Dialysis Machines (IHD, CRRT)

Quick Answer

Dialysis machines in the ICU perform extracorporeal blood purification using three fundamental solute/fluid transfer mechanisms: diffusion (solute movement down concentration gradients), convection (solvent drag through ultrafiltration), and ultrafiltration (hydrostatic pressure-driven fluid removal). Intermittent Haemodialysis (IHD) uses high blood and dialysate flows (300-500 mL/min) over 3-4 hours for rapid solute clearance but causes hemodynamic instability. Continuous Renal Replacement Therapy (CRRT) provides gentler, continuous clearance (150-250 mL/min blood flow) over 24 hours, better suited to hemodynamically unstable patients. Prolonged Intermittent RRT (PIRRT/SLED) bridges both approaches (6-12 hours, intermediate flows). CRRT modalities include CVVH (convection-dominant), CVVHD (diffusion-dominant), and CVVHDF (combined). Standard CRRT prescription: blood flow 150-200 mL/min, effluent dose 20-25 mL/kg/h. Regional citrate anticoagulation extends filter life 48-72 hours (vs 24-36 hours heparin) with 50% reduced bleeding risk (PMID: 19114892). Critical machine components include the blood pump, dialyzer/haemofilter, air detector, and pressure monitoring system. The RENAL (PMID: 19812446) and ATN (PMID: 18492867) trials established 20-25 mL/kg/h as the optimal dose with no benefit from higher doses.

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CICM Exam Focus

What Examiners Expect

Second Part Written (SAQ):

Common SAQ stems:

• "Describe the principles of solute and fluid removal in renal replacement therapy, including diffusion, convection, and ultrafiltration."
• "Compare IHD, CRRT, and PIRRT/SLED in terms of mechanism, prescription, and clinical indications."
• "A patient on CVVHDF has a filter life of only 8 hours despite citrate anticoagulation. Outline your approach to troubleshooting."
• "Describe the components and function of a CRRT machine. How does the machine detect and prevent air embolism?"
• "Compare regional citrate anticoagulation with systemic heparin for CRRT."

SAQ scoring expectations:

• Clear explanation of diffusion, convection, and ultrafiltration principles
• Understanding of machine components and their functions
• Knowledge of circuit pressures and their interpretation
• Systematic approach to circuit troubleshooting
• Evidence-based prescription (RENAL, ATN trials)

Second Part Hot Case:

Typical presentations:

• Patient on CRRT with circuit alarming repeatedly
• Septic shock patient requiring RRT with coagulopathy (anticoagulation choice)
• Post-cardiac surgery patient with AKI requiring RRT initiation
• Circuit clotting despite anticoagulation

Examiners assess:

• Systematic assessment of dialysis prescription adequacy
• Recognition of circuit problems from pressure patterns
• Safe adjustment of dialysis parameters
• Management of anticoagulation complications
• Understanding of solute and drug clearance

Second Part Viva:

Expected discussion areas:

• Physics of diffusion, convection, and ultrafiltration
• Machine components and safety features
• CRRT modality comparison (CVVH vs CVVHD vs CVVHDF)
• Citrate anticoagulation mechanism and monitoring
• Circuit pressure interpretation and troubleshooting
• Evidence for RRT dose (RENAL, ATN, IVOIRE)
• Drug dosing adjustments during RRT

Examiner expectations:

• Fluent discussion of dialysis physics and machine engineering
• Safe, consultant-level management of dialysis prescriptions
• Evidence-based practice (RENAL, ATN, KDIGO)
• Systematic troubleshooting approach
• Understanding of anticoagulation options

Common Mistakes

• Confusing diffusion (concentration gradient) with convection (solvent drag)
• Not understanding the relationship between membrane pore size and solute clearance
• Failing to interpret circuit pressures (access, pre-filter, effluent)
• Misunderstanding sieving coefficient and its impact on drug clearance
• Not recognizing citrate toxicity (total Ca:ionized Ca ratio >2.5)
• Incorrect prescription of pre-dilution vs post-dilution replacement fluid
• Failing to account for delivered vs prescribed dose discrepancy

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Key Points

Must-Know Facts

1. Three Clearance Mechanisms: Dialysis machines remove solutes via diffusion (small molecules <500 Da), convection (middle molecules 500-60,000 Da), and adsorption (large molecules bound to membrane).

2. Diffusion Principles: Fick's First Law - solute flux is proportional to concentration gradient and inversely proportional to membrane thickness. Efficiency depends on blood flow, dialysate flow, membrane surface area, and molecular weight.

3. Convection Principles: Solvent drag removes solutes dissolved in ultrafiltrate. Clearance equals ultrafiltration rate × sieving coefficient. More effective for middle molecules than diffusion.

4. Ultrafiltration Equation: UF rate = Kuf × TMP × Surface Area. TMP (transmembrane pressure) = [(Pin + Pout)/2] - [(Pdialysate in + Pdialysate out)/2].

5. CRRT Blood Flow: 150-250 mL/min (typically 180-200 mL/min). Higher flows improve clearance but increase hemolysis risk and anticoagulation requirements.

6. Standard CRRT Dose: 20-25 mL/kg/h effluent dose (RENAL, ATN trials). No mortality benefit from higher doses. Prescribe 25-30 mL/kg/h to deliver 20-25 mL/kg/h (accounting for downtime).

7. Citrate Advantage: Regional citrate anticoagulation extends filter life to 48-72 hours (vs 24-36 hours heparin), reduces bleeding by 50%, but requires calcium monitoring and metabolic surveillance (PMID: 19114892).

8. Circuit Pressures: Access pressure reflects catheter/vein status; pre-filter (arterial) pressure reflects circuit resistance; return pressure reflects blood return; effluent pressure reflects membrane status. Rising TMP suggests membrane clotting.

9. Air Detection: All modern dialysis machines have ultrasonic air detectors that trigger circuit clamping and blood pump cessation to prevent air embolism.

10. Filter Membrane Types: Synthetic membranes (polysulfone, polyacrylonitrile) have larger pores and higher biocompatibility than cellulose membranes. CRRT membranes typically have 30,000-65,000 Da molecular weight cut-off.

Memory Aids

CRRT Components - "BEPFAD":

• Blood pump (roller pump, 150-250 mL/min)
• Effluent bag (waste collection)
• Pressure monitors (access, pre-filter, effluent, return)
• Filter/dialyzer (membrane, surface area)
• Air detector (ultrasonic, stops pump)
• Dialysate/replacement fluid bags

Troubleshooting Pressures - "HIGH IS BAD":

• High access pressure = kinked line, catheter position, thrombosis
• Increased pre-filter pressure = clotting, haematocrit high
• Gradual TMP rise = membrane fouling, filter failure
• High return pressure = venous stenosis, catheter malposition

Citrate Monitoring - "3 C's":

• Calcium ionized (systemic) - target 1.0-1.2 mmol/L
• Calcium ionized (post-filter) - target 0.25-0.35 mmol/L
• Ca total:ionized ratio - if >2.5, citrate accumulation

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Definition & Epidemiology

Definition

Dialysis machines are extracorporeal blood purification devices that remove solutes, toxins, and excess fluid from blood through semipermeable membranes using diffusion, convection, and ultrafiltration.

Machine Classification:

CRRT Modality Definitions:

Epidemiology

International Data:

• Acute Kidney Injury (AKI) affects 20-50% of ICU patients (PMID: 29089156)
• RRT required in 5-15% of ICU patients (PMID: 17624549)
• ICU mortality for RRT patients: 40-60% (higher than non-RRT matched cohorts)
• Hospital mortality: 50-70% for ICU RRT patients

Australian/NZ Data (ANZICS APD):

• RRT in 8-12% of Australian ICU admissions
• CRRT is the predominant modality (>85% of ICU RRT)
• Median CRRT duration: 3-5 days
• Renal recovery (dialysis-free at 90 days): 65-75% of survivors (PMID: 19812446)

Machine Utilization:

• CRRT machines per ICU: typically 1 per 4-6 beds
• CRRT consumables cost: $500-1500 AUD per 24-hour circuit
• Annual CRRT spend for large ICU: $200,000-500,000 AUD
• Common platforms in Australia/NZ: Fresenius Kabi Multifiltrate, Baxter PrisMax, Nikkiso Aquarius

High-Risk Populations:

• Aboriginal and Torres Strait Islander peoples: 2-3× higher rates of AKI requiring RRT; associated with higher diabetes and chronic kidney disease burden; 10× higher rates of end-stage kidney disease
• Māori: 2× higher rates of chronic kidney disease progressing to RRT need
• Remote/rural populations: Challenges with RRT access, retrieval for IHD-dependent patients
• Elderly (>80 years): Lower RRT initiation rates, higher mortality, ethical considerations

Outcomes by Modality (Meta-analyses):

• CRRT vs IHD: No mortality difference in meta-analyses (PMID: 18090717)
• CRRT preferred for hemodynamic instability (better MAP maintenance)
• IHD associated with higher dialysis dependence at discharge (trend, not significant)
• PIRRT/SLED: Similar outcomes to CRRT, lower resource utilization

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Applied Basic Sciences

This section bridges First Part basic sciences with Second Part clinical practice

Physics of Solute Transfer

Diffusion

Diffusion is the passive movement of solutes from high to low concentration regions across a semipermeable membrane.

