Renal Replacement Therapy

Indications

  • Classic mnemonic "AEIOU": Acidosis, Electrolyte disturbances (ie hyperkalemia), Ingestions, Overload (fluid), Uremia
  • No clear cutoff values for acidosis, hyperkalemia, degree of fluid overload, uremia, etc. 
  • Some suggestion that initiation of continuous renal replacement therapy (CRRT) in patients with less fluid overload (ie <20%) is associated with improved mortality in the PICU though this remains an association and not causal. Randomizing patients to CRRT at different degrees of fluid overload would help answer this question. See the below table for studies that have demonstrated this association between fluid overload at CRRT initiation and outcome. 
     Nonetheless, there is a move towards initiating CRRT earlier rather than later in critically ill pediatric patients
  • However, in contrast, some adult studies have suggested improved outcomes with later initiation of CRRT (Schneider et al, Nephrol Dial Transplant 2012, Elseviers et al, Crit Care 2010). 
  • AKIKI, NEJM 2016, a French multicenter RCT of 620 adult ICU patients (on vasoactives and/or mechanical ventilation) with KDIGO stage 3 AKI randomized to early or delayed initiation of renal replacement therapy showed no differences in mortality with early vs. delayed initiation (48.5 vs 49.7%, respectively). Furthermore, 49% of the patients in the delayed group did not require renal replacement therapies.It should be noted that a large proportion of patients receiving iHD (>50%) vs CRRT (~30%).

Fundamentals of Dialysis and Ultrafiltration

  • Diffusion: Transport of solutes across a semi-permeable membrane, generated by a concentration gradient. In dialysis, this is generated using a dialysate solution running countercurrent to the blood and separated from the blood via a semi-permeable membrane. The composition of the dialysate (generally physiologic electrolyte levels) determines the concentration gradient, and this, along with the dialysate flow rate, determines the amount of diffusion or removal of electrolytes that occurs
Figure 1: Diffusion across a semi-permeable membrane

 
  • Convection: Solutes are transported across a semi-permeable membrane with solvents (fluid) as a result of solute drag due to a transmembrane pressure. 
Figure 2: Convection
  • Ultrafiltration: Movement of fluid (plasma water) through a semi-permeable membrane due to a pressure gradient
  • Adsorption: Molecules adhere to the surface of semi-permeable membrane, removing it from the circulation (can occur with TNF and other cytokines, beta-2 microglobulin, etc)
Figure 3: Adsorption to the Membrane


Figure 4: Membrane Selectivity Based On Molecular Size

Figure 5: Clearance Based On Molecular Size


Peritoneal Dialysis (PD)

  • peritoneal membrane used as a dialyzing membrane
  • Dialysis fluid instilled into the peritoneal space permits diffusion of particles out of the blood (ie with a hypertonic solution, water moves out of the blood)'
  • As plasma water moves out of the blood, it also drags solute and so convection occurs
  • Fluid removal slower and more gentle
  • Adjustments in fluid osmolality and dwell time can be made to adjust volume removed
  • Also provides metabolic control and can correct uremia
  • Need access to intraabdominal space
  • Risk for infection/peritonitis
  • High dextrose solutions can lead to hyperglycemia
  • Reduction of diaphargmatic excursion due to filling of the abdomen
  • Potential issues in critically ill patients who may have ascites and already be at risk for intraabdominal hypertension/abdominal compartment syndrome

Intermittent Hemodialysis (iHD)

  • Rapid and high efficiency fluid removal and metabolic control
  • Optimal modality for particle removal (ie toxins) such as ammonia
  • The rapidity of fluid removal may be a drawback in critically ill patients who may be hemodynamically unstable
  • Vascular access critical with need for large caliber catheters to facilitate sufficient blood flow for dialysis to occur and for clotting to be prevented

Continuous Renal Replacement Therapy (CRRT)

  • Extracorporeal device that essentially functions as a kidney, providing continuous fluid removal and blood purification
  • Utilizes a semi-permeable membrane (filter) with counter-current dialysate fluid to remove fluid and particles via diffusion, convection, as well as adsorption

Examples:

1) SCUF: Slow Continuous Ultrafiltration: Basically, take blood out from the patient, pass it through a semipermeable membrane at pressure, leading to fluid removal (ultrafiltration) with some solute loss as a result of convection. No dialysate solution or replacement fluid is used.

Figure 6: SCUF 

2) CVVH: Continuous Veno-venous hemofiltration: Utilizes convection but no dialysate fluid so no diffusion
3) CVVHDF: Continuous veno-venous hemodiafiltration: Utilizes convection as well as a dialysate fluid to produce diffusion

