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2025 PACUPrep BCCCP Preparatory Course Renal Replacement Therapies (RRT) Renal Replacement Therapies in the ICU

Lesson 20, Topic 4

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Renal Replacement Therapies in the ICU

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Complication Monitoring and Management in RRT

Objective

Develop a plan to monitor and manage common metabolic and procedural complications of Renal Replacement Therapy (RRT).

Introduction

Complications associated with Renal Replacement Therapy (RRT) significantly impact morbidity and mortality in the Intensive Care Unit (ICU). Early recognition of these complications and coordinated multidisciplinary management are essential for optimizing patient outcomes.

Scope of Complications

This chapter focuses on common RRT-related complications, including:

Electrolyte disturbances (e.g., hypophosphatemia, hypomagnesemia, hypokalemia)
Metabolic derangements related to citrate anticoagulation (e.g., metabolic alkalosis, hypernatremia, citrate toxicity)
Hemodynamic instability (intradialytic hypotension)
Vascular access-related infections (Catheter-Related Bloodstream Infections – CRBSI)

Impact and Multidisciplinary Roles

These complications can lead to interruptions in RRT delivery, prolonged ICU stays, and increased mortality. A multidisciplinary team approach is crucial. Pharmacists play a key role in monitoring for complications, guiding electrolyte and drug dosage adjustments, and contributing to the development and implementation of RRT protocols.

Key Pearl

Proactive monitoring and early intervention for RRT-related complications are associated with reduced overall morbidity and may contribute to improved chances of renal recovery.

1. Electrolyte Abnormalities

Continuous solute clearance during RRT, particularly with continuous modalities (CRRT), predisposes patients to significant electrolyte losses, most commonly hypophosphatemia, hypomagnesemia, and hypokalemia. Prevention through dialysate/replacement fluid customization and timely supplementation are key management strategies.

A. Pathophysiology and Risk Factors

RRT efficiently removes small, water-soluble solutes with low protein binding, including phosphate, magnesium, and potassium.
High effluent flow rates (dialysate and/or replacement fluid) and the use of phosphate-free or low-electrolyte solutions exacerbate these losses.
Additional risk factors include pre-existing malnutrition, sepsis-induced catabolism, refeeding syndrome, and aggressive ultrafiltration goals.

B. Prevention Strategies

Customize dialysate and replacement fluid compositions to include physiological concentrations of electrolytes. For example, adding phosphate to achieve a concentration of approximately 1.2 mmol/L.
Regularly monitor serum phosphate, magnesium, and potassium levels, typically every 6 to 12 hours, especially during the initial phase of RRT or with high-intensity therapy.
Adjust RRT prescription (e.g., effluent rate) if electrolyte losses are excessive and difficult to manage with supplementation alone.

C. Treatment Protocols (Pharmacotherapy)

1. Phosphate Supplementation

Management of Hypophosphatemia during RRT
Feature	Description
Mechanism	Restores intracellular phosphate, crucial for ATP production, oxygen transport (2,3-DPG), and cellular membrane integrity.
Indication	Serum phosphate <2.0 mg/dL (0.65 mmol/L) or symptomatic hypophosphatemia (e.g., muscle weakness, respiratory failure, altered mental status).
Agent Selection	Sodium phosphate (preferred if serum potassium is normal/high) or potassium phosphate (if concomitant hypokalemia exists).
Dosing (IV)	15–30 mmol elemental phosphorus IV infused over 4–6 hours. Maximum infusion rate generally 7.5 mmol/hour to minimize risk of calcium-phosphate precipitation.
Dosing (Oral)	If tolerated and gut absorption is adequate: 250–500 mg elemental phosphorus PO three times daily.
Monitoring	Serum phosphate every 6 hours during repletion. Monitor serum calcium, magnesium, and potassium. Assess ongoing losses via effluent if possible.
Contraindications	Hypercalcemia, severe hypokalemia (for potassium phosphate products if not also supplementing K+), significant volume overload (consider concentrated forms).
Administration Note	Infuse IV phosphate slowly. Avoid co-administration with calcium-containing solutions in the same line. Match dosing to ongoing RRT losses and patient’s clinical status.

