Prescriptions in CRRT Timothy E Bunchman MD Professor & Director Pediatric Nephrology Timothy.bunchman@vcuhealth.org pedscrrt@gmail.com www.pcrrt.com

Factors effecting clearance in CRRT BFR Surface area of the membrane Surface areas of the membrane usually correspond to the surface area of the child, yet there are limited options with most companies so many of us “make do” Surface areas range from 0.1 to 1.6 M2 Convection vs Diffusion Duration

Convective Clearance To increase clearance by convection, increase ultrafiltration rate (will require more replacement fluids)

D Diffusive Clearance To increase clearance by diffusion, increase dialysate flow rate

Sieving Coefficients Solute (MW) Convective Coefficient Diffusion Coefficient Urea (60) 1.01 ± 0.05 1.01 ± 0.07 Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06 Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04* Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04** Calcium (protein bound) 0.67 + 0.1 0.61 + 0.07 Cytokines (large) adsorbed minimal clearance *P<0.05 **P<0.01

Typical prescription for AKI BFR 3-5 mls/kg/min Surface area ~ to body surface area Replacement or diffusive rate at ~ 2000 mls/hr/1.73 M2 (Maxvold data) 35-45 mls/kg/hr (Ronco Lancet 2000 data) Net ultrafiltration rates Target similar to urine out put to 0.5-2 mls/kg/hr but will be dictated by hemodynamics

Comparison of Urea Clearance: CVVH vs CVVHD (Maxvold et al, Crit Care med. 2000 Apr;28(4):1161-5) p = NS Urea Clearance (mls/min/1.73 m2) BFR = 4 mls/kg/min FRF/Dx FR = 2 l/1.73 m2/hr SAM = 0.3 m2

Indications for CRRT may effect decision making of the prescription AKI with electrolyte disturbance the prescription above will work But What if the child is in state of hyper-metabolism then more may be needed In born error of metabolism Intoxications Liver failure Deep et al, Crit Care Med. 2016 Oct;44(10):1910-9. What if the requirement is less Hyperosmolar states

HD to Convective HF High Flux HD 8 liter CVVH Lithium 4 liter CVVH mmol/l 4 liter CVVH 2 liter CVVH Time

Ammonia Clearance HD Begins HF Ends HD Ends HF Begins at 8 l/hr 1800 HF Ends HD Ends 1600 HF Begins at 8 l/hr 1400 1200 Ammonia (micromol/l) 1000 800 600 400 200 1 2 3 5 7 11 15 17 19 Time (hours)

Hyperosmolar state..less is better Child with AKI with a Serum glucose of 1300 mg/dl BUN of 90 mg/dl Na of 175 meq/dl (uncorrected) Measured osmols of 482 mmol/l An adjustment of the Na of the dialysate (we added 60 meq/l for a final Na bath of 200 meq/l) An inefficient prescription is warranted to avoid a rapid shift in osmols Frequent (? Q 2-4 hr) re evaluations and Na bath adjustments are needed

Time Hrs

Comparison of RRT modalities Modality CRRT SLED HD (standard or HF) PD CFPD BFR 3-5 mls/kg/min access dependent 10-20 mls/kg/pass 20-40 mls/kg/pass Dialysis Flow Rate 0-4 liters/hr 6 liters /hr 30-50 liters/hr 0.5-2 liters/hr Convective Flow Rate Systemic Anticoagulation Heparin or citrate Heparin or none none Thermic control Yes yes partial Ultrafiltration control Solutions Industry made On Line production Drug clearance Continuous Intermittent Nutritional clearance Hemodynamic stability (1 best; 4 least) 1 4 5 3 2 Solute clearance

Summary The idea of “one size fits all” for a prescription is fraught with error for each indication may need some adjustment Selecting a prescription for the indication at the beginning will allow for a more efficient mode or RRT with a benefit to the child