Dialy-trauma in RRT: Clinical Scenario

🩸💥 When CRRT Heals… but Slowly Hurts—Will You Notice the Dialy-Trauma? 💥🩸

By Dr Tapas Kumar Sahoo

Dr Tapas Kumar Sahoo

MD FNB FICCM FCCP(USA) EDIC(UK)

Canadian Critical Care Fellowship (University of Toronto),
MBA (Healthcare Management)

Associate Director & Head, Critical Care
Medanta Hospital, Ranchi, India

A 55-year-old woman with severe community-acquired pneumonia complicated by septic shock is receiving CRRT at 25 mL/kg/h with regional citrate anticoagulation for 72 hours. After 72 hours:

Serum phosphate: 1.8 mg/dL; Mg²⁺: 1.4 mg/dL
Core temperature: 35.5 °C despite active warming
Prealbumin: ↓ 30% from baseline
CRP: 200 mg/L; IL-6 markedly elevated
Therapeutic-drug monitoring (TDM) for meropenem and vancomycin unavailable
Proximal muscle weakness
Serum lactate: 2.8 mmol/L
Hemodynamics stable on norepinephrine 0.05 µg/kg/min (MAP ~65 mmHg)
ABG: pH 7.55; HCO₃⁻: 34 mmol/L; total calcium 11.2 mg/dL; ionized calcium 0.9 mmol/L (requiring escalated calcium infusion)

Key Questions at the Bedside

(Click / Tap on Questions to Reveal Content)

Q1: Given hypophosphatemia and risk of diaphragmatic dysfunction, should you elect a phosphate-enriched dialysate prescription to maintain continuous phosphate balance, or rely on intermittent intravenous phosphate repletion to avoid rebound hyperphosphatemia?

Clinical Dilemma:
The patient shows hypophosphatemia (1.8 mg/dL) after 72 hours of CRRT. She’s also developing proximal muscle weakness, suggesting early neuromuscular impact, possibly involving the diaphragm.

Answer :
Opt for a phosphate-containing dialysate/replacement fluid early in CRRT to maintain continuous phosphate balance. This approach prevents the common pitfall of delayed recognition and correction of phosphate loss during continuous therapy.

Bedside tip: If your centre does not stock phosphate-enriched CRRT fluids, consider customising replacement fluids with added potassium or sodium phosphate under pharmacy guidance.

Why not IV boluses alone?

They lead to peaks and troughs, risking under-correction or rebound hyperphosphatemia.
They require frequent monitoring and adjustments, especially in unstable ICU patients.

Why it matters:
Sustained low phosphate levels impair diaphragmatic contractility and ATP generation, which is clinically significant in ventilated patients. Timely correction prevents ventilator weaning failure.

Practical Approach at Bedside:

Use phosphate-containing fluid from day 1 of CRRT in patients with high risk of loss (sepsis, prolonged CRRT, high effluent rates).
Monitor serum phosphate every 12–24 hours in the acute phase.
Titrate additional IV phosphate only if persistent deficits occur.

References:

Bellomo R et al. Crit Care Resusc. 2002;4(4):290–296.

Ostermann M et al. Intensive Care Med. 2020;46:2280–2301.

Q2: In the absence of therapeutic-drug monitoring for meropenem and vancomycin, which strategy optimally ensures antimicrobial adequacy without undue toxicity: prolonged or continuous infusion following standard loading doses, empiric augmented loading regimens, or pragmatic reliance on CRRT-mediated drug clearance as a safety buffer against supratherapeutic levels?

Clinical Dilemma:
CRRT is running, and you lack therapeutic drug monitoring (TDM) for meropenem and vancomycin. The patient is in septic shock with high IL-6 levels and increasing inflammatory burden. Your goal is effective antimicrobial coverage while avoiding toxicity.

Answer :
Choose prolonged or continuous infusion after a weight-based standard loading dose for time-dependent antibiotics like meropenem and vancomycin. This strategy optimizes %fT>MIC (free time above minimum inhibitory concentration), the key pharmacodynamic target for these drugs.

Why it works better:

CRRT increases clearance and drug volume of distribution → standard bolus dosing often underdoses.
Prolonged infusion stabilizes serum concentrations, improves tissue penetration, and reduces the risk of subtherapeutic levels during early critical illness when capillary leak and inflammation peak.

Why not empiric augmented dosing?

Risk of accumulation, especially if CRRT downtime or filter saturation occurs.
You lack real-time TDM to guide titration.

Why not rely solely on CRRT clearance?

CRRT modalities differ widely in clearance capacity.
Drug removal may vary based on membrane type, effluent dose, and drug protein binding.

Practical Bedside Protocol:

Meropenem: 2g IV over 3 hours every 8h OR continuous infusion 3-6g/day after 2g loading
Vancomycin: 25–30 mg/kg loading → continuous infusion 15–25 mg/kg/day, adjust per renal recovery

References:

Roberts JA, CJASN. 2012;7(4):562–77.
Abdul-Aziz MH, Lancet Infect Dis. 2020;20(6):698–707.