2. Magnesium Sulfate Supplementation

Management of Hypomagnesemia during RRT
Feature	Description
Mechanism	Repletes intracellular magnesium, a cofactor for numerous enzymatic reactions, and stabilizes neuromuscular and cardiac electrical function.
Indication	Serum magnesium <1.5 mg/dL (0.6 mmol/L) or symptomatic hypomagnesemia (e.g., arrhythmias, tetany, seizures).
Dosing (IV)	1–2 grams of magnesium sulfate IV infused over 1 hour for mild to moderate deficits. Larger doses or continuous infusions may be needed for severe deficits or ongoing losses. Repeat doses every 6 hours as needed based on serum levels.
Monitoring	Serum magnesium every 6 hours during repletion. Monitor for signs of hypermagnesemia (e.g., hypotension, loss of deep tendon reflexes, respiratory depression).
Contraindications	Severe heart block, myasthenia gravis (relative contraindication, use with caution). Reduce dose in renal impairment if not on RRT.
Administration Note	Infuse slowly (e.g., 1 gram per hour) to minimize risks of hypotension, flushing, and bradycardia.

3. Potassium Chloride Supplementation

Management of Hypokalemia during RRT
Feature	Description
Mechanism	Repletes total body potassium stores, essential for maintaining normal cardiac conduction, neuromuscular function, and cellular metabolism.
Indication	Serum potassium <3.5 mEq/L (mmol/L).
Dosing (IV)	10–20 mEq of potassium chloride IV infused over 1 hour. Maximum infusion rate typically 10 mEq/hour via peripheral line, up to 20 mEq/hour (or rarely 40 mEq over 2 hours) via central line with continuous ECG monitoring for severe hypokalemia.
Dosing (Oral)	If tolerated: 20–40 mEq PO two to three times daily.
Monitoring	Serum potassium every 4–6 hours during repletion. Continuous ECG monitoring if serum K+ <3.0 mEq/L, if rapid infusion rates are used, or if arrhythmias are present.
Contraindications	Hyperkalemia, anuria (if not on RRT or RRT is interrupted). Use with caution in patients on ACE inhibitors or potassium-sparing diuretics.
Administration Note	Use a central line for infusion rates >10 mEq/hour. Adjust potassium concentration in dialysate/replacement fluid to maintain target serum levels.

Key Pearls

Routine, frequent monitoring of electrolytes and customization of RRT solutions are paramount in preventing severe deficits.
Hypophosphatemia, in particular, has been linked to diaphragmatic weakness and prolonged duration of mechanical ventilation in critically ill patients.

2. Citrate Anticoagulation-Related Complications

Regional Citrate Anticoagulation (RCA) is increasingly used in CRRT due to its efficacy in prolonging filter life and reducing bleeding risk compared to systemic heparin. However, RCA can lead to metabolic complications such as metabolic alkalosis, hypernatremia, or, less commonly, systemic citrate accumulation (citrate toxicity).

A. Citrate Lock (Metabolic Alkalosis & Hypernatremia)

Mechanism: Citrate is metabolized in the liver (primarily) and other tissues to bicarbonate (1 mole of trisodium citrate yields 3 moles of bicarbonate). The sodium load from the citrate solution (e.g., trisodium citrate) can also contribute to hypernatremia if not balanced by RRT fluid removal and composition.
Recognition: Elevated serum bicarbonate (HCO3–) >28 mEq/L, elevated serum sodium (Na+) >145 mEq/L. Patients may exhibit symptoms of alkalosis (e.g., confusion, arrhythmias, tetany if ionized calcium is also affected) or hypernatremia (e.g., thirst, altered mental status).
Management:
- Decrease the citrate infusion rate (if post-filter ionized calcium target allows).
- Adjust the bicarbonate concentration in the dialysate or replacement fluid (e.g., switch to a lower bicarbonate solution or use a chloride-based solution).
- Increase the calcium concentration in the systemic calcium replacement infusion if ionized calcium is low, as alkalosis can decrease ionized calcium.
- Ensure appropriate net sodium removal by RRT.

B. Systemic Citrate Accumulation (Citrate Toxicity)

Mechanism: Occurs when citrate clearance (primarily hepatic) is impaired (e.g., severe liver dysfunction, shock states with hypoperfusion) relative to the citrate infusion rate. Accumulated citrate chelates systemic ionized calcium, leading to hypocalcemia. It can also lead to an anion gap metabolic acidosis as citrate itself is an anion.
Recognition:
- Elevated anion gap metabolic acidosis (unexplained by lactate or ketones).
- Low systemic ionized calcium (iCa2+) <1.0 mmol/L despite adequate calcium replacement.
- An elevated total calcium to ionized calcium ratio (Total Ca2+/iCa2+) >2.5 (when total calcium is in mg/dL and ionized calcium is in mmol/L, a common unit mismatch that requires careful interpretation; ideally both are in mmol/L, where a ratio >2.2-2.5 is concerning). This ratio indicates that a significant portion of total calcium is bound to citrate.