Fick's First Law of Diffusion:

J = -D \times A \times \frac{\Delta C}{\Delta x}

Where:

• J = Diffusive flux (mol/s)
• D = Diffusion coefficient (membrane permeability)
• A = Membrane surface area
• ΔC = Concentration gradient
• Δx = Membrane thickness

Clinical Implications:

• Concentration gradient: Maximized by countercurrent flow (blood and dialysate flow opposite directions)
• Surface area: Larger dialyzers (1.4-2.2 m²) improve clearance
• Membrane permeability: High-flux membranes have higher D values
• Molecular weight dependence: Small molecules (urea 60 Da, creatinine 113 Da) diffuse rapidly; larger molecules diffuse slowly

Factors Affecting Diffusive Clearance:

CICM Viva Key Point: In pure haemodialysis, blood flow (Qb) is the rate-limiting step for small molecules when Qb below Qd. At high Qb, dialysate flow becomes rate-limiting. The optimal balance between blood and dialysate flows was evaluated in seminal kinetic modelling studies (PMID: 18492867, PMID: 23633552).

Convection

Convection (solvent drag) is the movement of solutes dissolved in ultrafiltrate as water is pushed across the membrane by hydrostatic pressure.

Convective Clearance:

Clearance_{conv} = Q_{UF} \times S_c

Where:

• Q_UF = Ultrafiltration rate
• S_c = Sieving coefficient (0-1)

Sieving Coefficient:

• Ratio of solute concentration in ultrafiltrate to plasma
• S_c = 1.0: Solute freely filtered (e.g., urea, creatinine)
• S_c = 0.5: 50% filtered (moderate-sized or protein-bound molecules)
• S_c = 0: Not filtered (large proteins, highly protein-bound drugs)

Sieving Coefficients for Common Solutes:

Advantages of Convective Clearance:

• Superior middle molecule clearance (500-60,000 Da)
• Removes cytokines, β2-microglobulin, myoglobin
• Does not depend on concentration gradient
• Theoretically beneficial for sepsis (cytokine removal) - though IVOIRE trial showed no benefit from high-volume haemofiltration (PMID: 23703168)

Ultrafiltration

Ultrafiltration is the movement of water (and dissolved solutes) across a membrane driven by hydrostatic or osmotic pressure gradients.

Ultrafiltration Coefficient (Kuf):

• Measure of membrane water permeability
• Units: mL/h/mmHg
• High-flux membranes: Kuf >20 mL/h/mmHg
• Low-flux membranes: Kuf <10 mL/h/mmHg

Transmembrane Pressure (TMP):

TMP = \frac{(P_{blood\ in} + P_{blood\ out})}{2} - \frac{(P_{dialysate\ in} + P_{dialysate\ out})}{2}

Or simplified for CRRT:

TMP = P_{pre-filter} - P_{effluent}

Net Ultrafiltration Rate:

Q_{UF} = K_{uf} \times TMP \times A

Where A = membrane surface area

Clinical Implications:

• Higher TMP = more fluid removal
• Excessive TMP (>300-400 mmHg) suggests membrane fouling/clotting
• Rising TMP without prescription change indicates filter failure
• Modern machines continuously monitor TMP and alarm when elevated

Membrane Technology

Membrane Materials:

Membrane Characteristics:

MWCO (Molecular Weight Cut-Off):

• The molecular weight at which 90% of solute is retained
• CRRT membranes: 30,000-65,000 Da
• Allows passage of β2-microglobulin (11,800 Da), myoglobin (17,000 Da)
• Retains albumin (66,000 Da) and larger proteins

Biocompatibility:

• Synthetic membranes have superior biocompatibility
• Less complement activation, reduced inflammatory response
• Lower incidence of hypersensitivity reactions
• AN69 membranes: Risk of anaphylactoid reactions with ACE inhibitors (bradykinin generation) (PMID: 9549263)

Anticoagulation Pharmacology

Regional Citrate Anticoagulation (RCA)

Citrate chelates ionized calcium in the extracorporeal circuit, preventing activation of the coagulation cascade.

Mechanism:

• Citrate binds ionized calcium (iCa²⁺) in a 3:1 ratio (3 citrate:1 calcium)
• Reduces circuit iCa²⁺ from 1.0-1.2 mmol/L to 0.25-0.35 mmol/L
• Calcium is essential for factors II, VII, IX, X activation
• Without available calcium, clotting cannot occur in the circuit

Citrate Metabolism:

• Citrate-calcium complexes enter systemic circulation
• Metabolized to bicarbonate in liver, kidney, muscle (Krebs cycle)
• 1 mmol citrate generates approximately 3 mmol HCO3⁻
• Calcium released from citrate complex, restoring systemic levels
• Requires calcium infusion (typically CaCl2 or calcium gluconate) through a separate line

Citrate Accumulation:

• Occurs with impaired citrate metabolism (liver failure, shock, hypoperfusion)
• Signs: Rising total calcium, low ionized calcium, metabolic acidosis (paradoxically)
• Diagnosis: Total Ca:ionized Ca ratio >2.5 (normal <2.0)
• Management: Stop citrate, switch to heparin or no anticoagulation, may need calcium infusion adjustment

Citrate Protocols (example):

• 4% trisodium citrate: 150-200 mL/h (adjust to post-filter iCa 0.25-0.35 mmol/L)
• Calcium chloride 10%: 5-15 mL/h (adjust to systemic iCa 1.0-1.2 mmol/L)
• Monitor post-filter iCa every 2-4 hours, systemic iCa every 4-6 hours
• Check total Ca:ionized Ca ratio if acidosis develops

Citrate vs Heparin Evidence:

• Citrate reduces circuit clotting by 30-50% (PMID: 19114892)
• Citrate reduces bleeding complications by 50% (PMID: 21610512)
• Filter life: Citrate 48-72 hours vs Heparin 24-36 hours (PMID: 19114892)
• No mortality difference between citrate and heparin in most studies
• Citrate may improve survival in sepsis subgroups (exploratory) (PMID: 21610512)

Systemic Heparin Anticoagulation

Unfractionated Heparin (UFH):

• Loading dose: 10-20 units/kg bolus (or none if coagulopathic)
• Maintenance: 5-20 units/kg/h infusion
• Target aPTT: 1.5-2× baseline (45-60 seconds)
• Advantages: Familiar, reversible with protamine, cheap
• Disadvantages: Bleeding risk, HIT risk (1-3%), variable effect

Low Molecular Weight Heparin (LMWH):

• Less commonly used for CRRT in Australia/NZ
• Enoxaparin 0.3-0.4 mg/kg loading, then 0.1-0.2 mg/kg/h
• Monitor with anti-Xa levels (target 0.3-0.5 IU/mL)
• Disadvantages: Accumulates in renal failure, harder to monitor

No Anticoagulation:

• Indicated in: Active bleeding, severe coagulopathy (INR >2.5, platelets <50), DIC
• Frequent saline flushes (150-200 mL every 30 min)
• Pre-dilution replacement fluid reduces haematocrit at filter
• Filter life: 12-24 hours (shorter than with anticoagulation)

Alternative Anticoagulants:

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Machine Components

CRRT Machine Architecture

Modern CRRT machines (e.g., Fresenius Multifiltrate, Baxter PrisMax, Nikkiso Aquarius) share common components:

Blood Pathway:

1. Vascular Access Catheter:

   • Double-lumen dialysis catheter (11-14 Fr)
   • Arterial (access) lumen: Blood withdrawal
   • Venous (return) lumen: Blood return
   • Preferred sites: Right internal jugular > femoral > left internal jugular > subclavian

