8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis

ABIM Critical Care Medicine Study Guide Exam

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1 Chapter 1: Exam Orientation: Format, Blueprint & Study Strategy

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2 Chapter 2: Acute Respiratory Failure & ARDS

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3 Chapter 3: Obstructive Airways, Pulmonary Vascular & Pleural Emergencies

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4 Chapter 4: Airway, Parenchymal & Nonthrombotic Pulmonary Emergencies

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5 Chapter 5: Mechanical Ventilation Modes, Dyssynchrony & Liberation

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6 Chapter 6: Shock Syndromes & Hemodynamic Principles

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7 Chapter 7: Vasoactive Therapies & Mechanical Circulatory Support

7.1 Vasopressors & Inotropes: Pharmacology & Clinical Titration 7.2 Temporary Mechanical Circulatory Support: IABP, Impella & TandemHeart 7.3 Venoarterial ECMO (VA-ECMO) & Differential Hypoxemia 7.4 Post-Cardiac Arrest Care, Targeted Temperature Management & Neuroprognostication

8 Chapter 8: Acute Kidney Injury & Renal Replacement Therapy

8.1 KDIGO AKI Classification, Etiologies & Diagnostic Evaluation 8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis 8.3 Indications & Timing for RRT in Critical Illness: AKIKI & STARRT-AKI

9 Chapter 9: Electrolyte, Acid-Base & Endocrine Emergencies

9.1 Severe Dysnatremias: Hyponatremia, Hypernatremia & Osmotic Demyelination 9.2 Potassium, Calcium, Magnesium & Phosphate Disorders 9.3 Complex & Mixed Acid-Base Disorders: Boston vs Copenhagen vs Stewart 9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis

10 Chapter 10: Glycemic Control, Hyperammonemia, Pituitary & Adrenal Disorders

10.1 ICU Glycemic Control & Severe Hypoglycemia 10.2 Non-Hepatic Hyperammonemia & Metabolic Encephalopathy 10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency

11 Chapter 11: Acute Coronary Syndromes & Cardiac Arrhythmias

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12 Chapter 12: Acute Heart Failure, Valvular & Pericardial Emergencies

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14 Chapter 14: Sepsis & Systemic Infectious Diseases

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15 Chapter 15: ICU-Acquired & Severe Focal Infections

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16 Chapter 16: Focal, Special-Host & Systemic Infections

16.1 CNS Infections Beyond Bacterial Meningitis: Encephalitis, Brain Abscess & Epidural Abscess 16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections 16.3 Infective Endocarditis, Device Infections & Other Focal Cardiovascular Infections 16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention 16.5 Gastrointestinal & Hepatobiliary Infections: Fulminant C. difficile, Typhlitis, CMV Colitis & Abscesses

17 Chapter 17: Neurocritical Care & Coma

17.1 Coma, Altered Mental Status & Acute Delirium in the ICU 17.2 Status Epilepticus & Non-Convulsive Status Epilepticus 17.3 Acute Ischemic Stroke & Intracranial Hemorrhage

18 Chapter 18: Cerebrovascular Syndromes, Encephalopathy & Withdrawal States

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19 Chapter 19: Intracranial Hypertension & Neuromuscular Weakness

19.1 Intracranial Pressure Monitoring, Cerebral Perfusion & Tiered ICP Management 19.2 Acute Neuromuscular Respiratory Failure, ICU-Acquired Weakness & Brain Death Determination

20 Chapter 20: Traumatic Brain Injury, Spinal Cord Injury & Toxin-Mediated Paralysis

20.1 Traumatic Brain Injury Management & Paroxysmal Sympathetic Hyperactivity 20.2 Acute Spinal Cord Injury, Neurogenic Shock & Autonomic Dysreflexia 20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis

21 Chapter 21: Gastrointestinal, Hepatic & Abdominal Emergencies

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22 Chapter 22: Luminal GI Emergencies & Complications of Cirrhosis

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24 Chapter 24: Thoracic Trauma, Environmental Injury & Obstetric Critical Care

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25 Chapter 25: Transplantation, Donor Management & Post-Cardiac Surgery Care

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26 Chapter 26: Hematologic Emergencies, Toxicology, Critical Ultrasound & ICU Liberation