Calcium Replacement for Citrate Toxicity

Calcium Replacement in Citrate Anticoagulation
Feature	Description
Mechanism	Restores systemic ionized calcium levels to counteract chelation by citrate, maintaining normal neuromuscular excitability and cardiac function.
Indication	To maintain systemic ionized calcium within the target range (typically 1.0–1.2 mmol/L or 1.1-1.3 mmol/L depending on local protocol) during RCA, and to treat hypocalcemia due to citrate accumulation.
Agent Selection	Calcium gluconate (often preferred for peripheral administration due to lower osmolality and less vein irritation) or calcium chloride (provides more elemental calcium per gram, often used for central administration or severe hypocalcemia). 1g calcium gluconate = ~93mg elemental Ca; 1g calcium chloride = ~273mg elemental Ca.
Dosing	Typically administered as a continuous IV infusion, titrated based on frequent monitoring of systemic ionized calcium. Bolus doses (e.g., 1-2 grams of calcium gluconate or 0.5-1 gram of calcium chloride IV over 10–20 minutes) may be needed for acute symptomatic hypocalcemia or rapidly falling levels. Continuous infusion rates vary (e.g., 0.5–2.0 mmol/hr of elemental calcium).
Monitoring	Systemic ionized calcium (iCa2+) every 4-8 hours (or more frequently if unstable or titrating). Post-filter iCa2+ to assess anticoagulation efficacy (target typically 0.25-0.4 mmol/L). Monitor for signs of hypercalcemia.
Contraindications	Hypercalcemia. Use with caution in patients receiving digoxin (hypercalcemia potentiates digoxin toxicity).
Administration Note	Titrate calcium infusion to maintain systemic ionized Ca2+ within the desired range (e.g., 1.0–1.2 mmol/L). If citrate toxicity is suspected (rising total/ionized Ca ratio, metabolic acidosis), reduce citrate dose or switch to alternative anticoagulation.

Key Pearls

Monitor acid-base status (pH, HCO3-, anion gap) and electrolytes (Na+, total and ionized Ca2+) every 6–8 hours during RCA, or more frequently if concerns arise.
A rising total calcium to ionized calcium ratio (Total Ca2+/iCa2+) above 2.5 (ensure consistent units, typically mg/dL for total and mmol/L for ionized, or both in mmol/L) is a strong indicator of impaired citrate metabolism and impending citrate toxicity.

3. Intradialytic Hypotension (IDH)

Intradialytic hypotension, defined as a significant drop in blood pressure during RRT, is a common complication, particularly with intermittent hemodialysis but also seen in CRRT if fluid removal is aggressive. It arises from ultrafiltration rates exceeding plasma refill capacity and rapid osmotic shifts, potentially leading to RRT interruption and end-organ injury.

A. Etiology and Monitoring

Causes:
- Excessive or rapid ultrafiltration (UF) rate relative to intravascular volume and plasma refilling rate.
- Autonomic dysfunction (common in diabetic or uremic patients).
- Rapid solute removal leading to osmotic shifts and decreased plasma osmolality.
- Cardiac dysfunction (pre-existing or acute).
- Vasodilation from medications or sepsis.
Monitoring:
- Monitor Mean Arterial Pressure (MAP) and heart rate frequently (e.g., every 5-15 minutes during intermittent HD, hourly or more often with CRRT if unstable).
- Consider invasive hemodynamic monitoring (e.g., arterial line, CVP) in hemodynamically unstable patients or those at high risk for IDH.
- Advanced hemodynamic monitoring tools (e.g., cardiac output monitoring) may be used in select complex cases.

B. Preventive Strategies

Individualize the UF rate, aiming for <10–13 mL/kg/hour in intermittent HD; ensure net fluid balance goals are appropriate in CRRT.
Use cooled dialysate (e.g., 35–36 °C) which can enhance vasoconstriction and reduce IDH incidence.
Consider sodium profiling (varying dialysate sodium concentration during treatment) or biofeedback systems that adjust UF based on relative blood volume monitoring (available on some HD machines).
Ensure accurate assessment of dry weight/target fluid status.
Hold antihypertensive medications immediately prior to intermittent HD if appropriate.