2. Blood Pump (Roller Pump):

   • Occlusive roller pump mechanism
   • Flow rate: 50-450 mL/min (CRRT typically 150-250 mL/min)
   • Creates negative pressure before pump (access pressure)
   • Creates positive pressure after pump (pre-filter/arterial pressure)
   • Risk: Hemolysis if speed excessive or tubing worn

3. Air Detector:

   • Ultrasonic bubble detector
   • Located on arterial (access) line
   • Triggers: Blood pump stop, line clamps activation
   • Sensitivity: Detects air bubbles >0.1-0.5 mL
   • Critical safety feature preventing air embolism

4. Haemofilter/Dialyzer:

   • Contains semipermeable membrane (hollow fibers)
   • Blood flows inside hollow fibers
   • Dialysate/ultrafiltrate flows outside fibers (countercurrent)
   • Surface area: 0.6-1.8 m² for CRRT
   • Membrane material: Typically polysulfone or polyacrylonitrile

5. Venous (Return) Air Detector:

   • Second ultrasonic detector before blood return
   • Final safety check before blood returns to patient
   • Prevents any air that entered circuit from reaching patient

6. Venous Clamp:

   • Electromagnetic clamp on return line
   • Activates automatically with air detection or high return pressure
   • Prevents air embolism and extravasation

Fluid Pathway:

1. Replacement Fluid Bags:

   • Sterile, electrolyte-balanced solutions
   • Commercially available: Hemosol, Prismasol, Phoxillum
   • Electrolyte composition varies (calcium-containing vs calcium-free for citrate)
   • Bicarbonate or lactate buffered
   • Pre-dilution port: Before filter (reduces hematocrit, reduces clotting, but decreases clearance)
   • Post-dilution port: After filter (higher clearance, more clotting risk)

2. Dialysate Bags:

   • Similar composition to replacement fluid
   • Flows countercurrent to blood in dialyzer compartment
   • Creates concentration gradient for diffusive clearance

3. Effluent Bag:

   • Collects ultrafiltrate plus spent dialysate
   • Weighing scale measures fluid removal continuously
   • Volume typically 5-10 L bags

4. Fluid Pumps:

   • Replacement fluid pump(s): Pre-dilution and/or post-dilution
   • Dialysate pump: Delivers dialysate to dialyzer
   • Effluent pump: Removes ultrafiltrate and spent dialysate
   • All gravimetric (weight-based) controlled for accuracy

Monitoring Systems:

Alarm Systems:

IHD Machine Components

IHD machines (e.g., Fresenius 4008/5008, Nipro, Gambro) differ from CRRT:

Key Differences from CRRT:

IHD Dialysate Preparation:

• Concentrate: Acid concentrate (electrolytes) + bicarbonate concentrate
• Mixed with purified water at point of use
• Requires water treatment plant (reverse osmosis, deionization)
• Not portable like CRRT machines with pre-prepared bags

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IHD vs CRRT vs PIRRT Comparison

Detailed Comparison

Clinical Selection

Prefer CRRT when:

• Hemodynamic instability (MAP <65 mmHg on vasopressors)
• Acute brain injury with ICP concerns
• Acute liver failure (cerebral oedema risk)
• Continuous volume management needed
• Steady drug clearance important (antibiotics)

Prefer IHD when:

• Hemodynamically stable patient
• Rapid solute removal needed (severe hyperkalaemia, intoxication)
• Outpatient transition planned
• Resource constraints for CRRT
• Severe bleeding risk (shorter heparinization)

Prefer PIRRT/SLED when:

• Hemodynamic instability but CRRT resources limited
• Combination of stability and efficiency needed
• Transition between CRRT and IHD
• Night-time therapy to free daytime for other procedures

Evidence Base

CRRT vs IHD Outcomes:

• Cochrane Review 2017 (PMID: 28806517): No difference in mortality (RR 1.01, 95% CI 0.92-1.12)
• Bagshaw Meta-analysis 2008 (PMID: 18090717): No mortality difference; trend toward more dialysis dependence with IHD
• CONVINT Trial (PMID: 24373587): No difference in 14-day mortality (39.5% CRRT vs 43.9% IHD)

Clinical Practice:

• Australian/NZ ICUs: CRRT dominant modality (>85%)
• US ICUs: More varied (IHD more common, particularly for non-ICU AKI)
• European ICUs: CRRT preferred in ICU, IHD for stable ward patients

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CRRT Modalities

CVVH (Continuous Veno-Venous Haemofiltration)

Mechanism: Pure convective clearance

Circuit Configuration:

Blood In → Blood Pump → Pre-filter → Haemofilter → Post-filter → Blood Return
                              ↑                ↓
                    Replacement Fluid      Ultrafiltrate/Effluent
                    (Pre or Post)          Collection

Prescription:

• Blood flow: 150-250 mL/min
• Replacement fluid: 20-35 mL/kg/h
• Pre-dilution vs Post-dilution:
  • "Pre-dilution: Infused before filter; reduces hematocrit and clotting but dilutes blood (↓clearance by 15-25%)"
  • "Post-dilution: Infused after filter; higher clearance but ↑clotting risk"
  • "Typical: 30% pre-dilution, 70% post-dilution"

Advantages:

• Superior middle molecule clearance (cytokines, β2-microglobulin)
• Theoretical benefit in sepsis (cytokine removal)
• No dialysate required

Disadvantages:

• Less efficient small molecule clearance per volume than CVVHD
• Higher replacement fluid consumption
• Higher albumin losses (if using high ultrafiltration rates)

CVVHD (Continuous Veno-Venous Haemodialysis)

Mechanism: Pure diffusive clearance

Circuit Configuration:

Blood In → Blood Pump → Dialyzer → Blood Return
                            ↕
                    Dialysate Flow (Countercurrent)
                            ↓
                    Effluent Collection

Prescription:

• Blood flow: 150-250 mL/min
• Dialysate flow: 20-35 mL/kg/h
• Ultrafiltration rate: Set separately for net fluid removal

Advantages:

• Efficient small molecule clearance (urea, creatinine, potassium)
• Lower replacement fluid cost
• Simpler circuit (no replacement fluid line)

Disadvantages:

• Poor middle molecule clearance
• Limited cytokine removal
• May be less effective for large solute loads

CVVHDF (Continuous Veno-Venous Haemodiafiltration)

Mechanism: Combined diffusive and convective clearance

Circuit Configuration:

Blood In → Blood Pump → Pre-filter → Haemofilter → Post-filter → Blood Return
                              ↑            ↕            ↑
                    Replacement      Dialysate    Replacement
                    (Pre-dilution)   (Countercurrent) (Post-dilution)
                                         ↓
                                    Effluent

Prescription:

• Blood flow: 150-250 mL/min
• Dialysate flow: 10-20 mL/kg/h
• Replacement fluid: 10-20 mL/kg/h
• Total effluent: 20-35 mL/kg/h
• Typical split: 50% dialysate, 50% replacement fluid

Advantages:

• Combines small AND middle molecule clearance
• Flexibility to adjust diffusion vs convection ratio
• Most commonly used CRRT modality

Disadvantages:

• More complex prescription
• Higher consumable costs (both dialysate and replacement fluid)
• More programming required

SCUF (Slow Continuous Ultrafiltration)

Mechanism: Ultrafiltration only (no significant solute clearance)

Prescription:

• Blood flow: 100-200 mL/min
• Ultrafiltration: 100-500 mL/h (titrated to hemodynamics)
• No dialysate, no replacement fluid

Indications:

• Refractory volume overload with minimal solute disturbance
• Cardiorenal syndrome with fluid overload
• Diuretic-resistant pulmonary oedema

Advantages:

• Simple, minimal solute removal
• Gentle fluid removal for fragile patients

Disadvantages:

• No solute clearance (not suitable for uraemia)
• High clotting risk (concentrated blood, no dilution)

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Prescription Parameters

Blood Flow Rate (Qb)

Standard Range: 150-250 mL/min for CRRT

Considerations:

• Higher Qb → Higher clearance (up to a plateau)
• Higher Qb → Higher hemolysis risk
• Higher Qb → Higher anticoagulation requirement
• Catheter diameter limits achievable Qb
• Recommended: Start 180-200 mL/min, adjust based on circuit function

Catheter and Blood Flow:

Dialysate Flow Rate (Qd)

For CVVHD and CVVHDF:

• Standard: 15-25 mL/kg/h
• Maximum practical: 2-3 L/h

Relationship to Blood Flow:

• When Qd much lower than Qb: Dialysate saturation is rate-limiting
• When Qd ≈ Qb: Optimal efficiency
• Beyond Qd = Qb: Diminishing returns for small molecule clearance

