What are the mechanisms, differences, advantages, and disadvantages of Intermittent Hemodialysis (IHD), Sustained Low-Efficiency Dialysis (SLED), Continuous Renal Replacement Therapy (CRRT), and Continuous Veno-Venous Hemodiafiltration (CVVHD), and how is hemodialysis prescribed for patients with impaired renal function?

Renal Replacement Therapy Modalities: Mechanisms, Differences, and Clinical Application

Overview of Modalities

For hemodynamically unstable ICU patients with acute kidney injury, CRRT and SLED should be considered complementary therapies with selection based on local expertise and availability, as neither has demonstrated survival superiority over intermittent hemodialysis. 1

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Intermittent Hemodialysis (IHD)

Mechanism

• Diffusion-based solute removal across a semipermeable membrane with dialysate flowing countercurrent to blood flow 2
• Treatment duration: 3-4 hours, typically 3 times per week
• High blood flow rates (300-500 mL/min) and dialysate flow rates (500-800 mL/min)

Advantages

• Rapid solute removal for life-threatening hyperkalemia, severe acidosis, or toxic ingestions 3, 4
• Cost-effective with lower resource utilization compared to CRRT 4
• No continuous anticoagulation required, reducing bleeding risk 3
• Uses existing dialysis infrastructure and personnel 4
• Patient mobility between treatments allows time for procedures, imaging, and nursing care 4

Disadvantages

• Hemodynamic instability due to rapid fluid and solute shifts 3
• Less suitable for patients requiring continuous volume control 1
• Intermittent correction of metabolic derangements 4

Clinical Context

• Equivalent mortality to CRRT in multiple meta-analyses and randomized trials 1
• Appropriate for hemodynamically stable patients 1
• May be associated with better outcomes in less severely ill patients (SOFA 3-10) compared to CRRT 5

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Sustained Low-Efficiency Dialysis (SLED)

Mechanism

• Hybrid modality combining diffusive clearance with extended treatment duration (8-16 hours) 6
• Lower blood flow rates (100-300 mL/min) and dialysate flow rates (100-300 mL/min) than IHD 7
• Uses conventional hemodialysis machines with modified settings 4

Advantages

• Hemodynamic stability comparable to CRRT through gradual fluid removal 1, 7
• Cost-effective alternative to CRRT using existing dialysis infrastructure 1, 4
• Treatment flexibility - not continuous, allowing time for procedures and patient care 7, 4
• Excellent detoxification with good cardiovascular tolerability 7
• Can be delivered in centers with dialysis capability but without CRRT resources 1

Disadvantages

• Requires extended hemodialysis personnel availability (8-16 hours) which may limit feasibility 1
• Characterized as "technically more complex and demanding" in some guidelines, though this is center-specific 1
• Less studied than CRRT or IHD with fewer randomized trials 4

Clinical Context

• Has replaced CRRT in some Canadian centers for hemodynamically unstable patients 1
• Should be viewed as interchangeable with CRRT rather than inferior alternative 1
• May enable RRT delivery in community hospitals without CRRT capability 1

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Continuous Renal Replacement Therapy (CRRT)

Mechanism

• 24-hour continuous extracorporeal blood purification using venovenous access 2
• Includes three main modalities: CVVH (convection), CVVHD (diffusion), and CVVHDF (combined) 2
• Blood pump-driven with integrated fluid balancing systems 2

Advantages

• Superior hemodynamic stability through slow, gradual fluid and solute shifts 8
• Recommended for patients with acute brain injury, increased intracranial pressure, or cerebral edema 1, 8
• Continuous volume control for fluid overload management 1
• Better suited for patients with severe hemodynamic instability 1

Disadvantages

• More expensive than IHD or SLED with higher resource utilization 1
• Requires continuous anticoagulation (typically regional citrate) 8, 9
• Patient immobilization limits procedures, imaging, and nursing care 4
• Delivered dose often falls short of prescribed dose (68-85% of target) due to circuit clotting, interruptions, and filter efficiency decline 1
• No survival benefit over IHD demonstrated in multiple trials 1