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27 Chapter 27: Transfusion Medicine, Hematologic & Oncologic Disorders

27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis 27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States 27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity

28 Chapter 28: Clinical Pharmacology, Adverse Drug Reactions & Specific Poisonings

28.1 Pharmacokinetic Principles, Dose Adjustment & Drug Interactions in Critical Illness 28.2 Adverse Drug Reactions: Anaphylaxis, Severe Cutaneous Reactions & Hyperthermic Syndromes 28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia

29 Chapter 29: Ethics, Research Methods, Administration & Abdominal Ultrasound

29.1 Advance Care Planning, Nonbeneficial Treatment, Informed Consent & Confidentiality 29.2 Critical Care Research Methods, Statistics, IRB Oversight & Quality Improvement 29.3 Abdominal, Vascular & Procedural Point-of-Care Ultrasound

8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis

Key Takeaways Explain This Topic AI

Continuous renal replacement therapy (CRRT) provides continuous solute clearance and fluid removal over 24 hours, whereas intermittent hemodialysis (IHD) delivers high-intensity solute extraction over 3 to 4 hours.

KDIGO suggests (2B) CRRT rather than IHD for hemodynamically unstable patients, and CRRT is preferred for those with acute cerebral edema, elevated intracranial pressure (ICP), or acute liver failure, preventing the rapid osmolar shifts and cerebral herniation triggered by IHD (reverse urea effect).

The fundamental clearance mechanisms differ by modality: CVVH utilizes pure convection (solvent drag) to clear small and middle molecules ( 500 to 50 , 000 Da 500\text{ to }50,000\text{ Da} 500 to 50 , 000 Da ); CVVHD utilizes pure diffusion (concentration gradient) to maximize small solute clearance; and CVVHDF combines both.

KDIGO ranks dialysis catheter sites right internal jugular first, then femoral, then left internal jugular, and subclavian last, because subclavian catheters cause central vein stenosis that can destroy future permanent access.

Regional citrate anticoagulation (RCA) is the standard of care for CRRT circuits, but mandates active monitoring for citrate accumulation (total-to-ionized calcium ratio > 2.5 > 2.5 > 2.5 , refractory hypocalcemia, high anion gap metabolic acidosis) in patients with severe hepatic failure or shock.

Last updated: October 2026

Physical Principles of Extracorporeal Clearance

Renal replacement therapy relies on three distinct physical transport mechanisms across a semipermeable synthetic membrane to restore fluid, electrolyte, and acid-base homeostasis:

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1. Diffusion (Dialysis)

Diffusion represents the passive movement of solute molecules down a concentration gradient governed by Fick's law of diffusion . In a dialysis circuit, blood flows through hollow capillary fibers while sterile dialysate fluid flows in the opposite direction (counter-current) outside the fibers. The rate of diffusive transport ( J d J_d J d ​ ) is proportional to the concentration difference across the membrane, the membrane surface area ( A A A ), the solute diffusion coefficient ( D D D ), and inversely proportional to membrane thickness ( x x x ):

J d = − D ⋅ A ⋅ Δ C x J_d = -D \cdot A \cdot \frac{\Delta C}{x} J d ​ = − D ⋅ A ⋅ x Δ C ​

Diffusion is highly efficient for small, unbound water-soluble molecules ( < 500 Da < 500\text{ Da} < 500 Da ), such as urea ( 60 Da 60\text{ Da} 60 Da ), potassium ( 39 Da 39\text{ Da} 39 Da ), sodium ( 23 Da 23\text{ Da} 23 Da ), and creatinine ( 113 Da 113\text{ Da} 113 Da ). However, diffusive clearance declines logarithmically as molecular weight increases, offering minimal clearance for middle molecules ( > 1 , 000 Da > 1,000\text{ Da} > 1 , 000 Da ).

