1. PCRRT PRESCRIPTIONS in ARF Patrick D. Brophy MD University of Michigan Pediatric Nephrology

2. Objectives Define ARF Prescriptions: Based on What? –Case Format –Modality –BFR –UF rate –Dialysate/FRF rates –Other issues – anticoagulation, access

3. Acute Renal failure Definition: A life threatening abrupt cessation/reduction of urinary output to less than 300ml/m 2 caused by prolonged renal ischemia in most cases (may occasionally present as high output renal failure- high urinary output with increasing BUN and Creatinine) Can lead to severe hypertension (fluid overload) metabolic abnormalities (acidosis, hyperkalemia) requiring emergent therapy

4. ARF-- Etiology Developing Countries –Hemolytic-Uremic Syndrome (31%) –Glomerulonephritis (23%) –Post-Op Sepsis/Prerenal ischemia Chan et.al. PIR, 23:2002 Industrialized Countries –Intrinsic Renal Disease (44%) –Post-Op Septic Shock (34%) –Organ/Bone Marrow Transplant (13%)

5. ARF—Treatment Options Conservative- fluid management and nutrition Renal Replacement Options: –Hemodialysis- Hemodynamic Instability –Peritoneal Dialysis- efficiency –CVVH(D)/(DF)- Hemodynamically less volatile than HD, Can provide optimal fluid and nutritional management & Clearance

6. Classic Case –10kg infant (75 cm) BSA=0.45m 2, high vent settings-lungs wet, ? sepsis –up 2 kg from dry weight, no urine for 12 hr –HR 160, BP 80/40 on pressors, pH 7.2 –Creatinine= 1.0 mg/dl BUN 40, lactate 4.0, iCa=1.0, K=5.8 PEDIATRIC PRESCRIPTION for CRRT

7. This patient clearly is in need of Hemofiltration ISSUES: Determining the prescription –CAVH(D)/(DF) vs CVVH(D)/(DF) –Blood Flow Rate –Ultrafiltrate (dialysate/FRF rate) –Access & Machinery –Fluids for dialysate/Filter Replacement –Anticoagulation Approach

8. CAVH(D) vs CVVH(D) CAVH(D) –Initial form of therapy, Dependent on BP of patient (difficult to control UF), Technologically easier (require 2 catheters) CVVH(D) –Newer machines, 1 catheter, improved solute clearance, increased extracorporeal volume, standard of care

9. Werner et al.,1994, Critical Care Medicine, 22, 320-325 Goals: Evaluation of CVVH using 4 week old lambs (pediatric size ~ 12.2 kg) Compared 3 systems postdilution, predilution and hemofiltration (post-filter replacement) with counter-current dialysis (standardized UF, BFR and hemofilter)

10. Werner et al.,1994, Critical Care Medicine, 22, 320-325

11. Conclusions –1) CVVH(D) feasible in this size group –2) Stable blood flow rates from 5-10 ml/kg/min –3) BFR in this range with UF rates of 1ml/kg/ min can produce urea clearance of 1 ml/kg/min (without causing to large a negative intrafilter pressure) –4) dialysis didn’t increase urea clearance (animals not uremic though)

12. Bunchman et al 1995, AJKD, 25,17-21

16. Zobel et al,1991 in Contiuous Hemofiltration. Contrib Nephrol. V93 pp257-260

17. Dialysate/ Ultrafiltration Rates No Study has identified effective, safe UF or dialysate flow rates in Children. For HEMODIALYSIS– NET UF rate of 0.2ml/kg/min is tolerated (Donckerwolke – Ped Neph 8:103-106,1994)-This extrapolates out to 1 ml/kg/ hr (NET UF) over 48 hr of continuous hemofiltration.

18. Dialysate/ Ultrafiltration Rates The UF rate/plasma flow rate [=BFRx(1-HCT)] ratio should < 0.35-0.4 in order to avoid filter clotting (Golper AJKD 6: 373-386,1985) Dialysate flow rates ranging from 10-20 ml/min/m 2 (~2000ml/1.72m 2 /hr) are usually adequate (experiential but consistent with adult data)

19. Ronco et al. Lancet 2000; 351: 26-30

20. Conclusions: –Minimum UF rates should reach at least 35 ml/kg/hr –Survivors in all their groups had lower BUNs than non-survivors prior to commencement of hemofiltration

21. Access & Machinery Machinery: –PRISMA, DIAPACT, BAXTER, EDWARDS, FRESENIUS Access: –If poor blood flow- no point in continuing! –Generally want to keep Venous pressure no > 200 mm Hg –IJ placement preferable (triple lumen ideal!) –Size based on Patient’s size

22. Bicarbonate Vs Lactate Fluid Commercial vs Custom Solutions For FRF or Dialysate –Generally Bicarbonate based solutions preferable (no definitive study to support this- but easier to interpret lactic acidosis) –FDA approved: ie. Normocarb (D –only) –Cost effectiveness: pharmacy/nursing costs

23. Anticoagulation HeparinCitrateNone –No good head to head studies comparing Heparin vs. Citrate in Pediatrics –Center specific and Comfort level

24. Other Considerations Nutrition: –CRRT allows optimization of nutritional supplementation (esp in high catabolic states- such as ARF)- but it also contributes to a negative nitrogen balance –Aim for anabolic state- 1.5 g/kg/day protein is inadequate – 2-3 g/kg/day better, with 20-30% increase in caloric intake over resting energy expenditure –Maxvold et.al. Crit Care Med 28:2000

25. Recommendations for Pediatric Prescription CVVH/CVVHD/CVVHDF—D useful when limited by membrane UF capacity Pre/Post FRF or Dialysate Combined UF+dialysate flow rates 10-20 ml/min/m2 (~2000ml/1.72m2/hr) {INCREASE WITH TOXINS) –At 0.45m2 = 540ml/hr (exceeds adult recommendations) Net UF rate 1 ml/kg/hr BFR (4-10 ml/kg/min)-Huge blood flow circulations in small infants

26. Recommendations Continued Access-Dual lumen 8 Fr (triple Lumen if available) Bicarbonate based Dialysate or FRF Anticoagulation- based on patient circumstance and center experience Maximize Nutrition (good communication among caregivers imperative)

27. ACKNOWLEDGEMENTS –MELISSA GREGORY –ANDREE GARDNER –JOHN GARDNER –THERESA MOTTES –TIM KUDELKA –LAURA DORSEY & BETSY ADAMS