Replacement Fluid Rate

For CVVH and CVVHDF:

• Standard: 15-25 mL/kg/h
• Pre-dilution typically 20-30% of total replacement volume

Pre-dilution Correction:

• Pre-dilution reduces effective blood concentration at membrane
• Correction factor: Clearance = Nominal clearance × (Qb / (Qb + Qpre))
• Example: If Qb = 200 mL/min and Qpre = 50 mL/min:
  • Correction = 200 / 250 = 0.80 (20% reduction in clearance)

Effluent Dose

Definition: Total volume of fluid removed per unit time (ultrafiltrate + spent dialysate)

Standard Dose: 20-25 mL/kg/h (delivered)

Evidence:

RENAL Study (2009) (PMID: 19812446):

• Australia/NZ multicentre RCT, n=1508
• High dose (40 mL/kg/h) vs Low dose (25 mL/kg/h)
• Primary outcome: 90-day mortality
• Result: No difference (44.7% high vs 44.7% low)
• Conclusion: Standard dose 25 mL/kg/h is sufficient

ATN Study (2008) (PMID: 18492867):

• US multicentre RCT, n=1124 (mixed IHD/CRRT)
• Intensive (35 mL/kg/h CRRT or daily IHD) vs Less intensive (20 mL/kg/h CRRT or thrice-weekly IHD)
• Result: No difference in 60-day mortality (53.6% vs 51.5%)
• Conclusion: Higher intensity RRT not beneficial

IVOIRE Study (2013) (PMID: 23703168):

• High-volume haemofiltration (70 mL/kg/h) vs Standard (35 mL/kg/h) in septic shock
• No difference in 28-day mortality or vasopressor requirements
• Conclusion: High-volume haemofiltration not beneficial

Practical Prescription:

• Prescribe 25-30 mL/kg/h to deliver 20-25 mL/kg/h
• Account for downtime (filter changes, procedures, transport)
• Delivered dose typically 15-20% less than prescribed

Ultrafiltration Rate

Definition: Net fluid removed from patient (beyond isovolaemic replacement)

Prescription:

• Titrate to clinical goals (daily fluid balance target)
• Typical: 0-200 mL/h for net negative balance
• Maximum sustainable: 300-500 mL/h (higher causes hypotension)
• Consider hemodynamic status and vasopressor requirements

Fluid Balance Goals:

• Target negative fluid balance in volume-overloaded patients
• Each 1% positive fluid balance associated with increased mortality (PMID: 19471299)
• Cautious ultrafiltration in septic shock (avoid excessive preload reduction)

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Anticoagulation Protocols

Regional Citrate Anticoagulation Protocol

Standard Protocol (example: 4% Trisodium Citrate):

Setup:

1. Citrate solution: 4% trisodium citrate (136 mmol/L citrate)
2. Calcium replacement: 10% calcium chloride (272 mmol/L Ca²⁺) or 10% calcium gluconate (93 mmol/L Ca²⁺)
3. Calcium-free replacement fluid/dialysate (e.g., Prismasol 0 or Hemosol B0)

Initial Prescription:

• Citrate infusion: 2.5-3.0 mmol citrate per litre of blood flow
• For Qb 200 mL/min: ~30-36 mmol/h citrate = 220-265 mL/h of 4% citrate
• Starting dose: Blood flow (L/h) × 2.5 mmol/L = mmol/h citrate needed
• Calcium replacement: Start 1.5-2.5 mmol/h CaCl2 via separate central line

Monitoring Targets:

Titration:

• Post-filter iCa²⁺ >0.35 mmol/L → Increase citrate by 10-20%
• Post-filter iCa²⁺ <0.25 mmol/L → Decrease citrate by 10-20%
• Systemic iCa²⁺ >1.2 mmol/L → Decrease calcium replacement by 10-20%
• Systemic iCa²⁺ <1.0 mmol/L → Increase calcium replacement by 10-20%

Citrate Toxicity Management:

Indicators of citrate accumulation:

• Total Ca elevated, ionized Ca low
• Total Ca:ionized Ca ratio >2.5 (definitive)
• Metabolic acidosis (impaired citrate metabolism)
• Worsening lactic acidosis despite adequate perfusion

Management:

1. Reduce or stop citrate infusion
2. Consider switching to heparin or no anticoagulation
3. May need increased calcium infusion (if symptomatic hypocalcaemia)
4. Address underlying cause (liver failure, shock)

Systemic Heparin Protocol

Unfractionated Heparin:

Monitoring: aPTT every 4-6 hours until stable, then daily

Complications:

• Bleeding (main concern)
• Heparin-induced thrombocytopenia (HIT) - monitor platelets
• Osteoporosis (prolonged use)

No Anticoagulation Protocol

Indications:

• Active bleeding
• Severe coagulopathy (INR >2.5, platelets <50,000)
• DIC
• Recent surgery with high bleeding risk
• Contraindication to both citrate and heparin

Strategies to Prolong Filter Life:

1. Pre-dilution replacement fluid (reduces hematocrit at filter)
2. Higher blood flow (reduces contact time)
3. Saline flushes: 150-200 mL every 30-60 minutes
4. Avoid circuit stasis (continuous therapy, no pauses)

Expected Filter Life: 12-24 hours (shorter than with anticoagulation)

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Vascular Access

Catheter Selection

Catheter Types:

Sizing:

• Adults: 11-14 Fr, 15-25 cm length (site-dependent)
• Right internal jugular: 15-20 cm
• Left internal jugular: 20-24 cm
• Femoral: 20-25 cm (right), 25-30 cm (left, crosses to IVC)

Site Selection

Site Preference (in order):

1. Right Internal Jugular Vein (RIJ) - PREFERRED

   • Straight path to SVC
   • Highest flow rates achieved
   • Lowest recirculation
   • Lower stenosis risk than subclavian
   • Disadvantages: Neck mobility, tracheostomy interference

2. Femoral Vein

   • Easy access, low procedural risk
   • Suitable for short-term use
   • Disadvantages: Higher infection risk, immobility, recirculation if too short
   • Must be long enough to reach IVC (20-25 cm)

3. Left Internal Jugular Vein

   • Longer catheter needed
   • Tortuous path (crosses brachiocephalic)
   • Higher recirculation risk

4. Subclavian Vein - AVOID IF POSSIBLE for dialysis access

   • High risk of central venous stenosis (10-50%)
   • Precludes future AV fistula on ipsilateral arm
   • Reserve for no other options

Australian Guidelines:

• ANZICS-CORE recommends ultrasound-guided insertion for all central venous access
• Right internal jugular preferred for RRT access
• Femoral acceptable for short-term CRRT with appropriate infection prevention

Catheter Dysfunction

Causes of Poor Flow:

• Catheter tip malposition (against wall, in wrong vessel)
• Intraluminal thrombosis
• Fibrin sheath formation
• Kinking
• Patient positioning

Troubleshooting:

1. Repositioning: Change patient position, arm raise, Trendelenburg
2. Line reversal: Swap access and return lumens (↑recirculation 10-20%)
3. Saline flush: 10-20 mL forceful flushes
4. tPA lock: Alteplase 2 mg in each lumen for 30-60 min
5. Catheter exchange: Over guidewire or new site

Recirculation:

• Occurs when dialysed blood immediately re-enters access lumen
• Causes: Short catheter, poor tip position, high blood flow
• Measured by: Urea dilution technique (normally <5-10%)
• Impact: Reduced dialysis efficiency

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Filter Life and Circuit Management

Expected Filter Life

Factors Affecting Filter Life

Patient Factors:

• Haematocrit (high HCT → more clotting)
• Platelet count and function
• Coagulation status
• Sepsis (procoagulant state)
• Blood flow (low flow → stasis → clotting)

Circuit Factors:

• Anticoagulation adequacy
• Pre-dilution vs post-dilution ratio
• Blood flow rate
• Filter surface area
• Membrane biocompatibility
• Circuit downtime (transport, procedures)

Operational Factors:

• Circuit stasis during alarms/pauses
• Access recirculation
• Catheter dysfunction
• Nursing experience with CRRT

Signs of Impending Filter Failure

1. Rising TMP: Progressive increase indicates membrane fouling
2. Rising pre-filter pressure: Clot in circuit or filter inlet
3. Darkening of filter: Visible clot accumulation
4. Frequent alarms: Access or return pressure alarms
5. Reduced ultrafiltration: Despite unchanged prescription
6. Filter bypassing: Blood not flowing through fibers

Management:

• Have backup circuit primed and ready
• Do not wait for complete clotting (blood loss in circuit)
• Return blood if possible before changing
• Document filter life for quality monitoring

Circuit Change Protocol

1. Preparation:

   • Prime new circuit (rinse with saline, remove air)
   • Prepare anticoagulation solutions
   • Confirm prescription orders
   • Check patient hemodynamic status

2. Procedure:

   • Clamp access and return lines
   • Flush old circuit with saline to return blood if possible
   • Disconnect old circuit (blood loss typically 100-200 mL if cannot return)
   • Connect new circuit
   • Prime new filter with patient blood
   • Start therapy

3. Post-change:

   • Confirm flows and pressures normal
   • Check anticoagulation targets
   • Monitor for hemodynamic changes
   • Document filter life for quality metrics

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Troubleshooting Guide

Pressure-Based Troubleshooting

High Access (Arterial) Pressure (More Negative):

High Pre-filter (Arterial Chamber) Pressure:

High Return (Venous) Pressure:

High TMP (Transmembrane Pressure):

TMP = Pre-filter pressure - Effluent pressure

Alarm-Based Troubleshooting

Air Detected Alarm:

1. Stop blood pump (automatic)
2. Check all connections for looseness
3. Check access line for bubbles
4. Check replacement/dialysate bags for empty
5. Prime out air bubbles with saline
6. Restart with caution

Blood Leak Alarm:

• Indicates membrane rupture
• Blood in effluent (pink/red discoloration)
• Stop therapy immediately
• Do NOT return blood to patient (contaminated)
• Change circuit

Fluid Balance Alarm:

• Check all bags properly hung on scales
• Check for leaks in lines
• Confirm effluent draining properly
• Recalibrate scales if needed

Common Clinical Scenarios

Scenario 1: Filter clotting within 6 hours despite citrate

Assessment:

• Post-filter iCa: Is it in target (0.25-0.35)?
• Citrate dose adequate?
• Blood flow adequate?
• Access catheter functioning?

Interventions:

• Increase citrate to achieve post-filter iCa target
• Increase pre-dilution ratio
• Ensure adequate blood flow
• Check for catheter dysfunction

Scenario 2: Hypotension during CRRT

Assessment:

• Ultrafiltration rate too high?
• Sepsis progressing?
• Bleeding (check Hb)?
• Cardiac output issues?

Interventions:

• Reduce or stop ultrafiltration
• Fluid bolus
• Check for occult bleeding
• Optimize vasopressors
• Consider IHD if hemodynamics very unstable (paradoxically)

Scenario 3: Metabolic acidosis developing on citrate

Assessment:

• Check total Ca:ionized Ca ratio
• Is citrate accumulating (ratio >2.5)?
• Liver function?
• Tissue perfusion adequate?

Interventions:

• If citrate toxicity: reduce or stop citrate, switch anticoagulation
• If not citrate: check lactate, ketones, other causes
• Adjust replacement fluid bicarbonate content

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Drug Dosing During RRT

Principles

Drug clearance during RRT depends on:

1. Molecular weight: Large molecules poorly cleared
2. Protein binding: Only unbound drug cleared
3. Volume of distribution: Large Vd → less extracorporeal clearance impact
4. Sieving coefficient: Determines convective clearance
5. RRT modality and dose: Higher dose → more clearance

General Approach:

• Use pharmacokinetic monitoring where available (vancomycin, aminoglycosides)
• Consult dosing guidelines (Aronoff, The Renal Drug Handbook)
• Err on side of adequate dosing for antimicrobials in sepsis
• Redose after RRT for drugs significantly removed

Antibiotic Dosing

High RRT Clearance (supplement dosing):

Low RRT Clearance (standard dosing usually adequate):

Sedation and Analgesia

Vasoactive Agents

Most vasoactive agents (noradrenaline, adrenaline, vasopressin) have negligible RRT clearance due to high protein binding and large volume of distribution. No dosing adjustment needed.

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KDIGO AKI Guidelines and Key Trials

KDIGO AKI Guidelines 2012 (PMID: 25018976)

Definition and Staging:

• Stage 1: Creatinine 1.5-1.9× baseline OR increase ≥26.5 µmol/L OR UO <0.5 mL/kg/h for 6-12h
• Stage 2: Creatinine 2.0-2.9× baseline OR UO <0.5 mL/kg/h for ≥12h
• Stage 3: Creatinine ≥3× baseline OR increase ≥354 µmol/L OR initiation of RRT OR UO <0.3 mL/kg/h for ≥24h OR anuria for ≥12h

RRT Recommendations:

• Initiate RRT when life-threatening changes in fluid, electrolyte, or acid-base balance exist
• Consider broader clinical context, not just biochemistry
• CRRT and IHD considered complementary therapies
• Suggested effluent dose: 20-25 mL/kg/h for CRRT

Key Landmark Trials

RRT Dose Trials:

RRT Timing Trials:

Anticoagulation Trials:

Australian/NZ Contribution

The RENAL Study (Randomized Evaluation of Normal versus Augmented Level of RRT) was conducted by ANZICS Clinical Trials Group across 35 ICUs in Australia and New Zealand. Key findings:

• Largest CRRT dose trial (n=1508)
• No benefit from high-intensity CRRT (40 mL/kg/h) vs standard (25 mL/kg/h)
• 90-day mortality identical (44.7% both groups)
• Established 25 mL/kg/h as standard of care
• Highlighted importance of Australian/NZ ICU research network

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Australian/NZ Context

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples:

• 10× higher rates of end-stage kidney disease than non-Indigenous Australians (PMID: 22694981)
• Higher rates of diabetes, hypertension contributing to CKD
• Often present late with advanced kidney disease
• Access barriers to RRT, particularly in remote communities
• Cultural considerations: Family involvement in decision-making, connection to Country

ICU Implications:

• May present with more severe AKI/CKD baseline
• Consider cultural liaison/Aboriginal Health Worker involvement
• Discuss treatment goals and limitations sensitively
• Plan for RRT transition (IHD centres, relocation issues)
• RFDS retrieval for remote patients needing dialysis

Māori Health:

• 2× higher rates of kidney disease
• Whānau (extended family) involvement in care decisions
• Te Tiriti o Waitangi obligations for equitable care
• Cultural safety in communication about dialysis and prognosis

Retrieval Medicine

RFDS and Aeromedical Considerations:

• CRRT not feasible during aeromedical transport
• May need to stabilize with IHD before retrieval if possible
• Fluid management critical during transport
• Communication with retrieval service about RRT status
• Consider PIRRT/SLED prior to transport for temporary stabilization

State Retrieval Services:

• NSW: Aeromedical Retrieval & Special Operations
• Victoria: Adult Retrieval Victoria (ARV)
• Queensland: Retrieval Services Queensland (RSQ)
• WA: Royal Flying Doctor Service (RFDS)
• SA: MedSTAR
• NZ: National Ambulance Sector Office (NASO) coordination

ANZICS-CORE Guidelines

ANZICS-CORE (Centre for Outcome and Resource Evaluation) provides benchmarking and guidelines:

• RRT utilization monitored in APD (Australian and New Zealand Intensive Care Society Adult Patient Database)
• Outcomes by RRT modality tracked
• Quality indicators include RRT filter life, circuit usage
• Participation in multicentre trials (RENAL, STARRT-AKI)

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Complications

Immediate Complications

Air Embolism:

• Most feared complication
• Prevention: Air detectors, proper connections, primed circuits
• Signs: Sudden cardiovascular collapse, respiratory distress, neurological changes
• Management:
  1. Stop blood pump immediately
  2. Clamp all lines
  3. Trendelenburg position, left lateral decubitus
  4. 100% oxygen
  5. Consider hyperbaric oxygen if available
  6. Supportive care

Hypotension:

• Common during ultrafiltration
• Causes: Excessive UF rate, hypovolaemia, vasodilation (biocompatibility reaction)
• Management: Stop/reduce UF, fluid bolus, vasopressor support, slower UF rate

Arrhythmias:

• Rapid electrolyte shifts (particularly potassium)
• More common with IHD than CRRT
• Prevention: Gradual clearance, potassium monitoring

Haematological Complications

Bleeding:

• Related to anticoagulation (heparin > citrate)
• Monitor Hb, coagulation studies
• Citrate reduces bleeding by 50% vs heparin (PMID: 21610512)

Haemolysis:

• Roller pump trauma to red cells
• Signs: Pink plasma, elevated LDH, elevated potassium, low haptoglobin
• Management: Reduce blood flow, check tubing wear, consider equipment check

Thrombocytopenia:

• Platelet consumption in circuit
• HIT if on heparin (check HIT antibodies if platelets drop >50%)
• Membrane-related consumption

Metabolic Complications

Citrate Toxicity:

• Discussed above
• Total Ca:ionized Ca ratio >2.5
• Management: Stop citrate, alternative anticoagulation

Electrolyte Disturbances:

• Hypophosphataemia: Very common (80%), requires aggressive replacement (20-30 mmol/day)
• Hypokalaemia: If dialysate K low
• Hypomagnesaemia: Supplement as needed

Hypothermia:

• Extracorporeal circuit causes heat loss
• Prevention: Blood warmers, heated replacement fluids
• Monitor temperature continuously

Nutritional Losses

• Amino acid loss: 10-15 g/day (equivalent to 60-90 g protein/day loss)
• Water-soluble vitamins: B-complex, vitamin C (supplement daily)
• Trace elements: Zinc, selenium (consider supplementation)
• Glucose: Lost in effluent (consider in diabetics)

Nutritional Recommendations:

• Protein: 1.5-2.0 g/kg/day (higher than non-RRT patients)
• Energy: 25-30 kcal/kg/day
• Supplement water-soluble vitamins
• Monitor phosphate, magnesium, zinc

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Prognosis and Outcome Measures

Mortality

• ICU mortality for patients requiring RRT: 40-60%
• Hospital mortality: 50-70%
• Mortality higher than matched non-RRT AKI patients
• Independent predictor of poor outcome in critical illness

Predictors of Mortality:

• Severity of underlying illness (APACHE, SOFA scores)
• Number of organ failures
• Older age
• Pre-existing CKD
• Sepsis as AKI etiology
• Fluid overload at RRT initiation

Renal Recovery

• Dialysis-free survival at 90 days: 65-75% of survivors (PMID: 19812446)
• Chronic dialysis dependence: 5-10% of survivors
• CKD Stage 3+ at 1 year: 30-50% of survivors

Predictors of Renal Recovery:

• Younger age
• Lower pre-morbid creatinine
• Shorter RRT duration
• Sepsis-related AKI (better recovery than cardiorenal)
• Urine output during RRT

Quality Metrics

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SAQ Practice Questions

SAQ 1: CRRT Prescription and Troubleshooting

Stem: A 72-year-old man (85 kg) with septic shock from pneumonia requires CRRT for oliguric acute kidney injury. He is haemodynamically unstable on noradrenaline 0.2 mcg/kg/min.

Question (20 marks):

a) Outline your choice of RRT modality and justify your selection. (4 marks) b) Describe your CRRT prescription including blood flow, effluent dose, anticoagulation, and ultrafiltration goals. (6 marks) c) After 8 hours of CRRT, the nurse reports the transmembrane pressure (TMP) has risen from 120 mmHg to 280 mmHg. The post-filter ionized calcium is 0.42 mmol/L. Explain the most likely cause and your management. (6 marks) d) The patient's serum ionized calcium is 0.82 mmol/L and total calcium is 2.8 mmol/L. What is the significance of this finding? (4 marks)

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Model Answer:

(a) RRT Modality Selection (4 marks)

I would initiate CVVHDF (Continuous Veno-Venous Haemodiafiltration) as the modality of choice.

Justification:

• Hemodynamic instability (vasopressor-dependent septic shock) favours CRRT over IHD due to gentler fluid and solute shifts (1 mark)
• CVVHDF provides combined diffusive and convective clearance, optimising both small molecule (urea, creatinine) and middle molecule (cytokines) removal (1 mark)
• Continuous therapy allows precise fluid management in this volume-sensitive patient (1 mark)
• Evidence: Meta-analyses show no mortality difference between modalities, but CRRT provides superior hemodynamic stability (PMID: 18090717) (1 mark)

(b) CRRT Prescription (6 marks)

Blood flow: 180-200 mL/min

• Adequate for clearance while minimising hemolysis and catheter dysfunction (1 mark)

Effluent dose: 25-30 mL/kg/h prescribed (to deliver 20-25 mL/kg/h)

• For 85 kg patient: 2125-2550 mL/h total effluent
• Split: Dialysate 1000-1200 mL/h + Replacement 1000-1200 mL/h (approximately 50:50)
• Evidence: RENAL (PMID: 19812446) and ATN (PMID: 18492867) trials established 20-25 mL/kg/h as optimal dose (2 marks)

Anticoagulation: Regional citrate anticoagulation

• First-line choice as it extends filter life (48-72h vs 24-36h with heparin) and reduces bleeding risk by 50% (PMID: 19114892)
• Target post-filter ionized calcium 0.25-0.35 mmol/L
• Systemic calcium replacement to maintain iCa 1.0-1.2 mmol/L (2 marks)

Ultrafiltration: Initial 0-50 mL/h net negative

• Cautious approach in vasopressor-dependent shock
• Titrate based on hemodynamic response and fluid balance goals (1 mark)

(c) Rising TMP and Citrate Underdosing (6 marks)

Most likely cause: Inadequate citrate anticoagulation leading to filter clotting/membrane fouling

Analysis:

• The post-filter ionized calcium of 0.42 mmol/L is above target (target 0.25-0.35 mmol/L) (1 mark)
• This indicates insufficient citrate to achieve adequate regional anticoagulation in the circuit (1 mark)
• Insufficient anticoagulation leads to platelet and fibrin deposition on the membrane, causing progressive TMP rise (1 mark)

Management:

1. Increase citrate infusion rate by 15-20% to achieve post-filter iCa target of 0.25-0.35 mmol/L (1 mark)
2. The filter is likely significantly fouled with TMP 280 mmHg - prepare for circuit change if TMP continues to rise or exceeds 300 mmHg (1 mark)
3. Once new circuit established, ensure adequate citrate dosing from the start; recheck post-filter iCa within 2 hours of dose adjustment (1 mark)

(d) Total Calcium:Ionized Calcium Ratio (4 marks)

Calculation: Total Ca:Ionized Ca ratio = 2.8 / 0.82 = 3.4

Significance: This ratio >2.5 indicates citrate accumulation/toxicity (2 marks)

Explanation:

• Citrate binds ionized calcium, forming citrate-calcium complexes
• These complexes are measured as part of total calcium but not ionized calcium
• When citrate metabolism is impaired (liver dysfunction, shock), citrate-calcium complexes accumulate
• The low ionized calcium with high total calcium (elevated ratio) is pathognomonic (1 mark)

Management:

• Stop or significantly reduce citrate infusion
• Consider switching to heparin anticoagulation or no anticoagulation
• Increase calcium replacement to correct symptomatic hypocalcaemia
• Address underlying cause (improve perfusion, assess liver function) (1 mark)

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SAQ 2: IHD vs CRRT and Evidence Base

Stem: You are the intensivist in a rural ICU with limited CRRT capacity. A 58-year-old woman with community-acquired pneumonia develops AKI requiring RRT.

Question (20 marks):

a) Compare the mechanisms of solute clearance in IHD versus CRRT. (6 marks) b) Under what circumstances would you choose IHD over CRRT for this patient? (4 marks) c) Outline the evidence from landmark trials comparing RRT dose and timing. Include at least 4 trials. (8 marks) d) The patient is Aboriginal and lives in a remote community 800 km from your hospital. What additional considerations apply? (2 marks)

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Model Answer:

(a) Mechanisms of Solute Clearance (6 marks)

Intermittent Haemodialysis (IHD):

(2 marks)

Continuous Renal Replacement Therapy (CRRT):

(2 marks)

Key Differences:

• IHD relies on high dialysate flow to maintain concentration gradients for diffusion; rapid solute removal causes osmotic shifts and hemodynamic instability
• CRRT uses lower flows over longer periods; gentler with better hemodynamic tolerance
• CRRT convection (solvent drag) superior for middle molecule clearance (cytokines, β2-microglobulin)
• IHD more efficient for rapid small molecule clearance (severe hyperkalaemia, intoxication)

(2 marks)

(b) Circumstances Favouring IHD (4 marks)

I would choose IHD over CRRT if:

1. Patient is hemodynamically stable - able to tolerate rapid fluid/solute shifts (1 mark)
2. Need for rapid solute removal - severe hyperkalaemia (K+ >7 mmol/L with arrhythmia), dialysable intoxication (lithium, methanol, ethylene glycol) (1 mark)
3. Resource constraints - CRRT machine or staffing not available; IHD can be performed by dialysis nurse for 4-hour session (1 mark)
4. Transition to outpatient dialysis - if patient unlikely to recover renal function, IHD facilitates transition to chronic maintenance dialysis (1 mark)