Q3: Faced with persistent core hypothermia at 35.5 °C, is it preferable to integrate in-line circuit heating—accepting increased risk of filter clotting and cytokine activation—or to tolerate mild hypothermia and conservatively manage its metabolic and hemodynamic sequelae?

Clinical Dilemma:
Your patient is persistently hypothermic at 35.5 °C despite external warming during ongoing CRRT. You’re concerned about metabolic effects, circuit clotting, and immunologic implications of hypothermia.

Answer :
Avoid in-line heating of CRRT fluids unless absolutely necessary. Instead, intensify external warming measures (e.g., forced-air blankets, warmed IV fluids, ambient temperature optimization). Mild hypothermia (35–36 °C) is usually tolerable if systemic perfusion and oxygen delivery are adequate.

Why not in-line heating?

In-line heaters can promote protein denaturation, circuit clotting, and cytokine activation within the extracorporeal circuit.
These changes can worsen systemic inflammation and reduce filter lifespan.

Can mild hypothermia be tolerated?
Yes, provided the patient is:

Hemodynamically stable
Maintaining adequate oxygen delivery (normal ScvO₂, lactate ≤2.5)
Free from hypothermia-related arrhythmias or coagulopathy

What to monitor at bedside:

Lactate and acidosis trends
Coagulation profile (especially if active bleeding or thrombocytopenia)
Core temp every 4 hours
Filter life and circuit pressures

Practical Tip:
Warming blanket + heated ambient room + warmed IV fluids ≈ sufficient in most ICU settings. In-line heating is reserved for deep hypothermia (<34°C) with clear metabolic compromise.

References:

VA/NIH ATN Trial. N Engl J Med. 2008;359(1):7–20.
Clark E et al. Nephrol Dial Transplant. 2023;38(1):83–91.

Q4: With systemic inflammatory markers remaining elevated, does escalating effluent flow to 35 mL/kg/h to enhance cytokine removal justify the attendant increase in nutrient and drug losses, or does such intensification exacerbate dialy-trauma without demonstrable improvement in patient-centered outcomes?

Clinical Dilemma:
Despite 72 hours of CRRT, inflammatory markers remain elevated (CRP 200 mg/L, IL-6 high). The patient is catabolic, and there’s a temptation to increase effluent dose from 25 to 35 mL/kg/h to enhance cytokine clearance.

Answer :
Do not escalate the effluent dose unless there’s a clear metabolic indication (e.g., severe hyperammonemia, intoxication, refractory acidosis). Increasing CRRT intensity above 25 mL/kg/h does not improve mortality or renal recovery, and it can exacerbate protein and micronutrient loss—worsening the very inflammation you’re aiming to treat.

What the evidence says:

The RENAL Trial and VA/NIH ATN Trial found no benefit in high-dose CRRT (>35 mL/kg/h) in sepsis or AKI outcomes.
Higher doses lead to greater albumin, amino acid, phosphate, and trace element losses, often unmeasured but clinically relevant.

Why the cytokine clearance argument falls short:

CRRT removes only small to medium-sized cytokines and doesn’t correct the production–clearance imbalance in overwhelming sepsis.
IL-6 half-life and tissue binding mean that blood clearance doesn’t equal clinical benefit.

Clinical risk of higher dose:

Hypophosphatemia, hypokalemia
Negative nitrogen balance
Drug underdosing
Aggravation of metabolic alkalosis

Bedside strategy:

Continue 20–25 mL/kg/h dosing
Focus on source control, optimal antibiotics, and supportive care
Consider adsorptive therapies (e.g., CytoSorb) only in select patients under research protocols

References:

RENAL Study Investigators. N Engl J Med. 2009;361(17):1627–38.
Clark E et al. Nephrol Dial Transplant. 2023;38(1):83–91.

Q5: Should you institute intravenous peptide infusions or simply escalate enteral protein delivery, recognizing the paucity of randomized data to guide one approach over another?

Clinical Dilemma:
The patient is on CRRT for 72+ hours with significant inflammation and a 30% drop in prealbumin. You suspect ongoing protein losses and want to optimize nutrition. Should you escalate enteral protein delivery or start intravenous peptide/amino acid infusions?

Answer :
Prioritize enteral protein delivery, escalating to 2.0–2.5 g/kg/day if tolerated. Reserve IV amino acids or peptide formulas only for:

Severe catabolic states
Prolonged CRRT with high protein losses
Documented enteral intolerance or ileus

Why enteral first?

Supports gut integrity and immune modulation
Reduces the risk of infection compared to parenteral routes
Allows for stepwise titration based on tolerance

Why not IV peptides routinely?

No strong evidence for improved outcomes
Higher costs and potential for overfeeding
Difficult to monitor nitrogen balance accurately
May delay transition to full enteral feeding

CRRT-specific nutrition tip:

CRRT removes 10–15 g/day of amino acids
Prealbumin is a useful dynamic marker of nutrition and inflammation
Use urea nitrogen appearance (UNA) or nitrogen balance when feasible to tailor protein delivery

Practical Bedside Protocol:

Start at 1.5 g/kg/day → titrate up to 2.5 g/kg/day as tolerated
Use semi-elemental formulas if malabsorption suspected
If unable to meet >60% of needs via enteral route by day 4–5, consider IV amino acid support

References:

Singer P et al. Clin Nutr. 2019;38(1):48–79.
Compher C et al. 2022;46(1):12–41.