C. Therapeutic Measures

Norepinephrine

Norepinephrine for Intradialytic Hypotension
Feature	Description
Mechanism	Potent α1-adrenergic agonist, leading to peripheral vasoconstriction and increased systemic vascular resistance, thereby increasing blood pressure. Also has modest β1-agonist effects increasing heart rate and contractility.
Indication	Refractory intradialytic hypotension (MAP <65 mmHg or symptomatic) unresponsive to initial measures like UF reduction/cessation, Trendelenburg position, or fluid boluses (if patient is not fluid overloaded). More commonly used in CRRT for underlying shock.
Dosing	Initiate at a low dose (e.g., 0.02–0.05 μg/kg/min) and titrate rapidly to achieve target MAP (typically ≥65 mmHg). Usual dose range 0.02–0.5 μg/kg/min, but higher doses may be needed in severe shock.
Monitoring	Continuous MAP monitoring (ideally via arterial line). Assess organ perfusion markers (urine output, mental status, lactate, capillary refill). Monitor for arrhythmias and signs of peripheral ischemia.
Contraindications/Cautions	Hypovolemia (correct first if possible). Use with caution in patients with severe peripheral vascular disease or mesenteric ischemia. Extravasation can cause tissue necrosis (administer via central line if possible, especially for prolonged or high-dose use).
Administration Note	Central venous access is preferred for prolonged or high-dose infusions. If initiated peripherally, monitor IV site closely. Wean slowly once underlying cause of hypotension is addressed or RRT session is complete.

Key Pearls

Individualize ultrafiltration rates based on careful assessment of volume status and real-time hemodynamic response.
In patients with persistent hypotension during RRT despite fluid management, early initiation of low-dose vasopressor support (if appropriate for underlying condition) may prevent prolonged organ hypoperfusion and allow continuation of necessary RRT.

4. Preventing and Managing Catheter-Related Bloodstream Infections (CRBSI)

Vascular access catheters for RRT are a significant source of nosocomial infections. Catheter-Related Bloodstream Infections (CRBSIs) prolong ICU stay, increase healthcare costs, and are associated with substantial morbidity and mortality. Adherence to strict infection control bundles and judicious catheter management are critical for prevention.

A. Infection Control Bundles for Prevention

Hand Hygiene: Perform hand hygiene (alcohol-based hand rub or soap and water) before and after palpating catheter sites, as well as before and after inserting, replacing, accessing, repairing, or dressing a catheter.
Maximal Barrier Precautions: Use maximal sterile barrier precautions (cap, mask, sterile gown, sterile gloves, and large sterile drape) during catheter insertion.
Skin Antisepsis: Prepare clean skin with a >0.5% chlorhexidine preparation with alcohol before catheter insertion and during dressing changes. Allow antiseptic to dry completely before insertion.
Catheter Site Selection: Prefer subclavian vein for non-tunneled catheters in adults to minimize infection risk, if not contraindicated. Avoid femoral site in adults if possible due to higher infection risk, though evidence is evolving. Ultrasound guidance for insertion is recommended to reduce mechanical complications and potentially infections.
Daily Review of Catheter Necessity: Assess the need for the catheter daily and remove it promptly when no longer essential.
Dressing Care: Use sterile gauze or sterile, transparent, semipermeable dressings to cover the catheter site. Change dressings when damp, loosened, or soiled, or according to institutional protocol (e.g., transparent dressings every 5-7 days, gauze dressings every 2 days).

B. Diagnosis and Management of Suspected CRBSI

Diagnosis:
- Obtain paired blood cultures: one set from the suspected catheter lumen and another from a peripheral venipuncture site.
- CRBSI is often diagnosed by differential time to positivity (DTP): growth from catheter-drawn culture ≥2 hours before peripheral culture with the same organism. Quantitative blood cultures or specific molecular tests can also be used.
- Clinical signs: Fever, chills, hypotension, or unexplained leukocytosis in a patient with a central venous catheter. Erythema, tenderness, or purulence at the catheter exit site suggests an exit-site infection or tunnel infection.
Management:
- Catheter Removal: Generally recommended for patients with sepsis, hemodynamic instability, endocarditis, suppurative thrombophlebitis, persistent bacteremia/fungemia (>72 hours despite appropriate antibiotics), or tunnel/port pocket infection. Short-term non-tunneled catheters with CRBSI should usually be removed.
- Systemic Antibiotics: Initiate empiric broad-spectrum antibiotics based on local antibiogram and patient risk factors, then tailor therapy once culture and sensitivity results are available. Duration is typically 7-14 days for uncomplicated CRBSI if catheter is removed.
- Catheter Salvage: May be considered for long-term tunneled catheters or ports in select cases of uncomplicated CRBSI (no signs of sepsis, tunnel/port infection, or metastatic infection) caused by less virulent organisms, often in conjunction with antibiotic lock therapy.