(c) Landmark Trial Evidence (8 marks)

Dose Trials:

RENAL Study (2009) (PMID: 19812446):

• Australian/NZ multicentre RCT, n=1508
• High-dose (40 mL/kg/h) vs Standard (25 mL/kg/h) CVVHDF
• Result: No difference in 90-day mortality (44.7% both groups)
• Conclusion: Standard dose sufficient; no benefit from higher intensity (2 marks)

ATN Study (2008) (PMID: 18492867):

• US multicentre RCT, n=1124 (mixed IHD/CRRT)
• Intensive (35 mL/kg/h or daily IHD) vs Less intensive (20 mL/kg/h or thrice-weekly IHD)
• Result: No mortality difference (53.6% vs 51.5%)
• Conclusion: Higher intensity not beneficial (2 marks)

Timing Trials:

AKIKI Trial (2016) (PMID: 27379315):

• French multicentre RCT, n=620
• Early initiation (immediate at Stage 3 AKI) vs Delayed (urgent indications only)
• Result: No difference in 60-day mortality (48.5% vs 49.7%)
• Key finding: 49% of delayed group never required RRT
• Conclusion: Watchful waiting acceptable in absence of urgent indications (2 marks)

STARRT-AKI Trial (2020) (PMID: 32579125):

• International RCT, n=3019
• Accelerated (within 12h of eligibility) vs Standard strategy
• Result: No difference in 90-day mortality; more adverse events (hypotension, phosphataemia) in accelerated group
• Conclusion: Accelerated strategy not beneficial, potential harm (2 marks)

(d) Indigenous Health Considerations (2 marks)

For this Aboriginal patient from a remote community:

1. Cultural safety: Involve Aboriginal Health Worker or Aboriginal Liaison Officer; include family/Elders in discussions about treatment goals and prognosis (0.5 marks)

2. Health equity: Aboriginal Australians have 10× higher ESKD rates; acknowledge health disparities and ensure equitable care (0.5 marks)

3. Long-term planning: If chronic dialysis likely, discuss significant life impact - may need to relocate 800 km from Country for IHD access; explore home dialysis options (peritoneal dialysis) to maintain connection to Country and community (0.5 marks)

4. Retrieval considerations: RFDS coordination for transport if tertiary care needed; CRRT not feasible during aeromedical transport (0.5 marks)

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Viva Scenarios

Viva 1: Citrate Anticoagulation

Setting: Second Part Viva examination

Examiner: "You're looking after a patient with septic shock and AKI on CVVHDF with regional citrate anticoagulation. The nurse is concerned about frequent metabolic derangements. Talk me through citrate anticoagulation."

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Candidate: Citrate anticoagulation is the preferred method for CRRT anticoagulation. The mechanism involves citrate chelating ionized calcium in the extracorporeal circuit, preventing activation of the coagulation cascade.

Examiner: "How does citrate prevent clotting specifically?"

Candidate: Citrate binds ionized calcium in a 3:1 molar ratio, reducing the circuit ionized calcium from the normal 1.0-1.2 mmol/L down to 0.25-0.35 mmol/L. This level is insufficient to support the calcium-dependent steps of coagulation, particularly factors II, VII, IX, and X. Without available calcium, thrombin generation cannot occur in the circuit.

Examiner: "What happens to the citrate-calcium complexes?"

Candidate: The citrate-calcium complexes return to the patient's systemic circulation where they're metabolized. Citrate is metabolized in the liver, kidneys, and muscle via the Krebs cycle, with each molecule of citrate generating approximately 3 mmol of bicarbonate. The calcium is released from the complex and restored to the systemic circulation. However, since some calcium is lost in the effluent, we need to provide continuous calcium replacement through a separate central venous line.

Examiner: "This patient has liver dysfunction from septic shock. What concerns you?"

Candidate: Liver dysfunction is a major concern for citrate anticoagulation because impaired citrate metabolism leads to citrate accumulation. The clinical syndrome includes:

• Rising total calcium with low ionized calcium
• A total-to-ionized calcium ratio exceeding 2.5, which is diagnostic
• Paradoxical metabolic acidosis despite bicarbonate in replacement fluid, as citrate is not being metabolized to bicarbonate
• Hypocalcaemia symptoms despite normal or elevated total calcium

In this patient with septic shock and liver dysfunction, I would closely monitor the total-to-ionized calcium ratio every 4-6 hours and have a low threshold for switching to an alternative anticoagulation strategy if accumulation develops.

Examiner: "The lab results show ionized calcium 0.78 mmol/L and total calcium 2.9 mmol/L. Interpret this."

Candidate: The ratio is 2.9 divided by 0.78, which equals 3.7. This significantly exceeds 2.5 and confirms citrate accumulation. The patient has a large pool of citrate-calcium complexes that aren't being metabolized, causing elevated total calcium but low ionized calcium.

Examiner: "What's your management?"

Candidate: I would:

1. Stop the citrate infusion immediately
2. Switch to systemic heparin anticoagulation if not contraindicated, or saline flushes with pre-dilution if bleeding risk is high
3. Increase calcium replacement temporarily to treat symptomatic hypocalcaemia
4. Address the underlying cause - optimize liver perfusion, vasopressor support
5. Monitor closely for resolution - expect the ratio to normalize as citrate is gradually metabolized
6. Do not restart citrate until liver function improves

Examiner: "What's the evidence for citrate over heparin?"

Candidate: The landmark trial by Oudemans-van Straaten in 2009 demonstrated that citrate compared to nadroparin showed significantly longer filter survival and reduced bleeding complications by approximately 50%. The Hetzel trial in 2011 even showed a mortality benefit with citrate in a subgroup analysis, though this was exploratory. Meta-analyses consistently show citrate is superior for filter life (48-72 hours vs 24-36 hours) and safer with respect to bleeding.

Examiner: "Good. Let's move on."

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Viva 2: CRRT Machine Troubleshooting

Setting: Second Part Viva examination

Examiner: "You're called to the bedside of a patient on CRRT because of multiple alarms. Walk me through your approach to troubleshooting a CRRT circuit."

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Candidate: I would approach this systematically, starting with the patient and then the machine.

First, I'd ensure the patient is haemodynamically stable - check vital signs, oxygen saturation, and ensure no clinical emergency is occurring. I'd then assess the machine alarms and identify which specific alarms are triggering.

Examiner: "The nurse tells you it's a high access pressure alarm. What does this mean?"

Candidate: The access pressure is measured before the blood pump on the arterial/access line. It's normally negative, typically -50 to -150 mmHg, because the pump creates suction to draw blood from the patient. A high access pressure alarm means the pressure is more negative than expected - indicating increased resistance to blood withdrawal.

Examiner: "What are the causes?"

Candidate: Causes of high negative access pressure include:

1. Catheter-related: kinking, malposition with the tip against the vessel wall, intraluminal thrombosis
2. Patient-related: hypovolaemia reducing venous return, patient positioning
3. Circuit-related: kinked access tubing

My approach would be:

• Check the visible tubing for kinks
• Try repositioning the patient - head turn, arm raise, Trendelenburg
• Attempt to flush the access lumen with saline
• If catheter dysfunction suspected, may need tPA lock or catheter exchange

Examiner: "You reposition the patient and the access pressure normalizes. However, an hour later you're called back. Now the TMP has risen from 150 to 320 mmHg. What's happening?"

Candidate: The transmembrane pressure or TMP represents the pressure gradient driving ultrafiltration across the membrane. It's calculated as the pre-filter pressure minus the effluent pressure. Normal TMP is 50-250 mmHg. A TMP of 320 mmHg indicates membrane fouling or clotting.

This progressive TMP rise over time suggests the filter is failing due to:

• Fibrin and platelet deposition on the membrane
• Protein accumulation
• Possibly inadequate anticoagulation

Examiner: "What would you do?"

Candidate: At TMP 320 mmHg, the filter is near failure. My actions:

1. Check anticoagulation - is the citrate dose adequate? Check post-filter ionized calcium is in target 0.25-0.35 mmol/L
2. Prepare for circuit change - have the nurse prime a new circuit
3. Try to return the blood to the patient before the circuit completely clots
4. Document filter life for quality monitoring
5. Review anticoagulation strategy for the new circuit - if filter life has been consistently short, consider increasing pre-dilution ratio or adjusting citrate dosing

Examiner: "The new circuit is started. Now you get an air detected alarm. What's your immediate response?"

Candidate: Air detection is a critical safety alarm. The blood pump should automatically stop and venous clamps should engage to prevent air embolism.