Figure 7: CVVHDF

Anticoagulation for CRRT

  • Need to anticoagulate as the blood that comes into contact with the artificial tubing/filter of the CRRT machine is prone to clot
  • Generally achieved with regional anticoagulation, meaning only the blood that is entering the CRRT circuit is anticoagulated via the entire patient (systemic anticogaulation)
  • Done using citrate, which chelates calcium. Calcium is a critical cofactor in nearly every step of the coagulation cascade.
  • Hence, blood is drawn out of the patient, Citrate is infused into it, reducing the ionized calcium from a normal value of ~ 1.0-1.2 mmol/L to a value of 0.25-0.4 mmol/L, thus effectively anticoagulating it as it traverses the CRRT circuit
  • The patient requires a Calcium Chloride infusion to restore their ionized calcium or else they would be effectively systemically anticoagulated (and likely have cardiovascular collapse from hypocalcemia)
  • Citrate lock can occur. Citrate is normally cleared by the liver. Hence, in the setting of liver injury or failure, citrate can accumulate, still bound to calcium. Hence, the patient's total calcium may be very high, yet their ionized calcium remains normal
    • Treatment: Increase the dialysate infusion rate which increases the amount of citrate removed from the blood, thus returning less citrate to the patient
    • Decrease blood flow rate and citrate rate (decreases the rate of citrate delivery to the liver, thus allowing proportionally more clearance- but also decreases the effectiveness of your renal replacement therapy)
    • Reset the citrate and calcium infusion to the starting rate, which decreases the amount of citrate being delivered to the patient, allowing the current citrate levels to be metabolized by the patient
    • Hold citrate and calcium infusions for a short time period (requires frequent monitoring of circuit and patient ionized calcium)
  • Titrate calcium chloride infusion to achieve patient ionized calcium level goals of 1.1-1.3 mmol/L. 
  • Titrate citrate infusion to achieve circuit ionized calcium levels of 0.25-0.4 mmol/L

General Dosing Guidelines

  • Blood Flow Rate – 5ml-10ml/kg/min 
  • Dialysate Rate – 2000ml/m2/1.73 
And/Or 
  • Replacement Rate – 2000ml/m2/1.73 
  • Post: 50 – 100 ml/hour (Prevent clotting in venous chamber) 
  • Dialysate and Replacement Combined Rate 2000ml/m2/1.73 (Any combination)
  • Patient Fluid Removal Rate – Net Loss 1-2ml/kg/hr
  • Standard Solution – PrismaSol 
    • Na 140 mEq/L 
    • Cl 106.2 mEq/L 
    • HCO3 32 mEq/L 
    • Mg 1.2 mg/dL 
    • Additives: Potassium 0 – 4 mEq/L (Standard 3 mEq/L), Phosphate 0.75 – 1.5 mg/dL (Standard 1.5mg/dL)

Filter Sets:

  • M 60 Filter Set 
    • < 25 Kg Patients 
    • Priming Volume – 93 ml 
    • Membrane Characteristics – AN69 
    • Membrane Size – 0.6 m2 
    • Maximum BFR – 180 ml/min 
    • Maximum Ultrafiltration – 38-55 ml/min (2280 – 3300 ml/hour)
    • BFR 100-180 respective

  • HF 1000 Filter Set 
    • > 25 Kg Patients 
    • Priming Volume – 165 ml
    • Membrane Characteristics - PAES (Polyarylethersulfone) 
    • Membrane Size – 1.15 m2 
    • Maximum BFR – 400 ml/min 
    • Maximum Ultrafiltration – 74 ml/min (4440 ml/hour) 
    • BFR – 200 ml/min

Initiation Procedures:

  • Extracorporeal circulating volume is less the 10% of the patients total calculated blood volume. 
    • Standard Initiation with a saline primed circuit, if the circuit volume is < 10% of the patients calculated blood volume 
  • Bypass Maneuver Initiation with PRBC, if the circuit volume is >10% of the patients calculated blood volume 
    • Prior to initiation, obtain a patient ABG with ICa ++. 
    • Protocol includes infusion of 30mEq NaHCO3- pre-filter at initiation
  • Have calcium chloride, volume, Sodium Bicarbonate, and vasoactives available for initiation (i.e. epinphrine spritzer)
Figure 8: Citrate and Calcium Titration Guidelines

Special Considerations for CRRT

  • The AN-69 membrane (M60 filter) used for smaller patients (<25 kg) is known to be associated with profound hypotensive events upon blood contact with the membrane. This is thought to be related to bradykinin release and is thought to be more profound with low blood pH. Hence, pretreating with bicarbonate to ensure a less acidic pH is often done. The AN-69 membrane also appears to provide relatively high IL-6 clearance
  • Fever can be masked as the extracorporeal circuit effectively acts like a large radiator, hence vigilance for infection is critical
  • Protein (essential amino acids) can be lost with CRRT, hence, protein supplementation (generally ~ 3 g/kg/day) is recommended


References

1) Tobe SW, Aujla P, Walele AA, Oliver MJ, Naimark DM, Perkins NS, Beardsall M: A novel regional citrate anticoagulation protocol for CRRT using only commercially available solutions. J Crit Care 18: 121–129, 2003
2) S. Walters, C. Porter, P.D. Brophy: Dialysis and pediatric acute kidney injury: choice of renal support modality.Pediatr Nephrol. 24:37-48 2009
3) J.A. Foland, J.D. Fortenberry, B.L. Warshaw, et al.: Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med. 32:1771-1776 2004
4) S.L. Goldstein, H. Currier, C. Graf, et al.: Outcome in children receiving continuous venovenous hemofiltration. Pediatrics. 107:1309-1312 2001