2. Convection (Hemofiltration)

Convection refers to the bulk transport of solute driven across a semipermeable membrane alongside plasma water in response to a hydrostatic pressure gradient—a physical phenomenon termed solvent drag . A high transmembrane pressure (TMP) forces large volumes of plasma water across the membrane into the effluent compartment as ultrafiltrate. Solutes small enough to pass through the membrane pores are swept along in the solvent stream. The convective clearance ( K c K_c K c ​ ) is determined by the ultrafiltration rate ( Q uf Q_{\text{uf}} Q uf ​ ) and the sieving coefficient ( S S S ) of the molecule:

K c = Q uf × S K_c = Q_{\text{uf}} \times S K c ​ = Q uf ​ × S

The sieving coefficient ranges from 0 (completely rejected by the membrane, such as albumin, molecular weight 66.5 kDa 66.5\text{ kDa} 66.5 kDa ) to 1.0 (freely permeable, identical concentration in plasma water and ultrafiltrate, such as urea). Convective clearance is remarkably effective for both small molecules and middle-to-large molecules ( 500 to 50 , 000 Da 500\text{ to }50,000\text{ Da} 500 to 50 , 000 Da ), such as β 2 \beta_2 β 2 ​ -microglobulin ( 11.8 kDa 11.8\text{ kDa} 11.8 kDa ), circulating pro- and anti-inflammatory cytokines ( 8 to 30 kDa 8\text{ to }30\text{ kDa} 8 to 30 kDa ), myoglobin ( 17 kDa 17\text{ kDa} 17 kDa ), and vancomycin ( 1.4 kDa 1.4\text{ kDa} 1.4 kDa ).

3. Ultrafiltration

Ultrafiltration represents the net convective movement of plasma water across the membrane driven by transmembrane pressure, used therapeutically to achieve net negative fluid balance and resolve hypervolemia.

Continuous Modalities: SCUF, CVVH, CVVHD, and CVVHDF

Continuous renal replacement therapies (CRRT) operate 24 hours a day to provide gradual, continuous clearance and fluid control. Modalities differ based on the fluid streams employed:

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1. Slow Continuous Ultrafiltration (SCUF)

Mechanics : Blood is pumped through the circuit without dialysate ( Q d = 0 Q_d = 0 Q d ​ = 0 ) and without replacement fluid ( Q rf = 0 Q_{\text{rf}} = 0 Q rf ​ = 0 ). Ultrafiltrate is generated at low rates ( 100 to 300 mL/h 100\text{ to }300\text{ mL/h} 100 to 300 mL/h ) solely to remove fluid.

Indications : Isolated volume overload refractory to diuretics in patients who are hemodynamically precarious, where uremia, hyperkalemia, and acid-base derangements are absent.

Limitations : Minimal solute clearance; will not treat uremia or severe acidosis.

2. Continuous Veno-Venous Hemofiltration (CVVH)

Mechanics : Solute clearance occurs entirely by convection. Massive ultrafiltrate volumes ( 20 to 35 mL/kg/h 20\text{ to }35\text{ mL/kg/h} 20 to 35 mL/kg/h ) are generated and discarded. To prevent rapid hypovolemic exsanguination, physiological electrolyte replacement fluid is infused into the blood circuit.

Pre-dilution vs. Post-dilution Replacement :

Pre-dilution : Replacement fluid is infused into the circuit prior to the filter . This dilutes the blood entering the capillary fibers, lowering the circuit hematocrit and solute concentration. Pre-dilution decreases hemoconcentration within hollow fibers, reduces membrane protein fouling, lowers transmembrane pressure, and substantially prolongs filter lifespan. However, because it dilutes the plasma entering the filter, solute clearance efficiency per liter of effluent is reduced by 15 to 20 % 15\text{ to }20\% 15 to 20% , requiring a proportionally higher prescribed effluent flow rate.

Post-dilution : Replacement fluid is infused into the venous bubble trap after the filter . Because undiluted blood enters the filter, convective solute clearance is 100 % 100\% 100% efficient. However, as ultrafiltrate is extracted along the length of the capillary fibers, the intra-luminal blood becomes progressively hemoconcentrated. This increases the filtration fraction ( F F FF FF ) , elevating blood viscosity and circuit thrombosis risk.

Filtration Fraction Formula :

F F = Q uf Q p × 100 % = Q uf Q b × ( 1 − Hct ) × 100 % FF = \frac{Q_{\text{uf}}}{Q_p} \times 100\% = \frac{Q_{\text{uf}}}{Q_b \times (1 - \text{Hct})} \times 100\% FF = Q p ​ Q uf ​ ​ × 100% = Q b ​ × ( 1 − Hct ) Q uf ​ ​ × 100%

Important

The filtration fraction in post-dilution CVVH must be maintained < 20 to 25 % < 20\text{ to }25\% < 20 to 25% . An F F > 25 % FF > 25\% FF > 25% precipitates rapid protein coating of membrane pores, hemoconcentration, hollow fiber clotting, and early circuit loss.