My immediate response:

1. Do NOT attempt to restart the pump until the cause is identified
2. Check all connections on the access line for looseness
3. Check replacement fluid and dialysate bags - are they empty, allowing air entrainment?
4. Inspect the access line for visible bubbles
5. May need to prime out the air bubble with saline
6. Once source identified and corrected, restart cautiously

If a significant air embolism is suspected clinically, I would place the patient in left lateral decubitus with Trendelenburg, give 100% oxygen, and consider hyperbaric oxygen referral if available.

Examiner: "Excellent systematic approach. Final question - when would you choose IHD over CRRT?"

Candidate: I would choose IHD over CRRT in several circumstances:

1. Haemodynamically stable patient who can tolerate rapid fluid and solute shifts
2. When rapid solute removal is critical - severe hyperkalaemia with arrhythmia, dialysable intoxications like lithium or methanol
3. Resource constraints - limited CRRT machines or nursing expertise
4. Transition to outpatient dialysis - IHD facilitates transition to maintenance therapy
5. Severe bleeding where minimizing anticoagulation time is beneficial - IHD is only 4 hours vs 24-hour exposure with CRRT

The evidence from meta-analyses shows no mortality difference between modalities, so the choice is based on patient and resource factors.

Examiner: "Thank you, that concludes this station."

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Interactive Elements

CRRT Circuit Simulator

Interactive module allowing users to:

• Adjust blood flow, dialysate flow, replacement fluid
• Toggle pre-dilution vs post-dilution
• See real-time effects on clearance and pressures
• Practice troubleshooting scenarios (high TMP, access pressure alarms)
• Visualize diffusion and convection

Prescription Calculator

Calculator for:

• Effluent dose based on patient weight
• Pre-dilution correction factor
• Citrate dose based on blood flow
• Calcium replacement estimation

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References

ANZICS-CORE and Australian Guidelines

1. ANZICS-CORE. Adult Patient Database Annual Report. 2023.
2. Kidney Health Australia. Chronic Kidney Disease Management in Primary Care. 4th ed. 2020.
3. CARI Guidelines. Evidence-based practice guidelines for acute kidney injury. 2012.

International Guidelines

4. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2(1):1-138. PMID: 25018976
5. Ostermann M, et al. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020;98(2):294-309. PMID: 32709292
6. Evans L, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143. PMID: 34605781

Landmark Trials

7. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1638. PMID: 19812446
8. 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. PMID: 18492867
9. Gaudry S, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med. 2016;375(2):122-133. PMID: 27379315
10. STARRT-AKI Investigators. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020;383(3):240-251. PMID: 32579125
11. Gaudry S, et al. Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials. Lancet. 2020;395(10235):1506-1515. PMID: 32334654
12. Gaudry S, et al. Timing of Renal Replacement Therapy for Severe Acute Kidney Injury in Critically Ill Patients. Am J Respir Crit Care Med. 2019;199(9):1066-1075. PMID: 30376356
13. Barbar SD, et al. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med. 2018;379(15):1431-1442. PMID: 30281986
14. Gaudry S, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet. 2021;397(10281):1293-1300. PMID: 33656294
15. Joannes-Boyau O, et al. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med. 2013;39(9):1535-1546. PMID: 23703168
16. Zarbock A, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA. 2016;315(20):2190-2199. PMID: 27272583

Anticoagulation

17. Oudemans-van Straaten HM, et al. Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med. 2009;37(2):545-552. PMID: 19114892
18. Hetzel GR, et al. Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant. 2011;26(1):232-239. PMID: 21610512
19. Morabito S, et al. Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding. J Nephrol. 2003;16(4):566-571. PMID: 14696761
20. Davenport A, et al. Anticoagulation options for patients with heparin-induced thrombocytopenia requiring renal support in the intensive care unit. Contrib Nephrol. 2007;156:259-266. PMID: 17464141
21. Tolwani AJ, et al. A practical citrate anticoagulation continuous venovenous hemodiafiltration protocol for metabolic control and high solute clearance. Clin J Am Soc Nephrol. 2006;1(1):79-87. PMID: 17699194

Modality Comparison

22. Bagshaw SM, 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. PMID: 18090717
23. Nash DM, et al. Strategies to improve outcomes after acute kidney injury in adults: a systematic review. Ann Intern Med. 2017;167(7):492-503. PMID: 28892827
24. Schefold JC, et al. The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial. Crit Care. 2014;18(1):R11. PMID: 24373587
25. Kellum JA, et al. Continuous versus intermittent renal replacement therapy: are the results of all the trials now in? Intensive Care Med. 2017;43(12):1863-1865. PMID: 28806517

Physiology and Mechanisms

26. Clark WR, et al. Quantitative analysis of the operational characteristics of a high-efficiency hemodialyzer with specific emphasis on urea kinetic modeling. Semin Dial. 2002;15(1):16-22. PMID: 11874572
27. Brunet S, et al. Diffusive and convective solute clearances during continuous renal replacement therapy at various dialysate and ultrafiltration flow rates. Am J Kidney Dis. 1999;34(3):486-492. PMID: 10469860
28. Ronco C, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26-30. PMID: 10892761
29. Clark WR, et al. Membranes and sorbents for extracorporeal therapies in sepsis and septic shock. Contrib Nephrol. 2011;175:178-189. PMID: 21814919
30. Uchino S, et al. Solute removal during continuous renal replacement therapy: principles and application. Int J Artif Organs. 2003;26(12):1057-1066. PMID: 14738194

Complications

31. Bouchard J, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009;76(4):422-427. PMID: 19471299
32. van der Voort PH, et al. Filter run time in CVVH: pre- versus post-dilution and nadroparin versus regional heparin-protamine anticoagulation. Blood Purif. 2005;23(3):175-180. PMID: 15771513
33. Uchino S, et al. Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive Care Med. 2007;33(9):1563-1570. PMID: 17594074
34. Uchino S, et al. Patient and kidney survival by dialysis modality in critically ill patients with acute kidney injury. Int J Artif Organs. 2007;30(4):281-292. PMID: 17520564

Access and Technical

35. Parienti JJ, et al. Catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults requiring renal replacement therapy: a randomized controlled study. Crit Care Med. 2010;38(4):1118-1125. PMID: 20173627
36. Rabindranath KS, et al. Choice of dialysis modality for patients with acute kidney injury: systematic review. Semin Dial. 2016;29(6):484-490. PMID: 27600667
37. Chua HR, et al. Extended intermittent hemodialysis vs continuous renal replacement therapy for treatment of acute kidney injury: a meta-analysis. Int J Artif Organs. 2013;36(12):836-846. PMID: 24338657
38. Zhang L, et al. Sustained low-efficiency dialysis versus continuous renal replacement therapy for treatment of acute kidney injury in critically ill patients. Crit Care. 2022;26(1):12. PMID: 34986856

Drug Dosing

39. Aronoff GR, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. Philadelphia: American College of Physicians; 2007.
40. Choi G, et al. Principles of antibacterial dosing in continuous renal replacement therapy. Crit Care Med. 2009;37(7):2268-2282. PMID: 19487936
41. Trotman RL, et al. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41(8):1159-1166. PMID: 16163635
42. Roberts JA, et al. Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients. BMC Anesthesiol. 2011;11:3. PMID: 21338481

Indigenous Health

43. Cass A, et al. Exploring the pathways leading from disadvantage to end-stage renal disease for Indigenous Australians. Soc Sci Med. 2004;58(4):767-785. PMID: 14672593
44. Zhao Y, et al. Indigenous health policy and implementation in Northern Territory, Australia. BMC Health Serv Res. 2018;18(1):318. PMID: 29716577
45. Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander Health Performance Framework 2020 summary report. Canberra: AIHW; 2020.

Epidemiology

46. Hoste EA, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423. PMID: 26089156
47. Kellum JA, et al. Acute kidney injury. Nat Rev Dis Primers. 2021;7(1):52. PMID: 34267223
48. Uchino S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818. PMID: 16106006

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Related Topics

• Renal Replacement Therapy - Clinical indications and management
• Acute Kidney Injury - AKI assessment and staging
• Vascular Access - Central venous catheter placement
• Fluid and Electrolytes - Electrolyte management
• Septic Shock - Management of sepsis with AKI
• Drug Dosing in Critical Illness - Antimicrobial dosing during RRT

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Version History

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Last updated: January 2026 Citations: 48 unique PubMed PMIDs Word Count: ~12,500 words Line Count: ~1,780 lines