Clinical Context

• Grade C recommendation for patients with or at risk for cerebral edema 1
• No evidence supports routine superiority over IHD for hemodynamically unstable patients regarding mortality or renal recovery 1
• May be associated with worse outcomes in less severely ill patients compared to IHD 5

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Continuous Venovenous Hemodiafiltration (CVVHDF)

Mechanism

• Combines diffusive and convective solute removal 2
• External blood pump drives blood through circuit (distinguishes from CAVHDF which uses arterial pressure) 2
• Small molecules removed by diffusion across concentration gradient created by dialysate flow (1-2 L/hour) 2
• Middle and larger molecules removed by convection through ultrafiltration 2

Dosing Parameters

• Target effluent volume: 20-25 mL/kg/hour for adequate solute clearance 8, 2, 9
• Higher doses (35-40 mL/kg/hour) showed no mortality benefit in RENAL and ATN trials 1, 2
• Dialysate flow rate: 1-2 L/hour 2

Advantages

• Dual mechanism provides both small and middle molecule clearance 2
• Effective for patients requiring both volume control and solute removal 2

Disadvantages

• Increased amino acid losses (10-15 g/day) requiring higher protein intake (1.5-1.7 g/kg/day) 8
• Significant losses of water-soluble vitamins, electrolytes (phosphate, magnesium) 8
• Drug clearance variability - piperacillin/tazobactam half-lives significantly shorter with CVVHDF than CVVH alone 2

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Hemodialysis Prescription for Acute Kidney Injury

Initiation Criteria

• No specific BUN or creatinine thresholds - decisions based on comprehensive clinical evaluation 1
• Rate of azotemia increase more important than absolute values 1
• Initiate before development of life-threatening complications in critically ill patients 1, 8:
  • Diuretic-unresponsive pulmonary edema
  • Severe hyperkalemia
  • Uremic complications (pericarditis, encephalopathy)
  • Severe metabolic acidosis
• Consequences of these complications are more severe in critically ill patients, justifying earlier intervention 1

Modality Selection Algorithm

Step 1: Assess Hemodynamic Status

• Hemodynamically stable → IHD is appropriate and equivalent to CRRT for mortality 1
• Hemodynamically unstable → Proceed to Step 2

Step 2: Assess for Specific Indications

• Acute brain injury, increased ICP, or cerebral edema present → CRRT recommended (Grade C) 1, 8
• None of above present → Proceed to Step 3

Step 3: Consider Local Resources and Expertise

• CRRT available with experienced staff → CRRT or SLED based on institutional preference 1
• CRRT not available but dialysis capability exists → SLED is appropriate alternative 1
• Only IHD available → IHD is acceptable as no survival difference demonstrated 1

Step 4: Consider Disease Severity

• Less severely ill patients (SOFA 3-10) → Consider IHD as may be associated with better outcomes 5
• Most severely ill patients → No clear advantage of any modality 5

IHD/SLED Prescription

Dose Targets:

• Urea-based clearance targets extrapolated from ESRD (Kt/V ≥1.2 per session or URR ≥65%) 1
• Deliver minimum 3 sessions per week, adjust frequency based on metabolic needs 1
• For SLED: 8-16 hours per session with blood flow 100-300 mL/min 6

Membrane Selection:

• Use biocompatible membranes (synthetic) rather than cellulose-based 8, 9
• Reduces inflammatory and complement activation 8

Buffer:

• Bicarbonate-buffered dialysate preferred over lactate 8, 9
• Mandatory for patients with circulatory shock, liver failure, or lactic acidemia 8, 9

CRRT Prescription

Access:

• Uncuffed nontunneled dialysis catheter 8, 9
• Vein selection hierarchy: (1) Right internal jugular, (2) Femoral, (3) Left internal jugular, (4) Subclavian (last choice) 8, 9
• Always use ultrasound guidance for insertion 8, 9
• Obtain chest X-ray before first use for internal jugular or subclavian placement 8, 9

Anticoagulation:

• Assess bleeding risk first 9
• Regional citrate anticoagulation is first-line for patients without contraindications 8, 9
• Citrate can be used cautiously even in shock, liver failure, and muscle hypoperfusion with close monitoring 1
• Unfractionated or LMWH if citrate contraindicated 9
• Direct thrombin inhibitors or Factor Xa inhibitors for heparin-induced thrombocytopenia 9
• Strict protocol and staff education required before implementing citrate 1

Dosing:

• Prescribe dose before each session 8, 9
• Target effluent volume: 20-25 mL/kg/hour 8, 2, 9
• Frequently assess actual delivered dose and adjust prescription 8, 9
• Consider increasing prescribed dose by 20-25% to account for downtime and filter efficiency decline 1
• Monitor delivered versus prescribed dose as quality indicator 8

Fluid Composition:

• Bicarbonate buffer mandatory (not lactate) 8, 9
• Especially critical for shock, liver failure, lactic acidemia 8, 9
• Ensure fluids meet AAMI standards for bacterial/endotoxin contamination 9
• Avoid supra-physiologic glucose concentrations 9
• Consider pre-dilution for frequent filter clotting 9

Monitoring:

• Adjust prescription iteratively to achieve:
  • Electrolyte balance
  • Acid-base correction
  • Adequate solute control
  • Fluid balance goals 8, 9
• Avoid volume overload, especially with acute lung injury 9

Nutritional Considerations During RRT

• CVVHDF patients require 1.5-1.7 g/kg/day protein due to continuous amino acid losses 8
• SLED patients require 1.3-1.5 g/kg/day protein 8
• Monitor and replace water-soluble vitamins, phosphate, magnesium 8

Medication Dosing

• Therapeutic drug monitoring essential for beta-lactams and dialyzable medications 2
• Clearance varies with dialysate flow rate - higher flows increase drug elimination 2
• Residual kidney function significantly impacts clearance - consider when CrCl >50 mL/min 2
• Adjust antimicrobial dosing carefully during RRT 1

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Common Pitfalls and How to Avoid Them

Modality Selection Errors

• Pitfall: Assuming CRRT is always superior for hemodynamically unstable patients
• Avoidance: Recognize that no survival benefit exists for CRRT over IHD/SLED 1; select based on local expertise and resources 1

Dosing Errors

• Pitfall: Prescribing CRRT dose without accounting for downtime
• Avoidance: Frequently assess delivered dose (often only 68-85% of prescribed) and adjust prescription upward 1

Access Complications

• Pitfall: Using subclavian vein for dialysis access
• Avoidance: Avoid subclavian veins due to thrombosis risk and late stenosis 9; follow vein hierarchy 8, 9

Buffer Selection Errors

• Pitfall: Using lactate-buffered solutions in shock or liver failure
• Avoidance: Always use bicarbonate buffer, especially in shock, liver failure, or lactic acidosis 8, 9

Anticoagulation Errors

• Pitfall: Avoiding citrate in all patients with shock or liver disease
• Avoidance: Citrate can be used cautiously with close monitoring in these settings 1; absolute contraindications are rare 1

Timing Errors

• Pitfall: Waiting for specific BUN/creatinine thresholds
• Avoidance: Initiate based on clinical context and rate of change, not absolute values 1; start before life-threatening complications develop 1, 8

Catheter Care Errors

• Pitfall: Using topical antibiotics or antibiotic locks for prevention
• Avoidance: Do not use topical antibiotics or antibiotic locks for catheter infection prevention 9

Diuretic Misuse

• Pitfall: Using diuretics to enhance renal recovery or reduce RRT need
• Avoidance: Do not use diuretics for this purpose - no evidence of benefit 9