3. Continuous Veno-Venous Hemodialysis (CVVHD)

Mechanics : Solute clearance occurs entirely by diffusion. Counter-current dialysate fluid runs through the outer dialysate compartment ( Q d = 20 to 30 mL/kg/h Q_d = 20\text{ to }30\text{ mL/kg/h} Q d ​ = 20 to 30 mL/kg/h ) while blood flows through the inner hollow fibers. Ultrafiltration is added independently to achieve the desired net negative fluid balance.

Advantages : Eliminates the high transmembrane pressures and hemoconcentration seen in pure convection, reducing circuit clotting while providing outstanding small-solute (urea, potassium) clearance.

4. Continuous Veno-Venous Hemodiafiltration (CVVHDF)

Mechanics : Combines convective and diffusive clearance. Both counter-current dialysate fluid ( Q d Q_d Q d ​ ) and convective replacement fluid ( Q rf Q_{\text{rf}} Q rf ​ ) are infused simultaneously.

Advantages : Maximizes simultaneous clearance of small molecules (via diffusion) and middle-to-large molecules (via convection) while keeping the filtration fraction well within safe operating limits ( < 20 % < 20\% < 20% ).

Modalities Comparison Table

Modality Primary Transport Dialysate Flow ( Q d Q_d Q d ​ ) Replacement Fluid ( Q rf Q_{\text{rf}} Q rf ​ ) Primary Clinical Role

SCUF Ultrafiltration None ( 0 mL/h 0\text{ mL/h} 0 mL/h ) None ( 0 mL/h 0\text{ mL/h} 0 mL/h ) Isolated fluid overload, no uremia

CVVH Convection (solvent drag) None ( 0 mL/h 0\text{ mL/h} 0 mL/h ) High ( 20 to 35 mL/kg/h 20\text{ to }35\text{ mL/kg/h} 20 to 35 mL/kg/h ) Cytokine/toxin removal, rhabdomyolysis

CVVHD Diffusion (gradient) High ( 20 to 35 mL/kg/h 20\text{ to }35\text{ mL/kg/h} 20 to 35 mL/kg/h ) None ( 0 mL/h 0\text{ mL/h} 0 mL/h ) Small solute clearance, low circuit clotting

CVVHDF Convection + Diffusion Moderate ( 10 to 20 mL/kg/h 10\text{ to }20\text{ mL/kg/h} 10 to 20 mL/kg/h ) Moderate ( 10 to 20 mL/kg/h 10\text{ to }20\text{ mL/kg/h} 10 to 20 mL/kg/h ) Comprehensive clearance in multiorgan failure

IHD Rapid Diffusion + UF Very High ( 500 to 800 mL/min 500\text{ to }800\text{ mL/min} 500 to 800 mL/min ) None Stable patients, rapid clearance of severe poisonings

SLED Extended Diffusion + UF Moderate ( 100 to 300 mL/min 100\text{ to }300\text{ mL/min} 100 to 300 mL/min ) None Hybrid therapy, daytime intermediate clearance

CRRT vs. Intermittent Hemodialysis (IHD): Clinical Indications

Randomized trials (such as the Hemodiafe and SHARF trials) and meta-analyses show similar survival with CRRT and IHD across broad ICU cohorts, and KDIGO considers them complementary. KDIGO suggests CRRT rather than IHD (grade 2B) for hemodynamically unstable patients and for patients with acute brain injury or raised intracranial pressure, for the reasons below:

1. Hemodynamic Instability and Septic Shock

Intermittent hemodialysis removes solutes and fluid rapidly over a contracted 3- to 4-hour window, requiring high blood flow rates ( 300 to 450 mL/min 300\text{ to }450\text{ mL/min} 300 to 450 mL/min ) and ultrafiltration rates frequently exceeding 1 , 000 to 1 , 500 mL/h 1,000\text{ to }1,500\text{ mL/h} 1 , 000 to 1 , 500 mL/h . This rapid volume extraction outpaces the physiological plasma refilling rate from the interstitial space, precipitating intradialytic hypotension in up to 40% of critically ill patients.