C. Antibiotic Lock Solutions (for Catheter Salvage)

Antibiotic Lock Therapy for CRBSI
Feature	Description
Mechanism	Instillation of a highly concentrated antibiotic solution into the catheter lumen(s) to achieve levels far exceeding the minimum inhibitory concentration (MIC) for biofilm-embedded organisms, aiming to sterilize the catheter.
Indication	Attempted salvage of a long-term tunneled catheter or port in a patient with uncomplicated CRBSI (no systemic sepsis, no exit-site or tunnel infection) when catheter removal is highly undesirable. Used in conjunction with systemic antibiotics.
Agent Selection & Dosing	Common agents include: Vancomycin (e.g., 1–2 mg/mL) Gentamicin or other aminoglycosides (e.g., 1–5 mg/mL) Ceftazidime or Cefazolin (e.g., 1-2 mg/mL) Ethanol (e.g., 70%) for certain situations, though compatibility and efficacy vary. Concentration and choice depend on the organism and local protocols. Instill a volume sufficient to fill the catheter lumen (typically 1.5–3 mL per lumen).
Dwell Time & Duration	Dwell time is typically several hours (e.g., 2–12 hours, or between RRT sessions). Duration of lock therapy is usually 5–14 days, concurrent with systemic antibiotics.
Monitoring	Monitor for resolution of clinical signs of infection. Repeat blood cultures after completion of therapy to confirm eradication. Check catheter patency. Monitor for potential side effects of absorbed antibiotics (rare if properly managed).
Contraindications/Cautions	Systemic sepsis, tunnel or exit-site infection, suppurative thrombophlebitis, endocarditis. Not recommended for infections due to S. aureus or Candida spp. if catheter removal is feasible. Risk of promoting antibiotic resistance.
Administration Note	Aspirate the lock solution from the catheter lumen before resuming infusion of systemic fluids or medications to minimize systemic absorption of the highly concentrated antibiotic and potential toxicity. Ensure compatibility of lock solution with catheter material.

Key Pearls

Limit the use of temporary, non-cuffed, non-tunneled dialysis catheters to the shortest possible duration (ideally ≤2 weeks if ongoing RRT is needed, transitioning to a more permanent access if possible) to minimize infection risk.
Ultrasound-guided insertion for all central venous catheters, including RRT catheters, is recommended to increase success rates and reduce mechanical complications, which can be nidi for infection. Consider site rotation if multiple catheterizations are anticipated.

References

Gautam SC, Lim J, Jaar BG. Complications Associated with Continuous RRT. Kidney360. 2022;3:1980–1990.
Pistolesi V, Zeppilli L, Fiaccadori E, et al. Hypophosphatemia in critically ill patients with AKI on RRT. J Nephrol. 2019;32:895–908.
Zarbock A, Kullmar M, Kindgen-Milles D, et al. RCA vs systemic heparin in CRRT: RCT. JAMA. 2020;324:1629–1639.
Parienti JJ, Thirion M, Megarbane B, et al. Femoral vs jugular catheterization in RRT: RCT. JAMA. 2008;299:2413–2422.
Lok CE, Huber TS, Lee T, et al. KDOQI Guideline for Vascular Access: 2019 update. Am J Kidney Dis. 2020;75(4 Suppl 2):S1–S164.

2025 PACUPrep BCCCP Preparatory Course

Pulmonary

Participants 432

Renal Replacement Therapies in the ICU

Complication Monitoring and Management in RRT

Objective

Introduction

Scope of Complications

Impact and Multidisciplinary Roles

1. Electrolyte Abnormalities

A. Pathophysiology and Risk Factors

B. Prevention Strategies

C. Treatment Protocols (Pharmacotherapy)

1. Phosphate Supplementation

2. Magnesium Sulfate Supplementation

3. Potassium Chloride Supplementation

2. Citrate Anticoagulation-Related Complications

A. Citrate Lock (Metabolic Alkalosis & Hypernatremia)

B. Systemic Citrate Accumulation (Citrate Toxicity)

Calcium Replacement for Citrate Toxicity

3. Intradialytic Hypotension (IDH)

A. Etiology and Monitoring

B. Preventive Strategies

C. Therapeutic Measures

Norepinephrine

4. Preventing and Managing Catheter-Related Bloodstream Infections (CRBSI)

A. Infection Control Bundles for Prevention

B. Diagnosis and Management of Suspected CRBSI

C. Antibiotic Lock Solutions (for Catheter Salvage)

References