Q6: Now that hemodynamics have stabilized, should you transition her to SLED to reduce cumulative dialy-trauma, or continue CRRT in light of its demonstrated advantages for renal recovery in unstable AKI populations as evidenced by the ATN and RENAL trials?

Clinical Dilemma:
The patient is now hemodynamically stable on minimal vasopressors (MAP ~65 mmHg). CRRT has been ongoing for 3 days. You’re considering switching to SLED to reduce the cumulative burden of continuous therapy.

Answer :
Transitioning to SLED is appropriate and safe in patients who are hemodynamically stable or on minimal vasopressor support. There is no evidence from RCTs that prolonged CRRT leads to improved renal recovery or survival in this setting.

Why consider transitioning?

SLED is intermittent (6–12 hours), so less continuous fluid/electrolyte and protein removal → fewer nutrient losses
More flexible for mobilization, investigations, and nursing care
Cost-effective and logistically easier in resource-limited ICUs

Bedside considerations before switching:

Vasopressor dose ≤0.05 µg/kg/min
Stable MAP for ≥12 hours
No signs of fluid overload or unstable ICP

Practical Tip:
Start with 8–10 hr SLED runs, ultrafiltration at 100–200 mL/hr, monitor BP and electrolytes closely. Resume CRRT if instability recurs.

References:

VA/NIH ATN Trial. N Engl J Med. 2008;359(1):7–20.
RENAL Study Investigators. N Engl J Med. 2009;361(17):1627–38.

Q7: Considering that continuous ultrafiltration alters intravascular volume status, can dynamic indices such as stroke-volume variation or pulse-pressure variation validly guide fluid-removal prescriptions during CRRT, or are these parameters fundamentally confounded by the extracorporeal circuit?

Clinical Dilemma:
You’re managing ultrafiltration goals in a patient on CRRT. Dynamic indices like SVV and PPV are being considered to guide fluid removal. However, you’re unsure of their reliability in the setting of continuous extracorporeal therapy.

Answer :
SVV and PPV are unreliable in CRRT patients because:

The extracorporeal circuit alters preload and afterload
CRRT may cause dampening of arterial waveforms
Mechanical ventilation settings and ultrafiltration flow rates further confound readings

Why this matters:
Inaccurate use of SVV/PPV may overestimate fluid responsiveness, leading to inappropriate ultrafiltration and hemodynamic compromise.

Preferred bedside strategies:
Use a multimodal approach instead:

Passive Leg Raise (PLR) + real-time cardiac output monitoring
Lung ultrasound for extravascular lung water
Focused echocardiography for IVC variability, cardiac function
Trend net fluid balance, urine output, weight, and lactate

Practical Tip:
If using dynamic indices, ensure:

Full mechanical ventilation with fixed tidal volume ≥8 mL/kg
No spontaneous breathing efforts
Stable rhythm (no AFib)
Still, validate against clinical context and other dynamic tests.

Reference:

Monnet X, Teboul JL. Ann Intensive Care. 2016;6(1):37.

Q8: Regional citrate anticoagulation can induce metabolic alkalosis, citrate accumulation, and hypocalcemia—how should you adjust the citrate infusion rate, calcium replacement strategy, or consider an alternative anticoagulation modality to mitigate anticoagulation-related dialy-trauma?

Clinical Dilemma:
The patient has been on RCA for 72 hours. ABG shows alkalosis (pH 7.55, HCO₃⁻ 34 mmol/L) and iCa 0.9 mmol/L despite rising total calcium and escalated calcium infusion. You’re concerned about citrate accumulation and metabolic complications.

Answer :
This scenario indicates a classic citrate-related triad:

Metabolic alkalosis from bicarbonate generation
Low ionized calcium despite normal/high total calcium
Escalating calcium requirements, suggesting accumulation

Management Strategy:

Reduce citrate rate or switch to a lower-concentration citrate solution
- Aim to lower systemic citrate load while maintaining circuit patency
Titrate calcium gluconate infusion to maintain iCa >1.0 mmol/L
- Target gap between total and ionized calcium <2.5 mg/dL
Switch to an alternative anticoagulant (e.g., heparin, no anticoagulation) if:
- Lactate is rising
- Liver dysfunction impairs citrate metabolism
- Severe or refractory alkalosis persists

Bedside Clue:
Check the total calcium to ionized calcium ratio:

>2.5 suggests citrate accumulation
Consider this especially if liver dysfunction or shock is present

Monitoring Tips:

ABG and iCa every 6–12 hours
Watch for bradycardia, tetany, or hypotension
Track calcium infusion rates; sudden escalation often precedes citrate toxicity

References:

Khadzhynov D et al. Blood Purif. 2015;40(4):314–322.
KDIGO AKI Guidelines, 2012.

🩸💥 When CRRT Heals… but Slowly Hurts—Will You Notice the Dialy-Trauma? 💥🩸 By Dr Tapas Kumar Sahoo

Dr Tapas Kumar Sahoo