Intradialytic hypotension induces transient myocardial stunning , compromises mesenteric and coronary perfusion, and critically causes recurrent ischemic renal insults , transforming recovering tubular epithelium back into necrotic tissue and significantly prolonging time to renal recovery. Conversely, CRRT extracts fluid slowly ( 50 to 200 mL/h 50\text{ to }200\text{ mL/h} 50 to 200 mL/h ) over 24 hours, preserving mean arterial pressure, coronary perfusion, and promoting renal recovery.

2. Acute Brain Injury, Cerebral Edema, and Acute Liver Failure

In patients with acute intracranial pathology—including acute liver failure (ALF) with hyperammonemia, severe traumatic brain injury (TBI), large hemispheric ischemic stroke, or intracranial hemorrhage— conventional intermittent hemodialysis should be avoided (KDIGO suggests CRRT) because rapid solute removal can precipitate cerebral edema and herniation via dialysis disequilibrium syndrome :

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Because CRRT clears urea continuously and slowly, plasma osmolality remains stable, preventing osmotic gradients between the intravascular space and brain tissue. In acute liver failure, CRRT also continuously removes neurotoxic circulating ammonia, reducing cerebral glutamine synthesis and astrocytic swelling.

Vascular Access and Circuit Anatomy

Reliable vascular access is the lifeline of CRRT. Access failure accounts for > 30 % > 30\% > 30% of unplanned circuit downtime, causing circuit clotting, blood loss, and inadequate dialytic delivery.

Catheter Selection and Anatomical Sites

Acute CRRT utilizes large-bore, dual-lumen non-tunneled catheters (typically 12 to 14 French in caliber) placed under real-time ultrasound guidance:

Right Internal Jugular (RIJ) Vein : The first-choice, preferred anatomical site . The RIJ provides a direct, straight vertical course into the superior vena cava and cavoatrial junction. It exhibits the lowest rates of vascular recirculation, lowest risk of catheter kinking, and preserves the thoracic vasculature. Recommended catheter length: about 15 cm 15\text{ cm} 15 cm (about 20 cm 20\text{ cm} 20 cm for the left internal jugular vein).

Femoral Vein : The second-choice site . Excellent in emergency situations, agitated patients, severe cervical trauma, or patients with profound coagulopathy where non-compressible arterial puncture in the neck is perilous. However, femoral catheters require longer designs ( 20 to 25 cm 20\text{ to }25\text{ cm} 20 to 25 cm ) to ensure the tip reaches the large-caliber inferior vena cava. Short femoral catheters terminate in the common iliac vein, predisposing to high recirculation rates ( > 20 % > 20\% > 20% ) and flow obstruction.

Left Internal Jugular Vein : Third choice; its tortuous course through the brachiocephalic vein increases catheter dysfunction and recirculation.

Subclavian Vein : Last choice for temporary dialysis access (KDIGO; preferably on the dominant-hand side if it must be used). Subclavian dialysis catheters carry a high incidence of central vein stenosis (reported in up to 40-50%). Fibrotic stenosis of the subclavian vein permanently destroys the ipsilateral upper extremity for future arteriovenous fistula (AVF) or graft (AVG) creation should the patient progress to end-stage kidney disease.

Warning

Avoid the subclavian vein for temporary acute dialysis access unless the internal jugular and femoral options are unavailable.

Circuit Anticoagulation: Regional Citrate vs. Systemic Heparin

Extracorporeal blood contact with foreign synthetic plastic tubing and membrane hollow fibers rapidly activates the intrinsic and contact coagulation cascades, causing circuit thrombosis. Modalities of anticoagulation include:

1. Regional Citrate Anticoagulation (RCA)

KDIGO suggests (2B) regional citrate anticoagulation rather than heparin for CRRT in patients without contraindications. RCA provides potent, complete anticoagulation confined exclusively to the extracorporeal circuit, completely eliminating the systemic bleeding risks associated with heparin.

