Continuous Kidney Replacement Therapy (CKRT)

• Uses an extracorporeal circuit similar to that used for intermittent hemodialysis

• Runs continuously for the duration of the circuit life, which is usually several days

• Particles can be removed by diffusion (same as hemodialysis), convection, or a combination of the two

• Fluid is removed by ultrafiltration with hydrostatic pressure across the dialyzer membrane

• The total clearance can be approximated by the total effluent rate (QE), the rate at which fluid is drained into the effluent bag

• Continuous clearance, particularly convective clearance, results in significant solute loss over time

  • Electrolytes must be monitored closely and often replaced

CKRT typically performed in

• Critically ill children

• With oliguric AKI

• That have failed medical management

Indications for CKRT rather than HD or PD

• Hemodynamic instability (accurate, predictable ultrafiltration over time)

• Large volume needs (e.g., nutritional support, FFP, high volume meds)

• Need for convective (vs. diffusive) clearance

  • Certain toxins/overdose agents may be more effectively removed via convective clearance

Clearance

• Diffusive clearance

  • Molecules move down a concentration gradient

• Generally speaking, diffusive clearance works better for small molecules and convective clearance works better for middle molecules

Types of continuous kidney replacement therapy

• SCUF: slow continuous ultrafiltration

  • Removal of fluid without replacing any fluid

• CVVH: continuous veno-venous hemofiltration

  • Pure convective clearance

  • Removal of fluid and replacement with a physiologic fluid

• CVVHD: CVV-hemodialysis

  • Pure diffusive clearance (same as HD)

  • Countercurrent fluid with dialysis

• CVVHDF: CVV-hemodiafiltration

  • Combined convective and diffusive clearance

  • Use of replacement fluids as well as countercurrent flow

• Prime replaces the blood that is brought into

• Normal saline

  • Default choice

• 5% albumin

  • Somewhat hemodynamically unstable patients

  • Lots of aluminum in albumin products

• Blood prime

  • Uses a single pass dialysis approach

    • Qb 30 mL/min

    • Qd 3600 mL/h (2x Qb)

    • All other rates off

    • Run for 5-6 minutes if using HF1000 or 2-3 minutes if using HF20 filter set

    • Give 1 mEq/kg NaHCO3 and 10 mg/kg CaCl to patient prior to start

• Circuit to circuit change

  • Probably the least likely to cause hypotension

  • Used for unstable patients or if trying to avoid another blood prime

  • Suboptimal if line is sluggish

  • Not possible if the circuit has clotted or stopped

• Returning the prime at the end of circuit life

  • If blood prime is used, do not return the blood to the patient

    • The blood in the circuit is the same

• HF1000

  • Set volume is 165 mL

• HF20

  • Set volume 60 mL

• Composed of polyarylethersulfone (PAES)

  • Biocompatible

HF20 and HF1000 have equivalent clearance at equivalent rates within the blood flow range that the HF20 is meant to operate

Max rates of HF1000 are much higher but this is really not relevant for the weight ranges that we use for the HF20

Only time that this would really matter is if the patient had massive UF requirements, e.g., intraoperative - so we use HF1000 in the OR

Other filters are available

• M series

  • M100: set volume 152 mL

  • M60: set volume 93 mL

  • Acrylonitrile (AN69)

• In septic patients they get better cytokine clearance

• Larger pores and higher sieving coefficients for cytokines

• Data do not support this practice

Risk of bradykinin release syndrome

• Profound hypotension 6-10 minutes after starting CVVH

  • Due to increased bradykinin production

  • Reaction between blood and bio-incompatible membrane

  • More common with blood prime and with AN-69 filters

  • Treat with bicarbonate, volume, calcium and epinephrine

• Can be prevented:

• 
  

  • Hackbarth RM, et al. Zero balance ultrafiltration (Z-BUF) in blood-primed CRRT circuits achieves electrolyte and acid-base homeostasis prior to patient connection. Pediatric Nephrology. 2005. 20:1328-1333.

• Rarely seen with HF (PAES) filters

• Heparin

  • systemic anticoagulant

  • Risk of iatrogenic hemorrhage

  • Can use ECMO ***

  • Dosing:

    • Loading dose: 5-25 units/kg (usually 10-20)

    • Maintenance dose: 10-20 units/kg

    • Run directly into the access line

  • Monitoring goal:

    • PTT: 40-60 (low dose), 50-70 (standard dose)

    • ACT: 120-150 (low dose), 150-180 (standard dose)

    • Anti-Xa: 0.2-0.4 (low dose)

• Citrate

  • Regional anticoagulation

  • Coagulation cascade is Ca dependent

    • Infused immediately post arterial lumen of catheter

    • Binds calcium, interfering with coagulation

    • Normocalcemia restored by infusing CaCl systemically

  • Dosing:

    • Initial citrate rate: 1.5 x Qb

      • Liver failure: 1x Qb

    • Initial Ca rate: 0.6x Qb (40% of citrate)

      • Liver failure: 0.4-1.0x citrate rate

  • Monitoring goals:

    • Circuit iCa 0.25-0.4

    • Patient iCa 1.1-1.2

    • Liver failure:

      • Circuit iCa: 0.35-0.55

      • Patient iCa: 1.1-1.2

  • Advantages:

    • Extremely effective

    • FFP administration has no effect on anticoagulation

    • iStat Ca monitoring rapid

  • Disadvantages:

    • Arterial limb not anticoagulated

    • Metabolic alkalosis

    • Hypernatremia

    • Requires another central line for CaCl administration

      • CaCl can be infused into the return/venous line

    • Citrate accumulation

  • Citrate toxicity

    • Liver metabolizes calcium citrate to H2O and HCO3-

      • Liver dysfunction decreases metabolism

      • Calcium citrate builds up in body

    • Patient/circuit ionized calciums remain the same

    • Total calcium increases

      • Tend to monitor until Ca increase to 13-15 mg/dL range

    • Treatment:

      • Reduce Qb (less citrate required)

      • Increase circuit iCal target

      • Increase clearance

      • Reset citrate/calcium at lower infusion rates

        • E.g., reset to starting doses, or drop both rates by 10-20%

      • Replace replacement fluid with lower bicarb dialysate or NS (only helps alkalosis, not total calcium)

      • Heparin

        • Wholesale switch

        • Alternatively, low dose infusion into arterial lumen with higher circuit iCal range

• Blood flow rate (Qb)

• Dialysate flow rate (Qd)

• Pre blood pump (PBP)

• Replacement fluid (QR, post-filter)

• Ultrafiltration (QUF)

  • AKA "patient fluid removal (PFR)"

• Unlike with HD, clearance/dose is NOT necessarily dependent on blood flow

• Blood flow rate (Qb)

  • Often determined by access

  • 3-6 mL/kg/min

  • 10-12 mL/kg/min may be necessary in neonates

  • 
    

• Dose

  • No data in kids, must extrapolate from adult studies

• RENAL Study: 1508 adults enrolled

  • Divided into low dose and high dose

• "CRRT dose should be dynamic and adapted to changes occurring in the acuity, physiology and metabolic profile of the critically ill patient"

  • Higher doses may be required initially or during the course of therapy

• Typical dosing at our center: 35-45 mL/kg/hour

  • Split between dialytic (QD) and convective (PBP + QR + QUF)

• Downside to higher clearance: cost, hypoPO4, higher clearance of amino acids and medications

  • We modify our fluids to approximate serum

  • Recommend more aggressive med dosing

  • Aggressive nutritional supplementation

  • We add phosphate

• Neonatal hyperammonemia: target 800 mL/h/1.73m2, which approximates iHD

• In patients with acute liver failure, higher doses may be necessary initially (80-120 mL/kg/h)

• We use BGK 2/0 and B22GK 4/0

• Typically we modify further with

  • 2 mEq/L K

  • 0.5-1 mEq/L Mg

  • 1-1.5 mmol/L PO4

• Splitting between dialytic and convective clearance is a convention

• AKI

  • Progression/irreversibility of AKI

  • Oliguria

  • Refractory fluid overload or prevention of fluid overload

  • Inadequate nutrition delivered

    • Malnutrition is one of the modifiable risk factors for AKI. If having to restrict calorie delivery to avoid severe fluid overload, then CKRT may enable you to dleiver

  • Uremia if symptomatic

    • Encephalopathy

    • Pericarditis

    • Bleeding

  • Hyperkalemia

  • Metabolic acidosis

  • Symptomatic

• Non-AKI indications

Starting CKRT: timing of initiation

• No consensus

• AKI

  • Evidence of progression / lack of evidence of recovery

  • Failure of optimal medical management

    • Calculate projected ins/outs over next 24 hours

  • Severe, refractory hyperkalemia or acidosis

  • Symptomatic uremia (typically BUN >110-120)

• Fluid overload

  • >10% warrants consideration

  • Evidence of increasing fluid requirements

  • Prevention of fluid overload (FFP, nutrition, medications)

• No increase in survival for accelerated group

• Higher continued KRT dependence in accelerated group

  • 10.4% vs 6%

  • Relative risk 1.74 (95th CI, 1.24-2.43)

  • Results consistent with IDEAL-ICU and AKIKI

• If clinical equipoise, no benefit to starting dialysis early

  • Only if

• Stop CKRT when the kidneys recover

• ATN study

  • Spontaneous fall in creatinine

  • UOP >30 mLK/h (~0.5 mL/kg/h)

  • Did 6 hour urine collection

  • Stopped if creatinine clearance >20

  • Continued if creatinine clearance <12

• IDEAL-ICU

  • In delayed therapy, did not start KRT if UOP increased to 1000 mL/24 hours

• [***]

• Roller pumps are three-headed, decreasing the peaks/troughs of the pressures to enable lower blood flow to be utilized

• Vidal study

• Garzotto studies

• Goldstein et al 2021

• 97% of patients survived CARPEDIEM to discharge vs only 44% to discharge

  • ICU survival was not different

• CARPEDIEM registry: 17 sites

• [*** comparison table]

• Prescription is per treatment, not per hour

• Must be changed every 72 hours

• No Hct line, no SvO2 monitor

https://ajkdblog.org/2022/03/01/nephmadness-2022-neonatal-nephrology-region/