urine collection for creatinine clearance (CrCl). RRT can generally be discontinued if CrCl >15-20 mL/min. (Ongoing trials at the time of writing were still examining optimal discontinuation timing.)

10. Organ Support

RRT itself is the organ support intervention for AKI-related fluid/electrolyte/metabolic complications; see the AKI protocol for the broader AKI management framework this fits within.

11. Consultation Matrix

12. Monitoring Framework

Daily electrolytes (minimum) during active CRRT, ionized calcium monitoring with citrate anticoagulation, daily renal function trend, delivered therapy time tracking (to catch under-dosing from downtime), temperature monitoring (aware of warmer-related fever-detection blind spot), drug level monitoring where available.

13. Complications

Hypotension, electrolyte derangement (hypophosphatemia, hypokalemia, hypomagnesemia), hypothermia, citrate-associated metabolic alkalosis or hypocalcemia, catheter thrombosis/malfunction, circuit clotting (heparin-related) or citrate toxicity (impaired liver metabolism states), infection (catheter-related, masked fever detection). Prevention: appropriate anticoagulation choice for the clinical scenario, daily electrolyte monitoring with proactive repletion, warmer use with heightened clinical infection vigilance, correct citrate/calcium monitoring. Rescue: alteplase lock for catheter malfunction (never systemic), catheter replacement, modality switch if one approach proves hemodynamically intolerable.

14. Escalation & De-escalation

Escalate: conventional RRT indications not resolving with current dose/modality -> increase flow rate (esp. for severe acidosis/hyperkalemia), correct for under-delivered therapy time, consider modality switch.

De-escalate: renal recovery evidence (falling creatinine at steady state or rising urine output, CrCl >15-20 mL/min) -> discontinue RRT, monitor for recurrent need.

15. ICU Discharge Criteria

RRT discontinued with confirmed renal recovery trajectory, OR stable on a defined outpatient dialysis plan (tunneled catheter, coordination with outpatient nephrology) if recovery is not expected, electrolytes/acid-base stable, vascular access plan established for ongoing needs.

16. Documentation & Medicolegal Checklist

17. Key Guidelines

KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;(suppl 2):1-138.

18. Landmark Trials

VA/NIH Acute Renal Failure Trial Network (ATN) Study — both the IHD-frequency arm and the CRRT-intensity arm found no benefit to higher-intensity/more-frequent therapy. RENAL Replacement Therapy Study Investigators trial (40 vs 25 mL/kg/h effluent) — confirmed no survival advantage with higher CRRT intensity. Bagshaw SM, Berthiaume LR, Delaney A, et al. Continuous versus intermittent renal replacement therapy for critically ill patients with AKI: meta-analysis. Crit Care Med. 2008;36(2):610-617.

19. Controversies

Despite theoretical physiologic advantages, CRRT has not demonstrated a survival benefit over IHD or PIRRT in rigorous trials — modality choice remains a hemodynamic-tolerance and logistics decision, not an evidence-mandated one, and institutions vary considerably in default practice. The "ideal" CRRT dose remains debated at the margins despite the large negative-intensity trials, particularly for niche indications like severe hyperkalemia/acidosis where higher flow may still be reasonably pursued despite the lack of a proven mortality benefit at that specific indication level. Optimal RRT discontinuation timing is genuinely unresolved (ongoing trials referenced at time of source writing), and premature discontinuation risking AKI relapse must be balanced against unnecessary prolongation of an invasive therapy.

20. References

1. Cummings J, Vijayan A. Renal Replacement Therapy. Washington Manual of Critical Care, 4th ed, 2025 (Ch. 48).
2. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical practice guideline for acute kidney injury. Kidney Int. 2012;(suppl 2):1-138.
3. VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7-20.
4. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1638.
5. Bagshaw SM, Berthiaume LR, Delaney A, et al. Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med. 2008;36(2):610-617.

See also: Acute Kidney Injury (Renal System) for the broader AKI management framework this protocol's therapy fits within.