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Mechanism : Trisodium citrate ( N a 3 Citrate Na_3\text{Citrate} N a 3 ​ Citrate ) is infused pre-filter into the arterial blood line. Citrate chelates free ionized calcium ( Ca 2 + \text{Ca}^{2+} Ca 2 + ) into soluble calcium-citrate complexes. Because ionized calcium is an obligate co-factor for the tenase and prothrombinase complexes and platelet activation, driving circuit ionized calcium down to 0.25 to 0.35 mmol/L 0.25\text{ to }0.35\text{ mmol/L} 0.25 to 0.35 mmol/L completely paralyzes the coagulation cascade inside the filter.

Systemic Neutralization : As blood returns to the patient through the venous line, an infusion of calcium chloride ( C a C l 2 CaCl_2 C a C l 2 ​ ) or calcium gluconate is administered to replenish systemic calcium stores and maintain systemic ionized calcium strictly between 1.10 and 1.30 mmol/L 1.10\text{ and }1.30\text{ mmol/L} 1.10 and 1.30 mmol/L .

Systemic Metabolism : In the patient's liver, skeletal muscle, and renal cortex, the absorbed citrate enters the mitochondrial tricarboxylic acid (Krebs) cycle, where each molecule of citrate is oxidized to yield three molecules of bicarbonate ( HCO 3 − \text{HCO}_3^- HCO 3 − ​ ) .

Citrate Toxicity / Accumulation ("Citrate Lock")

When systemic metabolism of citrate is severely impaired—characteristically in acute liver failure , decompensated cirrhosis, or profound shock states with severe tissue hypoperfusion and lactic acidosis (mitochondrial failure)—citrate cannot enter the Krebs cycle and accumulates in the circulation.

The Diagnostic Triad of Citrate Toxicity

Elevated Total-to-Ionized Calcium Ratio : Unmetabolized circulating citrate binds systemic calcium, expanding the chelated fraction. Total serum calcium appears elevated or normal, while physiologically active ionized calcium drops. A ratio of:

Total Calcium (mmol/L) Systemic Ionized Calcium (mmol/L) > 2.5 \frac{\text{Total Calcium (mmol/L)}}{\text{Systemic Ionized Calcium (mmol/L)}} > 2.5 Systemic Ionized Calcium (mmol/L) Total Calcium (mmol/L) ​ > 2.5

(Both values must be in the same units; convert total calcium from mg/dL to mmol/L by dividing by 4.0.) A ratio above 2.5 strongly suggests citrate accumulation.

2. Escalating Calcium Infusion Requirements : The infusion pump must continually increase calcium delivery to maintain a stable systemic ionized calcium level.

3. Worsening Metabolic Acidosis with an Elevated Anion Gap : Because citrate is an unmeasured circulating organic tri-anion, its accumulation expands the serum anion gap ( [ Na + ] − [ Cl − ] − [ HCO 3 − ] [\text{Na}^+] - [\text{Cl}^-] - [\text{HCO}_3^-] [ Na + ] − [ Cl − ] − [ HCO 3 − ​ ] ) while failing to yield bicarbonate.

Tip

Distinguishing Citrate Toxicity from Citrate Overload :

Citrate Toxicity (Impaired Metabolism) : Total-to-ionized calcium ratio > 2.5 > 2.5 > 2.5 , refractory systemic hypocalcemia, metabolic acidosis with high anion gap .

Citrate Overload (Normal Metabolism but Excessive Administration) : Citrate is metabolized rapidly into bicarbonate, exceeding renal or dialytic clearance, producing metabolic alkalosis and hypernatremia with a normal total-to-ionized calcium ratio ( < 2.5 < 2.5 < 2.5 ).

2. Systemic Unfractionated Heparin

Historically the most common anticoagulant, infused pre-filter and titrated to a systemic activated partial thromboplastin time (aPTT) of 45 to 65 seconds or circuit anti-Xa activity of 0.25 to 0.35 IU/mL 0.25\text{ to }0.35\text{ IU/mL} 0.25 to 0.35 IU/mL .

Major Disadvantages : Carries a 10 to 25 % 10\text{ to }25\% 10 to 25% incidence of major systemic hemorrhage, induces heparin-induced thrombocytopenia (HIT Type II), and demonstrates unpredictable resistance in septic patients due to acquired antithrombin III deficiency .